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BACKGROUND OF THE INVENTION
The present application is a continuation-in-part of application Ser. No. 07/636,487, filed on Dec. 31, 1990.
This invention pertains to the art of methods and devices capable of separating oxygen from air, and more particularly, to the separation of oxygen from air to supplement an otherwise deficient oxygen supply, such as in aircraft flying at high altitudes.
DESCRIPTION OF RELATED ART
It is common for aircraft traveling at high altitudes to supplement oxygen to pilots and passengers via the use of stored oxygen. Typically, the oxygen is stored in heavy, bulky steel cylinders. The cylinders are replenished between flights from a ground-based oxygen source. The present invention could be utilized to eliminate the need for such cylinders and thereby reduce the weight of an aircraft's oxygen supplying equipment. Because weight is a critical consideration in aviation, advantages in runway length required, fuel required, and other significant advantages are obtainable by decreasing the weight necessary for supplying oxygen to passengers and crew.
Extra cylinders are normally carried in the event that some aspect of the flight goes amiss. For example, if a runway is shut down, or if the landing gear on the airplane does not function properly, it may be necessary for the aircraft to fly for a few hours longer than originally estimated. Due to these occurrences, extra cylinders of oxygen are carried on aircraft to allow for these contingencies. If a method was available whereby cylinders could be replenished over the course of the flight, contingency cylinders would not be necessary.
Some devices have been developed to separate, concentrate, or generate oxygen from ambient air. Many of these devices are based on nitrogen adsorption systems which concentrate oxygen from air to deliver a maximum of 95% O 2 by removing nitrogen from ambient air. U.S. Pat. No. 4,449,990 describes one such apparatus. Such devices require a parasitical purging of one tank by pure oxygen from another tank in order to maintain effectiveness. Further, moisture in a system can be damaging to the nitrogen adsorption material.
To overcome the foregoing deficiencies in the art, applicant saw the need for a lightweight device which could generate pure oxygen from pressurized air to supplement or replace oxygen stored in cylinders on aircraft.
The present invention contemplates a new and improved oxygen generation system which overcomes many of the foregoing difficulties and deficiencies in the prior art while providing better and more advantageous overall results.
SUMMARY OF THE INVENTION
In accordance with the present invention, a new and improved oxygen concentration system is provided which utilizes an electrochemical process. More particularly, in accordance with the invention, the oxygen concentration system includes an electrochemical oxygen generator which has an outer surface and selectively extracts oxygen from air by an electrochemical reaction. The generator is contained within a first enclosure which has a top end and a bottom end. The first enclosure is contained within a second enclosure which also has a top end and a bottom end. The second enclosure is contained within a third enclosure which also has a top end and a bottom end. A first annulus is formed between the outer surface of the generator and an inner surface of the first enclosure. A second annulus is formed between an outward surface of the first enclosure and an inward surface of the second enclosure. A third annulus is formed between an outward surface of the second enclosure and an inward surface of the third enclosure. Near the top end of the third enclosure, there is an inlet. Pressurized air enters the inlet and travels downwardly in the third annulus, upward in the first annulus, and downward in the second annulus, exiting the oxygen concentration system through the second annulus.
According to a further aspect of the invention, the second enclosure is made of a non-insulating material.
According to another aspect of the invention, the air entering the third annulus is cooler than the air in the second annulus, the second enclosure transferring heat from the air in the second annulus to air in the third annulus.
According to another aspect of the invention, the third annulus contains the coolest air in the system.
According to another aspect of the invention, the system comprises ports which extend between the third annulus to the first annulus. The ports isolate air traveling in the ports from air within the second annulus. The ports extend through the first and second enclosures at a point adjacent the bottom and of the third enclosure. In one embodiment, the inner and outer surface of the ports have fins which increase heat transfer from air outside the port to the port and heat transfer from the port to the air inside the port.
According to another aspect of the invention, the top end of the second enclosure is covered with an inner outer dome. The inner outer dome has inward and outward surfaces, the inward surface being reflective.
According to another aspect of the invention, the top end of the third enclosure comprises an outer upper dome, an apex of the outer upper dome comprising an orifice.
According to another aspect of the invention, an oxygen concentration system for producing oxygen from pressurized air comprises an electrochemical oxygen generator which has an outer surface and selectively extracts oxygen from air by an electrochemical reaction. Inner and outer enclosures are concentric with the generator, the generator being received within the inner enclosure which is in turn received with the outer enclosure. An inner annulus is formed between the generator and the inner enclosure and an outer annulus is formed between the inner enclosure and the outer enclosure. Air in the outer annulus is cooler than air in the inner annulus. The system operates on pressurized air and is independent of orientation.
According to another aspect of the invention, an oxygen concentration system suitable for replenishing oxygen cylinders on aircraft comprises a plurality of electrochemical oxygen generators, the generators are arranged in a hexagonal array and selectively produce oxygen from air by an electrochemical reaction. The generators have an outer surface. A first enclosure has top and bottom ends and inward and outward surfaces. The plurality of generators are received within the first enclosure. The first enclosure is thermally insulated to keep heat from the generators within the first enclosure. The top end of the first enclosure is open. The bottom end of the first enclosure comprises a bottom dome. An apex of the bottom dome comprises an orifice. The orifice is connected to conveying means extending between the orifice and the plurality of generators. The conveying means, in the preferred embodiment a series of rods, conveys oxygen produced by the generators to the orifice; the orifice being connected to a mechanical compressor to fill associated oxygen storage cylinders. A second enclosure has a top and bottom end and inward and outward surfaces. The first enclosure is concentrically received within the second enclosure. The top end of the second enclosure comprises an inner upper dome. The inner upper dome is made of non-insulating material and has a reflective surface. The bottom end of the second enclosure comprises an inner bottom dome. The inner bottom dome is made of an insulating material and has a reflective surface. A third enclosure has a top and bottom end and inward and outward surfaces. The second enclosure is concentrically received within the third enclosure. The top end of the third enclosure comprises an outer upper dome; an apex of the outer upper dome terminating in an orifice. The bottom end of the first enclosure comprises an outer bottom dome. The outer bottom dome is made of an insulating material. A first annulus is formed by the outer surface of the plurality of generators and the inward surface of the first enclosure. A second annulus is formed by the outward surface of the first enclosure and the inward surface of the second enclosure. A third annulus is formed by the outward surface of the second enclosure and the inward surface of the third enclosure. Ports connect the third annulus to the first annulus. The ports extend through holes in the first and second enclosures. The ports are aerodynamically shaped so as to reduce losses within the second annulus. The ports have fins extending into the second annulus to transfer heat from air in the second annulus to the port. The port also has fins extending inwardly into the port to transfer heat from the port to air in the port.
According to a still further aspect of the invention, a method of replenishing oxygen storage cylinders comprises the steps of energizing an electrochemical generator, the generator capable of generating oxygen from air on application of an electric current;
introducing pressurized air to said generator;
directing oxygen produced by the generator to associated oxygen storage cylinders in replenishing the cylinders therewith;
directing oxygen-depleted air from the generator in a heat-exchanging relationship to cooler incoming pressurized air.
One advantage of the present invention is the provision of a device which can operate independent of orientation. Namely, in that the device operates on the basis of pressurized air, rather than convection or some other orientation-sensitive phenomena. The system can operate effectively regardless of orientation. This is important when the device is used in aircraft such as jet fighters which may assume any orientation during the course of a mission.
Another advantage of the invention is the reduced weight over an amount of oxygen storage cylinders necessary to supply an equivalent amount of oxygen. As stated earlier, aviation is highly dependent on the weight necessary to accomplish a certain task. By reducing the number and/or size of oxygen cylinders required for a mission, advantages in fuel, speed, runway length, and aircraft design are obtainable.
Another advantage of the present invention is the efficient conservation and utilization of heat generated by the electrochemical oxygen generators. Because these generators operate at high temperatures, and because the oxygen must cool down before suitable for consumption by humans, the invention utilizes heat transfer techniques and specific configurations to keep as much heat as possible in the generator itself and use cooler incoming air to cool down the exiting gases. Energy savings result from using warm exiting air to preheat incoming cooler air.
Still other benefits and advantages of the invention will become apparent to those skilled in the art upon a reading and understanding of the following detailed specification.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention may take physical form in certain parts and arrangements of parts, a preferred embodiment of which will be described in detail in the specification and illustrated in the drawings which form a part hereof and wherein:
FIG. 1 is a plan view, partially in section, of one embodiment of a tubular, stepped, stacked, oxygen generator used in this invention, showing the cell configuration, in sealed portions, power contacting connections, and source of air;
FIG. 2 shows another embodiment of the oxygen generator used in this invention, in plan view partially in section;
FIG. 3 is front elevational view in partial cross-section showing one embodiment of the present invention with the rods removed for clarity;
FIG. 4 is an enlarged front elevational view in partial cross-section showing the upper half of the embodiment shown in FIG. 3;
FIG. 5 is an enlarged front elevational view in partial cross-section showing the lower half of the embodiment shown in FIG. 3;
FIG. 6 is an end view of one of the ports according to the invention; and,
FIG. 7 is a top cross-sectional view of the invention taken along line 7--7 of FIG. 3.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings, wherein the showings are for purposes of illustrating a preferred embodiment of the invention only, and should not be used to limit the scope of the invention, FIG. 3 shows a front, elevational, cross-sectional view of the invention.
The invention essentially comprises a specially designed housing enclosing an oxygen generator 10. The oxygen generator 10 generates oxygen from air via an electrochemical process. The specially designed housing orients airaround the generator 10 in specially advantages ways.
In some applications, due to oxygen flow rate demands or geometric constraints, a single tubular generator 10 is a preferred configuration. In other applications, a plurality of generators 10 will be the preferred configuration. When a plurality of generators 10 is used, a preferred configuration of the generators 10 is in the form of a hexagonal array.
The number of generators 10 in each array are determined by the oxygen production requirements of the system and by the following mathematical formula: ##EQU1##where
X=total number of generators in array
N=number of generators along a radius of the array
A series of numbers which are solutions to the above equation are:
1, 7, 19, 37, 61, 91, 127, 169, 217, 271, . . .
For example, in array featuring nineteen tubular generators 10, the array would feature a single generator 10 in the center, surrounded by six generators 10, which in turn are surrounded by twelve generators 10. In the embodiments shown in FIGS. 3-5, N=2 and the array comprises seven generators 10.
The hexagonal configuration of the array is advantageous for minimizing thevolume necessary to accommodate a certain number of generators 10. The hexagonal shape permits a large number of generators 10 to be put into a small volume.
For example, the following chart shows how the hexagonal arrangement of thegenerators 10 allows for greatly increased oxygen production without a proportionate increase in volume required. The chart describes several embodiments of the invention.
__________________________________________________________________________ Generator Diameter = 2 inches Generator Voltage = 37 volts Generator Current = 36 amps Generator Length = 39 inches System Height = 60 inches No. Cells = 53 Cell Length = 0.7 inches Cell Area = 2.8 sq. in. Oxygen System System System Power PowerNo. of Delivery Diameter Volume Weight Required RequiredGenerators (1 pm @ RTP) (inches) (cu. ft.) (lbs) (kW) (hp)__________________________________________________________________________ 1 7 8 2 41 1 2 7 50 11 3 56 9 1219 137 16 7 139 25 3437 268 21 12 263 49 6661 442 26 18 419 81 10991 659 31 26 628 121 163127 921 36 35 870 170 227__________________________________________________________________________
The hexagonal configuration also aids in retaining heat within first enclosure 120. Finally, the configuration provides for uniform heating of the generators 10 within the first enclosure 120 via radiation.
The determination of the number of generators 10 necessary for a specific oxygen generation system requires an initial evaluation of the volume available for the generators 10.
When a range of acceptable generator 10 lengths is determined, the area of generators 10 can be determined by knowing the surface areas of individualcells within the generator 10. In the one embodiment, each cell had an areaof 18 cm 2 , a driving current density of 1.5 A/cm 2 , and a cell current of 27 A. The oxygen production would be (27 A/cell)(3.80 ml/A-min)=102.6 ml O 2 /min-cell. Multiplying this number by the number of cells per generator 10 yields the oxygen production of each generator 10. By increasing the current density, the number of cells 12 can be decreased. By adjusting the number of cells per generator 10, the number of generators 10 can be adjusted to fit within the hexagonal array as described above.
A second, currently preferred, embodiment of an oxygen concentration systemhas been developed which utilized seven electrochemical generators 10. The embodiment was developed for an aircraft application requiring an oxygen deliver rate of 13.1 liters/min.
The physical dimensions of the system appear in Table A. The weight of the system components appear in Table B. The electrical parameters, power requirements, and oxygen delivery are detailed in Table C.
TABLE A______________________________________Generator Diameter 2.05 in.Generator Spacing 0.5 in.Effective Diameter 2.55 in.Generator Length 39.37 in.No. of Cells 53System Length 60 in.Generators/System 7Diameter of Hexagonal Array 8 in.Insulation Thickness 2 in.Annuli Gap 1 in.Overall Diameter 16 in.Total Cross-Sectional Area 200 sq. in.Volume 7 cu. ft.______________________________________
TABLE B______________________________________Generator Weightcells 5.33 lbs.two end caps 0.38 lbs.Alumina Tube 0.15 lbs.Inconel Rod 0.80 lbs.Weight/generator 6.66 lbs.Total Weight-Seven Generators 47 lbs.Insulation 14 lbs.Enclosures 21 lbs.Electronics 18 lbs.Total System Weight 100 lbs.______________________________________
TABLE C__________________________________________________________________________ CurrentOxygenVoltage Current Density Power Required (watts)(1 pm)(volts) (amps) (mA/cm.sup.2) O.sub.2 T.sub.e * Heat (Cool) Total__________________________________________________________________________13.1 9.57 9.29 516 622 418 1960 300038.3128 27.16 1509 5323 0 (2323) 532328.7521 20.38 1132 2996 999 (995) 399519.1614 13.59 755 1332 190 1478 30009.58 7 6.79 377 333 48 2620 30005.48 4 3.88 216 109 0 2891 3000__________________________________________________________________________*T.sub.e = electronics
The operation of the generators 10 and the electrochemical reaction by which the generators 10 concentrate oxygen from air will be discussed later in this specification.
With reference to FIGS. 3 and 4, a first enclosure 120 surrounds the generators 10. The first enclosure 120 is annular in shape, having an inward surface 122, and outward surface 124, and a top and bottom end 126,128. The portion of the first enclosure 120 between the inward surface 122 and the outward surface 124 comprises the interior of the first enclosure 120. The interior 144 of the first enclosure 120 is insulated with aluminosilicate. In the preferred embodiment, the insulation 144 is 2 inches thickand has a reflective backing which holds the fibers together, as well as contributing to the efficiency of the device by reflecting infrared radiation back into the generators 10. The preferred insulation material is manufactured by the Carborundum Company under the trade name Fiberfrax® HSA Systems.
The first enclosure 120 is concentrically arranged about the center of the generators 10. The top end 126 of the first enclosure 120 is open. With reference to FIG. 5, the bottom end 128 comprises an outer bottom dome 130which terminates at an apex in an orifice 132. The outer bottom dome 130 ismade of a thermally insulating material. Within the outer bottom dome 130 there is an inner bottom dome 136. The inner bottom dome 136 is also made of a thermally insulating material. An inward surface 137 of the inner bottom dome 136 is made of a reflective material, so as to reflect infrared radiation back into the generators 10. The inner bottom dome 136 has a larger radius of curvature than the outer bottom dome 130. Outer edges of the inner bottom dome 136 are attached to the inward surface 122 of the first enclosure in an airtight seal, preventing transmission of gasfrom one side of the inner bottom dome 136 to the other.
With reference to FIGS. 1, 2, 4, and 5, the generators 10 are supported within the oxygen generation system via rods 30. The rods 30 function to support the generators 10 within the system. The rods 30 also can be used to heat the generators 10 in a manner that will be discussed below. With reference to FIG. 1, the rods 30, along with sleeves 34, also function as conveying means to convey oxygen produced by the oxygen generators 10 downwardly through the first enclosure 120 to the orifice 134 and eventually to associated storage cylinders. An annulus is formed between the sleeve 34 and rod 30. Oxygen produced by the generator 10 exits the device through this annulus. For ease of illustration and discussion, the rods alone will be illustrated in most of the FIGURES.
With reference to FIGS. 3-5 and 7, a first annulus 140 is formed between outer surfaces of the generators 10 and the inward surface 122 of the first enclosure 120. The first annulus 140 serves as a passageway for air within the system.
With reference to FIGS. 3, 4, and 7, a second enclosure 150 comprises inward and outward surfaces 152, 154 and top and bottom ends 156, 158. Thesecond enclosure 150 is made of a thermally-non-insulating material so thatheat may be transferred through it easily. In the preferred embodiment, this material is aluminum The top end 156 of the second enclosure 150 comprises an inner upper dome 160. The inner upper dome 160 is made of thermally-non-insulating, but reflecting material. In the preferred embodiment, this material is aluminum. The reflective material is on the inward side of the inner upper dome 160 and is effective to reflect infrared radiation which emanates from the generators 10 back within the first annulus 140. The inner upper dome 160 is closed. The bottom end 158 of the second enclosure is open.
A second annulus 170 is formed between the outward surface 124 of the firstenclosure and the inward surface 152 of the second enclosure.
A third enclosure 180 comprises inward and outward surfaces 182, 184 and top and bottom ends 186, 188. The top end 186 of the third enclosure 180 comprises an outer upper dome 190. The third enclosure 180 concentrically receives the second enclosure 150 which concentrically receives the first enclosure 120. An apex of the outer upper dome 190 terminates in an orifice 192.
The bottom end 188 of the third enclosure 180 is attached to the outer surface 154 of the second enclosure 150.
With reference to FIGS. 3 and 5-7, near the junction of the bottom end 188 of the third enclosure and the outward surface 154 of the second enclosure150 are a plurality of ports 200. The ports 200 are tubular-like passageways through the first and second enclosures 120, 150. The ports 200 prevent air in the ports 200 from mixing with air in the second annulus 170. The ports 200 are aerodynamically-shaped to reduce losses arising from air which is travelling downwardly in the second annulus 170 impacting the ports 200. In the preferred embodiment, the ports 200 are angled so that air exiting the third annulus 210 is tangentially received into the area beneath the generators 10. In FIG. 5, in the preferred embodiment, fins 194, 195 are placed on the outward surface and inward surface of the ports. Fins 194 on the outward surface of the ports 200 areeffective to transfer heat from air in the second annulus to the ports themselves. Fins 194 on the inward surface of the ports 200 are effective to transfer heat from the ports 200 themselves to the air travelling in the ports 200. In the preferred embodiment, there are three ports 200 about the circumference of the oxygen generation system.
With reference to FIGS. 3, 4, and 7, a third annulus 210 is formed between the outward surface 154 of the second enclosure and the inward surface 182of the third enclosure 180.
An upper end 230 of each of the rods 30 and each of the sleeves 34 is fixedly attached to the inward surface of the inner upper dome 160 but do not penetrate the inner upper dome 160. In other words, the upper ends 230of the rods 30 and sleeves 34 comprise a closed passageway for oxygen travelling along the rod 30. To exit the system, oxygen must travel downwardly to a lower end 232 of each rod 30.
With reference to FIG. 5, the lower ends 232 of each of the rods 30 and each of the sleeves 34 are fixedly attached to the inner bottom dome 136. The lower ends 232 penetrate the inner bottom dome 136, allowing oxygen totravel from the generators 10 to the rods 30 to a reservoir 236 between theinner bottom dome 136 and the outer bottom dome 130. The oxygen that collects in the reservoir 236 is pushed out orifice 132 due to pressure generated by the electrochemical reaction itself, as is explained later inthis specification.
The operation of the enclosures and annuli in regards to oxygen generation will now be explained with reference to FIGS. 1-7. Because the system operates at a pressure slightly above ambient, the system is operative independent of its orientation. The system is not "pressurized" in the sense that the housings 120, 150, 180 and domes 160, 190 are designed to withstand large pressure differences. Typically, the compressors of the aircraft's jet engine are used to provide compressed air at pressures between ambient and 400 pounds per square inch (psi). Typically, incoming air pressure will be slightly above ambient and total losses over the system are about 1 psi. The pressurized air is introduced into orifice 190. The pressurized air so introduced impacts the outer surface of the inner upper dome 160 and travels downwardly in the third annulus 210 untilreaching the ports 200. For the purposes of this explanation, directions such as "upward" and "downward" will be utilized with reference to FIG. 3,with the top of the page being "up" and the bottom of the page being "down". It is important to understand that one of the benefits of this invention is that it can operate effectively regardless of orientation. Inother words, whether or not orifice 192 is at the "top" of the generation system, air will travel through the device in the manner described below. The pressure of the incoming air can be used to modulate the flow rate of air, which in turn can be used to modulate the temperature of the device. Since the exhaust air carries away some heat generated by the generators 10, a change in the air flow rate affects the temperature of the device.
Air passes downwardly in the third annulus 210, to and through the ports 200 and into the area beneath the generators 10. As the air passes upwardly through the generators 10, oxygen is produced in an electrochemical reaction which will be described below. Oxygen so producedtravels through an annulus formed between a hollow sleeve 34 and solid rods30 to discharge tube 220 where a mechanical compressor (not shown) stores the oxygen in associated storage cylinders (not shown). As the air passes through the generators 10, it is heated significantly and exits the top end 126 of the first enclosure 120. The air at this location of the deviceis the hottest air in the oxygen generation system.
The heated air now impacts the inward surface of the inner upper dome 160. The inward surface is thermally-non-insulating but is reflective. These qualities enable the inner upper dome 160 to transfer heat from the hot air exiting the generators 10 to the cooler air entering the system through orifice 192. At the same time, the reflective nature of the inner upper dome 160 reflects infrared heat back to the generators 10 and the first annulus 140.
After impacting the inward surface of the inner upper dome 160, the air is directed by the shape of the inner upper dome 160 into the second annulus 170. The air passes downwardly through the second annulus 170 and eventually out of the system. During the time the hot air is travelling downwardly in the second annulus 170, it is cooled in two ways. First, theair flows over ports 20 and fins 194. Heat from the air is transferred to the ports 200 and eventually to air flowing in the ports 200 via fins 195.Second, air in the second annulus 170 is juxtaposed beside the coolest air in the system, that incoming air in the third annulus 210. This arrangement provides a couple of advantages. First, energy is conserved inthat air in the third annulus 210 is heated by the air in the second annulus 170. Further, the coolest air in the system is positioned at the outer surface, i.e. the third annulus 210. This causes the outward surface184 of the third enclosure to be cool, which provides safety and comfort benefits. Even though the device operates at very high temperature, on theorder of 900° C., the outer surface is cool to the touch and the danger of burns to humans or other heat-sensitive entities around the oxygen generation system is minimized.
An important material-related feature is the use of silver lead wires for electrical connections. Because the device operates at about 900° C., care must be taken to chose materials which will retain operational and dimensional stability at those temperatures. Silver melts at 961° C., and therefore can remain dimensionally stable at these operating temperatures. Another advantage is that silver will not oxidize.While gold and platinum will also work, silver is preferred for applications which operate at temperatures below its melting point becauseit is less expensive and is not subject to oxidation, as is platinum. Platinum, with a melting point of 1,769° C., is the preferred material at operating temperatures above the melting points of gold and silver. The top end 230 of rod 30 is preferably used as the electrical contact for incoming electrical power. The top end 230 is relatively cool.
With reference to FIG. 1, the operation of the electrochemical oxygen generator 10 will now be explained. In this explanation, the term "tubular" is meant to include any axially elongated structural form havinga closed cross-section. The term "air electrode" means that electrode whichcontacts ambient air on the outside of the generator and allows formation of oxygen ions from oxygen in the air. The term "oxygen electrode" means that electrode which allows formation of oxygen gas from oxygen ions and allows passage of the oxygen gas into the interior of the generator. The term "dense" means at least 95% of the theoretical density.
The generator 10 is driven by a DC power source. Aircraft typically utilizea 28 volt DC power supply. The generator 10 operates at from 65° C. to 1,100° C. with preheated air and is able to extract pure oxygen at the electrolyte surface at a rate proportional to the electric current.
Referring now to FIG. 1 of the drawings, a high temperature electrochemicaldevice 10 useful as an oxygen generator is shown, having a closed cross-section, preferred tubular form, and comprising a plurality of adjacent electrochemical cells, the active lengths of which are shown as first cell 12 and adjacent cell 12', arranged end to end. In some embodiments, a single tubular oxygen generator is used. In other applications, such as some which require higher flow rates, a series of tubular oxygen generators can be placed within a single inner housing. In such cases, the currently preferred arrangement is a hexagonal array. A currently preferred embodiment features seven generators 10 in such a hexagonal array. The cells 12 are electrically connected in series throughcontinuous, spaced-apart solid oxide electrolyte bands or segments 14, continuous, spaced-apart air electrode band 16, continuous, spaced-apart interconnection segments 18, and continuous, spaced-apart oxygen electrodebands 20.
Optional, porous support 22, which is preferably from 20% to 40% porous (80% to 60% of theoretical density), and which is generally used, as shown, supports oxygen electrodes 20 and the rest of the structure. Dense,solid electrolyte 14 is disposed on top of part of the inner oxygen electrode 20 starting a predetermined length from a first end 20' of each oxygen electrode. Outer porous air electrode 16 is disposed on top of partof the electrolyte 14 and in contact with air 23 which surrounds the generator body 10.
Electrical connection from cell to cell is made by a stacked configuration,where dense, preferably 100% dense, gas impervious, electronically conductive inner-connection 18 is deposited over and contacts part of the uncovered portion of support 22 next to the oxygen electrode 20 from cell 12' and overlaps a portion of that oxygen electrode. Dense, gas impervious, ionically conducting, solid electrolyte 14 from first cell 12 is deposited on top of the inner, oxygen electrode 20 from cell 12 continuing beyond the end 21 of the oxygen electrode and onto the remaining uncovered portion of support 22, overlapping inter-connection 18next to cell 12' but not contacting the adjacent oxygen electrode band 20 of cell 12'. The combination of electrolyte and inner-connection closes off the porosity in the underlying support and oxygen electrode. Both electrolyte and inner-connection material are disposed between inner electrodes of adjacent cells, and this is essential in this design to prevent gas leakage.
In the embodiment shown in FIG. 1, the dense electrolyte 14 overlaps the dense inter-connection 18 between cells 12 and 12' and overlaps the dense inter-connection 18 near the positive terminal 26, which latter connectionforms a dense end portion for that device. This overlapping produces a gas impermeable barrier between the outside and the inside of the device.
Air electrode 16 from cell 12 is deposited on top of the electrolyte 14 from cell 12 continuing until contacting the inter-connection 18 between cells 12 and 12'. To prevent electrical shorting between cells, a gap region is maintained between the air electrode 16 of cell 12, and the electrolyte 14 of cell 12'. These coatings of materials can be laid down by any suitable application masking techniques, such as electrochemical vapor deposition, sputtering, powder sintering, plasma arc spraying, and the like. Electrochemical vapor deposition is a preferred method of depositing electrolyte and inter-connection materials, and reference may be made to U.S. Pat. No. 4,609,562 (Isenberg, et al.) herein incorporated by reference for details on that process.
This generator device is capable of generating oxygen gas from air upon application of an electrical current. Electrons from a DC power source (not shown) are fed into a terminal 24 (negative terminal), preferably of round washer design having an extended bus bar contact area. The electronspass through the air electrode 16 of cell 12', where oxygen in the air 23 which need not be pressurized, is reduced at the operating temperature of the generator, preferably 650° C. to 1,100° C., to provide oxygen ions O = , which pass through the ionically conductive, electronically non-conducting (does not pass e - ) solid electrolyte 14. The oxygen ions recombine to form pure O 2 gas at the oxygen electrode 20 and pass through the porous support 22 into the central chamber 25. The reactions are: ##STR1##
As shown in FIG. 1, electrons release in the oxygen electrode 20 from cell 12', pass through inter-connection 18 between cell 12 and cell 12' into the air electrode 16 of cell 12, where identical electrode reactions occur, with electrons generated in the oxygen electrode 20 from cell 12 finally passing to terminal 26 (positive terminal) of similar design as terminal 24, through the adjacent interconnection 18 and air electrode 16,and back to the DC power supply.
Thus, the tubular segment of inter-connection material between cells provides electrical continuity (allows a flow of electrons) from the outerair electrode from a first cell 12' to the inner oxygen electrode of a second cell 12, on the same device or tube, in a series arrangement. Also,air 23 is prevented from directly passing into the central chamber 25 by a continuous, dense, preferably 100% dense, barrier of electrolyte bands or segments 14 and inter-connect segments 18. The dense electrolyte bands or segments, in part, overlap and seal to the dense inter-connection segments18. This air impermeability of the generator body is essential to providinghigh purity O 2 in the central chamber. While length 12 and 12' define the "active" lengths of the two cells shown in FIG. 1 and in FIG. 2, electrode and electrolyte components shown extending out beyond the activelength, are considered the active part from that particular cell. The incoming air 23 may preheated consistent with the overall system design previously described prior to contact with the air electrodes 16 of the generator.
A variety of end closures or portions, preferably dense, can be used in theapparatus shown. In FIG. 1, the dense inter-connection portion 18', near the positive terminal, and the dense electrolyte portion 14', near the negative terminal, are overlapped at the ends of the device and disposed transverse to the axial length of the device, as shown, to provide end closures. A high temperature resistant metal, central, axial rod 30, tube or the like, of, for example, Inconel (nickel-chromium alloy), having threads at each end, can be use in conjunction with metal end sheets 28 and 28', to secure the sheets and the dense inter-connection and electrolyte portions in a compressed relationship. As shown, one end of the rod 30 would be screwed into a mated thread, machined into the inner side of sheet 28', and the other end would be screwed down onto insulatingrings 32 by an effective spring means (not shown), applying axial pressure to the end sheets, and assuring a gas tight fit against the flat metal terminals 24 and 26. In a preferred embodiment, the generator 10 is preheatable by placing a voltage differential at the opposite ends of the axial rod 30. In such embodiments, the rod 30 material is chosen to develop the desired heat at the desired current levels.
A suitable, high temperature resistant metal or ceramic tubular sleeve 34, having a plurality of vents or holes 36 therethrough, suitably sealed to end sheet 28, can provide oxygen delivery through the end closures 18', asshown by the O 2 arrows. Inconel and alumina would both be suitable as the sleeve 34. In some instances, it may be desirable to have oxygen delivery though both ends. Alternatively, an additional hole can be drilled through end closure 18', and air electrode 16, terminal 26 ceramicring 32 and end sheet 28, and a tube inserted for oxygen delivery, similar to 38 in FIG. 2. This tube 38 can be made to cooperate with discharge tube220 of FIG. 3. The design of FIG. 1 utilizes a substantial amount of metal hardware in contact with ceramic components. There, positive and negative terminals contact air electrode material at each end of the device. The design of FIG. 2, while having more complicated terminal connections, can provide a primarily all-ceramic device, eliminating some possible problemsof varying coefficients of thermal expansion between selected metals and ceramics.
In FIG. 2, the cell structure and inter-connection between cells are essentially the same as the device of FIG. 1, utilizing the same materialsand substantially the same cell connection design. However, ceramic end portions or caps 40 and 42 are used in place of the end overlapping inter-connection 18' and end overlapping electrolyte 14' design of FIG. 1.This use requires a sinter seal comprising very fine ceramic particles (notshown) between end portions or caps 40 and 42 and the ceramic support 22. The ceramic end portions are preferably dense, to the degree of being gas impervious, and are preferably of the same material as the support tube. Preferably, the ceramic support tube 22, in both embodiments, will be a zirconia material, such as stabilized zirconia, most preferably calcia-stabilized zirconia, for example (ZrO 2 ) 0 .85 (CaO) 0 .15. This material, is pressed and highly densified form, is preferably also used as the ceramic end portions or caps 40 and 42 in FIG.
Preferably, a seal (end portion or cap to support tube) is produced by squeezing in a preformulated paste of very fine particle size calcia stabilized zirconia into the gap region when the end portions or caps are inserted. The ceramic end seal assembly is then dried and sintered in place, to complete fabrication. The narrow gap of the joint, the long, tortuous path, and the near-ambient pressure during operation of the device will all contribute to minimize leakage of any air into the centralchamber 25 so that high purity O 2 can be provided. A minor amount of sintering aid, such as FeO for example, can be used in the adhesive paste and can also be used in both the support tube and end caps. Other suitableceramic materials can also be used for the support tube, and the end caps which overlap the end of support tube 22.
While the device of FIG. 1 relies primarily on a pressure seal between overlapping end inter-connection material 18', overlapping end eleotrolytematerial 14', contacting metal terminals 24 or 26, ceramic spacers 32, and metal sheets 28 and 28', any useful high temperature adhesive can also be used between those components to assure minimal air permeation into central chamber 25.
The terminal connections on the device of FIG. 1 are of simple round washerdesign, having an extending bus bar contact area secured by pressure tightening rod 30, where the terminals 24 and 26 are preferably silver (m.p. 961° C.), but can also be platinum (m.p. 1,769), or palladiumand alloys of palladium and platinum with silver, if the device is to be operated close to its 1,100° C. maximum operating temperature.
In the device of FIG. 2, terminal attachments are of circular band design, and directly electrically contact the top surface of the inter-connection material at one end and the air electrode material at the other end of thedevice, and require cushioning layers. The negative terminal 24 electrically contacts the air electrode 16, preferably through a fiber metal ring 44, preferably of silver-palladium fibers. A metallic split ring clamp constitutes the terminals 24 and 26, which are shown partly in section. The terminals 24 and 26 are preferably silver-palladium alloy, but can also be solid nickel, preferably coated with silver-palladium alloy. Terminal 26 in the FIG. 2 design electrically contact inter-connection material 18 and may require an additional fiber metal ring 46, preferably of silver-palladium. Also shown in FIG. 2 are bus bar,bolt, nut, lock washer assemblies 48. Oxygen gas from the central chamber 25 shown in FIG. 2 can be delivered through tube 38, which is preferably of a ceramic such as calcia-stabilized zirconia, or by any other appropriate means at one or both ends.
Useful and approximate, non-limiting dimensions for both oxygen generator device designs are porous support tube: 44 mm inside diameter, 50 mm outside diameter by 1,000 mm long; porous oxygen electrode: 15 mm long by 1 mm thick; dense interconnection: 0.05 mm to 2 mm thick; dense electrolyte: 11 mm long by 0.05 mm thick; and porous air electrode: 15 mm long by 0.1 mm thick. The unit would be a single stack, having a multiplicity of series-connected cells each about 1.1 cm long having an area of approximately 18 cm 2 . For sake of simplicity, the drawings are not shown to scale.
Useful porous support tube materials, preferably from 4 mm to 10 mm thick, have been previously discussed, The oxygen electrode 20, preferably from 0.5 mm to 2 mm thick, is a 20% to 40% porous, sintered oxide material selected from doped and undoped oxides or mixtures of oxides in the pervoskite family, such as CaMnO 3 , LaNiO 3 , LaCoO 3 , and preferably LaMnO 3 , or other electronically conducting mixed oxides generally composed of rare earth oxides mixed with oxides of cobalt, nickel, copper, iron, chromium and manganese, and combinations of such oxides. Dopants when used are preferably selected from calcium, strontium,and magnesium, with strontium dopant preferred. The most preferred oxygen electrode is lanthanum manganite doped with strontium, for example La 0 .9 Sr 0 .1 MnO 3 . The air electrode is preferably applied by dip slurry application and sintering.
The dense inter-connection material, 18, can be selected from the group consisting of platinum-zirconia, palladium-zirconia, silver-palladium-zirconia, palladium, platinum, palladium-silver, doped lanthanum manganite, and doped lanthanum chromite. The preferred inter-connection material is selected from the group consisting of doped lanthanum manganite, palladium, platinum, and palladium-silver. Dopants for the lanthanum manganite or lanthanum chromite are selected from the group consisting of calcium, strontium, and magnesium, with strontium dopant preferred. The most preferred inter-connection is doped lanthanum manganite. The inter-connection material is gas impervious and near 100% dense. It can be applied by well known vapor deposition techniques, and isusually from 0.05 mm to 2 mm thick. Densification can be achieved by a variety of techniques besides vapor deposition, including vapor sputtering, plasma spray, flame spray, and the like. In some cases, the inter-connection, oxygen electrode, and air electrode can be the same material differing only in density and application technique, with the interconnection being the high density component.
The dense electrolyte 14, preferably from 0.02 mm to 0.15 mm thick, is a zirconia material, preferably at least 99% dense and most preferably 100% dense. The zirconia can be stabilized, that is, doped with a number of elements. Rare earth element stabilized zirconia, specifically yttria-stabilized zirconia is preferred, as it allows excellent oxygen ionmobility. A most preferred composition is (ZrO 2 ) 0 .92 (Y 2 O 3 ) 0 .08. Other mixed oxides can be used. The material must be effective to transfer ionic oxygen. It can be applied by chemical vapor deposition, plasma spray, flame spray, or sintering techniques.
The porous air electrode, 16, preferably from 0.05 mm to 2 mm thick, is a 20% to 60% porous material selected from metal-ceramic materials selected from the group consisting of platinum-zirconia, palladium-zirconia, and silver-palladium-zirconia, or a porous, sintered oxide selected from the group consisting of doped lanthanum manganite and doped lanthanum chromitewhere the preferred dopants are calcium, strontium, and magnesium, with strontium dopant preferred. Palladium-zirconia is the most preferred air electrode material. The air electrode must be effective to allow reductionof O 2 in the air to oxygen ions.
The number of cells 12 needed to provide a required volume of O 2 gas from air can be calculated for a given gas temperature. For a unit delivering 3 liters/minute of oxygen, delivered at 25° C., having cells of 18 cm 2 area, for a driving current density of 1.5 A/cm 2 and a cell current of 27 A(1.5 A/cm 2 ×18 cm 2 ); oxygen production per cell would be approximately 27 A/cell×3.80 ml/A-min=102.6 ml/min-cell. If a 3 liter/minute of O 2 at 25° C. are required, the number of cells needed would be 3000 ml O 2 /min÷102.6 ml O 2 /min-cell=29 cells/stack.
The device operates at 900° C. at a current density of 1.5 amperes/cm 2 , with pressurized air delivery to the device. The preferred embodiment oxygen generator 10 was manufactured by Westinghouse Electric Corporation.
The power dissipated as heat in the oxygen concentration system maintains the operating temperature. For example, in a system designed to deliver 3 liters per minute at (2 amp/cm 2 ) at 25° C. and atmospheric pressure, the power required to maintain 900° C. is about 500 watts. An oxygen concentration system sufficient to deliver this flow rateat these conditions would have 22 cells operating at 631 millivolts and 36 amperes/cell. The heat generated by such a system is 500 watts and the operating temperature will be maintained by the electrochemical productionof oxygen.
One advantage to this oxygen generation system is its ability to generate oxygen at flow rates which are proportional to the electrical current supplied to the generator 10. For example, if a flow rate of 1 liter/minute is desired, the oxygen generation system requires only 12 amperes be supplied to the generator 10. The cell voltage is calculated byOhms Law and will be 210 millivolts. The power dissipated in this case is only 55 watts. This is not enough heat to maintain the operating temperature and the generator 10 cannot operate correctly. The difference between the oxygen generation heat and the temperature maintenance heat must be made up by an additional heater. The preferred additional heater is axial rod 30 discussed above. One advantage of the use of the Inconel rod 30 as a heat source is that electric current can be imposed on the rod30 such that the rod dissipates an amount of heat required to maintain the operating temperature of the system. In some applications where the oxygenflow rate is low, the generators 10 may not generate enough heat to maintain operation of the device. In these cases, the rod 30 can be used as a heat source.
Another advantage of using the rod 30 to generate heat is the uniformity ofthe heating. High heating rates can be obtained upon the initial start up with the rod 30 centered inside the generators 10. Because the generators 10 are symmetrical about the rods 30, and because the generators 10 themselves are enclosed within concentric enclosures 120, 150, 180, stresses developed due to uneven heating are minimized.
Another advantage of the rod 30 and the cylindrical layout of the oxygen concentration system is the efficient use of heat. For example, if the heat source was to be located outside of the generators 10, then a portionof the heat would be directed toward the generators 10 and the remainder portion would be dissipated away from the generators 10. Because the rod 30 passes through the center of the generators, substantially all of the heat generated by the rods 30 heat the generators 10.
The invention has been described with reference to the preferred embodiment. Obviously, modifications and alterations will occur to others upon reading and understanding the preceding detailed description. It is intended that the invention be construed as including all such modifications and alterations insofar as they come within the scope of theappended claims or the equivalents thereof.
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An oxygen concentration system for producing oxygen from pressurized air comprises an electrochemical oxygen generator which selectively extracts oxygen from air by an electrochemical reaction. The oxygen concentration system includes first, second, and third concentric enclosures. The three enclosures produce three annuli formed between the enclosures. Air enters the top of the outermost enclosure, travels downwardly through the outermost annulus, crosses over the second annulus to the oxygen generators via ports, travels upwardly through the oxygen generators and back downwardly through the second annulus. By orienting the downward flow of the oxygen-depleted air next to the downward flow of the cooler incoming air, the incoming air is heated by the outgoing hot air, thereby increasing comfort to the user and reducing energy requirements.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to loading dock equipment and in particular to dock levelers that are used to span the distance between a loading dock and the bed of a vehicle. Specifically, it deals with an improved mechanical latch for the lip of a dock leveler.
2. Prior Art
A conventional dock leveler has a deck assembly which typically stores in a position level with the dock floor, and has a pivoting lip assembly which extends outward to rest on the vehicle which is being loaded. The lip must hinge downward approximately 90 degrees for the lip to be removed from the vehicle and to store the dock leveler with the lip hanging in a pendant position. To move the dock leveler from the stored position to the operative position, the leveler is raised, the lip is extended from the pendant position and the leveler is then lowered until it is supported by the lip resting on the transport vehicle. The use of various mechanisms as a mechanical latch to hold the lip in the extended position until it rests on the transport vehicle is well known in the industry. U.S. Pat. No. 2,974,33 discloses a pawl mounted to the dock leveler engaging a lug on the lip. U.S. Pat. No. 3,249,956 discloses a releasable lip latch that is supported by a spring which will yield to allow the lip to fold if it is inadvertently struck by a backing truck. Both U.S. Pat. No. 3,662,416 and U.S. Pat. No. 4,398,315 show over-center toggle mechanisms as a latch which is yieldable to allow the lip to fold if it is inadvertently subjected to an excessive downward load.
U.S. Pat. No. 4,937,906 discloses a lip counterbalance spring attached to the frame instead of the deck as is conventional in this technology. The purpose is to provide extra force to extend the lip. The advantage of this system is that the lip is at least partially counterbalanced throughout the operating range of the leveler. Another more complicated system is disclosed in U.S. Pat. No. 6,112,353 disclosing a yieldable lip latch.
A major limitation of prior art mechanical lip latches has been that the lip latch does not automatically disengage and allow the lip to fall to the pendant position if the lip is extended when a transport vehicle is not present and when safety legs or cross traffic legs are engaged. Safety legs or cross traffic legs are well known in the dock leveler industry and are used to limit the distance that the deck will fall if the transport vehicle inadvertently pulls away when the leveler is supported by the lip resting on the vehicle. However the presence of safety legs can cause problems for prior art mechanical lip latches. Several designs including U.S. Pat. No. 3,662,416 and U.S. Pat. No. 5,475,888 disclose a means to release the lip latch when the dock leveler descends to its lowest position. However when safety legs or cross traffic legs are engaged, the dock leveler is prevented from descending to its lowest position and the latch will remain engaged until the lip is manually lifted to allow the latch to release. A second problem with mechanical lip latches is referred to in the industry as “stump out” and occurs when the bed of the transport vehicle is lower than the lip when the safety legs engage the frame of the leveler. Unless the dock operator notices the problem and retracts the safety legs, the lip will be supported by the lip latch and not by the bed of the vehicle. A fork truck driven over the lip will force it down and cause severe damage to the lip latch.
One attempt to address this problem has been the use of a viscous damper commonly referred to as a “hydrashock” to replace the lip latch. Such a device is shown in U.S. Pat. No. 5,323,503. The lip is able to freely extend but the rate of fall of the lip is retarded by the viscous resistance of the damper. Thus if the lip is left extended without the support of a transport vehicle, the lip slowly falls by gravity. While eliminating some of the problems associated with mechanical lip latches, the viscous damper has its own significant limitations. The viscosity of the oil in the damper changes with temperature. As the viscosity decreases in warm weather the rate of fall of the lip increases and the lip may not remain extended long enough to properly engage the bed of the transport vehicle. Conversely as the viscosity increases in cold weather, the rate of fall of the lip may be so slow that it impedes the ability to move the leveler from the transport vehicle to the stored position with the lip pendent. Most dock levelers with such devices provide multiple mounting positions of the damper so that the force resisting lip falling may be modified for large changes in ambient temperature.
Another attempt to provide a yieldable latch is set forth in U.S. Pat. No. 4,398,315. The configuration disclosed is a latch that releases by buckling within the link to the lip rather than by a latch mounted to the dock leveler. Another proposed solution is found in U.S. Pat. No. 6,112,353 which employs a yieldable lip latch with a compensating link supporting the lip bellcrank.
Dock levelers use various means to raise the deck and extend the lip. Dock levelers which are upwardly biased with springs are typically “walked down” from the elevated position by dock worker placing his weight on the deck and the rate of decent is relatively rapid. Dock levelers which use powered means such as an electric actuator, hydraulic cylinder or inflatable bag to raise the leveler have a slower rate of decent. While the viscous damper may provide satisfactory performance for a “walk-down” type of mechanical leveler, it is much less suitable for use with power actuated levelers having a slower rate of descent. If the viscous damper were stiff enough to hold the lip extended until the leveler lowered the lip to the transport vehicle then an unacceptably long time would be required to allow the lip to fall while restoring the leveler.
SUMMARY OF THE INVENTION
This invention is a mechanical lip latch that automatically disengages at multiple positions of deck height depending on whether the safety legs are engaged. The latch is disengaged at the lower limit of downward travel of the dock leveler. The lower limit is determined by whether the safety legs are engaged or retracted. The latch also has multiple positions of engagement to ensure that the lip is supported even if it is not fully extended. The latch is also designed to yield and disengage to protect it from damage if excess force is applied to the lip.
The first preferred embodiment has a lip extension structure suited for the faster activation speed of an upwardly biased “walk down” dock leveler. The second preferred embodiment has a lip extension method better suited for the slower activation speed of a powered up, a downwardly biased dock leveler. In each of these embodiments the ability to vary the lip tension is a significant benefit. For example the ability to increase the tension may be limited so that the lip can fall when the leveler is raised from a high truck.
In the third preferred embodiment a single lip spring is attached to the deck to maintain support for the lip and additionally is releasably attached to the frame. This spring is engaged to the frame only when the lip nearly fully pendant and therefore the spring tension may be increased as the deck is raised to extend the lip without the necessity of using a lip cam as in the second preferred embodiment. This embodiment also uses a lip latch which is biased toward the release position only when the deck is lowered to the working position. Thus a second spring to overcome the release spring when the deck is raised is unnecessary.
In the first and second preferred embodiments the lip spring tension is varied but the increase in tension has a limit or else the lip may not fall when the leveler is raised from the bed of a truck that is high. In the third embodiment a single lip spring is employed, attached to the deck to maintain support for the lip. It is releasably attached to the frame. The spring is engaged with the frame only during the period of time when the lip is nearly fully pendant and therefore the spring tension may be sufficiently increased as the deck is raised to extend the lip without requiring the lip cam of the second embodiment. The third embodiment also has a lip latch which is biased toward to release position only when the deck is lowered to the operative position and thus does not require a second spring to overcome the force of the release spring.
In accordance with this invention there is a provision for a multi-position latch trip. This allows the release of a mechanical lip latch at multiple positions of deck height as a function of the deployment state of the safety legs.
This invention will be described more completely by reference to the drawing and the description of the preferred embodiments that follow.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is a sectional side view of the first preferred embodiment of this invention with the leveler raised and the lip in the pendant position;
FIG. 2 is a sectional side view of the first preferred embodiment of this invention with the leveler raised and the lip held by the lip latch in a partially extended position;
FIG. 3 is a sectional side view of the first preferred embodiment of this invention with the leveler raised and the lip held by the lip latch in a fully extended position;
FIG. 4 is a sectional side view of the first preferred embodiment of this invention with the leveler lowered to an operative position and the lip latch deflected by an external force on the lip;
FIG. 5 is an exploded view showing the safety legs, lip latch trip rod and trip bar;
FIG. 6 is a sectional side view of the first preferred embodiment of this invention with the leveler lowered to rest on the safety legs and the lip latch disengaged;
FIG. 7 is a sectional side view of the first preferred embodiment of this invention with the safety legs retracted and the leveler almost fully lowered;
FIG. 8 is a sectional side view of the first preferred embodiment of this invention with the leveler fully lowered and the lip latch disengaged;
FIG. 9 is a partial sectional side view of the second preferred embodiment of this invention with the leveler raised and the lip in the pendant position;
FIG. 10 is an enlarged partial sectional view of the latch assembly of the second preferred embodiment of this invention;
FIG. 11 is a partial sectional side view of the second preferred embodiment of this invention with the leveler raised and the lip held by the lip latch in a partially extended position;
FIG. 12 is a partial sectional side view of the second preferred embodiment of this invention with the leveler fully lowered and the lip latch disengaged;
FIG. 13 is a sectional side view of the third preferred embodiment of this invention with the lip extended and resting on a transport vehicle;
FIG. 14 is an enlarged view of the latch bar;
FIG. 15 is an enlarged view of the hook assembly for the lip spring;
FIG. 16 is a sectional side view of the third preferred embodiment of this invention with the deck raised to remove the lip from the transport vehicle;
FIG. 17 is a partial sectional side view of the third preferred embodiment of this invention with the lip latch forcing the hook into engagement with the frame;
FIG. 18 is an enlarged view of the latch release rod;
FIG. 19 is a partial sectional side view of the deck raised and the hook providing increased tension for the lip spring;
FIG. 20 is a sectional side view of the third preferred embodiment of this invention with the leveler lowered to an operative position and the lip latch deflected by an external force on the lip;
FIG. 21 is a partial sectional side view of the third preferred embodiment of this invention with the leveler fully lowered and the lip latch disengaged.
FIG. 22 is a perspective view of the lip latch of the fourth preferred embodiment of this invention;
FIG. 23 is a sectional side view of the fourth preferred embodiment of this invention with the leveler raised and the lip held by the lip latch in an extended position; and
FIG. 24 is a sectional side view of the fourth preferred embodiment of this invention with the with the leveler lowered to the working range, the lip held by the lip latch in an extended position, and the lip latch spring biased toward the disengaged position.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring now to FIGS. 1 through 8 the essential components of the first preferred embodiment of this invention will be described, it being understood that a typical dock leveler has other constructional features, not illustrated. A loading dock is shown with a driveway approach 1 , a dock face 2 , and a dock floor 3 with a recessed pit 4 . A transport vehicle 5 is shown in front of the dock. The dock leveler 10 is typically mounted in the pit 4 . A frame has horizontal members 14 and a vertical brace 15 both of which rest in the pit. The leveler frame also has stop blocks 16 and lip keepers 17 at the forward end of the horizontal members 14 . A trip plate 18 , shown in broken lines in FIG. 1, is attached to the far side of one horizontal member 14 at a predetermined distance below the top of the stop block 16 . The leveler 10 has a deck 20 which has a top plate 21 , a plate 22 that forms a front header and a plate 23 that forms a rear header. Deck beams 24 attached to the top plate and header bars provide structural strength to the assembly. The deck 20 is pivoted to the frame at pivot 25 .
A lip 30 is pivoted to the deck on a pin 26 inserted in hinge tubes 27 attached to the front header bar 21 and hinge tubes 32 attached to the lip plate 31 . Control arms 33 are attached to the lip plate 31 . Although not illustrated, the leveler is held horizontal in the stored position with the lip 30 in the pendant position and retained in the lip keepers 17 . The lifting of the dock leveler to the position shown in FIG. 1 may be accomplished by any means including mechanical linkage and springs, electric actuator, hydraulic cylinder or inflatable bag. Such is not material to the functioning of this invention.
Two pairs of brackets 29 are attached to the front header plate 22 to carry the safety legs 70 on pivot pins 76 . As shown in FIG. 5 the safety legs comprise two vertical bars 71 . Each bar 71 is attached to a pivot boss 73 by an arm 72 . A cross bar 74 joins both vertical bars 71 to ensure that they move in and out of engagement together. One bar 71 carries a pin 75 to control the lip trip mechanism that will be described later. When in the forward position the vertical bars 71 are placed between the front header plate 22 and the stop blocks 16 to limit the downward travel of the deck 20 as shown in FIG. 6 . The safety legs 70 are urged forward to the operative position by a spring, not illustrated. To allow the deck to fall lower the safety legs must be manually retracted, typically by the operator pulling on a chain that is also not illustrated.
The deck 20 also carries a support bar 27 with a pivot pin 28 . A crank assembly 35 pivots on the pin 28 and carries pins 36 and 37 . A bar 40 is attached at one end to the pin 36 and at the other end to the lip control arms 33 by a pin 38 . A spring 41 is attached to the pin 37 on the crank assembly 35 by an adjusting bolt 44 and a nut 45 . The other end of the spring 41 is attached to two chains 42 and 43 which are attached to the deck 20 and a vertical frame brace 15 respectively.
As shown in FIG. 4, when the leveler is lowered to an operative position, near horizontal, the chain 43 is slack and the spring 41 is held by chain 42 attached to the deck 20 . The adjusting bolt 44 is positioned by the nut 45 to tension the spring 41 so that most of the weight of the lip 30 is counterbalanced. The tension of the spring must allow the lip to fall by gravity to the pendent position for storing.
Referring now to FIGS. 1, 2 and 3 , rotation of the deck 20 to the raised position causes the chain 43 to increase the tension of the spring 41 and thereby provide greater assistance in rotating the lip 30 to the extended position.
Referring now to FIGS. 1 through 8 the operation of the first preferred embodiment of the lip latch and extension mechanism will be described. As shown in FIG. 1, a latch bar 50 pivots on the pin 36 of the crank assembly 35 . One end of the latch bar 50 has a notch that provides two engagement surfaces 51 and 52 . The other portion of the latch bar 50 carries a release arm 53 and a pin 54 . A latch bracket 55 is attached to the deck and has a slotted opening which guides the end of the latch bar 50 yet allows some limited vertical travel. A latch plate 60 is attached to the latch bracket 55 by a bolt 56 , nut 57 and spring 61 . A chain 65 has one end attached to the bar 40 and the other end to a spring 66 which is then attached to the frame member 14 . A spring 67 has one end attached to the chain 65 and the other end attached to the pin 54 on the latch bar 50 . As the dock leveler is lifted toward the position shown in FIG. 1 the chain 65 is stretched taut and pulls the front of the bar 40 against the pin 38 , causing the lip 30 to rotate rapidly towards the extended position. The spring 66 stores energy and limits the force exerted on the chain 65 . The chain 65 and spring 66 also limit the upward travel of the deck 20 . Because the latch bar 50 heavier than the control arm 53 gravity urges the latch bar to fall out of engagement. The spring 67 is pulled taut by the chain 65 and causes the latch bar 50 to rotate clockwise into engagement with the latch plate 60 .
As the lip 30 approaches the extended position shown in FIG. 2 the line of the force exerted on the pin 38 moves much closer to the lip pivot pin 26 and the rotational moment exerted by the chain on the lip is greatly reduced. The lip 30 is urged toward the fully extended position by rotational inertia and by the force exerted on the lip bar 40 by the lip spring 41 acting on the crank assembly 35 . Because resistance to extension of the lip is dependent on the factors such as wear, debris and lack of lubrication, the energy available may not always be sufficient to fully extend the lip. FIG. 2 shows the lip 30 almost fully extended with the surface 51 of the latch bar 50 engaging the latch plate 60 . Although not fully extended, the lip 30 is still held in a position where it can properly engage the bed of a transport vehicle. Without the alternate latch position provided by the surface 51 , the lip would fall back to the pendant position as the deck is lowered. FIG. 3 shows the lip 30 fully extended with the surface 52 of the latch bar 50 engaging the latch plate 60 . Because the tension of the spring 41 is increased when the deck 20 is fully raised, the weight of the lip 30 may not be sufficient to overcome the spring 41 and hold the latch bar 50 in contact with the latch plate 60 .
The spring 67 maintains the latch bar 50 in the engaged position. As the deck 20 is lowered and the tension of both springs 41 and 67 is reduced and gravity urges the latch bar 50 to fall out of engagement with the latch plate 60 . The weight of the lip 30 acting on the bar 40 holds the end of the latch bar 50 against the latch plate 60 and the lip 30 is prevented from falling. When the deck 20 lowers and the lip 30 is supported by a transport vehicle, the load is removed from the latch bar 50 and it falls out of engagement with the latch plate 60 allowing the lip to fall when the dock leveler is stored.
FIG. 4 illustrates the dock leveler with the lip 30 extended and an external force “F” exerted essentially horizontally on the end of the lip. The spring 61 has sufficient compression to withstand the force exerted on the latch bar 50 by the weight of the lip 30 . When the force on the latch bar 50 exceeds the compression load of the spring 61 the spring will deflect and allow the latch plate 60 to rotate. The end of the latch bar 50 will then slip out of engagement with the latch plate 60 and the lip 30 will fall pendent.
The components that automatically disengage the lip latch 50 will now be described. As shown on FIG. 5 a trip bar 80 has a formed member 81 with its rearward end attached to a pivot boss 82 . An angle bracket 83 is attached near the forward end of the member 81 . A control surface 84 is formed into the middle part of the member 81 . FIG. 5 also shows a trip bar 85 that has a pivot hole 86 and an elongated hole 87 . As shown in this exploded view, the end of the rod 81 engages the hole 86 to carry the trip bar 85 . The pin 75 on the safety leg assembly 70 engages the elongated hole 87 in the trip bar 85 .
As illustrated in FIGS. 1, 2 and 3 the trip rod pivots on pin 28 . The forward end of the trip rod 80 is supported by the trip bar 85 which is supported at the top of the elongated hole 87 by the pin 75 on the safety legs 70 .
FIG. 6 illustrates how the lip latch is automatically disengaged as the deck 20 is lowered and the safety legs 70 rest on the stop blocks 16 . In FIGS. 1 through 4 the vertical position of the stop bar 85 is determined by the pin 75 on the safety legs 7 supporting the top of the elongated hole 87 . FIG. 6 has the stop block 16 cut away to show the stop plate 18 attached to the frame member 14 .
As the deck 20 falls the lower end of the trip bar 85 rests on the trip plate 18 . Thus the forward end of the trip rod 80 is held at a predetermined height above the trip plate 18 as the deck 20 is lowered to rest on the safety legs 70 . As the deck 20 moves down the trip rod 80 rotates upward relative to the deck 20 . The control surface 84 on the trip rod 80 engages the pin 54 on the latch bar 50 forcing the control arm 53 upward and the end of the latch bar 50 downward and out of engagement with the latch plate 60 . The lip 30 is now free to fall to the pendent position.
FIG. 7 illustrates the condition where the dock leveler with the safety legs moved to a retracted position. The pin 75 on the safety legs 70 causes the trip bar 85 to rotate rearward and expose the angle bracket 83 . Thus, as the deck 20 falls to the fully lowered position shown in FIG. 8, the trip bar 85 does not engage the trip plate 18 and the lip latch does not disengage prematurely. However when the deck 20 is fully lowered the angle bracket 83 engages the trip plate 18 and this causes the lip latch 50 to disengage from the latch plate 60 as described herein.
A second preferred embodiment of the invention is illustrated in FIGS. 9, 10 , 11 and 12 . This embodiment is better suited for a powered dock leveler where the rate of lifting the deck is much slower and there is insufficient rotational inertia of the lip to ensure that it is fully extended. With the exception of the lip latch and release components, the dock leveler has the same components as the first preferred embodiment.
FIG. 9 shows a roller 88 on the pin 28 . A latch bar 90 pivots on the pin 38 . The latch bar 90 has a cam surface 91 , a stop surface 92 and a latch surface 93 . The chain 65 is attached to the latch bar 90 rather than to the lip bar 40 as in the first preferred embodiment. The trip rod 180 is similar to the trip rod 80 of the first preferred embodiment except for having a different formed shape.
In FIG. 10 the latch housing 95 and spring housing 96 are mounted to the deck 20 . A latch assembly 100 has an adjustable bolt 101 , flange 102 and latch block 103 which is free to move axially in the latch housing 95 . A latch spring 97 is supported in the spring housing 96 and acts against a nut 98 to urge the flange 102 of the latch assembly 100 against the end of the latch housing 95 . The latch housing 95 also carries a latch release spring 99 .
When the lip is in the pendent position as shown in FIG. 9, tension in the chain 65 acts on the latch bar 90 to pull down on the pin 38 and cause the lip 30 to rotate. As the lip approaches the extended position shown in FIG. 11 the line of force exerted on the pin 38 moves much closer to the lip pivot pin 26 and the rotational moment exerted by the chain 65 on the lip 30 is greatly reduced. The lip 30 is urged toward the fully extended position shown in FIG. 11 by force exerted on the lip bar 40 by the lip spring 41 acting on the crank assembly 35 and by the cam surface 91 bearing on the roller 88 . Any increase in resistance to extension of the lip caused by factors such as wear, debris and lack of lubrication may be overcome by increasing the tension on the chain 65 . The lip 30 is fully extended when the stop surface 92 of the latch bar 90 contacts the roller 99 . The stop surface 92 also deflects the latch release spring 99 . The latch surface 93 is positioned against the end of the latch block 103 .
As in the first preferred embodiment, in this embodiment, the weight of the lip 30 may not be sufficient to overcome the spring 41 and hold the latch bar 90 in contact with the latch block 103 . The spring 67 maintains the latch bar 90 in the engaged position until the deck 20 has lowered. The tension of the spring 41 decreases and the weight of the lip 30 is sufficient to hold the latch surface 93 against the end of the latch block 103 . When the deck 20 lowers and the lip 30 is supported by a transport vehicle, the load is removed from the latch bar 90 . Because forward travel of the latch block 103 is limited by the flange 102 bearing against the end of the housing 95 , the latch bar 90 moves away from the latch block 103 . The release spring 99 lifts the end of the latch bar out of engagement and the lip is free to fall. The latch spring 97 has sufficient compression to withstand the force exerted by the weight of the lip 30 acting on the latch bar 90 . However an external force exerted on the end of the lip will cause the latch spring 97 to deflect. The cam surface 91 acting on the roller 88 will cause the latch arm 90 to be lifted out of engagement with the latch block 103 and the lip will be free to fall.
FIG. 12 illustrates how the lip latch is automatically disengaged as the deck 20 is lowered and the safety legs 70 rest on the stop blocks 16 . As in the first preferred embodiment, in this embodiment, the lower end of the trip bar 85 contacts the trip plate causing the trip rod 80 to rotate upward as the deck 20 is lowered. The trip rod 80 engages the bottom surface of the latch bar 90 forcing the end of the latch bar out of contact with the latch block 103 and allowing the lip 30 to fall by gravity. As in the first embodiment, when the safety legs 70 are retracted the pin 75 on the safety legs 70 causes the trip bar 85 to rotate rearward and expose the angle bracket 83 . Thus as the deck 20 falls to the fully lowered position the angle bracket 83 engages the trip plate 18 and causes the lip latch 50 to disengage from the latch plate 60 as described previously.
A third preferred embodiment of the invention is illustrated in FIGS. 13 through 21. This embodiment is also suited for a powered dock leveler where the rate of lifting the deck is much slower and there is insufficient rotational inertia imparted to the lip 30 by the lip chain 65 to ensure that the lip is fully extended. FIG. 13 shows a dock leveler with the lip 30 resting on a transport vehicle 5 . The frame member 15 carries an anchor pin 19 . The deck 20 has a bracket 105 having a slotted hole 106 . A pair of link bars 107 are attached to the bracket 105 by a pin 108 . FIG. 15 shows a hook assembly 110 having a hook 111 and attachment holes 112 and 113 . A lever arm 114 projects upward and carries a cantilevered spring 115 . The hook assembly 110 is attached to the end of the link bars 118 by a pin 109 passing through the hole 112 . The spring 41 has one end attached to the hook assembly 110 through the hole 113 and the other end to the pin 37 on the crank 35 with the adjusting rod 44 and nut 45 . The rod 44 is adjusted so that most of the weight of the lip 30 is counterbalanced by the tension of the spring 41 while still allowing the lip to fall by gravity when the deck 20 is raised from the transport vehicle 5 . As shown in FIG. 13 the spring 41 pulls the hook assembly 110 into alignment between the end of the bracket 105 on the deck 20 and the pin 37 . The hook assembly 110 is thus held so that the hook 11 is positioned above the pin 19 on the frame member 15 .
When the deck 20 is raised to allow the lip to fall as shown in FIG. 16, the hook 111 does not engage the pin 19 . Consequently, the tension of the spring 41 is not increased as the deck 20 is raised.
FIG. 17 illustrates an enlarged partial view of the dock leveler in the stored position. A latch housing 120 has a latch plate 121 and is pivoted on the deck with a pin 122 . A bracket 123 is anchored to the deck 20 and the latch housing 120 is held in a forward position by the spring 61 , bolt 56 and nut 57 . The latch bar 125 , shown in FIG. 14, has two latch surfaces 126 and 127 . The latch bar 125 is attached to the pin 36 on the crank 35 and passes through the latch housing 120 . As shown in FIG. 13, when the lip is extended the latch bar 125 is moved forward away from the arm 114 on the hook assembly 110 . Because the lip is supported on the transport vehicle there is no load on the latch bar 125 and the spring 115 urges the latch bar 125 upward to lift the latch surfaces 126 and 127 out of engagement with the latch plate 121 . FIG. 16 shows the end of the latch bar 125 moving closer to the lever arm 114 of the hook assembly 110 as the lip 30 rotates toward the pendent position.
FIG. 17 shows the dock leveler in the stored position. When the lip 30 is fully lowered the end of the latch bar 125 contacts the lever arm 114 to rotate the hook assembly 110 and force the hook 111 to a position where it will engage the pin 19 when the deck 20 is raised.
FIG. 19 shows the deck fully raised with the hook 111 engaging the pin 19 . The deck 20 has rotated forward relative to the hook assembly 110 and the end of the spring 41 has been pulled rearward relative to the bracket 105 . The pin 108 has moved in the slotted hole 106 to allow the link bars 108 to move rearward with the spring 41 and hook assembly 110 . Thus the tensional force of the spring 41 may be increased to exceed the weight of the lip 30 so that the lip can be fully extended by the force of the spring 41 . As the lip 30 is extended the latch bar 125 moves forward and out of contact with the spring 115 allowing the latch bar to fall with the latch surface 127 placed to engage the latch plate 121 as shown in FIG. 19 .
As described in the second preferred embodiment, in this embodiment the alternate latch position 126 will allow the latch to engage even if the lip does not full extend. The cantilever spring 115 will not engage the end of the latch bar 125 until the deck 20 has lowered to a position where the hook assembly 110 no longer exerts extra tension on the spring 41 . Thus the latch bar 125 will remain in the engaged position until the weight of the lip 30 forces the latch surface 127 into contact with the latch plate 121 and the lip will remain extended. There is no requirement for a spring 67 attached to the chain 65 to hold the latch in the engaged position as in the first and second embodiments. Because the lever arm 114 is not in contact with the end of the latch bar 125 , the hook 111 will disengage the pin 19 when the deck is lowered to a working position as shown in FIG. 13 .
FIG. 20 illustrates how an external force exerted on the end of the lip 30 will cause the latch plate to disengage the latch bar 125 . The bolt 56 and nut 57 can be adjusted so that the compression of the spring 61 will support the lip 30 in the extended position. An excessive force on the lip will cause the spring 61 to deflect and allow the latch housing 120 to rotate about the pin 123 . The latch bar 125 will then be supported by the rear edge of the latch plate 121 . The front edge of the latch plate will rotate downward to disengage the latch surfaces 126 and 127 and the lip 30 will be allowed to fall.
FIG. 20 also illustrates a third embodiment of this invention that will release the lip latch 125 in multiple positions of the deck 20 depending on the position of the safety legs 70 . A latch release rod 130 is shown in FIG. 18 with a pivot boss 131 , a guide loop 132 and a contact bar 133 . FIG. 20 shows a latch trip angle 135 with a vertical leg 136 and horizontal leg 137 mounted on the frame member 14 . The release rod 130 is carried by the boss 131 mounted on the pin 75 of the safety legs 70 and the guide loop 132 carried by the latch bar 125 . When the safety legs 70 are forward in the engaged position the latch release rod 130 is held in a forward position with the contact bar 133 above the vertical leg 136 of the angle 135 . As the deck 20 lowers to bring the safety legs 70 into contact with the stop blocks 16 , the contact bar 133 will engage the vertical leg 136 and cause the release rod 130 to lift the latch bar 125 out of engagement with the latch plate 121 .
FIG. 21 shows the safety legs 70 retracted so that the deck 20 can be fully lowered. The latch release rod 130 is moved to a rearward position where the contact bar 133 will not engage the vertical leg 136 of the angle 135 . As the deck 20 reaches the fully lowered position the contact bar 133 will engage the horizontal leg 137 and cause the release rod 130 to lift the latch bar 125 out of engagement with the latch plate 121 and allow the lip 30 to fall pendent.
A fourth preferred embodiment of the invention is illustrated in FIGS. 22 through 24. This embodiment is also suited for a powered dock leveler where the rate of lifting the deck is much slower and there is insufficient rotational inertia imparted to the lip 30 by the lip chain 65 to ensure that the lip is fully extended. FIG. 22 shows the latch bar 190 having a cam surface 91 and a stop surface 92 . A latch surface 193 is recessed slightly from the cam surface 91 . A trip bar 195 projects horizontally from the side of the latch bar 190 and has a trip rod 196 attached at a downward angle.
FIG. 23 shows the deck 20 in the fully raised position and the lip 30 fully extended. The latch bar 190 has engaged the roller 88 on the pin 28 . FIG. 23 also shows a latch release spring 160 attached at the front end to a pivot bushing 161 mounted on the front header bar 22 . The rear of the latch release spring 160 is supported by a chain 162 attached to the upper lip spring chain 42 . Because the chain 42 is slack when the deck 20 is raised the latch release spring 160 does not engage the trip bar 195 on the lip latch bar 190 .
As in the first and second preferred embodiments, in this embodiment the tension of the spring 41 increases as the deck 20 is raised and the weight of the lip 30 may not be resting on the latch bar 190 . However in this embodiment the latch bar falls by gravity to the engaged position and there is no need of a spring 67 to hold the latch bar engaged as shown in FIG. 11 .
In operation, as the deck lowers the latch bar remains engaged by gravity and there is no danger that the latch bar will release accidentally even though the weight of the lip 30 may not be urging the latch surface 193 into contact with the roller 88 . As the deck 20 continues to lower the chain 43 attached to frame 15 causes the tension of the spring 41 to decrease until the spring is supported by the chain 42 attached to the deck 20 . FIG. 23 shows the deck 20 lowered to the working range. As the chain 43 is slackened the chain 42 is tightened and the rear of the latch release spring 160 is raised until it engages the trip bar 195 on the lip latch bar 190 . Because the weight of the lip 30 is resting on the latch bar 190 , the force of the latch release spring 160 cannot lift the latch bar 190 from the engaged position. However as the deck continues to lower and the end of the lip 30 is supported on the bed of the transport vehicle 5 then the spring 160 will lift the lip latch bar 190 from the engaged position and the lip 30 will fall when the deck 20 is raised. If no transport vehicle is in position as the dock 20 is lowered with the lip 30 held extended then the end of the trip bar 196 will engage the floor of the pit 4 and cause the lip latch bar 190 to disengage and allow the lip 30 to fall.
While this invention has been described with respect to the preferred embodiments, it will be apparent to those skilled in this art that modifications of this invention may be practiced without departing from the scope of the invention.
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A dock leveler having a frame and a deck pivotably mounted at one end thereof to the frame. A lip is pivotably mounted to the deck at another end thereof. A lip latch and lip extension mechanism are mounted to the leveler and comprises a lip latch pivotably connected to the deck by a crank mechanism and a latch bar pivotably connected to the crank mechanism. The latch bar has one end selectively engaging a latch bracket mounted to the deck. A bar is connected at one end to the crank mechanism and another end is operably connected to the lip. A first spring is operably connected to the crank mechanism and the frame. A second spring is operably connected to the bar and the frame. A third spring operably couples another end of the latch bar to the second spring. Upon upward movement of the deck the first spring urges the crank mechanism in a first direction to move the bar so that the lip is raised from a pendant position to an extended position and the latch bar moves based on movement of the crank mechanism and engages the latch bracket at a first point to hold the lip in the extended position and is maintained in engagement by the third spring.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to nesting devices.
2. Description of the Related Art
Nesting devices have been used successfully to reduce the amount of manual labour required to fabricate a variety of articles. Channel members are especially labour intensive since one must be nested into another before they can be stacked efficiently. A common type of channel member is a wall stud which in recent years has seen widespread use in the walls of modern buildings. The wall stud fabricating industry is heavily labour intensive and the risk of repetitive strain injury claims is high, in part due to the need to invert, nest and stack the wall studs. There remains a need for an automatic nesting device that will reduce the labour required for handling channel members.
It is therefore an object of the present invention to provide a novel nesting device.
SUMMARY OF THE INVENTION
Briefly stated, the invention involves a device for nesting articles of the type having a nesting surface with a number of formations thereon, comprising:
first locating means for locating a first article and second locating means for locating a second article,
actuating means for actuating the first and second locating means to cause the articles to nest together at the nesting surfaces, the actuating means including a first mechanism to actuate the first locating means and a second mechanism to actuate the second locating means, the first mechanism being arranged to actuate in advance of the second mechanism, in order to nest the articles with the formations in staggered relationship.
In another aspect of the present invention, there is provided a technique for nesting articles of the type having a nesting surface with a number of formations thereon;, the technique including the steps of:
providing a first location to receive a first article
providing a second location to receive a second article,
displacing the first location relative to the second location to bring the articles together at the nesting surfaces, wherein the first location is displaced ahead of the second location to permit the formations on one of the article to be staggered with the formations on the other of the articles.
In still another aspect of the present invention, there is provided a device for assembling articles, comprising:
a bed having a surface with a receiving area to receive articles and an assembly area for assembling the articles, the articles having a leading face and a trailing face;
first transfer means for transferring articles from the receiving area to the assembly area to form an assembled group of the articles;
first pressure means for maintaining pressure on the articles between the receiving area and the assembly area, the pressure means including a first pressure element adjacent the leading face of a leading one of the articles in the assembled group.
BRIEF DESCRIPTION OF THE DRAWINGS
Several preferred embodiments of the present invention will now be described, by way of example only, with reference to the appended drawings in which:
FIG. 1 is a fragmentary perspective view of a portion of a nesting device;
FIG. 1a is a sectional view of another portion of a nesting device;
FIG. 2 is sectional view taken on line 2--2 of FIG. 1;
FIG. 3 is another fragmentary perspective view of a portion of the nesting device of FIG. 1;
FIG. 4 is a sectional view taken on line 4--4 of FIG. 3;
FIG. 5 is a fragmentary sectional view taken on line 5--5 of FIG. 1;
FIG. 6 is a fragmentary sectional view of another portion of the nesting device of FIG. 1;
FIG. 7 is another fragmentary sectional view of another portion of the nesting device of FIG. 1;
FIG. 8 is still another fragmentary sectional view of another portion of the nesting device of FIG. 1;
FIG. 9 is a fragmentary sectional view of still another portion of the nesting device of FIG. 1;
FIG. 10 is a fragmentary sectional view of the portion illustrated in FIG. 9 in another operative position;
FIG. 11 is a schematic view of several operations of one portion of the nesting device illustrated in FIG. 1;
FIG. 12 is a perspective view of a portion of a another nesting device;
FIG. 13 is a schematic view of the operation of the portion illustrated in FIG. 12; and
FIGS. 14a, b and c are schematic views similar to FIG. 13 of yet another nesting device.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to the FIGURES, there is provided a nesting device 10 having a main frame 12 supporting a feed conveyor 14 to feed channel members 15 such as `wall studs` from an earlier fabricating station, not shown. The channel members are one example of an article having a nesting surface with a number of formations. thereon, in this case the side walls thereof, as will be described. The feed conveyor 14 has a downstream end located adjacent a pusher plate mechanism 16. The main frame 12 also includes a main bed 12a which supports a positioning conveyor 18. The positioning conveyor 18 receives the channel members 15 from the feed conveyor 14 by the action of the pusher plate mechanism 16 and displaces the channel members 15 in a direction perpendicular to the feed conveyor 14 toward an elongate aperture 20 formed in the opposite end of the main bed. The elongate aperture 20 serves as a discharge passage to deliver the channel members 15 to receiving means in the form of a secondary bed 22 as will be described. Located adjacent the elongate aperture 20 is a first proximity switch 24 to detect the presence of first channel member 15 and a second proximity switch 25 to detect the presence of a second channel member. Referring to FIG. 1a, the proximity switch 25 projects though a hole in the main bed 12a and activated by a passing channel member.
The pusher plate mechanism 16 includes a pusher plate 16a which is displaced across the feed conveyor 14 by way of a pair of bell cranks 16b each of which is pivoted to a portion 12b of the main frame 12. A gear 16c is fixed to each bell crank 16b and is driven by a toothed belt 16d, itself driven by an actuator 16e.
Referring to FIGS. 1 and 5, the positioning conveyor 18 is made up of three continuous cord members 18a each held between two pulleys 18b, 18c and emerging through a pair of narrow apertures 12c at the upstream end of the main bed 12a and the elongate aperture 20 at the downstream end of the main bed. Each of the pulleys at the upstream end is fixed to a shaft 18d. The shaft 18d is driven by a gear and chain arrangement which is driven by an electric motor as shown at 18e.
The pulleys at the downstream end of the main bed 12a are free to spin on shaft 26. It will be seen that another shaft 28 is located adjacent the elongate aperture 20 and parallel to the shaft 26.
A particular feature of the present invention is the use of a first locating means for locating a first article and second locating means for locating a second article. This is exemplified by the use of three pairs of paddles 30 which are attached to the shafts 26 and 28. Each of the paddles 30 has a surface 30a parallel with the main bed 12a when in a ready position and movable from the article-receiving ready position in a convergent upward direction as shown by the arrows in FIG. 4 toward a generally upright article-nesting position. Rather than being freely attached to the shaft as the pulleys, the paddles 30 are fixedly attached thereto and an actuating mechanism 32, shown in FIGS. 2 and 4, is provided to rotate the two shafts 26, 28 to cause the convergent upward motion of the paddles 30.
Referring to FIG. 2, the actuating mechanism 32 includes a pair of double link mechanisms shown generally at 34, each joined between a respective one of the shafts and an actuating plate 32a. One link is fixed to the shaft while the other link is pivoted to the actuating plate 32a. The actuating plate 32a is constrained to vertical travel along a vertical guide 32b by way of a sliding block 32c. The actuating plate 32a is driven by an actuator 32d mounted at its lower end to a portion of the main frame 12 and pivotally mounted at its upper end to the actuating plate 32a.
The actuating links 34 are arranged to enable one of the paddles 30 to be actuated in advance of the other inorder to nest said channel members with their formations in staggered relationship. To achieve this, the right hand link 34a is pivotally coupled to the actuating plate 32a by way of a pivot 34b which in turn extends through a vertically oriented slot 34c in the actuating plate 32a. The left hand link 32d, on the other hand, is pivotally coupled to the actuating plate 32a by way of a pivot 32e which in turn extends through a hole in the actuating plate 32a. In this manner, when the actuating plate 32a rises, the left hand link moves with it turing its associated paddle. The right hand link moves when the pin is at the lower end of the slot 32c. This causes the left hand paddle to rotate prior to the right hand paddle. If desired, the right hand paddle may be arranged to move in advance of the left hand paddle, simply by reversing the plate 32a. The selection of the set of paddles 30 to be advance depends on the orientation of the channel members 15 as they are fed onto the feed conveyor 14, as will be described.
Referring now to FIG. 5, the secondary bed 22 is located below the elongate aperture 20 and has an assembly surface 40. The secondary bed 22 has a receiving area 42 which receives successive pairs of nested channel members 15 from the elongate aperture 20 and an assembly area 44 wherein successive groups of nested channel members 15 are assembled. The receiving area 42 is bounded on one side by first transfer means in the form of a series of indexing pins 46 and on the other side by a series of indexing arms 48 (only one of each being shown for sake of brevity). Referring to FIGS. 5 and 6, each indexing pin 46 is mounted on a portion 12d of the main frame 12 by way of a bracket 46a and function as abutment means movable from a vertical transfer-inhibiting position to a horizontal position by an actuator 46b.
Each indexing pin 46 also includes a slave link 46c that is pivotally mounted to a slave arm 46d, allowing the actuator to pivot the series of indexing pins 46 at the same time.
Referring to FIGS. 7, 8 and 9, a series of keeper pins 50 are also provided as first pressure means to maintain slight pressure on the nested channel members 15, as will be explained. The keeper pins 50 are each mounted on one arm 52a of a bell crank and pivotally mounted to a portion 12e of the main frame. The other arm 52b of the bell crank is joined to an actuator 52c to rotate the bell crank. A slave arm 52d is also joined to the other arm to join the other keeper pins 50 together for actuation by the actuator 52c. Each of the keeper pins 50 is vertically movable, by way of actuator 52e, from its operative position as shown in FIG. 7 to a release position below the plane of the assembly area as shown in FIG. 8. The keeper pins 50 are activated by a limit switch (not shown) which triggers the actuator 52e when the keeper pins 50 reach a predetermined position.
Referring to FIG. 5, the indexing arms 48 are each driven by a parallel link mechanism 48a to 48d, with the link 48b fixed to another portion 12f of the main frame. An actuator 48e operates the indexing arms from the retracted position shown in FIG. 5 to the extended position shown in FIG. 7 to transfer a pair of nested channel members from the receiving area 42 toward the assembly area 44. The indexing arms are also slaved to others not shown, by being fixed to shaft 48f.
Referring now to FIGS. 5, 8 and 9, there is provided two sets of transfer arms, one of a first set shown at 60 and one of a second set shown at 62. The first set is located ahead of, and the second set behind, an assembled group of nested channel members 15. The first set of transfer arms each include a rollable cylinder 60a which is arranged to engage the side of a group of nested channel members. Each cylinder is mounted on the remote end one arm 60b of a bell crank. A slave link 60c is pivotally connected to the other arm 60d of the bell crank. An actuator 60e is pivotally connected to the actuating link and is anchored to another portion 12h of the main frame 12. The first transfer arms function as second pressure means for maintaining pressure on the group of nested channel members from the receiving area to the assembly area.
Each of the second transfer arms 62 is pivotally coupled to the remote end a link 62a, the other end of which is pivoted to yet another portion 12i of the main frame. Another link 62b is fixed to the link 62a and is pivoted to a slave link 62c. An actuator 62d is pivoted between the slave link 62c and another portion 12j of the main frame 12. Each of the second transfer arms 62 is movable from a vertical operative position as shown in FIG. 8 to a horizontal position as shown in FIG. 9 by way of an actuator shown at 62f. The second transfer arms function as second transfer means for transferring the group of nested channel members from the assembly area to a delivery area as will be described.
The first and second transfer arms are arranged to move from their positions on opposite sides of the assembly area 44 of the secondary bed 22 toward positions on opposite sides of a loading area shown at 70. The loading area is provided with a takeaway conveyor 72 to remove the group of nested channel members.
In use, the channel members 15 are delivered individually by the feed conveyor 14 and are timed to be ejected by the pusher plate 16a onto the positioning conveyor. The positioning conveyor 18 delivers the channel members the elongate aperture 20. As the first channel member approaches the elongate aperture 20, it will engage the second proximity switches 25 and will thereafter engage the first proximity switches 24. A subsequent channel member will then engage the second proximity switch. In this manner, the occurrence of the first signal by the first proximity switch detects the presence of initial channel member while the second signal by the second proximity switch detects the presence of the subsequent channel member.
When two channel members 15 are present at the two proximity switches, the paddles 30 are actuated by actuator 32 to cause each of the channel members 15 to be nested together.
A particular feature of the paddles is that they have a semicircular lower surface which provides an abutment surface for incoming channel members while two previous channel members are being nested. This prevents the paddles from pinching the incoming channel members (or operators' protuberances for that matter) during the nesting step.
A particular feature of the nesting device 10 is that one of the paddles 30 may be triggered to advance before the other, allowing one of the channel members 15 to begin its nesting motion ahead of the other. This is useful when the channel members 15 have uneven side walls as shown by schematic flow diagram of FIG. 11. FIG. 11 shows a number of positions through the motion of the paddles 30. In each case, each channel member 15 has a nesting surface with a number of formations thereon in the form of a `long` wall 15a which is higher than the adjacent `short` wall 15b. The free ends of each wall has an inwardly pointing right-angled flange 15c. It may be desirable to nest these channel members 15 with the short wall of the right channel member 15 above the adjacent long side wall of the left channel member 15 as shown in position f). If the short wall is allowed to fit inside and below the flange of the corresponding long wall, there is a risk that the channel members 15 will become locked together, especially if the difference between the length of the short and long walls is about equal to the thickness of the flange on the long wall.
Depending on where the channel members are positioned on the paddles, the channel members may move along the top surface of the paddle to adjust to the position appropriate for the nesting function to occur. For example, the channel members may be too close to one another prior the nesting function, so that during the initial rotation of the paddles, the channels may move away from one another. This can be seen throughout the views of FIG. 11.
When the paddles 30 reach their vertical position, the now nested channel members 15 are deposited through the elongate aperture 20 and come to rest as shown in FIG. 5 between the keeper pins 50, the indexing pins 46 and the indexing arms 48. The indexing pins 46 are then pivoted to their horizontal position and the indexing arms 48 transfer the nested channel members 15 to the assembly area 44 against the slight resistance of the keeper pins 50. The indexing pins 46 are then returned to their upright ready position for another pair of nested channel members 15. The nested channel members 15 are thus held together by the keeper pins 50 on one side and the indexing pins 46 on the other.
The indexing arms 48 are then returned to their ready position beside the receiving area 42. Each time a pair of nested channel members 15 are assembled in the assembly area 44, the keeper pins 0 maintain pressure until the assembled pairs accumulate to the point that the leading face of the assembled pairs engages the first transfer arms 60. At this point, the first transfer arms 60 take over the retaining pressure from the keeper pins 50, the keeper pins 50 retract and the actuator 52c returns them to their initial position. However, the keeper pins do not extend again until later in the procedure. At this point, there are four assembled pairs between the first transfer arms and the indexing pins 46.
A fifth pair of nested channels are deposited into the receiving area between the indexing pins 46 and the indexing arms, 48. The indexing pins are then moved to their horizontal position, causing the first four assembled pairs to move backward to contact the fifth pair under the pressure of the first transfer arms 60. The indexing arms 48 then transfer all five assembled pairs back into the assembly area 44. The second transfer arms move to their vertical position to take over the task of maintaining pressure against the trailing face of the assembled five assembled pairs from the indexing arms 48 which thereafter return to their original position on the right hand side of the receiving area 42. Meanwhile, the indexing pins 46 and the keeper pins 50 are returned to their upright ready positions on the left hand side of the receiving area to receive the first pair of the next group of assembled pairs.
With the five assembled pairs now between the first and second transfer arms, the first and second transfer arms transfer the five assembled pairs to the delivery area 70 as shown in FIG. 10. The five assembled pairs are thereafter removed from the delivery area 70 by the takeaway conveyor 72 toward a banding station. Once the five assembled pairs are removed by the takeaway conveyor 72, the first and second transfer arms may be returned to their original positions, with the first transfer arm ready to exert pressure on the leading face of the next group of four assembled pairs and the second transfer arm in the horizontal position as shown in FIG. 9.
While the nesting device 10 has been shown to assemble five nested pairs, it will be understood that the device can also be used to assemble other numbers of nested pairs, such as for example three to six nested pairs, provided that the assembly and delivery areas have the space to accommodate the number of pairs being assembled. In addition, the transfer arms 60 may be arranged to take over the task of maintaining pressure on the leading face of leading one of the group of assembled pairs at a different stage in the process, for example after the second, third or fourth nested pair has been transferred to the assembly area.
While the above embodiment makes use of a conveyor to transfer the channel members along the main bed, the main bed may instead be inclined so that this movement can occur by the force of gravity, as shown by the dashed lines at 12g in FIG. 5.
In addition, the paddles may be provided with a second degree of motion during the activation of the paddles as shown in FIGS. 12, 13 and 14. In this case, the paddles are mounted on a cam shaft arrangement wherein the rotational axis of the paddles is shifted horizontally, which will cause the opposing paddles to swing upward and later toward one another as the cam reaches its top dead center.
If the cam shifts the axis of rotation vertically, the rotation of the shaft will swing the paddles away from one another, then upward through 90 degrees of rotation and then back toward one another as the shaft approaches 180 degrees of rotation. This may be particularly useful for square channel members which can be moved away from their side-by-side position so that they can be nested together.
While the nesting device is useful for nesting channel members, there may be other equally useful applications to nest other articles, such as those that have a nesting surface with a number of formations thereon, including differently shaped or sized end walls, or extremities that have been treated in some fashion requiring one of the articles to be advanced ahead of the other.
In addition, there may be portions of the device 10 that may be used in other applications. For example, the portion of the device 10 below the main bed may be used to assemble groups of articles such as extrusions and the like downstream of an earlier station in the forming process, wherein the articles may be transferred from a receiving area to an assembly area with the use of a transfer means on the trailing face and a means for maintaining pressure on the leading face, and from the assembly area to a delivery area in a similar manner.
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Disclosed herein is a device for nesting articles of the type having a nesting surface with a number of formations thereon, comprising first locating means for locating a first article and second locating means for locating a second article, actuating means for actuating the first and second locating means to cause the articles to nest together at the nesting surfaces, the actuating means including a first mechanism to actuate the first locating means and a second mechanism to actuate the second locating means, the first mechanism being arranged to actuate in advance of the second mechanism, in order to nest the articles with the formations in staggered relationship. A technique is also disclosed for nesting articles.
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FIELD OF THE INVENTION
[0001] The present invention relates to a low specific gravity thermosetting resin composition and methods for preparing the same, and more particularly, to a low specific gravity thermosetting resin composition of high fluidization with excellent mechanical properties and methods for preparing the same, wherein the conventional thermosetting resin composition for a plastic body panel of an automobile is modified in such a manner that a part of conventional inorganic filler is replaced with a low specific gravity filler, and the type of a filler and a thickener are altered, thus having the advantage of being light-weighted as well as preventing the break-up of a low specific gravity filler which can normally occur under a general forming pressure, thereby having superior plasticity even when press forming under a low pressure.
BACKGROUND OF THE INVENTION
[0002] In general, the body panel of an automobile is manufactured by ‘sheet molding compound’ (referred to as SMC hereinafter) method. The source of the body panel of an automobile is a thermosetting resin and the specific gravity of a thermosetting resin varies according to the difference in mixing ratio, which depends on the manufacturing method and composition being used.
[0003] The schematic view of the SMC is shown in FIG. 1. In FIG. 1, intermediate resin mixture is coated to a predetermined thickness on top of carrier films present on both top and bottom by using a doctor blade, and glass fiber is infiltrated between them after it is cut into a predetermined length using a rotary chopper. The infiltrated glass fiber is then pressed while passing through a compaction roller and is finally formed into a sheet. SMC sheets do not have good workability due to insufficient viscosity, and the final product is obtained after maturing for about 3 days at 50° C. Thus obtained SMC sheets are introduced into a mold after they are cut into an appropriate size according to the size and shape of a desired product. In case of a body panel of an automobile, the product is relatively large and thus about 80-150 kgf/cm 2 of compacting pressure is required. However, the conventional thermosetting resin composition is not advantageous in that it is heavy because of its relatively high specific gravity and also requires an additional step of alloy thus not being economical with respect to cost-effectiveness.
SUMMARY OF THE INVENTION
[0004] Therefore, the object of the present invention is to provide a method for manufacturing a thermosetting composite with low specific gravity for a body panel of an automobile, which can be effectively used in manufacturing plastic body panel of an automobile in view of its light-weight acquired by replacing a part of an inorganic filler used in the conventional thermosetting resin composition. The thermosetting composite also has a superior plasticity in press forming even at a low-pressure condition, acquired by using a physical thickener to avoid the possible break-up of a filler of low specific gravity that can occur under normal forming pressure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] [0005]FIG. 1 is a schematic view showing the process of manufacturing SMC according to an embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0006] The present invention is described in detail as set forth hereunder. The compositions described and claimed are expressed as ingredients in a formulation that upon reaction and/or polymerization results in the composite compositions of this invention. One of skill in the art will realize the ingredients can change form and structure upon reaction or composition to form the composites of this invention.
[0007] The present invention relates to a thermosetting resin composition with low specific gravity comprising:
[0008] 1-30 wt % of unsaturated polyester-based resin;
[0009] 0.5-15 wt % of one selected from saturated crystalline polyester resin as a thickener as well as a low profile agent, unsaturated crystalline polyester resin as a thickener, or a mixture of these;
[0010] 1-15 wt % of a filler with low specific gravity;
[0011] 10-50 wt % of an inorganic filler;
[0012] 1545 wt % of a fiber-type reinforcing agent;
[0013] 0.5-35 wt % of a monomer;
[0014] 0.01-2 wt % of an initiator;
[0015] optionally 0.1-5 wt % of a parting agent; and
[0016] optionally 0.01-5 wt % of additives.
[0017] The present invention also relates to a method of manufacturing a thermosetting resin composition with low specific gravity comprising: 1-30 wt % of unsaturated polyester-based resin; 0.5-15 wt % of one selected from saturated crystalline polyester resin as a thickener as well as a low profile agent, unsaturated crystalline polyester resin as a thickener, and a mixture of these; 1-15 wt % of a filler with low specific gravity; 10-50 wt % of an inorganic filler; 15-45 wt % of a fiber-type reinforcing agent; 0.5-35 wt % of a monomer; 0.01-2 wt % of an initiator; optionally 0.1-5 wt % of a parting agent; and optionally 0.01-5 wt % of other additives.
[0018] The present invention relates to a low specific gravity thermosetting resin composition and its manufacturing method, which can not only reduce manufacturing cost by comprising a filler with low specific gravity added in addition to the conventional low pressure forming resin composition for manufacturing a body panel of an automobile which comprises a fiber-type reinforcing agent and a filler as active ingredients while using unsaturated polyester-based resin as a matrix, but also improve the surface smoothness of a formed product by incorporating saturated crystalline polyester resin, which serves as a thickener as well as a low profile agent.
[0019] The present invention, for the purpose of low pressure forming suitable for manufacturing the body panel of an automobile, incorporates a filler with low specific gravity in combination with an inorganic filler while using unsaturated polyester resin as a matrix. The resulting composition, although its mechanical properties such as mechanical strength are somewhat inferior to those of conventional SMC materials for an automobile, is shown to be an excellent material for low pressure forming with superior plasticity at a forming pressure of below 20 kgf/cm 2 , as well as superior storage stability.
[0020] The thermosetting resin composition with low specific gravity of the present invention is further explained by way of the manufacturing method described as follows.
[0021] The present invention uses unsaturated polyester-based resin as a matrix and it is preferred to be contained 1-30 wt % of the total composition, and more preferably 5-10 wt %. The unsaturated polyester-based resin is one or a mixture of more than two selected from the group consisting of iso-based resin, ortho-based resin, tere-based resin, modified bisphenol-based resin, and vinyl ester-based resin.
[0022] The present invention uses 0.5-15 wt %, preferably 1-10 wt %, of one selected from saturated crystalline polyester resin serving as a thickener as well as a low profile agent, unsaturated crystalline polyester resin as a thickener, and a mixture of these. If the amount is less than 0.5 wt %, the thickening effect and surface smoothness become poor, whereas physical properties become poor if the amount exceeds 15 wt %.
[0023] In an embodiment when saturated crystalline polyester resin is selected to be used, the surface smoothness of a formed product can be improved without using an additional low profile agent because it can serve both as a thickener and a low profile agent. On the other hand, when the above unsaturated crystalline polyester resin is selected to be used as a thickener, a low profile agent selected from the group consisting of polymethyl methacrylate (PMMA), polyvinyl acetate (PVAc), polyurethane (PU), polystyrene (PS), a polystyrene-based copolymer, or a mixture thereof is advantageously incorporated. The amount of low profile agent added is about 0-20%, in many embodiments 1-20 wt %, and preferably 2.5-10 wt % of the total resin composition.
[0024] The present invention uses an inorganic filler selected from the group consisting of calcium carbonate, mica, talc and clay, or mixture thereof, which is added 10-50 wt % of the total resin composition, and preferably 15-35 wt %. The density of calcium carbonate is around 2.7 g/cc, of mica around 3 g/cc, of talc around 2.8 g/cc, and of clay between 1.8 and 2.6 g/cc.
[0025] The present invention uses a filler with low specific gravity in combination with the above-mentioned inorganic filler, which results in cost reduction due to the light-weight of an automobile. By low specific gravity it is meant to have a specific gravity of about 1.5 g/cc or less, in a preferred embodiment 1 g/cc or less, more preferably 0.5 g/cc or less. In one embodiment the specific gravity of the filler is between about 0.1 g/cc and about 0.8 g/cc. The low specific gravity filler is preferably rigid and inorganic. Glass is a preferred inorganic filler, but glass typically has a density of about 2.8-3.5 g/cc. A hollow, i.e., gas filled, filler may advantageously be employed, for example hollow fibers, hollow spheres, other hollow bodies, and the like. A hollow glass sphere is preferred for the filler with low specific gravity. In one embodiment the specific gravity of glass spheres is about 0.37 g/cc. In another embodiment the specific gravity of the glass spheres is between 0.1 and about 0.6 g/cc. The amount used is 1-15 wt %, more preferably 3-10 wt %. If the amount is less than 1 wt %, the effect of light-weight becomes markedly reduced. In contrast, if the amount exceeds 15 wt %, the dispersion and distribution of resin composition during the mixing process become poor and also the physical properties become much worsened.
[0026] The present invention uses a fiber-type reinforcing agent which is fibers with a length less than about 10 mm in length, preferably 0.64-5.08 mm in length. The preferred amount of the reinforcing agent is 1545 wt %, and more preferably 20-35 wt %. The fiber is in one embodiment hollow.
[0027] The present invention uses a low molecular weight polymerizable compound, for example a polymerizable monomer or dimer, preferably a monomer, for thermosetting reaction and the preferred amount of the monomer is 0.5-35 wt %, and more preferably 2-25 wt %. The above monomer is in one embodiment selected from the group consisting of styrene, methyl methacrylate, divinyl benzene (DVB), α-methyl styrene, vinyl acetate, acrylate, or mixture thereof.
[0028] The present invention uses an initiator as a catalyst for thermosetting reaction and the preferred amount of the monomer is 0.01-2 wt %, and more preferably 0.1-1 wt %. The above initiator can be a peroxy-type initiator or other type initiator. In one embodiment the initiator is selected from the group consisting of peroxy ester, dialkyl peroxide, alkyl aryl peroxide, diaryl peroxide, peroxy ketal, ketone peroxide, and an azo compound.
[0029] The present invention uses a parting agent for the improvement of workability during release. The parting agent used in the present invention is either zinc stearate or calcium stearate. The amount of the parting agent is preferred to be 0.1-5 wt %, and more preferably 0.5-2 wt %.
[0030] In addition, the present invention optionally uses at least one additives selected from the group consisting of a pigment, a UV stabilizer, and a polymerization inhibitor, with the content being 0.01-5 wt %, and preferably 0.05-2 wt %.
[0031] While thickening is induced by using a metal oxide such as MgO, CaO, Mg(OH) 2 , and Ca(OH) 2 in general SMC materials, the present invention employs a thermosetting composite material for SMC method, which is thickened by using a crystalline polymer resin.
[0032] Low pressure forming SMC is a novel material that can reduce expenses required for installing facilities and molds during initial investment because it enables forming of parts even at a much lower forming pressure as compared to those of conventional SMC. As in the case with conventional SMC pressure forming, the SMC of the present invention is also equipped with both upper and lower molds. The raw SMC materials in the form of a sheet can be cut into a predetermined size, placed on top of a lower mold, wherein resin is filled in by applying a pressure of 5-30 kgf/cm 2 , and allowed to be cured for 2-5 min to finally produce a formed product.
[0033] Examples of major components of raw SMC materials for low pressure forming are unsaturated polyester, glass fiber and inorganic filler. Because the thickening mechanism of SMC of the present invention differs from those of conventional SMC, the compounding machine is a bit modified; namely, heating apparatus is installed near a compaction roller.
[0034] Thickeners used in general SMC are present in the form of a metal oxide such as MgO, CaO, Mg(OH) 2 , and Ca(OH) 2 , and are known to evenly disperse among unsaturated polyester polymer chains and induce chemical interactions thus achieving a thickening effect. In contrast, the present invention induces thickening effect by adding crystalline polyester instead of the above metal oxide. First, resin, crystalline polyester and other additives are dissolved by mixing them in a container kept at a temperature of higher than 80° C., delivered to carrier films by a doctor blade, added with glass fiber and then passed through a compaction roll as in the case of conventional SMC method. Here, it is heated to about 50° C. to maintain the crystalline polyester in a melted state within a predetermined mixing ratio, and crystallization takes place in the final step at room temperature thus resulting in a marked increase in viscosity.
[0035] Crystalline solid portion present in the crystalline polyester resin serves as a physical crosslinking point which not only shortens the thickening time but also makes an additional curing period unnecessary, thus enabling its immediate use in forming process after mixing. Besides, the thickening is not a chemical event and thus the storage stability is excellent and the workability and the properties can be well retained for about a year. These provide significant production advantages over the materials currently used.
[0036] Further, the present invention also aims at providing a resin composition wherein a thickener component can also serve as a low profile agent without adding an additional low profile agent to improve the surface smoothness of a formed product, and the resin composition can be used as a material suitable for manufacturing a body panel of an automobile having excellent external appearance of the surface as well as excellent mechanical properties. The amounts of glass fiber (specific gravity 2.5) and calcium carbonate (specific gravity 2.7), used as a reinforcing agent and an inorganic filler, respectively, are properly adjusted to make the specific gravity of the formed product kept in the range of 1.2-2, for example in a higher strength embodiment from 1.75-1.95, and for example in an intermediate-strength embodiment between about 1.3 and 1.7.
[0037] Thus obtained low pressure forming thermosetting plastic composite material can be used for manufacturing moving parts, side body panels, and hang-on parts such as hoods, doors, roofs, trunk lids, and the like of an automobile. In particular, about 15-35% reduction in body weight of an automobile can be achieved by manufacturing the body panel of an automobile to be 2.0-2.5 mm thick because the thickness of conventional steel is 0.65-0.75 m with specific gravity of 7.8. In addition, the materials manufactured by the SMC method according to the present invention can also contribute to cost reduction by having integration of parts because these materials are possessed with excellent corrosion resistance, impact resistance, dent resistance and plasticity as well as light-weight rendered on plastic materials.
[0038] In one embodiment of the invention there is a car panel formed from thermosetting resin composition consisting essentially of: between 1 and 30 wt % of unsaturated polyester-based resin; between 0.5 and 15 wt % of one selected from saturated crystalline polyester resin serving as a thickener as well as a low profile agent, unsaturated crystalline polyester resin as a thickener, or a mixture of these; between 1 and 15 wt % of a first inorganic filler with a specific gravity of less than about 1.5; between 10 and 50 wt % of a second inorganic filler; between 15 and 45 wt % of a fiber-type reinforcing agent; between 0.5 and 35 wt % of a low molecular weight polymerizable compound; between 0.01 and 2 wt % of an initiator; between 0.01 and 5 wt % of additives; and between 0.1 and 5 wt % of a parting agent. This composition is reacted to form a thermosetting composite which is formed into a car panel. In a preferred embodiment, the unsaturated polyester-based resin comprises iso-based resin, ortho-based resin, tere-based resin, modified bisphenol-based resin, vinyl ester-based resin, or a mixture thereof; the saturated crystalline comprises between 1 and 20 wt % of polymethyl methacrylate, polyvinyl acetate, polyurethane, polystyrene, and polystyrene-based copolymer; the first inorganic filler comprises hollow spheres, hollow fibers, hollow glass objects, or a mixture thereof with a specific gravity of between 0.1 and about 0.6 g/cc.; the second inorganic filler comprises calcium carbonate, mica, talc and clay; and the low molecular weight polymerizable compound comprises a monomer, dimer, or mixture thereof. Advantageously, the first inorganic filler has a specific gravity of about 0.1 to about 0.8, and the bulk density of the reacted composition is between about 1.3 and 1.7. In another embodiment, the first inorganic filler has a specific gravity of between about 0.1 and 0.6, and the bulk density of the reacted composition is between about 1.75 and 1.95. In a preferred embodiment, the first inorganic filler comprises hollow glass spheres that have a specific gravity of between about 0.1 and 0.8; the low molecular weight polymerizable compound comprises monomers of styrene, methyl methacryalte, divinyl benzene, α-methyl styrene, vinyl acetate, acrylate, or mixtures thereof; the second inorganic filler comprises calcium carbonate, mica, talc and clay; and the fiber-type reinforcing agent consists of glass fibers with a length less than about 10 mm in length present in amount between 20 and 35 wt %. Advantageously, the bulk density of the reacted composition of this preferred embodiment is between about 1.3 and about 1.75.
[0039] The invention also encompasses a sheet molding compound process for forming a formed product, particularly a car panel. The process requires: providing a composite sheet formed from a composition comprising between 1 and 30 wt % of unsaturated polyester-based resin, between 0.5 and 15 wt % of one selected from saturated crystalline polyester resin serving as a thickener as well as a low profile agent, unsaturated crystalline polyester resin as a thickener, or a mixture of these, between 1 and 15 wt % of a first inorganic filler with a specific gravity of less than about 1.5, between 10 and 50 wt % of a second inorganic filler, between 15 and 45 wt % of a fiber-type reinforcing agent, between 0.5 and 35 wt % of a low molecular weight polymerizable compound, between 0.01 and 2 wt % of an initiator, and between 0.1 and 5 wt % of a parting agent; placing the composite sheet in a mold adapted for a sheet-molding-compound-pressure-forming process; applying a compacting pressure, wherein the compacting pressure is 30 kgf per square centimeter or less; and curing the formed product. Advantageously, the first inorganic filler comprises hollow glass spheres that have a specific gravity of between about 0.1 and 0.8; the low molecular weight polymerizable compound comprises monomers of styrene, methyl methacryalte, divinyl benzene, α-methyl styrene, vinyl acetate, acrylate, or mixtures thereof; the second inorganic filler comprises calcium carbonate, mica, talc and clay; the fiber-type reinforcing agent comprises glass fibers with a length less than about 10 mm in length and is present in an amount between 20 and 35 wt %.; the parting agent comprises zinc stearate or calcium stearate; and the bulk density of the reacted composition is between about 1.3 and about 1.75.
[0040] This invention is explained in greater detail based on the following Examples but they should not be construed as limiting the scope of this invention.
COMPARATIVE EXAMPLE 1
[0041] About 500 kg of samples in the form of a sheet were manufactured by using SMC mixing machine for mass production. The conditions of temperature, pressure and time used for forming were 150° C., 20 kgf/cm 2 and 210 sec, respectively. Flat type formed product was obtained by sample molding. Unsaturated polyester resin was prepared by mixing OS-108™ and OS-980™ (available from Aekyung Chemical Co., Ltd, Korea). The reinforcing agent was prepared by cutting glass fiber (RS4800-433™, available from Owens-Corning Korea) of roving type into 2.54 mm in size and calcium carbonate (Omyacarb 1T™, available from Omya Co., Ltd, Japan) was used as an inorganic filler. C772™ (available from Scott Bader Co., Ltd., England) was used as unsaturated crystalline polyester resin. The composition and the mixing ratio are shown in the following table 1 and the physical properties of samples are shown in table 3.
COMPARATIVE EXAMPLES 2 AND 3
[0042] Low pressure forming SMC samples were manufactured by using the same conditions in the above Comparative Example 1 with the exception that the mixing ratio was modified. The specific mixing ratio used is shown in the following table 1 and the physical properties of samples are shown in table 3.
TABLE 1 *Comp. *Comp. *Comp. Classification (wt %) Ex. 1 Ex. 2 Ex. 3 Unsaturated polyester resin-1 (OS- 4.2 5.0 — 108 ™) Unsaturated polyester resin-1 (OS- 5.0 6.0 11.0 980 ™) Low profile agent (LPV-40 ™) 8.0 9.0 9.0 Unsaturated crystalline polyester 6.0 7.0 7.0 resin (C772 ™) Monomer (Styrene) 1.5 2.2 2.2 Initiator (t-butyl perbenzoate) 0.5 0.5 0.5 Parting agent (zinc stearate) 1.0 1.0 1.0 Thickener (CaO) 0.5 0.5 0.5 Inorganic filler (Omyacarb 1T ™) 48.3 43.8 43.8 Glass fiber (RS4800-433 ™) 25.0 25.0 25.0
EXAMPLES 1-4
[0043] Samples were manufactured by using the same conditions in the Comparative Example 1 with the exception that the types and contents of fillers were altered. The mixing ratio was determined considering the big difference in specific gravity present between the conventional inorganic filler (CaCO 3 ) and the filler with low specific gravity. As the filler with low specific gravity was used SCOTCHLITE™ Glass Bubble K-37™ (Bulk Density=0.37) (available from 3M Co., Ltd, USA), and C-772 or C-773 was used as a saturated crystalline polyester resin. The specific mixing ratio is shown in the following table 2 and the physical properties of samples are shown in table 3.
EXAMPLES 5-7
[0044] Samples were manufactured by using the same conditions in the Example 1 with the exception that various forming pressures of 15, 30, and 40 kgf/cm 2 were applied. The physical properties of thus manufactured samples were measured and the results are shown in table 3.
TABLE 2 * Ex. Classification (wt %) * Ex. 1 * Ex. 2 * Ex. 3 4-7 Unsaturated polyester resin-1 (OS- 15.1 11.5 11.6 12.1 108 ™) Unsaturated polyester resin-1 (OS- 3.0 3.3 3.5 3.5 980 ™) Low profile agent (LPV-40 ™) — 9.5 10.0 10.5 Unsaturated crystalline polyester — 7.0 7.0 7.0 resin (C772 ™) Unsaturated crystalline polyester 6.5 — — — resin (C773 ™) Monomer (Styrene) 4.5 2.5 3.0 3.5 Initiator (t-butyl perbenzoate) 0.5 0.5 0.5 0.5 Parting agent (zinc stearate) 1.0 1.0 1.0 1.0 Filler with Low Specific Gravity 3.5 4.3 6.0 7.6 (Glass Bubble K-37 ™) Inorganic filler (Omyacarb 1T ™) 36.5 29.6 24.5 19.3 Glass fiber (R54800-433 ™) 28.4 30.8 32.9 35.0 Others 1.0 1.0 1.0 1.0
[0045] [0045] TABLE 3 Tensile Flexural Flexural Impact Specific Strength Strength Modulus Strength Classification Gravity 1) (MPa) 2) (MPa) 3) (GPa) 3) (J/m) 4) *Comp. Ex. 1 1.95 77 170 12.1 790 *Comp. Ex. 2 1.85 83 172 11.8 850 *Comp. Ex. 3 1.81 79 175 11.5 820 **Ex. 1 1.63 75 170 11.4 780 **Ex. 2 1.50 74 165 11.0 710 **Ex. 3 1.42 71 162 10.6 685 **Ex. 4 1.31 69 158 10.1 650 **Ex. 5 1.32 68 159 10.2 660 **Ex. 6 1.33 69 157 9.8 630 **Ex. 7 1.35 68 156 10.0 620
[0046] As described above, the thermosetting resin composition of the present invention uses unsaturated polyester-based resin as a matrix and comprises predetermined amounts of an inorganic filler and a filler with low specific gravity. It is formed by means of an SMC method and then applied to an automobile, thereby enabling:
[0047] Reduction of body weight of an automobile by about 30-45% as compared to those of steel products, and by about 10-30% as compared to the conventional SMC;
[0048] Reduction of the initial set-up expense as well as expense for molds by about 10-30% as compared to the conventional SMC by using low pressure forming SMC; and
[0049] Reduction of deterioration in physical properties due to break-down of a filler with low specific gravity because of the low pressure forming.
[0050] Further, the thermosetting composite resin composition of the present invention has an excellent plasticity and mechanical properties thus enabling an integration of formed parts which can lead to cost reduction, increase in fuel efficiency, and reduction in exhaust gas such as CO 2 ; enabling to improve quality of a product and reduce maintenance/repair cost when used for manufacturing body panels of an automobile due to its excellent dent resistance and impact resistance; and enabling to be used as a material suitable for manufacturing automobile parts by using plastic materials for externally invisible inner panels of doors, hoods, and roofs; outer body panels; radiator support panel or chassis parts such as cross member due to its excellent durability, which does not require the additional alloy unlike as in steel plates.
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A low specific gravity thermosetting resin composition of high fluidization with excellent mechanical properties, and methods for preparing the same, wherein a thermosetting resin composition for outer plastic panel of an automobile is modified in that a part of the inorganic filler is replaced with a low specific gravity filler, and the type of a filler and a thickener are altered from those compounds normally used for car panels. The are light-weight. The process prevents the degradation of the low specific gravity filler which can normally occur under a general compacting pressure. The composition has superior plasticity even when press forming under a low pressure.
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TECHNICAL FIELD
[0001] The present invention relates to the field of nautical recreation, and more particularly relates to an inflating device that can be used to inflate an inflatable boat comprising two side tubes and a bottom, each including an independent air chamber, as well as inflatable boat equipped with such an inflating device.
BACKGROUND
[0002] An inflatable boat generally includes two independent side tubes each having a valve of the same model designed for inflation and deflation of the corresponding boat as well as a valve, often of another model designed for inflating and deflating the bottom of the inflatable boat.
[0003] However, the inflation of such an inflatable boat has the drawback of causing an asymmetry between the two tubes if the latter are inflated alternatingly with excessive pressure deviation.
[0004] These asymmetries are essentially due to the deformation of the inner wall separating the air chambers of the two tubes, that inner wall tending to curve toward the lower pressure air chamber.
[0005] This frequently occurs when one of the two tubes is completely inflated before inflating the other.
[0006] To avoid this drawback, the user must, during the inflation phase, connect and disconnect the pump several times, alternating between both of the valves of the two side tubes.
[0007] However, this independent inflation of the two side tubes is sometimes misunderstood, is laborious and allows a slight asymmetry to remain between the two air chambers of the two tubes, one always being irreparably more inflated than the other.
[0008] The standards in force in the field of inflatable boats provide that in the event of a puncture of one of the two side tubes, at least 50% of the inflatable volume of the inflatable boat must remain inflated, which rules out designs with two side tubes communicating through a single air chamber, which would nevertheless resolve the problem of the asymmetry.
BRIEF SUMMARY
[0009] The present invention aims to resolve all or some of the aforementioned drawbacks.
[0010] To that end, the present invention relates to an inflating device capable of being used for inflating an inflatable boat comprising two side tubes and a bottom respectively including an independent air chamber, said device being characterized in that it comprises a sealing body comprising an enclosure having at least three communication openings, each of the openings being connected to another opening with a passage allowing for airflow circulation, and namely a first opening to be connected to a first air routing means for supplying air to the air chamber of the first side tube of the inflatable boat, a second opening to be connected to a second air routing means for supplying air to the air chamber of the second side tube of the inflatable boat, a third opening to be connected to an inflating pump, and means for closing the passage between the first opening and the second opening, positioned in the enclosure, and movable between a first so-called open position in which the passage between the first opening and the second opening is open to a second so-called closed passage in which the passage between the first opening and the second opening is closed, and means for positioning the closing means in any intermediate position found between the open position and the closed position, the third opening being formed on the positioning means.
[0011] This arrangement makes it possible to inflate two tubes simultaneously from a single connection of the pump and also allows equilibrium of the pressure of the two tubes during inflation and separation of the air chambers of the two tubes once the inflation is done.
[0012] Furthermore, this arrangement results in making it possible to control the airflow passing between the two tubes through the inflating device, for example during re-equilibration made necessary following a pressure drop of one of the tubes.
[0013] According to one embodiment, the positioning means comprise the closing means.
[0014] According to one embodiment, the positioning means include a tappet member and a handling member embodying a motion conversion device of the screw-and-nut type converting a relative rotary motion of the handling member into a relative translatory motion of the tappet member so as to bring the blocking means into the closing position thereof.
[0015] This arrangement allows the user to go from one position to the other through a simple rotational movement.
[0016] According to one embodiment, the positioning means include a non-return device.
[0017] According to one embodiment, the enclosure includes two removable parts.
[0018] According to one embodiment, the inflating device includes mistake-proofing means for the closed position and/or for the open position, in particular for inflating position of the inflatable boat.
[0019] This arrangement facilitates the use of the inflating device.
[0020] According to one embodiment, the enclosure has a fourth opening to be connected to third air routing means for supplying air to the air chamber of the bottom of the inflatable boat, each of the openings being connected to another opening by a passage allowing for airflow circulation in the open position.
[0021] This arrangement makes it possible to inflate the side tubes and the bottom of the boat simultaneously.
[0022] According to the same embodiment, the passages between the first opening or the second open and the fourth opening are open in the open position of the closing means, and the passages between the first opening or the second opening and the fourth opening are closed in the closed position of the closing means.
[0023] This arrangement makes it possible to isolate each of the air chambers of the side tubes and the bottom.
[0024] Advantageously, the section of the fourth opening is undersized with respect to the sections of the first opening and the second opening.
[0025] This arrangement makes it possible to have the end of the inflation of the bottom, the air chamber of which generally has a smaller volume than that of the two side tubes, coincide with the end of inflation of the chambers of the side tubes and therefore protect the bottom from periodic overpressures due to pump movement during the inflation.
[0026] According to one embodiment, the closing means are removable from the enclosure.
[0027] This arrangement allows easy replacement of the closing means, for example in the event of loss of sealing, and allows simultaneous and rapid deflation of the air chambers of the inflatable boat connected to the inflating device.
[0028] The present invention also relates to an inflatable boat including an inflating device as previously described.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] In any case, the invention will be well understood using the following description, in reference to the appended diagrammatic drawing showing, as a non-limiting example, several embodiments of an inflating device according to the invention.
[0030] FIG. 1 shows an exploded perspective view of an inflating device in the closed position according to a first embodiment.
[0031] FIG. 2 shows a top perspective view of the inflating device of FIG. 1 in the deflating position.
[0032] FIG. 3 shows a bottom perspective view of the inflating device of FIG. 1 in the deflating position.
[0033] FIG. 4 shows a transverse cross-sectional view of the inflating device of FIG. 1 in the closed position.
[0034] FIG. 5 shows a transverse cross-sectional view of the inflating device of FIG. 1 in the deflating position.
[0035] FIG. 6 shows a transverse cross-sectional view of the inflating device of FIG. 1 in the inflating position.
[0036] FIG. 7 shows a first view of an alternative of the embodiment of FIGS. 1 to 6 .
[0037] FIG. 8 shows a second view of the device of FIG. 7 .
[0038] FIG. 9 shows a third view of the device of FIGS. 7 and 8 .
[0039] FIG. 10 shows an inflatable boat equipped with an inflating device according to the invention.
DETAILED DESCRIPTION
[0040] As illustrated in FIG. 10 , an inflating device 1 according to the invention may be used to inflate an inflatable boat 2 comprising a right side tube 3 , a left side tube 4 and optionally a bottom 4 each respectively comprising an independent air chamber 31 , 41 , 51 as well as air routing means 32 , 42 , 52 .
[0041] The air chambers 31 , 41 of the two side tubes 3 , 4 have the same volume.
[0042] As illustrated in the different embodiments shown in FIGS. 1 to 10 f , an inflating device 1 according to the invention comprises a sealed body 6 comprising an enclosure 7 having three communicating openings 11 , 12 , 13 connected to each other.
[0043] The first opening 11 is designed to be connected to the air routing means 32 designed to supply the air chamber 31 of the first side tube 3 of the inflatable boat 2 with air, the second opening 12 being designed to be connected to the second air routing means 42 designed to supply the air chamber 41 of the second side tube 4 of the inflatable boat 2 with air, the third opening 13 is designed to be connected to an inflating pump (not shown).
[0044] Furthermore, the first opening 11 and the second opening 12 have a same inner diameter or section so as to equitably distribute the air injected by the pump coming from the third opening 13 .
[0045] In the first embodiment illustrated in FIGS. 1 to 9 , the inflating device 100 includes a fourth opening 14 that can be connected to the other three openings 11 , 12 , 13 and designed to be connected to the air routing means 52 designed to supply the air chamber 51 of the bottom 5 of the inflatable boat 2 with air.
[0046] In this embodiment, the body 6 comprises two complementary parts 101 , 115 forming the enclosure 7 .
[0047] The first of these parts is formed by a baseplate 101 designed to be kept against the inflatable boat 2 .
[0048] This baseplate 101 comprises a body 105 with a substantially cylindrical shape that is completely open on one of said two bases.
[0049] This body 105 forms a first part of the enclosure 7 of the body 6 of the inflating device 100 .
[0050] The other of these two bases includes a first duct 102 with a cylindrical shape forming the first opening 11 and designed to be connected to the air routing means 32 , which in turn are designed to supply the air chamber 31 of the right tube 3 of the inflatable boat with air, a second cylindrical duct 103 forming the second opening 12 and designed to be connected to the air routing means 42 , which in turn are designed to supply the air chamber 41 of the left tube 4 of the inflatable boat 2 with air, and a third cylindrical duct 104 forming the fourth opening 14 and designed to be connected to the air routing means 52 , which in turn are designed to supply the chamber 51 of the bottom 3 of the inflatable boat 2 with air.
[0051] Each of these three hollow cylindrical ducts 102 , 103 , 104 transversely crosses the base of the body 105 of the baseplate 101 so as to emerge inside the enclosure 7 of the body 6 of the inflating device 100 .
[0052] The main axis of each of these three ducts 102 , 103 , 104 passes through the apex of an equilateral triangle positioned transversely to the crossed base of the body 105 of the baseplate 101 .
[0053] Thus, each of these three ducts 102 , 103 , 104 respectively comprises a protruding portion 110 , 111 , 112 of the crossed base of the body 105 of the baseplate 101 .
[0054] Furthermore, each of the ends of the protruding portions 110 , 111 , 112 is planar and positioned in a same plane as the other two, said plane in turn being positioned transversely to the cylindrical shape of the body 105 of the baseplate 101 and substantially at the height thereof.
[0055] The body 105 of the baseplate 101 also comprises a thread 109 positioned on its cylindrical inner surface, the function of which will be described later in the text.
[0056] Furthermore, on its cylindrical outer surface, the body 105 of the baseplate 101 comprises, in the direction from the base crossed by the ducts 102 , 103 , 104 toward the open base, a circumferential annular bead 106 followed by a circumferential annular slot 107 in which an O-ring 108 is positioned, the O-ring giving the baseplate 101 a greater lateral bulk than that of the circumferential annular bead 106 .
[0057] The bead 106 as well as the slot 107 occupy a predetermined position, the function of which will be described later in the text.
[0058] The second part is formed by positioning means 115 and comprises a second part of the enclosure 7 of the body 6 of the inflating device 100 .
[0059] These positioning means 115 are removable and have a substantially cylindrical shape that is completely open on one of said two bases and is designed to be engaged on the first part 101 or baseplate 101 so as to position the inflating device 100 in its different operational positions.
[0060] These positioning means 115 are formed by a tappet 120 and a handling member 130 of the tappet 120 .
[0061] The tappet 120 comprises a disk-shaped body 128 from which central guide means 121 extend on the one hand in the form of a triangular prism with curved surfaces whereof the curve radius is substantially equal to the radius of the three ducts 102 , 103 , 104 of the baseplate 101 , and cylindrical closing means 122 , 123 , 124 on the other hand, respectively designed to bear on the protruding portions 110 , 111 , 112 of the ducts 102 , 103 , 104 of the baseplate 101 of the inflating device.
[0062] In order to hermetically close these ducts 102 , 103 , 104 , each closing means 122 , 123 , 124 comprises a planar seal 125 positioned on its end face across from the protruding portions 110 , 111 , 112 and maintained at the center thereof by retaining means 126 in the shape of a “T”.
[0063] The central guide means 121 extend beyond the closing means 122 , 123 , 124 so as to perform their guiding function during the engagement of the positioning means 115 on the first part 101 or baseplate 101 and also comprise a central opening 127 emerging on the one hand on the outer face of the guide means 121 and on the other hand on the center of the body 128 of the disc-shaped tappet 120 .
[0064] The handling member 130 comprises a body 131 in the shape of a hollow cylinder with an open base and a quasi-closed base and having an inner cylindrical part 135 and an outer cylindrical part 137 that are coaxial to each other and both include an inner face and an outer face.
[0065] The inner face of the outer cylindrical part 137 of the handling member 130 comprises a diameter substantially equal to the outer diameter of the base 101 , allowing the O-ring 108 to ensure sealing between the enclosure 7 and the outside.
[0066] The tappet 120 is designed to be retained in translation but free in rotation inside the inner cylindrical part 135 of the handling member 130 .
[0067] To that end, the handling member 130 of the tappet 120 comprises a central rivet 134 extending from the center of the quasi-closed base of handling member 130 in the direction of the main axis of its cylindrical shape, passes through the central opening 127 formed on the guide means 121 of the tappet 120 , then retains the tappet 120 in translation against the handling member 130 in the direction of the main axes, which are then coaxial, of the tappet 120 and the handling member 130 .
[0068] Furthermore, the handling member 130 comprises a thread 136 positioned on the outer face of the inner cylindrical part 135 and designed to cooperate with the thread 109 of the base 101 as well as a circumferential annular bead 138 positioned on the end of the inner face of the outer cylindrical part 137 and designed to cooperate with the circumferential annular bead 106 of the base 101 .
[0069] Lastly, the handling member 130 comprises a duct 132 emerging in the inner cylindrical part 135 making up the third opening 13 of the enclosure 17 of the inflating device 100 designed to connect an inflating pump.
[0070] According to one alternative of this first embodiment, this inflating duct 132 comprises a non-return device 8 designed to prevent the air blown into the enclosure 7 by the inflating pump through the duct 132 from leaving the enclosure 7 through that same duct 132 .
[0071] Nevertheless, this non-return device 8 is not essential to the inflating device 100 .
[0072] In fact, most of the inflating pumps used to inflate the inflatable boat 2 are sealed at the piston.
[0073] Part of the air blown in by the inflating pump through the duct 132 can therefore emerge through that same duct 132 , in particular when air is taken from the inflating pump, but will never go beyond the piston of the inflating pump.
[0074] Thus, by acting only on the positioning means 115 of the inflating device 100 and in particular on the rotation of the handling member 130 of the tappet 120 , it is possible to position the inflating device 100 in a closed position P 2 as illustrated in FIG. 4 , in a deflating position PD as illustrated in FIG. 5 or in an inflating position PI as illustrated in FIG. 6 .
[0075] The inflating position PI and deflating position PD are more generally part of a so-called open position P 1 .
[0076] This consideration is valid for this first embodiment as well as the following embodiments described hereafter.
[0077] In the closed position P 2 illustrated in FIG. 4 , each planar seal 125 of each closing means 122 , 123 , 124 bears on the flank of each protruding portion 110 , 111 , 112 so as to hermetically close one of the ducts 102 , 103 , 104 under the action of the screwing of the thread 136 of the handling member 130 on the thread 109 of the baseplate 101 , thereby preventing any communication whatsoever between the openings 11 , 12 , 13 , and 14 .
[0078] Furthermore, the O-ring 108 exerts pressure on the one hand on the wall of the circumferential annular slot 107 and on the other hand on the wall of the inner face of the outer cylindrical part 137 of the handling member 130 , thereby partitioning the air located in the enclosure 7 from the outside air.
[0079] To return the inflating device 100 to its deflating position PD, illustrated in FIG. 5 , the user unscrews the handling member 130 from the baseplate 101 .
[0080] This first results in balancing the pressure of the air inside the air chambers 31 , 41 , 51 .
[0081] By continuing to gradually unscrew the handling member 130 , the user reaches a hard point generated by the action of the circumferential annular bead 138 of the handling member 130 on the circumferential annular bead 106 of the baseplate 101 .
[0082] At this stage of unscrewing, the enclosure 7 is still hermetically isolated from the outside.
[0083] By continuing to unscrew the handling member 130 beyond this hard point, the O-ring 108 no longer exerts pressure on the wall of the inner face of the outer cylindrical part 137 of the handling member 130 , then the thread 136 disengages from the thread 109 , thereby putting the enclosure 7 in communication with the outside.
[0084] At this stage, the positioning means 115 are separated from the baseplate 101 , thereby freeing the openings 11 , 12 , 14 so as to allow the air located in the air chambers 31 , 41 , 51 to exit to the outside.
[0085] When the user wishes to position the inflating device 100 in its inflating position PI illustrated in FIG. 6 , the user begins by engaging the positioning means 115 in the baseplate 101 while making sure to correctly engage the guide means 121 between the three protruding portions 110 , 111 , 112 of the ducts 102 , 103 , 104 on the one hand, and the thread 136 in the thread 109 on the other hand.
[0086] By screwing the thread 136 in the thread 109 , the guide means 121 move in translation along the outer lateral edge of the protruding portions 110 , 111 , 112 until reaching the hard point generated by the action of the circumferential annular bead 138 of the handling member 130 on the circumferential annular bead 106 of the base 101 .
[0087] By continuing to screw the seal beyond this hard point, the O-ring 108 again exerts pressure on the wall of the inner face of the outer cylindrical part 137 of the handling member 130 , thereby isolating the enclosure 7 from the outside.
[0088] The user connects the inflating pump to the duct 132 and blows air into the enclosure 73 the non-return device 8 .
[0089] The air passing through the duct 132 reaches the enclosure 7 on the one hand through the play remaining between the tappet 120 and the handling member 130 and on the other hand through orifices 129 formed in the closing means 122 , 123 , 124 necessarily putting the upper part of one of the closing means 122 , 123 , 124 across from the duct 132 due to one of the three positions allowed by the guide means 121 in communication with a side wall of the same closing means 122 , 123 , 124 emerging in the enclosure 7 .
[0090] In this inflating position PI, the air chambers 31 , 41 , 51 are inflated simultaneously and the pressure of one of them is balanced with respect to the other two.
[0091] At the end of inflation, the user returns the inflating device 100 to the closed position P 2 thereof illustrated in FIG. 4 by simply screwing the handling member 130 of the tappet 120 until it abuts on the planar seals 125 on the flanks of the protruding portions 110 , 111 , 112 of the ducts 102 , 103 , 104 .
[0092] During this transition from the inflating position P 1 to the closed position P 2 , the inner wall of the outer cylindrical part 137 of the handling member 130 slides on the O-ring 108 following the helical movement of the threads 109 , 136 , the O-ring 108 ensuring sealing between the enclosure 7 and the outside at all times.
[0093] FIGS. 7 to 9 illustrate another alternative of this first embodiment. Furthermore, this alternative is compatible with the alternative previously described involving eliminating the non-return device 8 .
[0094] According to this alternative, the inflating device 100 comprises mistake-proofing means 150 in particular including first positioning means 151 for the handling member 130 of the tappet 120 in the closed position P 2 , and second positioning means 152 for the handling member 130 of the tappet 120 in the open position P 1 and more particularly in the inflating position PI of the inflatable boat 2 .
[0095] In this alternative embodiment, the inner thread 109 of the stationary baseplate 101 and the thread 136 of the inner cylinder part 135 of the handling member 130 of the tappet 120 , cooperate over substantially a half-revolution to go from the closed position P 2 to an open position P 1 and vice versa.
[0096] Furthermore, still according to this alternative, the circumferential annular bead 106 and the circumferential annular bead 138 can be eliminated.
[0097] According to this alternative, the baseplate 101 comprises a peripheral portion 153 in the shape of a hollow cylinder with a small thickness, extending over its entire outer periphery, substantially along the same plane as the bottom of the body 105 of the baseplate 101 over a predetermined diameter greater than that of the outer cylindrical part 137 of the handling member 130 of the tappet 120 .
[0098] The outer cylindrical part 137 of the handling member 130 of the tappet 120 comprises a toroid peripheral annular portion 154 , extending over its outer lateral surface substantially along the same plane as the bottom of the positioning member 130 of the cylindrical tappet 120 , over a predetermined diameter smaller than that of the peripheral portion 153 of the baseplate 101 .
[0099] The first positioning means 151 of the handling member 130 of the tappet 120 in the closed position P 2 on the one hand comprise a first closing member 155 supported by the peripheral portion 153 of the baseplate 101 arranged to cooperate with a second closing member 157 supported by the handling member 130 of the tappet 120 .
[0100] The first closing member 155 has a generally parallelepiped shape with a small thickness extending substantially transversely to the plane in which the peripheral portion 153 of the baseplate 101 extends from a first predetermined peripheral position of that same peripheral portion 153 of the baseplate 101 to a height that is also predetermined.
[0101] Furthermore, this first closing member 155 has an opening 156 passing through its surface at a predetermined height and having a general rectangular shape.
[0102] The second closing member 157 has a generally parallelepiped shape and protrudes from the outer surface of the outer cylindrical part 137 of the handling member 130 of the tappet 120 with a predetermined height and thickness.
[0103] The second positioning means 152 of the handling member 130 of the tappet 120 in the open position P 1 and more particularly in the inflating position PI of the inflatable boat 2 comprise a first opening member 158 supported by the peripheral portion 153 of the baseplate 101 on the one hand, arranged to cooperate with a second opening member 159 supported by the handling member 130 of the tappet 120 .
[0104] The first opening member 158 is generally in the shape of a rod extending transversely to the plane in which the peripheral portion 153 of the baseplate 101 extends from a second predetermined peripheral position of that same peripheral portion 153 of the baseplate 101 at a height that is also predetermined.
[0105] The second predetermined peripheral position of the first opening member 158 is substantially positioned opposite the first predetermined peripheral position on the first closing member 155 on the peripheral portion 153 of the baseplate 101 .
[0106] The second opening member 159 is formed by a centered and transverse slit, formed on the second closing member 157 of the first positioning means 151 of the handling member 130 of the tappet 120 .
[0107] This slit 159 comprises a width substantially equal to that of the first opening member 158 in the form of a rod and divides the second closing member 157 in two parts.
[0108] Furthermore, the second closing member 157 comprises a shape substantially complementary to that of the opening 156 of the first closing member 155 and is then situated across from that same opening 156 when the handling member 130 of the tappet 120 is in its closed position P 2 .
[0109] Furthermore, the second closing member 157 comprises a thickness greater on the one hand than the distance separating the handling member 130 of the tappet 120 and the first closing member 155 , and on the other hand the distance separating that same handling member 130 of the tappet 120 and the first opening member 158 when the handling member 130 of the tappet 120 is positioned near the peripheral portion 153 of the base 101 after having been engaged therein.
[0110] Thus, when the user wishes to inflate the inflatable boat 2 , he begins by screwing the handling member 130 of the tappet 120 on the baseplate 101 , then connects a pump to the inflating duct 132 .
[0111] To that end, the inner thread 109 of the stationary baseplate 101 and the thread 136 of the inner cylindrical part 135 of handling member 130 of the tappet 120 , are arranged to limit the number of rotations of the handling member 130 of the tappet 120 on the baseplate 101 , that rotation preferably not exceeding one revolution.
[0112] The second closing member 157 and the second opening member or slit 159 then reach the first opening member or rod 158 .
[0113] The beveled shape of the first part of the second closing member 157 then exerts lateral pressure on the first opening member or rod 158 , which forces it to deform elastically until that same first opening member or rod 158 penetrates inside the second opening member or slit 159 located at the middle of the second closing member 157 .
[0114] The inflating device 100 is then in an open position P 1 , and more specifically in an inflating position PI in which the various air chambers 31 , 41 , 51 communicate with each other and in which the enclosure 6 is sealed.
[0115] In this position, the user then inflates the inflatable boat by actuating the inflating pump.
[0116] To bring the inflating device 100 toward its closed position P 2 , the user continues to screw the handling member 130 of the tappet 120 on the baseplate 101 , which frees the first opening member or rod 158 from the second opening member or slit 159 by causing a new elastic deformation of the first opening member or rod 158 following the action of the second part of the second closing member 157 .
[0117] By continuing to screw a half-revolution from the previous open position P 1 , the second closing member 157 reaches the first closing member 155 . The beveled shape of the first part of the second closing member 157 followed by the second part of the second closing member 157 then successively exerts lateral pressure on the first closing member 155 , which is then forced to deform elastically until the second closing member 157 penetrates inside the opening 156 formed in the first closing member 155 .
[0118] The inflating device 100 is then in the closed position P 2 , in which the various air chambers 31 , 41 , 51 are hermetic with respect to one another.
[0119] In this closed position P 2 , the toroid peripheral annular portion 154 of the handling member 130 of the tappet 120 bears on the thin hollow cylindrical peripheral portion 153 of the baseplate 101 .
[0120] According to another alternative of this first embodiment, the inflating duct 132 is positioned near the center of the handling member 130 of the tappet 120 .
[0121] Furthermore, according to other alternatives, the inflating duct 132 comprises a stopper 160 arranged to protect the inflating duct 132 , and the outer surface of the outer cylindrical part 137 of the handling member 130 of the tappet 120 comprises gripping means 161 assuming the form of cavities arranged to facilitate gripping of the positioning means 130 by a user.
[0122] According to the alternative of this first embodiment comprising doing away with the non-return device 8 , the user is forced to return the inflating device 100 toward the closed position P 2 thereof before disconnecting the inflating pump from the duct 132 , which gives the inflating device 100 additional security, thereby preventing the user from forgetting to return the inflating device 100 to the closed position P 2 thereof following inflation of the inflatable boat 2 .
[0123] In fact, only the closed position P 2 guarantees compliance with the standard according to which, following the step for inflating the inflatable boat 2 , the various air chambers 31 , 41 , 51 must be hermetic with respect to one another so as to guarantee 50% inflation of the inflatable boat 2 following a puncture.
[0124] Furthermore, this alternative makes it possible to deflate the inflatable boat 2 if the latter is overinflated by unscrewing and rescrewing the handling member 130 of the tappet 120 .
[0125] Although the invention has been described with respect to specific example embodiments, it is of course in no way limited thereto and encompasses all technical equivalents of the described means as well as combinations thereof.
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The present invention relates to an inflating device that can be used for inflating an inflatable boat having two sides and a bottom, each having an independent air chamber, the device including a sealed body with an enclosure having at least three communication openings, each of the openings being connected to another opening by a passage for the circulation of a flow of air, and in particular a first opening intended to be connected to a first air supply means intended to supply air to the air chamber of the first side fender of the inflatable boat, a second opening intended to be connected to a second air supply means intended to supply air to the air chamber of the second side fender of the inflatable boat, a third opening intended to be connected to an air pump, and means for shutting off the passage between the first opening and the second opening, the means being disposed in the enclosure and being able to move between a first position, called the open position, in which the passage between the first opening and the second opening is open, and a second position, called the closed position, in which the passage between the first opening and the second opening is closed.
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BACKGROUND OF THE INVENTION
[0001] This invention relates to luggage cases particularly designed to carry and protect laptop computers, known as laptop computer carrying cases. Particularly, the disclosed inventions relate to improvements in impact isolation structures that lend themselves to both hardside and softside case constructions, and more specifically to enhanced systems for protecting laptop computers when being carried in such laptop carrying cases.
[0002] One popular form of laptop computer protection uses compressible foam blocks or strips, or sealed air bladders to cushion the laptop computer. An example of such a system is shown in U.S. Pat. No. 4,339,039. Such blocks, strips, or bladders are positioned typically around the narrow side surfaces of the laptop computer and nestle between the corresponding perimeter wall of the carrying case (usually called the “rail”) and the computer. The carrying case structure absorbs some impact energy. The foam or bladder components positioned between the computer and the source of impact (the floor if the carrying case has been dropped) get squeezed, thus absorbing some of the energy of the impact and slowing the rate of deceleration that the laptop would otherwise experience.
[0003] In contrast with cases that use these compressible foam cushions or bladders to isolate laptop computers from direct impact, this inventive system uses one or most preferably two generally flat walls or panels flanking or parallel to a broad face of the laptop computer to help hold the laptop computer's edges and corners away from the rail during impact, and thus from direct impact with the rail, even when the case is dropped on a side or corner. Such panel-based isolation systems use a significant portion of the case itself to yield in response to the impact, thus absorbing more of a share of the energy of the impact. This leaves less of the impact energy for the computer itself to absorb.
[0004] Two types of panel systems represent the leading examples of such panel-based systems. The first is characterized by that shown in U.S. Pat. Nos. 5,524,754 and 5,217,119. These patents advocate the use of a sling of stretchy material hanging from the top portions of one or more vertical walls of a carrying case to suspend the laptop computer above the bottom rail of the case. On impact, the shock is taken by the stretchy sling and by the carrying case structure. The laptop computer, if the case has been dropped on its bottom, decelerates relatively slowly since the stretchy sling material continues to distend into the space allowed by the distance the laptop is suspended above the bottom of the case. This system works relatively well, at least if the carrying case is dropped in a vertical position, that is if the case impacts bottom first onto a horizontal surface. If the computer case were to fall on a side surface of the rail rather than the bottom, or tumble from a table top onto its top surface, the elastic sling would not isolate the laptop computer, and catastrophic damage to the computer would be more likely to occur.
[0005] A second panel system to which the instant invention is more closely akin is shown in U.S. Pat. No. 5,529,184 to Sadow, which patent, to the extent it is not inconsistent with this disclosure, is hereby incorporated by reference. Here, a laptop computer is strapped to the center of a drumhead-like panel comprising a membrane of generally non-stretching material tensioned like a drum skin on a peripheral frame made of a resilient, flexible material. Should the carrying case incorporating this inventive panel hit the floor at virtually any location around the periphery, the impact energy tends to be absorbed and retransmitted to the entire panel. The resulting distortion of the surrounding frame holds the laptop away from the impacted side during all but the most severe falls, thus helping to avoid direct contact with the floor. The panel and the rest of the carrying case absorb and dissipate much of the energy of impact.
[0006] This patent also discusses using two such panels; one on each side of the laptop computer intended to be protected from impact damage (see FIG. 3 of U.S. Pat. No. 5,529,184). Apparently, the computer is strapped to the center of one of the panels, with the other panel merely held to the first panel by straps 28 and 30 . Both panels are coated with a layer of foam plastic sponge for extra shock absorption.
[0007] However, until the invention detailed below, this system has lacked a practical application. Also, the system disclosed for strapping the laptop computer to the center of one of the tensioned membranes was cumbersome to use, and the shock absorbing ability of one or both of the resilient frames was compromised since the frames tend to bend out of the plane of the panel, potentially permitting the computer to bottom out.
[0008] Accordingly, it is an object of this invention to provide a panel-based shock absorbing system for a laptop computer carrying case that is remarkably effective in protecting the laptop computer from impacts in many directions.
[0009] It is another object of the invention to provide a system using two panel-type shock-absorbing systems that stabilize the panels for improved impact energy absorption.
[0010] It is a further object of this invention to provide a light, impact absorbing and isolating system for a laptop computer carrying case having an overall rectangular shape which can protect the attached laptop computer from impact resulting from being dropped onto virtually any side or corner of the case.
SUMMARY OF THE INVENTION
[0011] Accordingly, disclosed is a carrying case for a laptop computer including a first main compartment for holding the laptop computer, the main compartment sized to receive a laptop computer and having a shock absorbing insert comprising a first flat panel extending across the main compartment having at least one inextensible layer, a resilient hoop constrained by the inextensible layer, an upstanding frame sized to surround the laptop computer, the frame firmly affixed to the inextensible layer, a second flat panel extending across the main compartment, whereby the frame and the panels restrain the laptop computer when the carrying case is dropped.
[0012] The shock absorbing insert comprises two, substantially similar flat panels, each in turn comprising a flat envelope of generally inextensible fabric with one or more hoops of resilient wire, and the frame comprises a pair of similar frame constructions each affixed to one of the two flat panels, the two flat panels hinged to one another along an edge whereby the laptop computer can be placed between the flat panels and surrounded by the frame constructions.
BRIEF DESCRIPTION OF THE FIGURES
[0013] [0013]FIG. 1 shows a perspective view of a laptop computer carrying case embodying the disclosed invention.
[0014] [0014]FIG. 2 is a side view of the case shown in FIG. 1 as seen from the side opposite of that shown in FIG. 1.
[0015] [0015]FIG. 3 shows an interior panel of this carrying case, with a portion of the rest of the case shown in dashed lines.
[0016] [0016]FIG. 4 shows a view of the back side of the carrying case.
[0017] [0017]FIG. 5 is a perspective view of the shock-absorbing insert according to the subject invention.
[0018] [0018]FIG. 6 is another view of the shock-absorbing insert.
[0019] [0019]FIG. 7 is a plan view of the interior wire supports.
[0020] [0020]FIG. 8 is a side view of a subassembly of the shock-absorbing insert of FIGS. 6 and 7.
[0021] [0021]FIG. 9 is a front view of the subassembly shown in FIG. 8.
[0022] [0022]FIG. 10 is a cross-section and partially broken away view of the subassembly,
[0023] [0023]FIG. 11 is a back view of the subassembly.
[0024] [0024]FIG. 12 shows a vertical cross-section through the skeletal portions of the insert.
[0025] [0025]FIG. 13 is a partial cross-section taken through 13 - 13 of FIG. 5.
[0026] [0026]FIG. 14 is a perspective view of an alternate foam spacer construction.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0027] The Carrying Case
[0028] Except as otherwise detailed below, and except as necessary to accommodate the inventive shock absorbing insert as will be detailed, the laptop computer carrying case I has a generally conventional construction. One relatively simple version of this carrying case 1 is shown in FIGS. 1 through 5. The front panel 2 of the case includes a pair of gusseted pockets 3 and 4 . FIG. 3 shows the organizer panel 5 sewn into the interior of the upper pocket 3 of these two gusseted pockets. The back wall 6 of the case has a wide strap 7 sewn horizontally across the main body panel. The strap is sized to be slipped over the extendable handle used to steer upright luggage cases. A semicircular flap 8 , preferably of leather, is affixed to the main body panel to project just above the upper edge of this wide strap. This flap can be selectively adhered to the strap 7 as shown, using conventional hook and loop fasteners 9 or mating snaps, to help affix the carrying case to the extended steering handle of the wheeled case for easy transport.
[0029] The rail portion 10 of the case has two slide fasteners 11 extending around three of the four sides of the rail so that two main compartments 12 and 13 open from the case fan-fashion from the base side 14 of the rail. The base side of the rail has elongated molded rubber glides 15 to support the case in the upright position shown. Within the first 12 of the two main compartments is a shock absorbing insert or module 20 that will be detailed below. The second 13 of the main compartments is a conventional portfolio type paper organizer and will not be otherwise detailed.
[0030] The first of the two main compartments contains the shock-absorbing insert 20 shown in FIG. 5, etc. The module consists of two substantially similar, generally mirror image subassemblies 21 and 22 that normally hinge together at their bottom edges using strips of hook and loop fastener tape 23 and snaps 44 . This module is sized to just fit snugly within the rail portions 10 that extend around the first main compartment. Also, conventional snap fasteners 25 hold each subassembly to corresponding mating fasteners in its respective half of the first main compartment. Thus, when the main compartment of the carrying case is unzipped and opened, the module opens too to receive the laptop computer to be carried, or opens to permit access to the laptop computer secured within the module.
[0031] Each subassembly 21 and 22 in the pair of subassemblies making up the protective insert preferably consists of a textile wrapped tray-like structure. The broad face of each subassembly comprises a sewn, flat envelope 26 of tough, stretch resistant textile, such as nylon. Around each envelope's perimeter is a frame 27 comprising an inner frame of ABS extrusion 28 , a surrounding frame 29 of high density foam plastic, all contained in a sewn annular jacket 30 . This sewn annular jacket is firmly stitched at 38 and 44 around its inner and outer peripheries to the flat envelope 26 . Within each flat envelope is a layer of conventional flexible foam sheet 31 and several, preferably four, resilient hoops 32 of tempered wire. Each hoop has a special shape and position within the flat envelope to resist collapse on impact and to otherwise absorb and dissipate impact energy.
[0032] The first 33 of these hoops is sewn into the extreme peripheral edge of the flat envelope. This hoop defines the shape of the envelope in the plane of the subassembly. It is felt this hoop functions according to U.S. Pat. No. 5,529,184 referenced above, tensioning and distorting the textile panels of the envelope during impact. The additional hoops also flex and move on impact. The first additional hoop 34 has an overall circular shape in plan, and is made of the same tempered steel wire as the other hoops. Note that it just fits within the envelope, pressing outward at the center of each generally straight edge of the envelope. The envelope is stitched 50 through near the portions of this circular hoop near where the circular hoop contacts the straight edges of the envelope. The remaining two hoops 35 and 36 are essentially identical to one another, both having an extremely flattened or oval circular shape. Each extends diagonally across the textile envelope between opposite comers thereof, crossing one another in the middle of the envelope. The circular hoop and these remaining two hoops are inserted into the envelope through the pair of slide fasteners 37 shown in FIG. 12.
[0033] The perimeter frame comprising the annular jacket 30 of textile and the foam and ABS plastic extrusion is firmly sewn to one side of the flat textile envelope. The foam portion 29 is preferably made from a frame of non-crosslinked polyethylene foam having a density of about 2 pounds per cubic foot, such as the type available commercially from Pednar Products Inc., 13130 Spring Street, Baldwin Park, Calif. 91706. The ABS plastic frame 28 is sized to engage the inner periphery of this foam portion, and may be made up of two or more L-shaped sections arranged end to end or overlapping to form a closed rectangle which, together with a matching frame on the other of the subassemblies, defines the laptop computer containing volume.
[0034] [0034]FIG. 12 shows a schematic, cross-sectional view of the skeletal or support portions of the two subassemblies. The assembly of four tempered wire hoops 30 is shown on edge, while the foam and ABS plastic frames are shown in cross-section. This figure shows the two skeletal subassemblies positioned relative to one another, as they would be in FIG. 5 for example—ready to receive a laptop computer prior to closing the slide fastener of the first main compartment of the case containing these subassemblies.
[0035] [0035]FIG. 14 shows an alternate way to construct the foam frame portion. Here, instead of a continuous rectangular frame of the high-density polyethylene foam, each of four L-shaped foam shapes is die cut from a foam sheet. One or more holes 41 are cut through the foam sheets extending perpendicular to the plane of the frame. These holes reduce the amount of foam in the frame, thus reducing weight and increasing the compressibility of the foam selectively along the sides of the assembled frame. Note that, in this embodiment, there are no such holes at or near the corner portions 42 of the L-shaped components. This is to not decrease the stiffness or resistance to compression near these corners, while permitting a bit more compression in the straight portions of the frame. Note these L-shaped components include one or more layers of conventional, fiber reinforced strapping tape 43 . The tape is adhered to the outward facing surfaces of the foam shapes as well as the inward facing surfaces adjacent to the ABS inner frame when assembled. While the scope of this invention should not be limited by any theory of operation, it is felt that this strapping tape reinforcement tends to resist the possibility of the ABS frame corners cutting through the foam corners. The tape, being quite resistant to stretching, also helps involve more of the foam in absorbing impact. When the laptop computer presses on only one arm of this L-shaped construction during impact, the strapping tape pulls downwardly on the other of the arms, causing foam in that arm to compress, hopefully slowing the laptop computer further and preferentially absorbing some more impact energy.
[0036] The protective insert is assembled as follows. First, the textile portions of each subassembly are sewn together using conventional sewing techniques. One of the subassemblies includes a strip of elastic webbing that extends across one of the panels for optionally capturing the laptop computer intended to be transported. The hook and loop fasteners are used to hinge the two subassemblies together along their bottom edges. Snap fasteners (shown on the insert) fasten to mating straps on the inside surfaces of the first main compartment. One of the subassemblies is provided with a triangular gusset 24 and a slide fastener along its free edge, one each along the vertical sides as shown in FIG. 8. The other of the subassemblies has a mating slide fastener along each of its vertical sides (not shown.)
[0037] Note various slide fastener closable openings 39 into the textile portions of the subassemblies are used extensively to permit this sewing assembly to take place first, while later the tempered steel wire hoops, ABS and foam frame portions can be stuffed into their respective textile jackets and envelopes through these slide fastener closable openings. The wire hoops are passed through the L-shaped opening on outwardly facing sides of the flat textile envelope (FIGS. 5 through 7 and 11 ). The first of the hoops is sewn into the outermost edge of the flat envelope, and the circular hoop is sewn to trap it at select locations as mentioned above. The ABS and foam frames are assembled into the perimeter textile jacket and captured by the perimeter slide fastener (FIGS. 5 and 8 for example). Then, the two subassemblies are attached at their lower edges by their mating hook and loop tapes. Finally, the assembled insert is pushed into its operative position within the first main compartment.
[0038] In operation, the user need only open the slide fastener into the first main compartment, and insert a laptop computer. Then this slide fastener is closed. This brings the two subassemblies into abutting, face-to-face contact. The ABS and foam frame structures come together to support the now trapped laptop computer, each contributing its structural and shock absorbing capabilities to protect the laptop computer from much of the impact forces associated with dropping the laptop computer containing carrying case from typical heights. In fact, testing has shown that on average, a typical laptop computer experiences an average peak of about 55 g's acceleration when the case is dropped from a height of about 40 inches above a typical hard floor surface. This is the average acceleration, whether it is dropped on any corner or any side of the inventive carrying case. This acceleration figure is well below that typically required to permanently damage the led screen or other relatively delicate component of a typically constructed laptop computer.
[0039] While the scope of the present invention should not be limited to any particular theory of operation, it should be instructive to speculate on such in order to provide the reader with a full understanding of this invention and its preferred embodiment. It is felt that the multiple tempered wire hoops assembled as disclosed absorb and dissipate quite a bit of the impact energy, while supporting the ABS frames that engage the laptop computer's edge surfaces. Modes of energy absorption include elastic deformation of the hoops themselves as well as the inextensible textile panels constraining these hoops. Frictional interengagement of the hoops with the thin foam panel also trapped within the flat textile envelope, as well as between the hoops, also likely contributes to preferentially absorbing and dissipating impact energy.
[0040] The surrounding foam frame also absorbs some energy while slowing the movement of the laptop computer during impact. Likely, the more important roll of the foam frame, however, is laterally stabilizing the flat, tempered wire supported panels during impact. The inventor has found that during impact, wire supported panels, if not properly constrained, collapsed erratically during impact, that is, such panels tended to bend out of plane. Such bending not only short circuited the ability of the panel to absorb and retransmit the impact energies to other portions of the carrying case, but also failed to support and slowly decelerate the laptop computer during impact. The foam frame tends to maintain distance between the hoop containing panels, especially at the corners. The snugly fitting main compartment keeps the hoop containing panels from splaying outwardly. Thus the hoop containing panels are trapped by the main compartment on the outside and the foam and ABS frame on the inside.
[0041] Alternative constructions to the preferred embodiment described in detail above are contemplated by this invention. For example, the insert described above could itself comprise a protective case if the abutting outermost edges of the textile frame were provided with mating perimeter slide fasteners to firmly close and hold the two subassemblies together around the laptop computer to be protected. Also, other means besides the foam frame to support the laptop computer while constraining the distortion of the flat panels during impact are made obvious by this disclosure. For example, air bags, both vented and pressurized, could work, as well as a gridwork of truss-like struts made of plastic or springy metal, could serve this dual roll as well.
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Of the various carrying cases especially designed to isolate the contained laptop computer from impact forces, all are deficient in isolating the laptop computer from impacts from all directions, for example if the case containing the laptop computer were dropped on any side, edge or corner. The disclosed case provides a lightweight framed shock-absorbing insert to resist the impact and to channel much of the impact energy away from the laptop computer. This insert has two flat panels sandwiching the laptop computer. These panels flex in response to impact from any direction, while isolating the laptop computer from direct impact with the floor or the like during impact of the case with the floor. The panels are constrained from collapsing by bending out of the plane of the panel during most impacts. Constraining structures include a surounding frame between the outer edges flat panels, and surrounding textile constructions that cooperate to keep the flat panels parallel and generally flat during impacts.
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REFERENCE TO PENDING PRIOR PATENT APPLICATION
This is a continuation of prior U.S. patent application Ser. No. 09/896,258, now U.S. Pat. No. 6,692,513 filed Jun. 29, 2001 by Richard B. Streeter et al. for INTRAVASCULAR FILTER WITH DEBRIS ENTRAPMENT MECHANISM, which in turn claims benefit of U.S. Provisional Patent Application Ser. No. 60/215,542, filed Jun. 30, 2000 by Richard B. Streeter et al. for INTRAVASCULAR FILTER WITH DEBRIS ENTRAPMENT MECHANISM, which patent application is hereby incorporated herein by reference, and of U.S. Provisional Patent Application Ser. No. 60/231,101, filed Sep. 8, 2000 by Richard B. Streeter et al. for INTRAVASCULAR FILTER WITH DEBRIS ENTRAPMENT MECHANISM.
FIELD OF THE INVENTION
This invention relates to intravascular filtering apparatus and methods in general, and more particularly to apparatus and methods for filtering and irreversibly entrapping embolic debris from the vascular system during an intravascular or intracardiac procedure.
BACKGROUND OF THE INVENTION
Intracardiac and intravascular procedures, whether performed percutaneously or in an open, surgical, fashion, may liberate particulate debris. Such debris, once free in the vascular system, may cause complications including vascular occlusion, end-organ ischemia, stroke, and heart attack. Ideally, this debris is filtered from the vascular system before it can travel to distal organ beds.
Using known filter mechanisms deployed in the arterial system, debris is captured during systole. There is a danger, however, that such debris may escape the filter mechanism during diastole or during filter removal. Apparatus and methods to reduce debris escape during diastole or during filter removal may be desirable to reduce embolic complications.
SUMMARY OF THE INVENTION
An object of the invention is to provide a filtering mechanism that irreversibly entraps debris therein.
Another object of the invention is to provide a filtering mechanism that permanently captures debris from the intravascular system of a patient.
A further object of the invention is to provide a filtering mechanism with greater ability to collect debris in the intravascular system of a patient to decrease the number of complications attributable to such debris.
Another further object of this invention is to provide a filter holding mechanism suitable to be secured to a retractor used to create access to the heart and surrounding structures during heart surgery procedures.
A still further object is to provide a method for using a filtering mechanism in the intravascular system of a patient to permanently capture debris therefrom.
Another still further object of the present invention is to provide a method for introducing a filtering device in the aorta downstream of the aortic valve to restrict the passage of emboli while allowing blood to flow through the aorta during cardiovascular procedures, and to entrap debris collected in the filter so as to prevent its escape during cardiac diastole or during manipulation, repositioning or removal of the device from the aorta.
With the above and other objects in view, as will hereinafter appear, there is provided apparatus for debris removal from the vascular system of a patient, said apparatus comprising: a filtering device having a proximal side and a distal side said filter being sized to allow blood flow therethrough and to restrict debris therethrough and said filter having a first given perimeter, wherein blood flow in a first direction passes from the proximal side to the distal side of the filtering device; an entrapment mechanism having a proximal side and a distal side, the entrapment mechanism forming a selective opening to allow debris and blood flow passage in the first direction from the proximal side to the distal side therethrough, the selective opening having a restriction mechanism to prevent debris passage in a second direction opposite to said first direction the selective opening having a second given perimeter, the first given perimeter and the second given perimeter being deployed within the vascular system so as to form a chamber between the distal side of the entrapment mechanism and the proximal side of the filtering device, wherein the entrapment mechanism allows blood flow and debris to pass therethrough in the first direction, the filtering device allows blood flow to pass therethrough in the first direction, the restriction mechanism prevents debris from passing back through said selective opening in a second direction opposite to the first direction and the chamber contains the debris received through the entrapment mechanism so as to prevent the escape of the debris therein by said filtering device in the first direction and said restriction mechanism in said second direction.
In accordance with another further feature of the invention there is provided a method for filtering and entrapping debris from the vascular system of a patient, the method comprising: providing apparatus for filtering and entrapping debris from the vascular system of a patient, the apparatus comprising: a filter device being sized to allow blood flow therethrough and to restrict passage of debris therethrough, and the filter device having a first given perimeter, a proximal side and a distal side; and wherein the filtering device captures debris carried in a first direction of blood flow from the proximal side to the distal side thereof on the proximal side of the filter device; an entrapment mechanism having a proximal side and a distal side, the entrapment mechanism including a selective opening to allow passage of blood and debris therethrough, the selective opening being configured to allow passage of blood and debris carried therein therethrough in the first direction of blood flow from the proximal side to the distal side of the entrapment mechanism, the selective opening having a restriction mechanism to prevent debris passage from the distal side to the proximal side of the entrapment mechanism in a second direction opposite to the first direction, the selective opening forming a second given perimeter, and the first given perimeter and the second given perimeter being deployed within the vascular system so as to form a chamber between the distal side of the entrapment mechanism and the proximal side of the filtering device; wherein the entrapment mechanism allows blood and debris carried therein therethrough in the first direction of blood flow, the filtering device allows blood therethrough in the first direction of blood flow, and the restriction mechanism prevents debris back through the selective opening in the second direction of blood flow opposite to the first direction of blood flow such that the chamber entraps the filtered debris received therein for debris removal from the vascular system of the patient; inserting said apparatus into the vascular system of the patient; allowing blood and debris carried therein to flow through the entrapment mechanism, and into the chamber; and removing the apparatus from the vascular system of the patient.
The above and other features of the invention, including various novel details of construction and combinations of parts and method steps will now be more particularly described with reference to the accompanying drawings and pointed out in the claims. It will be understood that the particular devices and method steps embodying the invention are shown by way of illustration only and not as limitations of the invention. The principles and features of this invention may be employed in various and numerous embodiments without departing from the scope of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other objects and features of the present invention will be more fully disclosed or rendered obvious by the following detailed description of the preferred embodiments of the invention, which are to be considered together with the accompanying drawings wherein like numbers refer to like parts, and further wherein:
FIG. 1A is a perspective view of a deployable entrapment filtering device for debris removal showing the filtering device in its fully deployed shape as released from its cannula into the blood stream of a patient;
FIG. 1B is an exploded perspective view of the deployable entrapment filtering device of FIG. 1A showing the components thereof;
FIG. 1C is a schematic cross-sectional illustration depicting the deployable entrapment filtering device of FIGS. 1A and 1B during cardiac systole;
FIG. 1D is a schematic cross-sectional illustration depicting the deployable entrapment filtering device of FIGS. 1A and 1B during cardiac diastole;
FIG. 2A is an exploded perspective view of a deployable entrapment filtering device for debris removal showing the components thereof including a set of filter mesh entrapment leaflets;
FIG. 2B is a schematic cross-sectional illustration depicting the deployable entrapment filtering device of FIG. 2A during cardiac systole;
FIGS. 3A-3D are a series of schematic illustrations depicting a method of using the deployable entrapment filtering device of FIGS. 2A and 2B ;
FIG. 4A is an exploded perspective view of a deployable entrapment filtering device for debris removal showing the components thereof including a set of non-porous valve leaflets;
FIG. 4B is a schematic cross-sectional illustration depicting the deployable entrapment filtering device of FIG. 4A during cardiac systole;
FIGS. 5A-5D are a series of schematic illustrations depicting a method of using the deployable entrapment filtering device of FIGS. 4A and 4B ; and
FIGS. 6A-6D are schematic illustrations depicting an orthogonally deployable valve/filter apparatus.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
A filtration and entrapment apparatus 5 is shown in FIGS. 1A-5D for debris removal from the vascular system of a patient. Filtration and entrapment apparatus 5 generally includes a filter device 10 and an entrapment mechanism 15 . Filtration and entrapment apparatus 5 can be used to filter emboli during a variety of intravascular or intracardiac procedures, including, but not limited to, the following procedures: vascular diagnostic procedures, angioplasty, stenting, angioplasty and stenting, endovascular stent-graft and surgical procedures for aneurysm repairs, coronary artery bypass procedures, cardiac valve replacement and repair procedures, and carotid endardarectomy procedures.
Now looking at FIGS. 1A-1D , a preferred embodiment of the present invention is shown with filtration and entrapment apparatus 5 as described herein below.
FIG. 1A depicts the profile of filtration and entrapment apparatus 5 in its fully deployed shape, with filter device 10 and entrapment mechanism 15 released from cannula 20 into the blood stream (not shown). Prior to deployment, filter device 10 and entrapment mechanism 15 are collapsed within cannula 20 , e.g., by moving the proximal end 25 A proximally along center post 50 .
FIG. 1B depicts the primary components of filtration and entrapment apparatus 5 comprising filter device 10 and entrapment mechanism 15 in attachment to deployable frame 25 . In the present embodiment of the invention, filter device 10 comprises a filter mesh bag 30 , and entrapment mechanism 15 comprises a piece of coarse mesh 35 and a set of entrapment flaps 40 .
FIG. 1C depicts filtration and entrapment apparatus 5 deployed within an aorta 45 during cardiac systole. Blood and debris flow through opened deployable frame 25 , across course mesh 35 , between and through entrapment flaps 40 and into the end of the filter mesh bag 30 . Entrapment flaps 40 ensure unidirectional flow of blood and debris into filter mesh bag 30 .
FIG. 1D depicts filtration and entrapment apparatus 5 within the aorta 45 responding to any retrograde flow of blood and/or back pressure within the aorta 45 during cardiac diastole. The back flow of blood and/or back pressure causes filter mesh bag 30 to partially deform and entrapment flaps 40 to close against coarse mesh 35 . Coarse mesh 35 is of a structure adequate to permit the free flow of blood and debris through it and into filter mesh bag 30 , and serves as a supporting structure against which entrapment flaps 40 can close and remain in a closed position to prevent the escape of embolic debris.
Still looking at FIGS. 1A-1D , it should also be appreciated that the entrapment flaps 40 may be attached to structures other than deployable frame 25 , e.g., the entrapment flaps 40 may be attached to a center post 50 , or to coarse mesh 35 , etc. Furthermore, if desired, entrapment flaps 40 may be biased closed or biased open. In addition, entrapment mechanism 15 may consist of one or more flaps 55 , and have a configuration including, but not limited to, a single disk diaphragm (not shown), a semi-lunar configuration (not shown), a gill slit configuration (not shown), a multi-leaflet flap configuration (not shown), etc.
It should also be appreciated that, while in the foregoing description the apparatus shown in FIGS. 1A-1D has been described in the context of functioning as a filter, it may also function as a one-way check valve. To the extent that the apparatus shown in FIGS. 1A-1D is intended to function primarily as a one-way check valve, filter mesh bag 30 (see FIG. 1B ) may be retained or it may be omitted.
Looking next at FIGS. 2A and 2B , there is shown an alternative form of the present invention as a bidirectional flow filtration and entrapment apparatus 105 . Bidirectional flow filtration and entrapment apparatus 105 of FIGS. 2A and 2B generally comprises a filter device 110 and an entrapment mechanism 115 delivered by a cannula 120 to the interior of a vascular structure 122 (see FIGS. 3A-3D ); a deployable filter frame 125 ; a filter bag 130 attached to the perimeter of deployable filter frame 125 ; a compliant, soft outer cuff 135 (preferably formed out of a biologically inert material such as Teflon, Dacron, Silastic, etc.) for sealing filtration and entrapment apparatus 105 against the inner wall of vascular structure 122 when deployable filter frame 125 is expanded; entrapment leaflets 140 , preferably in the form of a fine filter mesh; a center post 150 (preferably formed out of steel or the equivalent) passing across the interior of the deployable filter frame 125 ; a hinge line 155 on entrapment leaflets 140 , connected to center post 150 , for permitting the entrapment leaflets 140 to open and close; co-aptation strands 160 extending across the interior of deployable filter frame 125 and providing a seat against which entrapment leaflets 140 may close during diastole; and a perimeter seal 165 (preferably formed out of expanded Teflon or the like). Perimeter seal 165 acts like a step to help support entrapment leaflets 140 during diastole.
In addition, it should also be appreciated that soft outer cuff 135 may comprise a radially expandable mechanism (e.g., a balloon, a decompressed sponge, a spring loaded leaflet, etc.) for sealing filtration and entrapment apparatus 105 against the inner wall of vascular structure 122 .
As noted above, entrapment leaflets 140 are preferably formed out of a fine filter mesh. This filter mesh is sized so that it will pass blood therethrough but not debris. Furthermore, this filter mesh is sized so that it will provide a modest resistance to blood flow, such that the entrapment leaflets will open during systole and close during diastole. By way of example but not limitation, the filter mesh may have a pore size of between about 40 microns and about 300 microns.
FIGS. 3A-3D illustrate operation of bidirectional flow filtration and entrapment apparatus 105 shown in FIGS. 2A and 2B . More particularly, cannula 120 of deployable filtration and entrapment apparatus 105 is first inserted through a small incision 170 in the wall of the vascular structure 122 (see FIG. 3A ). Then deployable filter frame 125 is deployed (see FIG. 3B ). Thereafter, during systole (see FIG. 3C ), blood flows through deployable filter from 125 , forcing entrapment leaflets 140 open, and proceeds through filter bag 130 . Any debris contained in the blood is captured by filter bag 130 and thereby prevented from moving downstream past bidirectional flow filtration and entrapment apparatus 105 . During diastole (see FIG. 3D ), when the blood flow momentarily reverses direction, entrapment leaflets 140 (shown in FIGS. 2A and 2B ) close, seating against co-aptation strands 160 (shown in FIGS. 2A and 2B ) extending across the interior of deployable filter frame 140 (shown in FIGS. 2A and 2B ). The blood passes through the fine mesh of entrapment leaflets 140 (shown in FIGS. 2A and 2B ), being filtered as it passes, thus permitting coronary profusion to take place during the diastolic phase. The fine mesh of entrapment leaflets 140 (shown in FIGS. 2A and 2B ) prevents debris from passing back through bidirectional flow filtration and entrapment apparatus 105 .
It should also be appreciated that with bidirectional flow filtration and entrapment apparatus 105 of FIGS. 2A , 2 B and 3 A- 3 D, entrapment leaflets 140 may be attached to structures other than center post 150 , e.g., they may be attached to co-aptation strands 160 , or to deployable filter frame 125 , etc. Furthermore, if desired, entrapment leaflets 140 may be biased closed, or biased open. In addition, entrapment mechanism 15 may consist of one or more flaps (not shown), and have a configuration including, but not limited to, a single disk diaphragm (not shown), a semi-lunar configuration (not shown), a gill slit configuration (not shown), a multi-leaflet flap configuration (not shown), etc.
Looking next at FIGS. 4A and 4B , there is shown a deployable valve/filter apparatus 205 . Deployable valve/filter apparatus 205 of FIGS. 4A and 4B generally comprises a filter device 210 and a valve entrapment mechanism 215 delivered by a cannula 220 to the interior of the vascular structure 222 ; a deployable valve/filter frame 225 ; a filter bag 230 attached to the perimeter of deployable valve/filter frame 225 ; a compliant, soft outer cuff 235 (preferably formed out of a biologically inert material such as Teflon, Dacron, Silastic, etc.) for sealing the filter device 210 against the inner wall of vascular structure 222 when deployable valve/filter frame 225 is expanded; valve leaflets 240 , preferably in the form of a blood-impervious material; a center post 250 (preferably formed out of steel or the equivalent) passing across the interior of deployable valve/filter frame 225 ; a hinge line 255 on valve leaflets 240 , connected to center post 250 , for permitting valve leaflets 240 to open and close; co-aptation strands 260 extending across the interior of deployable valve/filter frame 225 and providing a seat against which valve leaflets 240 may close during diastole; and a perimeter seal 265 (preferably formed out of expanded Teflon or the like). Perimeter seal 265 acts like a step to help support valve leaflets 240 during diastole.
In addition, it should also be appreciated that soft outer cuff 235 may comprise a radially expandable mechanism (e.g., a balloon, a decompressed sponge, a spring loaded leaflet, etc.) for sealing deployable valve/filter apparatus 205 against the inner wall of vascular structure 222 .
FIGS. 5A-5D illustrate operation of deployable valve/filter apparatus 205 of FIGS. 4A and 4B . More particularly, valve/filter apparatus 205 is first inserted through a small incision 270 in the wall of the vascular structure 222 (see FIG. 5A ). Then deployable valve/filter frame 225 is deployed (see FIG. 5B ). Thereafter, during systole (see FIG. 5C ), blood flows through deployable valve/filter frame 225 , forcing valve leaflets 240 open, and proceeds through filter bag 230 . Any debris contained in the blood is captured by filter bag 230 and thereby prevented from moving downstream past valve/filter apparatus 205 . During diastole (see FIG. 5D ), when the blood flow momentarily reverses direction, valve leaflets 240 (shown in FIGS. 4A and 4B ) close, seating against co-aptation strands 260 (shown in FIGS. 4A and 4B ) across the interior of deployable valve/filter frame 225 (shown in FIGS. 4A and 4B ). The closed leaflets 240 (shown in FIGS. 4A and 4B ) prevent blood from passing back through the valve/filter frame 225 (shown in FIGS. 4A and 4B ).
It should also be appreciated that with valve/filter apparatus 205 shown in FIGS. 4A , 4 B and 5 A- 5 D, valve leaflets 240 may be attached to structures other than center post 250 , e.g., they may be attached to co-aptation strands 260 , or to deployable valve filter frame 225 , etc. Furthermore, if desired, valve leaflets 240 may be biased closed, or biased open. In addition, valve entrapment mechanism 215 may consist of one or more flaps (not shown), and have a configuration including, but not limited to, a single disk diaphragm (not shown), a semi-lunar configuration (not shown), a gill slit configuration (not shown), a multi-leaflet flap configuration (not shown), etc.
Looking next at FIGS. 6A-6B , there is shown an orthogonally deployable valve/filter apparatus 305 . Orthogonally deployable valve/filter apparatus 305 of FIGS. 6A-6D generally comprises a filter device 310 and a valve entrapment mechanism 315 deployed at an angle substantially orthogonal to an axis 318 of a cannula 320 , such as a catheter introduced to the vascular system at a location which may be remote from the point of operation, in the interior of a vascular structure 322 ; a deployable valve/filter frame 325 ; a filter bag 330 attached to the perimeter of deployable valve/filter frame 325 ; a compliant, soft outer cuff 335 (preferably formed out of a biologically inert material such as Teflon, Dacron, Silastic, etc.) for sealing the filter device 310 against the inner wall of vascular structure 322 when deployable valve/filter frame 325 is expanded; valve leaflets 340 , preferably in the form of a blood-impervious material, having a first portion 350 in attachment to deployable valve/filter frame 325 , and a second portion 355 separable from deployable valve/filter frame 325 , so as to allow valve leaflets 340 to open and close; and a mesh material 360 extending across the interior of deployable valve/filter frame 325 and providing a seat against which valve leaflets 340 may close during diastole. In addition, it should be appreciated that mesh material 360 may comprise coaptation strands such as coaptation strands 160 as first shown in FIG. 2A .
In addition, it should also be appreciated that soft outer cuff 335 may comprise a radially expandable mechanism (e.g., a balloon, a decompressed sponge, a spring loaded leaflet, etc.) for sealing orthogonally deployable valve/filter apparatus 305 against the inner wall of vascular structure 322 .
In addition, it should also be appreciated that valve entrapment mechanism 315 may be mounted for blood flow in either direction within vascular structure 322 .
FIGS. 6A-6D illustrate operation of deployable valve/filter apparatus 305 . More particularly, deployable valve/filter apparatus 305 is first inserted through the interior of vascular structure 322 to a desired location (see FIG. 6C ). Then deployable valve/filter frame 325 is deployed (see FIG. 6D ). Thereafter, during systole (see FIG. 6A ), blood flows through deployable valve/filter frame 325 , forcing valve leaflets 340 open, and proceeds through filter bag 330 . Any debris contained in the blood is captured by filter bag 330 and thereby prevented from moving downstream past deployable valve/filter apparatus 305 . During diastole (see FIG. 6B ), when the blood flow momentarily reverses direction, valve leaflets 340 close, seating against mesh material 360 across the interior of deployable filter frame 340 . The closed leaflets 340 prevent blood from passing back through the valve/filter frame 325 .
It should also be appreciated that with valve/filter apparatus 305 shown in FIGS. 6A-6D , valve leaflets 340 may be attached to structures other than deployable valve/filter frame 325 , e.g., they may be attached to mesh material 260 , or to cannula 320 , etc. Furthermore, if desired, valve leaflets 340 may be biased closed, or biased open. In addition, valve entrapment mechanism 315 may consist of one or more flaps (not shown), and have a configuration including, but not limited to, a single disk diaphragm (not shown), a semi-lunar configuration (not shown), a gill slit configuration (not shown), a multi-leaflet flap configuration (not shown), etc.
The filter design as described herein to prevent the escape of captured debris during diastole or filter removal may also be applied to all intravascular filters. Such a filter design may comprise a one-way valve and a filtering mesh in series. Liberated debris may pass through the one-way valve and come to rest in the filtering mesh. The one-way valve ensures permanent entrapment of debris. Potential applications of such an apparatus extend to all percutaneous and surgical procedures on the heart and vascular system, including open heart surgery, balloon dilatation of cardiac valves and arteries, deployment of stents in arteries, diagnostic catheterizations, and other cardiac and vascular procedures. Advantages of such a system include more complete collection of liberated debris, with a resulting decrease in the complications attributable to such debris.
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Apparatus for filtering and entrapping debris in the vascular system of a patient, the apparatus including a filter to allow blood to flow therethrough and to restrict passage of debris, wherein the filter captures debris carried in a first direction of blood flow. The apparatus further includes an entrapment mechanism which allows passage of debris and blood therethrough, in the first direction of blood flow and prevents debris passage in a second direction. The entrapment mechanism and filter allow blood and debris therethrough in the first direction of blood flow. The entrapment mechanism prevents debris flow in the second direction of blood flow. A method for filtering and entrapping debris in the vascular system includes inserting the apparatus into the vascular system, allowing blood and debris carried therein to flow through the entrapment mechanism, and removing the apparatus and accumulated debris from the vascular system.
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This application is a continuation of application Ser. No. 07/763,254 filed Sep. 20, 1991, now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a recording apparatus for recording an image on a sheet in accordance with recording data.
2. Related Background Art
In a conventional recording apparatus, generally, a pinch roller comes into pressure contact with a carrying roller and the carrying roller is driven and rotated, thereby conveying a recording sheet and executing a predetermined recording onto the conveyed recording sheet. A driving force of a stepping motor or the like is transferred by using a gear train and the like in order to drive the carrying roller.
In the above recording apparatus, a recording head having recording elements which are constructed on a dot unit basis is driven due to the movement of a carriage, one line is recorded, and the recording sheet is conveyed by a distance of the recording of one line every completion of the one-line recording.
In recent years, the realization of a high recording density has progressed more and more and there are many apparatuses in which the recording elements are arranged on a micro unit basis of a few dots/mm.
In such a recording apparatus, for instance, when considering a case where ordinary characters are printed one line by one, a certain space generally exists between the lines and even if there is a difference of a carrying amount of the order of a unit which lies within a range from a few microns to hundreds of microns as a carrying precision among the lines, such a difference cannot be judged by the eyes.
However, for instance, in the case of graphics such that a picture or the like is formed on a micro dot unit basis, with a block graphic character (BGC) such as ruled lines of a table or the like, which have previously been formed on a character unit basis, or the like, the first line and the next line are adjacently formed. Thus, there is a problem such that in the case where a carrying precision is low and a difference of the carrying amount occurs between the lines, for instance, a white line appears between the lines or the lines are overlaid and a black line appears.
Although a carrying precision of a certain extent is needed in the character printing or the like, significances of the carrying speed, sound, and the like are higher. There is a problem such that if graphics or the like are recorded by a driving method which has been set in accordance with the character printing, the carrying precision is low, so that a white line, a black line, or the like appears between the lines.
On the contrary, according to a carrying method in which a largest significance is given to the carrying precision, there is an unpractical problem such that a sheet feeding speed upon character printing which is generally used becomes slow or the like.
SUMMARY OF THE INVENTION
The invention is made in consideration of the above drawbacks and it is an object of the invention to provide an improved recording apparatus.
Another object of the invention is to provide a recording apparatus which can execute the driving according to the kind of recording data in the relative movement of recording means and a sheet.
Still another object of the invention is to provide a recording apparatus which can prevent the generation of a white line, a black line, and the like upon printing of graphics or block graphic characters without deteriorating a total printing speed or noise level in the normal mode.
Further another object of the invention is to provide a recording apparatus in which in the character printing mode which is ordinarily frequently used, a sheet feeding of a high sheet feeding speed and low noise can be realized and, in the printing mode in the case where block graphic characters are included in graphics recording data, a sheet feeding of a high feeding precision can be realized.
The above and other objects and features of the present invention will become apparent from the following detailed description and the appended claims with reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view showing a structure of a recording apparatus according to the invention;
FIG. 2 is a block diagram showing a control section;
FIG. 3 is a flowchart showing a flow of a sheet feeding control according to the invention;
FIGS. 4 to 6 are diagrams for explaining a sheet feeding mode according to the invention; and
FIG. 7 is a flowchart showing a flow of a sheet feeding control of another embodiment of the invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
An embodiment of the invention will be described in detail hereinbelow with reference to the drawings.
<Whole structure>
A whole structure of an apparatus will be first described with reference to FIG. 1. A recording sheet 1 as a recording medium is carried by sheet carrying means 2. The recording sheet 1 is pressed to carrying rollers 2a by a sheet pressing member 3 so as to prevent floating up from a platen 4.
When the sheet 1 is carried, a carriage 5 is reciprocated along a guide rail 6. An image is recorded onto the sheet 1 by driving recording means 7. The sheet 1 after completion of the recording is discharged by discharging means 8.
A driving force of a carriage motor 9 as a driving source is transferred to the carriage 5 through a timing belt 10c which comprises transfer means 10, so that the carriage 5 is reciprocated.
A construction of each section in the recording apparatus will now be practically explained.
<Sheet carrying means>
The sheet carrying means 2 carries the recording sheet 1 to the recording means 7. In the embodiment, a recording sheet which has been fed from an ASF (Auto Sheet Feeder) 11 which is detachably attached to the recording apparatus or a recording sheet which has manually been inserted from a hand inserting port 12 is carried by the sheet carrying means 2.
The sheet carrying means 2 in the embodiment rotates the carrying rollers 2a in the direction indicated by an arrow a and carries the recording sheet 1 by front pinch rollers 2b 1 and rear pinch rollers 2b 2 which are rotated in association with the rotation of the carrying rollers 2a.
A plurality of carrying rollers 2a are attached to a roller shaft 2c whose both edges are rotatably supported to left and right side walls 13a and 13b of the frame of the apparatus.
A driving force from a carrier motor 2e is transferred to the roller shaft 2c by a driving transfer structure of the gear train mentioned above. Practically speaking, a carrying gear 2d 1 is attached to the roller shaft 2c. The gear 2d 1 is in engagement with an idler gear 2d 2 . Further, the idler gear 2d 2 is in engagement with a first transfer gear 2d 3 .
A second transfer gear 2d 4 is attached to a shaft of the first transfer gear 2d 3 . The driving force from the carrier motor 2e is selectively transferred to the first and second transfer gears 2d 3 and 2d 4 by a clutch mechanism (not shown).
Therefore, when the driving force of the carrier motor 2e is transferred to the first transfer gear 2d 3 , the rotating force is propagated to the carrying gear 2d 1 through the idler gear 2d 2 , so that the carrying rollers 2a are rotated.
The front and rear pinch rollers 2b 1 and 2b 2 are come into pressure contact with the surfaces of the carrying rollers 2a by a spring or the like (not shown), respectively, and are attached so as to be rotated in association with the rotation of the carrying rollers 2a. Therefore, the carrying force is applied to the recording sheet 1 because the sheet 1 is nipped by the carrying rollers 2a and the pinch rollers 2b 1 and 2b 2 which are rotating.
A paper pan which is curved along peripheral surfaces of the carrying rollers 2a is attached below the carrying rollers 2a. The paper pan is extended to the hand inserting port 12 and functions as a lower guide of the recording sheet 1 which has manually been inserted.
Further, upper guide plates are attached above the paper pan with a predetermined distance, thereby constructing a carrying path of the recording sheet 1.
In the above structure, when the carrier motor 2e is driven and the carrying rollers 2a are rotated in the direction of the arrow a in FIG. 1, the recording sheet 1 which has been fed from the ASF 11 is nipped by the front pinch rollers 2b 1 and the carrying rollers 2a and is turned back and carried in a U-shaped along the peripheral surfaces of the carrying rollers 2a. Further, the sheet 1 is subsequently nipped by the rear pinch rollers 2b 2 and the carrying rollers 2a and is carried to a recording position locating at an upper position.
On the other hand, the recording sheet 1 which has been fed from the hand inserting port 12 is nipped by the carrying rollers 2a and the rear pinch rollers 2b 2 and is carried to the recording position.
The ASF 11 for automatically feeding the recording sheet 1 to the carrying means 2 will now be simply explained.
The ASF 11 is detachably attached to the recording apparatus. Among the recording sheets 1 enclosed in a cassette 11a, the top sheet 1 is pressed to separating rollers 11c by a pressing spring. When the separating rollers 11c rotate in the direction of an arrow b, one of the sheets in the top layer is separated and fed and comes into contact with nipping portions between resist rollers arranged in the downstream direction of the cassette 11a and the upper rollers which are in pressure contact with the resist rollers. When the resist rollers rotate, the recording sheet 1 is nipped by the resist rollers and the upper rollers which are rotated in association with the rotation of the resist rollers and is fed to the sheet carrying means 2.
According to the mechanism to transfer the driving force to the resist rollers, a resist gear 11g is attached to a roller shaft 11f to which the resist rollers are attached and the resist gear 11g is in engagement with the idler gear 2d 2 through an idler gear 11g 1 .
On the other hand, according to the mechanism to transfer the driving force to the separating rollers 11c, a separating gear 11i is attached to a roller shaft 11h to which the separating rollers 11c are attached and idler gears 11j and 11k are sequentially in engagement with the gear 11i. Further, a gear 11l attached to the same shaft as that of the idler gear 11k is in engagement with the second transfer gear 2d 4 .
Therefore, when the carrier motor 2e is driven and the driving force is transferred through the above gear train, the separating rollers 11c or the resist rollers rotate.
<Sheet pressing member>
The sheet pressing member 3 presses the recording sheet 1 carried by the carrying means 2 to the carrying rollers 2, thereby preventing the recording sheet 1 from floating up from the platen 4.
The sheet pressing member 3 is made of a single plate-like member whose width is wider than a moving range of the carriage 5 so as to press the whole width region of the recording sheet 1 and is in pressure contact with the carrying rollers 2a by pressing means such as a spring or the like (not shown).
A front edge of the sheet pressing member 3 is located below the recording position by the recording means 7. The carried recording sheet 1 is pressed to the carrying rollers 2a by the member 3. Thus, the recording sheet 1 at the recording position doesn't float up from the platen 4.
<Carriage>
The carriage 5 is used to reciprocate the recording means 7 in the width direction of the recording sheet. 1.
The carriage 5 is slidably attached to the guide rail 6 whose both ends are fixed to the left and right side walls 13a and 13b and which functions as a guide member having a circular cross section.
The carriage 5 is attached so as to be rotatable around the guide rail 6 as a rotational shaft and is attached so that the front side of the carriage 5, that is, the side which faces the recording sheet 1, is inclined forward and downward. Thus, the front edge portion of the carriage comes into pressure contact with the sheet pressing member 3 by the dead weights of the carriage 5 and the recording means 7 mounted on the carriage 5.
Thus, a distance between the recording means 7 mounted on the carriage 5 and the recording sheet 1 is always maintained at a constant value.
The driving force of the carriage motor 9 is transferred to the carriage 5 by the transfer means 10 and the carriage 5 is reciprocated.
A driving pulley 10a is attached to one end of the moving range of the carriage 5 and a driven pulley 10b is attached to the other end. The carriage motor 9 is coupled to the driving pulley 10a. Further, the endless timing belt 10c serving as a transfer member is moved between the pulleys 10a and 10b parallel with the guide rail 6. A part of the timing belt 10c is fixed to the carriage 5.
<Recording means>
The recording means is mounted to the carriage 5 and records an ink image onto the recording sheet 1 which has been carried by the carrying means 2. An ink jet recording system is preferably used as the recording means in the apparatus.
The ink jet recording system comprises: liquid emitting ports each for emitting and spouting an ink liquid for recording as a flying liquid droplet; liquid channels communicated with the emitting ports; and emitting energy generating means each of which is provided in a part of the liquid channel and generates a emitting energy to form a flying liquid droplet of the ink liquid in the liquid channel. The emitting energy generating means is driven in accordance with an image signal and the ink liquid droplets are emitted, thereby recording an image.
As emitting energy generating means, for instance, it is possible to use either one of a method using a pressure energy generating means such as an electrical/mechanical transducing element such as a piezoelectric element or the like, a method using an electromagnetic energy generating means for generating a flying liquid droplet by irradiating an electromagnetic wave of a laser beam or the like and for allowing the electromagnetic wave to be absorbed into the ink liquid, a method using thermal energy generating means such as an electrothermal transducing element, and the like. Among the above methods, the method using the thermal energy generating means such as an electrothermal transducing element or the like is preferable because the emitting ports can be arranged at a high density and the recording head can be constructed in a compact size. In the embodiment, ink liquids are emitted by such a method. Capping means 16 is provided in a left edge portion in the moving range of the carriage 5. The capping means 16 has a function to cover the ink emitting surfaces of the recording head 7 in the non-recording mode or the like, thereby preventing the ink near the ink emitting ports of the recording head 7 from drying or the ink from solidifying due to such drying.
A pump (not shown) is connected to the capping means 16. The pump is driven to eliminate a defective emission of the ink, or to prevent such. The ink is sucked from the emitting port by a sucking force of the pump, thereby executing a recovering process.
<Discharging means>
The discharging means 8 is used to discharge the recording sheet which has been recorded by the recording means 7.
The discharging means 8 comprises discharging rollers 8a and spurs which are in contact therewith. A discharging gear 8d is attached to the edge portion of a roller shaft 8c of the discharging rollers 8a. The discharging gear 8d is in engagement with the idler gear 2d 2 .
Therefore, when the carrier motor 2e is driven, a driving force is transferred to the discharging rollers 8a and the rollers 8a are rotated, so that the recording sheet 1 is discharged by the cooperation of the discharging rollers 8a and the spurs. The discharged recording sheet 1 is stacked into a discharging stacker 8f located above the discharging rollers 8a.
A control according to the invention will now be described with reference to FIGS. 2 and 3.
FIG. 2 is a block diagram showing a control section of the recording apparatus shown in FIG. 1. Reference numeral 101 denotes a host computer to transmit print data and various kinds of control signals and 102 indicates a CPU for executing a communication control with the host computer 101 and a sequence control of the recording apparatus. The CPU 102 mainly comprises a well-known one-chip microcomputer having therein an ROM, an RAM, and the like. Reference numeral 103 denotes a head driver to drive a heat generating element as emitting energy generating means of the recording means 7; 104 a carrier motor driver to drive the carrier motor 2e; and 105 a carriage motor driver to drive the carriage motor 9.
FIG. 3 is a flowchart showing a flow of the control which is executed by the CPU 102. A program according to the flowchart has been stored in the ROM in the CPU 102.
The CPU 102 receives data sent from the host computer 101 in step S1. The data includes characters, BGC, graphics data for an image printing, or the like. After the data is received, the data of one line is printed in step S2. A driving signal is sent from the CPU 102 to the carriage motor driver 105. While the carriage motor 9 is being moved, a signal for recording is sent to the head driver 103. The energy generating means (heat generating element) of the recording head 7 is driven, thereby printing the data of one line.
After the data of one line is printed, a sheet feed amount before the next line is printed to be is discriminated. In the invention, a stepping motor is used as a carrier motor and the carrier motor 2e is driven by 15 steps in order to feed the recording sheet by 1/6 inch. For instance, as shown in FIG. 4, seven steps are used for through up and seven steps are used for through down.
In FIG. 4, an axis of abscissa denotes an elapsed time and an axis of ordinate indicates a driving speed (for instance, a unit is PPS (Pulses Per Second) or the like of the carrier motor 2e. A mark □ denotes a speed for the elapsed time of every step. The carrier motor 2e is driven while gradually increasing the speed in the former half seven steps. The carrier motor 2e is driven while gradually decreasing the speed in the latter half seven steps. Practically speaking, such a driving method denotes that a phase excitation switching time is first set to a long time and is set to the shortest time after seven steps and that the switching time is again set to a long time after that.
Returning to FIG. 3, the discriminating step S3 will now be described.
As mentioned above, since 14 steps are used for through up/down, for instance, in the case of feeding the sheet by a few steps, the above curve or table cannot be used. Therefore, in the case of feeding the sheet by a distance shorter than, e.g., 1/6 inch (15 steps), the carrier motor 2e is driven without using the table which can be used for a distance of 1/6 inch or more.
On the other bland, in the case where image data is transferred and graphics are printed, a sheet feed amount is ordinarily set to 12/90 inch. In the invention, the carrier motor 2e is driven by 12 steps. In the judgment in step S3, therefore, in the case of the graphics printing, the answer is NO and step S6 follows. In the case other than the graphics printing, it is determined that the sheet feed amount is equal to or larger than 1/6 inch. Thereafter, a check is made in step S4 to see if a BGC is included in the printing data or not. If NO, a sheet feeding by the through up/down, for instance, a sheet feeding using the curve shown in FIG. 4 is executed in step S5. If a BGC is included, a sheet feeding is executed by using another driving curve in step S6, that is, in the embodiment, by the constant driving in a manner similar to the case of the graphics printing.
The constant driving is executed by switching the phases by a curve shown in FIG. 5. In this case, the carrier motor is driven at a constant speed of 160 PPS.
As shown in FIGS. 4 and 5, a time which is required to feed the sheet of the same amount, for instance, by 1/6 inch is equal to 60 msec or less in the through up/down mode and is equal to 100 ms in the constant mode. Thus, the time in the constant mode is fairly longer than that in the through up/down mode.
The value of 160 PPS has been set on the basis of the results of the measurements of sheet feeding precisions at respective speeds.
When comparing the above two kinds of modes, since a consideration is made in the through up/down mode with respect to the sound, the noise is quieter than the case in the constant mode. With regard to the time which is required to feed the sheet, the time in the through up/down mode is shorter than that in the constant mode as mentioned above. The sheet feeding precision in the constant mode is higher than that in the through up/down mode.
By executing the control as mentioned above, although the sheet feeding time is long and the noise is generated in the case of printing graphics or BGC, the sheet is fed at a high precision. In the case of the ordinary character printing, the sheet can be fed in a short time and with low noise.
If a curve shown in FIG. 6 is used as another embodiment in place of the curve shown in FIG. 4, the sheet can be fed at a higher precision without largely changing the sheet feeding time and the sound generation.
According to the curve of FIG. 6, the phase switching time of the last two steps is equalized to the phase switching time in the constant mode shown in FIG. 5.
The sheet feeding precision depends on a stationary state of the motor. In the example of FIG. 6, attention is paid to such a point and there is used a phenomenon such that the sheet feeding precision is largely influenced in the latter half portion of the sheet feeding operation.
As shown in FIG. 7, a discriminating step S10 can be also inserted between steps S3 and S4 in FIG. 6, thereby discriminating whether the sheet feed amount is just equal to 1/6 inch or not. The BGC is a character such that ruled lines or the like when forming, e.g., a table can be formed by a method similar to that of a character. A height of BGC is set to 1/6 inch. Therefore, by feeding the sheet on a 1/6 inch unit basis, the BGC of the upper line and the BGC of the lower line are vertically connected, so that a vertical ruled line or the like can be formed. Accordingly, even if a BGC exists on a certain line, for instance, the BGC is not vertically connected in the case of the sheet feeding operation in which the next sheet feed amount is larger than 1/6 inch. Thus, a high precision is unnecessary.
Therefore, the sheet feeding method in which an importance is paid to the precision is used only in the case where a BGC exists and the sheet feed amount is equal to 1/6 inch.
In the above description, the through up/down system has been used in the ordinary character printing mode and the constant system has been used in the BGC or graphics printing mode. However, even in the case of the BGC or graphics printing mode, the through up/down system is used when a high speed of a certain degree is necessary or the like and a system different from that in the ordinary character printing mode may be used.
As described above, the driving speed of the driving means for driving the relative moving means for relatively moving the recording means and the sheet is controlled by different modes in accordance with the kind of recording data, so that the recording means and the sheet can be relatively moved by paying an importance to the elements which are needed in each recording data printing mode. For instance, in the ordinary character printing mode, the relative movement in which a precision is set to a relatively low value and an importance is paid to both of the speed and the sound is executed. In the graphics printing mode, a relative movement in which more importance is paid to precision than the speed and noise can be performed. In the ordinary character printing mode, silent printing can be realized without deteriorating a throughput. In the graphics or BGC printing mode, a printing can be performed without an undesired white line, black line, or the like.
The invention provides an excellent effect in a recording apparatus of the ink jet system for recording by forming flying liquid droplets by using a thermal energy, particularly, among the ink jet recording systems.
As for the typical construction and principle, it is preferable to embody the invention by using the fundamental principles disclosed in, for instance, the specifications of U.S. Pat. Nos. 4,723,129 and 4,740,796. The above system can be applied to any one of what are called on-demand type and continuous type systems. Particularly, in the case of the on-demand type, at least one driving signal which corresponds to recording information and causes a sudden temperature increase exceeding nucleate boiling is applied to an electrothermal transducing element arranged in correspondence to a sheet or a liquid channel in which a liquid (ink) is held, thereby causing thermal energy to be generated in the electrothermal transducing element. A film boiling is caused on a heat acting surface of the recording head. As a result, an air bubble in the liquid (ink) corresponding to the driving signal in a one-to-one corresponding relation can be formed. Therefore, the above system is effective. The liquid (ink) is emitted through an emitting port by the growth and contraction of the air bubble, thereby forming at least one liquid droplet. By applying a pulse-shaped signal as a driving signal, the growth and contraction of the air bubble are quickly properly executed, so that the emission of the liquid (ink) having, particularly, an excellent response speed can be accomplished. Therefore, the use of such a pulse signal is more preferable.
As a pulse-shaped driving signal, it is suitable to use a signal disclosed in the specifications of U.S. Pat. Nos. 4,463,359 and 4,345,262. A further excellent recording can be performed by using the conditions disclosed in the specification of U.S. Pat. Ser. No. 4,313,124 of the invention regarding the temperature rising rate on the heat acting surface.
As a structure of the recording head, in addition to the combination structure (linear liquid channel or right-angled liquid channel) of the emitting port, liquid channel, and electrothermal transducing element as disclosed in each of the above specifications, it is also possible to use a structure in which the heat acting portion is arranged in a bent region as disclosed in the specifications of U.S. Pat. Nos. 4,558,333 and 4,459,600.
Further, it is also possible to use a structure in which a slit common to a plurality of electrothermal transducing elements is used as an emitting port of the electrothermal transducing elements as disclosed in Japanese Laid-Open Patent Application No. 59-123670 or a structure in which an opening which absorbs a pressure wave of a thermal energy is made correspond to the emitting port as disclosed in Japanese Laid-Open Patent Application No. 59-138461.
Further, it is also possible to use a recording head of the full-line type having a length corresponding to a width of the maximum recording medium which can be recorded by the recording apparatus. As such a recording head, it is possible to use a recording head having either a structure in which such a long length is satisfied by a combination of a plurality of recording heads as disclosed in the above specifications or a structure as a single recording head which is integrally formed.
In addition, the invention is also effective in the case of using a recording head of an exchangeable chip type which can be electrically connected to the apparatus main body or to which the ink can be supplied from the apparatus main body by being attached to the apparatus main body or the case of using a recording head of the cartridge type in which an ink tank is provided integrally in the recording head itself.
The addition of recovering means, spare auxiliary means, and the like to the recording head is preferable since the recording operation can be further stabilized. Practically speaking, it is possible to add capping means for the recording head, cleaning means, pressurizing or suction means, and preheating means by an electrothermal transducing element or another heating element different therefrom or a combination thereof. It is also possible to execute a preemitting mode for performing another emission different from the recording. The above means and method are also effective to execute the stable recording.
Further, the recording mode of the recording apparatus is not limited to the recording mode of only a main color such as black or the like but the recording head can be integrally constructed or can be also realized by a combination of a plurality of recording heads. It is also possible to use an apparatus having a plurality of different colors or at least one of mixed full colors.
According to the embodiment of the invention described above, the explanation has been made with respect to the case of the liquid ink. However, it is possible to use an ink which is solidified at a room temperature or less, an ink which is softened at a room temperature, or an ink which is a liquid at a room temperature. Generally the above ink jet system, the ink is adjusted within a temperature range from 30° C. to 70° C. and a temperature control is executed so that a viscosity of the ink lies within a stable emitting range. Therefore, it is sufficient that the ink is in a liquid state when a using recording signal is applied.
In addition, a temperature elevation due to a thermal energy is positively used as an energy of a state change from a solid state of the ink to a liquid state, thereby preventing solidification of the ink. Or, the ink which is solidified in a leaving state is used to prevent the evaporation of the ink. It is also possible to use an ink having a characteristic such that it is liquefied by a thermal energy for the first time, such as ink which is liquefied by applying thermal energy in accordance with the recording signal and is emitted as a liquid ink, ink such that the solidification has already been started at a time point when it reaches the recording medium, or the like. In such a case, the ink is held as a liquid or solid matter in concave portions or through holes of a porous sheet and in such a state, the ink faces the electrothermal transducing element as disclosed in Japanese Laid-Open Patent Application Nos. 54-56847 or 60-71260. In the invention, the foregoing film boiling system is the most effective method for each of the above inks.
Further, a style of the recording apparatus of the invention is not limited to a style in which the recording apparatus is integratedly or separately installed as an image output terminal of an information processing apparatus such as word processor, computer, or the like as mentioned above. Or, the invention can be also applied to a copying apparatus in combination with a reader or the like or a facsimile apparatus having transmitting and receiving functions.
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A recording apparatus has a recording device to record an image onto a sheet in accordance with input recording data, a relative moving device to relatively move the sheet for the recording device, a driver to drive the relative moving device, and a controller to control a driving speed of the driver in different modes in accordance with the kind of recording data. In the case of graphics data or data including a block graphic character, the driver is controlled in a constant driving speed mode. In the case of ordinary character data, the driving speed of the driver is increased for a predetermined time and, thereafter, the driving speed is reduced for a predetermined time.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention generally relates to the field of implantable heart stimulation devices, such as pacemakers. More specifically, the present invention relates to a biventricular heart stimulator for stimulating both ventricles of a human heart and a method for controlling such a stimulator.
2. Description of the Prior Art
In a normal human heart, the sinus node, generally located near the junction of the superior vena cava and the right atrium, constitutes the primary natural pacemaker initiating rhythmic electrical excitation of the heart chambers. The cardiac impulses arising from the sinus node are transmitted to the two atrial chambers, causing depolarizations known as P-waves, which result in atrial chamber contractions. The excitation pulses are further transmitted to and through the ventricles via the atrioventricular (A-V) node and a ventricular conduction system, causing depolarizations known as R-waves which result in ventricular chamber contractions. An R-wave is also referred to as a QRS complex.
Implantable pacemakers generate electrical stimulation pulses and deliver such stimulation pulses to atrial and/or ventricular muscle tissue of a patient's heart at a prescribed rate and/or rhythm when, through disease or other causes, the heart is not able to maintain the prescribed heart rate or rhythm on its own. When the delivered electrical stimulation pulses are of sufficient energy, they cause the cardiac muscle tissue to depolarize, and therefore contract, thereby forcing the heart rate or rhythm to track the delivery of the stimulation pulses. When the delivered stimulation pulses are of insufficient energy, depolarization does not occur, and the heart rate or rhythm is not controlled by the pacemaker. Hence, for the pacemaker to perform its intended function, it is critically important that the delivered electrical stimulation pulses be of sufficient energy to depolarize the cardiac tissue.
The depolarization and ensuing contraction of the heart in response to a delivered cardiac stimulation pulse is generally referred to in the art as “capture”. Consequently, the term “non-capture” denotes the condition when a delivered stimulation pulse does not result in depolarization and contraction. When detecting capture, sensing circuitry checks for the depolarization of a cardiac chamber following and in response to a delivered stimulation pulse. Such a depolarization as a result of a delivered stimulation pulse is also referred to as an “evoked response” (ER) of that chamber. Furthermore, evoked response is detected during a selected time period following the delivery of a stimulation pulse. Such a time period is generally referred to as an “evoked response window”.
The energy of the electrical stimulation pulses generated by an implanted pacemaker is derived from the energy stored in the pacemaker power source or battery. The pacemaker battery has a limited amount of energy stored therein, and the generation of stimulation pulses represents by far the greatest drain of such energy.
The amount of energy needed to effectuate capture is known as the capture “threshold”. Hence, stimulation pulses of energy less than the capture threshold do not bring about capture, while stimulation pulses of energy greater than the capture threshold do bring about capture. By adjusting the energy of the electrical stimuli so that it is always greater than the capture threshold, but not too much greater, the limited energy of the pacemaker battery may thus be preserved. The battery energy is preserved for two reasons. Firstly, pulses having an energy content insufficient to cause capture, i.e. stimulation pulses below threshold level, are rarely generated. Such pulses represent wasted energy. Secondly, pulses having an excessive energy content, i.e. an energy content greatly exceeding the capture threshold, are also rarely generated. Such excess energy does not only represent wasted energy, but also energy that may disadvantageously cause pectoral stimulation and/or sensation.
Generally, a capture threshold search is performed at predetermined or preprogrammed intervals. A capture threshold search would begin at a desired starting point (either a high energy level or the level at which capture is currently occurring) and decrease the energy level until capture is lost. The value at which capture is lost is known as the capture threshold. Thereafter, in order to secure capture, a safety margin is added to the capture threshold to arrive at the energy content of the stimulation pulse. One of the key issues is to choose the safety margin such that it provides capture, while at the same time provides adequate energy savings and does not cause pectoral stimulation and/or sensation.
A single-chamber pacemaker delivers pacing pulses to one chamber of the heart, either one atrium or one ventricle, via either a unipolar or bipolar lead. Single-chamber pacemakers can operate in either a triggered mode or a demand mode. When operating in a demand mode, sensing and detection circuitry allow for the pacemaker to detect if an intrinsic cardiac depolarization, either an R-wave or a P-wave, has occurred within the defined timeout interval. If an intrinsic depolarization is not detected, a pacing pulse is delivered at the end of the time-out interval. However, if an intrinsic depolarization is detected, the pacing pulse output is inhibited to allow the natural heart rhythm to preside.
Biventricular pacemakers are now available and can provide either demand or trigger type pacing in both the right and the left ventricular chambers. In biventricular pacing, one bipolar lead is typically placed in the coronary sinus for pacing and sensing in the left ventricle. Another bipolar lead is positioned in the right ventricle for pacing and sensing in the right ventricle.
Generally, capture verification occurs on a beat-by-beat basis. If no capture is verified, i.e. a loss of capture is detected, the pacemaker provides a backup pulse with an increased energy content. If successive losses of capture are detected, this indicates that an increase in capture threshold has occurred. Then, the pacemaker responds by performing a threshold search, and sets the energy level of the successive stimulation pulses to the new capture threshold plus the added safety margin.
In a cardiac stimulation device arranged for biventricular stimulation, the stimulation threshold and the evoked response are measured both in the first and the second stimulated ventricle. However, a problem with known biventricular pacemakers equipped with features to assure capture after stimulation pulses, is that it is difficult to verify capture on every beat, particularly if the pacemaker operates with a delay between the first stimulation pulse delivered to the first ventricle and the last stimulation pulse delivered to the second ventricle. Such a delay is known as an interventricular delay or interval, or a VV delay, and is generally provided in order to control the contractions of the ventricles in desired manner.
After a delivered stimulation pulse, the evoked response detection window typically ends 50-100 ms after the stimulation. Thus, an interventricular delay chosen such that the stimulation pulse is delivered to the second ventricle during this period, will result in an interference with the detection of the evoked response resulting from a delivered stimulation pulse in the first ventricle. In other words, it would be difficult to verify loss of capture.
One attempt to address this problem has been to only verify capture or loss of capture in the second ventricle on a beat-by-beat basis. Thus, capture is not usually verified on a beat-by-beat basis in the first ventricle, but rather after certain programmable time intervals, for instance every 15 minutes or 1 000 heartbeats. At these instants, the evoked response (ER) window for the first ventricle is normally made clear from disturbing stimulation pulses in other places of the heart by a temporarily changed timing pattern for the delivery of stimulation pulses. For instance, the order of delivering stimulation pulses to the first and second ventricle could be shifted, the stimulation pulses could be simultaneous, or the time interval between the pulses to first and second ventricle, known as the interventricular delay, could be adjusted. When losses of capture is detected in the first ventricle, a capture threshold search is performed in order to adjust the stimulation level, if necessary, to the changed capture threshold.
To ensure capture between these capture verifications for the first ventricle, a fixed safety margin is introduced. This safety margin for the first ventricle is normally higher than the safety margin in the second ventricle to account for the fact that the capture verification is not performed on a beat-by-beat basis in the first ventricle.
Changes in capture threshold is normally very slow and the increased safety margin for the first ventricle is normally sufficient to avoid loss of capture in spite of the time period provided between successive capture verifications for the first ventricle. However, studies have shown that during rapid changes in the capture threshold, time periods without capture occur for the first ventricle. If this happens, there is a chance that the patient will not receive the intended cardiac therapy, which in turn can impair the ability of the patient to perform work and deteriorate the state of the heart disease. Such rapid changes could for instance be due to infections, metabolic changes, or medical drugs.
SUMMARY OF THE INVENTION
An object of the present invention is to address the above-mentioned problem of time periods with capture losses in a biventricular heart stimulator.
According to one aspect of the present invention, the above object is achieved by a biventricular heart stimulator for stimulating both ventricles of a human heart having a pulse generator for delivering stimulation pulses of varying amplitudes, and electrode leads for transmitting stimulation pulses from the pulse generator to a first and to a second of said ventricles, and for transmitting electric signals from the ventricles of the heart to the heart stimulator. The stimulator also has a control unit for controlling the pulse generating means, the control unit being configured to control the delivery of the pulses such that stimulation pulses in a single heart beat cycle are respectively first delivered to the first ventricle and then to the second ventricle. Furthermore, the stimulator has a sensing circuit arranged to check for capture or loss of capture in one of the ventricles in response to delivered stimulation pulses, the sensing circuit being controlled by the control unit and arranged to receive the electric signals transmitted by said electrode leads. Moreover, the control unit is arranged to perform as a result of loss of capture determined in one ventricle by the sensing circuit, preventive measures for prevention of loss of capture in the other ventricle, preferably as a result of at least two successive losses of capture.
According to another aspect of the present invention, there is provided a method of controlling a biventricular heart stimulator for stimulating both ventricles of a human heart. The method includes the steps of delivering successive stimulation pulses to a first ventricle and a second ventricle of the heart such that stimulation pulses in a single heart beat cycle are respectively first delivered to the first ventricle and then to the second ventricle, and determining capture or loss of capture by the heart in response to stimulation pulses delivered to one of said ventricles. Moreover, the method includes performing, as a result of detected loss of capture in one ventricle, preventive measures for prevention of loss of capture in the other ventricle. The preventive measures are preferably performed as a result of at least two successive losses of capture in the one ventricle.
Thus, the present invention is based on the insight that changes in capture threshold for one ventricle often are correlated to changes in capture threshold for the other ventricle. When losses of capture occurs in one of the ventricles, this may be an indication that losses of capture are also occurring in the other ventricle. Such losses of capture can be temporary losses of capture, or due to changes in the capture threshold. Regardless of which, losses of capture in one ventricle, triggers actions to be taken for preventing repetitious losses of capture in the other ventricle. Thereby, repetitious losses of capture in the ventricle for which capture or loss of capture can not be determined on beat-by-beat basis, may be significantly reduced or eliminated. As a result, the intended cardiac respiratory therapy (CRT) may be provided, and deterioration of the heart disease due to capture losses is reduced or avoided.
As has been described above, for certain interventricular delays, the delivery of stimulation pulses in the second ventricle may prevent or disturb reliable detection of capture in the first ventricle, whereby continuous detection of capture in the first ventricle may be omitted. Therefore, detection of capture is only performed for the second ventricle on a beat-by-neat basis. Thus, according to the present invention, upon detection of capture loss in the second ventricle, actions for preventing losses of capture in the first ventricle are taken. However, it must be noted that the reverse situation might occur, i.e. that in the normal mode of operation, continuous capture detection in the second ventricle is disabled, while continuous capture detection in the first ventricle is enabled.
Thus, in further accordance with the present invention, upon detection of capture loss in the first ventricle, actions for preventing losses of capture in the second ventricle may be taken. For example, if the stimulation pulse delivered to the first ventricle is sufficient to effectuate capture, then the first ventricle would depolarize and an R wave would propagate through the heart tissue. After a certain time delay, the R wave would also have been conducted to the second ventricle. If the stimulation pulse then delivered to the second ventricle would have been unsuccessful in effectuating capture, and the R wave from the first ventricle would have reached the electrode for detecting capture in the second ventricle during the evoked response window thereof, then the conducted R wave could be interpreted as an evoked response in the second ventricle.
In other words, if the interventricular delay is set, for example for reasons of optimizing the cardiac therapy for a particular patient, such that the conducted R wave could be mistakenly be detected as an evoked response during the evoked response window, then the evoked response detection in the second ventricle could be disabled. If capture can be detected in the first ventricle on a beat-by-beat basis, then the present invention is applicable for taking actions for preventing losses of repetitious losses of capture in the second ventricle triggered by detected losses of capture in the first ventricle.
Thus, when loss of capture has been determined for the first ventricle, actions can be taken for the second ventricle in the manner as stated above, e.g. performing an immediate check for capture, increasing the safety margin, decreasing the time between threshold searches, etc. Therefore, the present invention is not limited to performing preventing measures in the first ventricle as a result of detected loss of capture in the second ventricle, but is also applicable and includes performing preventing measures in the second ventricle as a result of detected loss of capture in the first ventricle.
Furthermore, there are a number of different actions or preventive measures that could be taken in order to achieve said improvements, some of which will be presented in the following description. However, it should be noted that the present invention is not restricted to a particular type of preventive measure.
According to one exemplifying embodiment, the action or preventive measure is an immediate or quick check for capture. Thus, when one or more losses of capture has been detected in one of the ventricles, an immediate check for capture is performed in the other ventricle. Of course, measures are taken for enabling said immediate check for capture, such as changing the interventricular delay or omitting the delivery of the stimulation pulse that adversely affects the accuracy of the capture verification. If the immediate check for capture is positive, i.e. capture being verified, then the mode of operation of the stimulator is restored. In other words, the capture on beat-by-beat basis is only preformed for one ventricle.
However, if the immediate check for capture is negative, a back-up pulse may be provided and a threshold search is performed for adjusting the energy content of the ensuing stimulation pulses, if the threshold search indicates that an adjustment is needed. According to one example, the mode of operation for the stimulator is then restored. According to another example, one or more further threshold searches are performed at given time intervals following the first search, and the stimulation energy level is adjusted accordingly.
According to another exemplifying embodiment, the detection of one or more losses of capture in one of the ventricles results in a decrease of the time period between successive searches for capture thresholds in the other ventricle. In other words, threshold searches are regularly performed at predefined or preprogrammed time intervals for the ventricle in which no capture detection is performed on beat-by-beat basis. When loss of capture has been detected in one ventricle, this triggers a change in the time interval between successive stimulation threshold searches. For instance, the threshold search interval could be decreased to half or a quarter of the regular search interval, or the threshold search could be reduced to a preselected time interval, such as one or a given number of hours. Preferably, the detected losses of capture trigger an immediate threshold search to be conducted.
The time interval between threshold searches is preferably restored to the predefined time interval following a selected number of searches or a selected time period. The selected time period could for instance be one such decreased time interval. However, repeated detection of capture loss during the period of shortened time interval will preferably result in the shortened interval being maintained. Then, each further trigger resulting from detected capture loss would preferably reset the count of said selected number of searches or selected time period before restoring the threshold search time interval.
According to yet another exemplifying embodiment, the action or preventive measure is an immediate increase in the safety margin for the other ventricle. Thus, upon detected of losses of capture in one of the ventricles, the setting for the stimulation energy content for stimulation pulses in the other ventricle is amended by increasing the safety margin. Thereby, the risk of capture losses occurring in the other ventricle, for instance due to a sudden increase in threshold level, is reduced. The increase of the safety margin is preferably between 0.1 to 1.0 Volt, more preferably between 0.2 and 0.6 Volt, and most preferred between 0.3 and 0.5 Volt.
According to one embodiment, the increased safety margin is maintained until the next regular threshold search has been performed. In another example, the increased safety margin could be applied during a selected time period and restored to its original setting if no losses of capture are determined during the selected time period.
According to a further exemplifying embodiment, an immediate threshold search is performed for the other ventricle as said preventive measure. Of course, if needed, the threshold search for the other ventricle is adapted to a possible threshold search for said one ventricle.
As understood by those skilled in the art, the different preventive measures or actions taken as described above can also be combined. As an example, and triggered by detected losses of capture in one ventricle, the safety margin could be increased and the time until the next threshold search be shortened in the other ventricle. Then, the increased safety margin would only be applied for a shorter period of time and energy would be preserved. In another example, the quick check for capture could, when negative, result in a decreased time interval between successive threshold searches and/or an increased safety margin being applied.
The trigger could be one single loss of capture in one ventricle for triggering said actions of the other ventricle. Preferably, though, a successive number of losses of capture is required in order to trigger said actions. In the most preferred case, two successive losses of capture triggers the preventive actions. However, other alternatives are also contemplated within the scope of the invention, such as any given number of successive losses or capture, or a given ratio of capture losses from a number of delivered pulses during a certain time period or a certain number of pulses. In one example, said trigger for the preventive actions in the other ventricle is predefined. According to another example, said trigger is a parameter selected by the physician.
Further objects and advantages of the present invention will be discussed below by means of exemplifying embodiments.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a simplified, partly cutaway view illustrating an implantable stimulation device in electrical communication via cardiac leads with a human heart for delivering multi-chamber stimulation and shock therapy.
FIG. 2 is a schematic illustration of possible threshold levels, stimulation energy levels and loss of capture for a biventricular heart stimulator without the utilization of the present invention.
FIG. 3 is a schematic illustration of possible threshold levels, stimulation energy levels and loss of capture for a biventricular heart stimulator according to a first embodiment of the present invention.
FIG. 4 is a schematic illustration of possible threshold levels, stimulation energy levels and loss of capture for a biventricular heart stimulator according to a second embodiment of the present invention.
FIG. 5 is a schematic illustration of possible threshold levels, stimulation energy levels and loss of capture for a biventricular heart stimulator according to a third embodiment of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following is a description of preferred embodiments in accordance with the present invention. This description is not to be taken in a limiting sense, but is made merely for the purpose of describing the general principles of the invention. Thus, even though a biventricular heart stimulator for sensing and stimulating in both the atria and ventricles will be described, the invention is also applicable to biventricular stimulators without atrial sensing and/or stimulation.
With reference first to FIG. 1 , there is shown a biventricular heart stimulator 10 in electrical communication with a human heart 1 via three cardiac leads 20 , 24 , and 30 suitable for delivering mufti-chamber stimulation and sensing. The stimulator could further be arranged to deliver cardioversion or shock therapy to the heart.
In order to sense atrial cardiac signals and to provide right atrial chamber stimulation therapy, the heart stimulator 10 is coupled to an implantable right atrial lead 20 having an atrial tip electrode 22 , which typically is implanted in the right atrial appendage.
In order to sense left atrial and ventricular cardiac signals and to provide left-chamber pacing therapy, the heart stimulator 10 is coupled to a coronary sinus lead 24 designed for placement in the coronary sinus region, via the coronary sinus, so as to position a distal electrode adjacent to the left ventricle, and possible additional electrode(s) adjacent to the left atrium. As used herein, the phrase “coronary sinus region” refers to the vasculature of the left ventricle, including any portion of the coronary sinus, great cardiac vein, left marginal vein, left lateral vein, left posterior ventricular vein, middle cardiac vein, and/or small cardiac vein, or any other cardiac vein accessible via the coronary sinus.
Accordingly, the coronary sinus lead 24 is designed to receive atrial and ventricular cardiac signals and to deliver left ventricular pacing therapy using at least a left ventricular tip electrode 26 , and left atrial pacing therapy using at least a left atrial ring electrode 27 . In the illustrated example, an optional left atrial coil electrode 28 is also provided for delivering shocking therapy. A complete description of a coronary sinus lead can be found in U.S. Pat. No. 5,466,254, entitled “Coronary Sinus Lead with Atrial Sensing Capability” (Helland), which is incorporated herein by reference.
Furthermore, the heart stimulator 10 is in electrical communication with the heart 1 via a right ventricular lead 30 comprising, a right ventricular tip electrode 32 , a right ventricular ring electrode 34 , a right ventricular (RV) coil electrode 36 , and a supraventricular (SV) coil electrode 38 . Typically, the right ventricular lead 30 is transvenously inserted into the heart 1 , for positioning the right ventricular tip electrode 32 in the right ventricular apex so that the RV coil electrode 36 is positioned in the right ventricle and the SVC coil electrode 38 is positioned in the superior vena cava. Accordingly, the right ventricular lead 30 is capable of receiving cardiac signals, and delivering stimulation in the form of pacing, cardioversion and shock therapy to the right ventricle.
Moreover, the heart stimulator 10 comprises electronic circuitry 12 and a battery (not shown). The electronic circuitry comprises at least one pulse generator for generating stimulation pulses to be delivered to the ventricles of the heart, and possibly to the atria thereof, sensing circuitry for receiving cardiac signals sensed by the cardiac leads 20 , 24 and 30 , and a controller. The controller controls both the sensing of cardiac signals and the delivery of stimulation pulses, for instance as to the duration, energy content and timing of the stimulation pulses.
In general biventricular operation, and in order to optimize the pacing therapy, a first stimulation pulse is normal first delivered to one ventricle of the heart. Then, following a short interventricular delay, generally in the range of 10 to 40 ms, a second stimulation pulse is delivered to the other ventricle. These will in the following be referred to as the first and the last ventricular pulses, as well as the first and the last ventricle. For most patients, in order to achieve the most effective pacing therapy in view of the present heart disorder, the first ventricle stimulated is the left ventricle, and the last ventricle stimulated is the right ventricle.
Furthermore, biventricular heart stimulators often, but not necessarily, have atrial stimulation functionality. Then, the heart stimulator delivers a respective atrial stimulation pulse before the delivery of the corresponding ventricular stimulation pulse. The time difference between these stimulation pulses is generally referred to as an AV-interval.
In the following, embodiments of the present invention will be described in more detail. It must be noted that, even though the following description is based on the assumption that capture detection on beat-by-beat basis is performed in the last ventricle, but not in the first, the description is also applicable to the reversed circumstances. In other words, “last ventricle” could be exchanged for “first ventricle” and vice versa in the following description and in the drawings. For ease of description, however, only the alternative of beat-by-beat capture detection in the last ventricle is described.
With reference now to FIG. 2 , there is shown in schematical form, the variations in threshold levels for the first and the last ventricle over time, the corresponding adjustments and adaptations of the stimulation energy levels for both ventricles, and a timeline indicating the possible losses of capture (LOC) for the first ventricle. It should be noted that, for illustration purposes, the variations in capture thresholds have been exaggerated.
Turning first to the diagram for the last ventricle, it can be seen that the capture threshold, indicated by the bold line, varies over time. The thin line indicates the stimulation energy level, which is set to exceed the threshold level with a certain, preselected safety margin. Whenever a change in stimulation energy level can be seen in the figure, this has been preceded by a threshold search to update and store information regarding the capture or stimulation threshold for the ventricle. Even though losses of capture are not specifically indicated for the last ventricle, threshold searches performed during a period of increase of the capture threshold are generally triggered by a loss of capture. Thus, all but one of the threshold increments displayed in the stimulation energy level curve for the last ventricle corresponds to losses of capture.
Turning then to the diagram for the first ventricle, all variations of stimulation energy levels are preceded by a threshold search. These threshold searches are conducted at regular time intervals, which results in capture losses when the capture threshold in the time period between successive threshold searches has increased more than the applied safety margin. This is indicated in the diagram where the curve for capture threshold intersects the curve for the stimulation energy level. In the centre of the figure, there is indicated the time periods during which the capture threshold exceeds the energy content of the stimulation pulses. During these periods, there may be complete loss of capture in the first ventricle, with impaired pacing therapy as a result.
With reference to FIG. 3 , there will now be described a first preferred embodiment of the present invention. In the figure, there are five diagrams wherein the bottom diagrams show variation in stimulation thresholds and corresponding adjustments of stimulation energy levels for the ventricle in which capture is sensed on a beat-by-beat basis, and the occurrences of capture losses (LOC) in that ventricle. The bottom diagram is similar to the corresponding diagram shown in FIG. 2 and the description above relating to this ventricle also applies for the present embodiment, and also for the embodiments described below with reference to FIGS. 4 and 5 . As stated above, this ventricle is referred to as the last ventricle. However, in particular circumstances, beat-by-beat basis could be performed in the first ventricle and disabled in the last. If so, the present embodiment and the embodiments to be described in the following would still be applicable.
The diagram at the centre shows the occurrences of threshold searches (TS) and immediate or quick checks for capture (QCC) in the other ventricle, which in this illustration is the first ventricle. Furthermore, the top diagrams show variations in stimulation thresholds and the adjustments of stimulation energy levels as a result of performed threshold searches, for the first ventricle, and the occurrences of capture losses (LOC) in the first ventricle.
As can be seen in FIG. 3 , LOC in the last ventricle triggers a threshold search to be performed for that ventricle. In general, a first detected LOC triggers a change in the timing of the pacing pulses, e.g. a change in the atrioventricular or AV delay (interval between an atrial stimulation and the subsequent ventricular stimulation), the PV delay (interval between a sensed P wave and the subsequent ventricular stimulation), or the interventricular or VV delay. This is performed in order move the evoked response window, such that the result of the capture detection is not a misinterpretation of a fusion beat. If a second, subsequent LOC then occurs, this will trigger the above mentioned threshold search for the last ventricle.
Turning to the first ventricle, threshold searches are performed at regular time intervals T TS , which is indicated in FIG. 3 . Thus, the stimulation energy levels remain constant in the time interval between the threshold searches. Furthermore, in accordance with the most preferred embodiment of the invention, the LOC in the last ventricle also triggers the occurrence of a quick check for capture (QCC), which is indicated in the figure as un-filled rhombs. When performing a QCC for the first ventricle, the VV interval is changed such that the V pulse for the last ventricle is not delivered during the evoked response window used for the first ventricle. Then, a capture detection is performed for the first ventricle.
Of course, there are other methods for performing a quick check for capture in the first ventricle, one of which could include the omission altogether of one pacing pulse for the last ventricle in order to prevent the pulse from disturbing the evoked response detection for the first ventricle.
If the QCC confirms that there is capture in the first ventricle, nothing will happen. The stimulation energy level will remain constant until the next threshold search is performed. However, if the QCC reveals that there is LOC in the first ventricle, an immediate threshold search is conducted such that the stimulation energy levels can be adjusted in adaptation to the changed capture threshold. This results in the time interval between the last two threshold searches, referred to in the figure as T LOC , being shorter than the regular threshold search interval. However, immediately following the threshold triggered by the LOC, the time interval is restored to T TS , which generally is set at 8 hours. Alternatively, but not displayed in the figure, a shortened time interval, T Temp , between the threshold search triggered by the LOC and the subsequent search could be used. For instance, this time interval could be T Temp =T TS /2, T LOC , or any other suitable, e.g. preprogrammable time interval.
Turning now to FIG. 4 , a further exemplifying embodiment is illustrated. Beginning from the bottom of the figure, diagrams showing capture threshold variations, adjustments of stimulation energy levels, and occurrences of capture losses (LOC) in the last ventricle have been illustrated, in the manner as is described above in relation to FIG. 3 .
The diagram at the centre of the figure shows the occurrences of threshold searches (TS) in the first ventricle. In the same manner in as in FIG. 3 , the top diagram shows variations in stimulation thresholds and the adjustments of stimulation energy levels as a result of performed threshold searches in the first ventricle. Furthermore, there is also shown the occurrences of capture losses (LOC) in that ventricle, which in this illustration is none.
In this embodiment, the preventive action for the first ventricle triggered by detected LOC in the last ventricle is an adjustment of the time interval between successive threshold searches. Thus, the threshold search interval following detected LOC in the last ventricle, T LOC , is less than the regular threshold search interval T TS . Preferably, and as illustrated in the figure, T LOC =T TS /2. However, other suitable time intervals are also contemplated within the scope of the invention.
In the preferred example, the shortened time interval between successive threshold searches is maintained as long as there is repeated LOC in the last ventricle. In the illustrated embodiment, the threshold search interval is restored to the regular time interval T TS when no LOC has occurred during a shortened search interval T LOC . In other words, at the expiry of a shortened time interval T LOC during which there has been no LOC in the last ventricle, the ongoing time interval is extended to the regular threshold search interval T TS . As another example, one or more further shortened time intervals could be used before returning to the regular time interval T TS . According to further examples, other selected time intervals during which the shortened threshold intervals are applied could be used.
Furthermore, in the illustrated embodiment, an immediate threshold search is carried out for the first ventricle in response to detected LOC in the last ventricle. Thereby, capture losses occurring in the first ventricle in the time period between the detected LOC in the last ventricle and subsequent threshold search in the first ventricle is eliminated. Moreover, the fact that a greater safety margin is used for the ventricle in which no beat-by-beat capture detection is performed, entails that for the vast majority of instances, ventricular losses of capture first occurs in the ventricle monitored on beat-by-beat basis. Thus, in the presently described embodiment, capture losses due to stimulation threshold changes may be virtually eliminated for the first ventricle.
According to a further embodiment, the detection of LOC in the last ventricle, preferably the detection of two successive LOC, triggers an immediate threshold search in the last ventricle, as well as an immediate threshold search in the first ventricle. In other words, whenever there is a threshold search in the last ventricle, there will also be a threshold search performed for the first ventricle.
With reference finally to FIG. 5 , a further exemplifying embodiment will be described. In the figure, the bottom two diagrams are the same as those illustrated in FIGS. 3 and 4 . The center diagram illustrates the instances at which threshold searches are performed, and at which an increased safety margin is applied, both illustrated events relating to the first ventricle. Similar to FIGS. 3 and 4 , the top diagrams show variations in capture or stimulation thresholds, the adjustments of stimulation energy levels, and the occurrences of capture losses (LOC) in that ventricle, which in this illustration also is none.
As can be seen in the figure, threshold searches are conducted at regular time intervals for the first ventricle. The safety margin applied following each threshold search is the same, and is greater than the threshold margin used for the last ventricle. However, following detected LOC in the last ventricle, an increased safety margin is immediately applied to the stimulation energy level for the first ventricle in the manner as described above. Thereby, contrary to the situation described with reference to FIG. 2 , an increase of the capture threshold for the first ventricle, during a time interval between successive threshold searches, which exceeds the regular safety margin, will thanks to the temporary increase in the safety margin not lead to loss of capture.
In the illustrated example, the safety margin is increased to twice the regular safety margin as a result of detected LOC in the last ventricle. Even though this is the preferred example, other examples are also contemplated within the scope of the invention. Furthermore, the increase in safety margin is preferably between 0.1 and 1.0 V, more preferably between 0.2 and 0.6 V, and even more preferably between 0.3 and 0.5 V. In the most preferred example, both the safety margin as well as the increase of the safety margin is 0.3 V. Preferably, the amount of safety margin increase, as well as the regular safety margin, is preprogrammed. However, either or both of the regular safety margin and the increase in safety margin could optionally be arranged to be programmable by the physician, in response to the needs and requirements for each particular patient.
In the present embodiment, the increased safety margin is maintained during a selected time period following the onset thereof. In the illustrated example, which is the most preferred alternative, the increased safety margin is maintained until the next ensuing threshold search in the first ventricle.
Even though the present invention has been described above using exemplifying embodiments thereof, alterations, modifications and combinations thereof may be made within the scope of the invention, as defined in the accompanying claims. For instance, the quick check for capture triggered by LOC in the last ventricle, as described with reference to FIG. 3 , could be combined with an increase in safety margin following a detected LOC in the first ventricle. Then, the increased safety margin could be maintained until the next threshold search, and there would be no need for an immediate threshold search as a result of the detected LOC in the first ventricle.
Although modifications and changes may be suggested by those skilled in the art, it is the intention of the inventors to embody within the patent warranted heron all changes and modifications as reasonably and properly come within the scope of their contribution to the art.
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In a biventricular heart stimulator and a method for controlling such a biventricular heart stimulator, successive stimulation pulses are delivered to the ventricles of a heart such that stimulation pulses in a single heartbeat cycle are respectively first delivered to the first ventricle and then to the second ventricle. Capture or loss of capture in response to stimulation pulses delivered to one ventricle is detected. As a result of a detected loss of capture, preventative measures are taken for preventing loss of capture in the other ventricle.
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PRIORITY CLAIM
[0001] This application claims benefit of copending U.S. Provisional Patent Application Ser. No. 60/809,141, filed May 25, 2006, which is hereby incorporated herein in its entirety.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates generally to beverage containers for use in containing and dispensing fluids such as water, juice and the like. More particularly, the present invention relates to a collapsible beverage container well suited for containing and dispensing drinking water.
[0004] 2. Related Art
[0005] Plastic beverage containers are widely used as a means for containing water, carbonated beverages, alcohol, juices, and a variety of other beverage substances. Plastic containers have replaced glass containers for many commercial and residential purposes because they are generally lighter in weight and more shatter-resistant than are many glass containers. One material commonly used in plastic beverage containers, polyethylene terephthalate (PET), has been found to provide enhanced clarity, recyclability, and ease of manufacture at a competitive price.
[0006] While the use of plastic for beverage bottles has proved commercially viable, the widespread use of plastic beverage bottles has resulted in a large volume of waste that must be recycled, treated in a land fill, incinerated, or otherwise managed after use of the bottles. Semi-rigid or “firm” plastic containers made of PET, such as carbonated beverage containers, generally occupy the same volumetric space whether empty or full, and are often not easily compressed after use. Even when partially compressed, these bottles do not easily collapse completely, resulting in a large, empty volume within the plastic containers that consumes unnecessary space when the container is discarded.
[0007] In addition, many conventional beverage bottles must be shipped empty to a filling facility where the bottles are filled with the beverage. As such, the bottles often must be cleaned at the filling facility, and rinsed thoroughly to ensure that all cleaning materials/chemicals are removed from the bottles, prior to filling the bottles with the beverage. Also, in many cases, these beverage containers must be labeled after filling (or very shortly before filling), in a facility separate from the one in which the containers were manufactured.
[0008] Also, when drinking water is provided to consumers in beverage containers, issues with transparency of packaging, and taste migration from the packaging to the beverage (water) being contained, are greatly enhanced in comparison to other beverages. For example, many juices and sports drinks exhibit a sufficiently robust color that packages that are meant to be transparent may not need to be perfectly transparent, as the juice or other drink is not itself transparent and thereby masks imperfections in the packaging. Also, juices and sports drinks generally exhibit a sufficiently robust taste such that migration of minor amounts of taste from the packaging into the juice or sports drink may not be detectable by most consumers. However, due to the exceptional clarity and subtle taste of drinking water, even the slightest cloudiness present in packaging, or the slightest migration of taste from packaging, can generally be detected by most consumers, and can leave them with a negative impression of the product.
SUMMARY OF THE INVENTION
[0009] The invention provides a beverage container, including a pair of flexible sidewalls defining therebetween a pouch area for containing a beverage. The flexible sidewalls can be comprised of a material having at least two material layers coupled to, or integrated with, one another. The layers can include at least an outer layer comprised of an outer barrier material; and an inner layer including an inner barrier material. The inner barrier material can be operable to be exposed to the beverage contained in the pouch area while resisting migration of contaminants through the sidewalls and into the beverage.
[0010] In accordance with another aspect of the invention, a beverage container is provided, including a pair of flexible sidewalls defining therebetween a pouch area for containing a beverage. A valving assembly can be coupled between edges of the sidewalls and can be operable to allow flow of the beverage from the pouch area while resisting flow of fluid into the pouch area. The valving assembly can include a membrane having at least one slit formed therein. The membrane can have a curvature that causes the slit to open when subject to flow of beverage from the pouch area and causes the slit to close when subject to flow of fluid into the pouch area.
[0011] In accordance with another aspect of the invention, a collapsible beverage container is provided, including a pair of flexible sidewalls defining therebetween a pouch area for containing a beverage. A valving assembly can be installed between the sidewalls adjacent a top of the beverage container. A pair of side seams can extend generally upwardly along side edges of the container. A bottom gusset frame can be expandable when the container is filled with at least some of the beverage to provide a stable support for the beverage container such that the container is substantially free-standing when at least partially filled with the beverage.
[0012] In accordance with another aspect of the invention, a collapsible beverage container suitable for containing and dispensing drinking water is provided, including a pair of flexible sidewalls defining therebetween a pouch area for containing drinking water. A valving assembly can be coupled between edges of the sidewalls and can be operable to allow flow of the drinking water from the pouch area while resisting flow of fluid into the pouch area. A bottom gusset frame can be expandable when the container is filled with at least some of the drinking water to provide a stable support for the beverage container such that the container is substantially free-standing when at least partially filled with the drinking water. The container can be operable to collapse as water is removed from the pouch area and to retain its collapsed configuration such that a volume of the pouch area is constantly and automatically reduced as the drinking water is expelled from the pouch area.
[0013] Additional features and advantages of the invention will be apparent from the detailed description which follows, taken in conjunction with the accompanying drawings, which together illustrate, by way of example, features of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1A is a front view of a flexible beverage container containing a liquid in accordance with an embodiment of the invention;
[0015] FIG. 1B is a side view of the container of FIG. 1A ;
[0016] FIG. 1C is a bottom view of the container of FIG. 1A ;
[0017] FIG. 2 is a front view of an unfilled (or empty) flexible beverage container in accordance with an embodiment of the invention;
[0018] FIG. 3 illustrates a series of flexible beverage containers, shown in varying degrees of filled or unfilled conditions;
[0019] FIG. 4 is a cross-sectional view of a layer of material used to form a flexible beverage container in accordance with an embodiment of the invention;
[0020] FIG. 5 is a schematic, partially sectioned side view of a portion of a valving assembly in accordance with an embodiment of the invention (a membrane portion is shown as sectioned);
[0021] FIG. 6A is a top view of the membrane of the portion of the valving assembly of FIG. 5 ; and
[0022] FIG. 6B is a top view of the membrane portion of FIG. 6A , shown with another slit configuration.
DETAILED DESCRIPTION
[0023] As used herein, the terms “top,” “bottom,” “sides,” and the like are used to aid in describing the various features of the invention in easily understandable terms. It is to be understood, however, that such terms in no may limit the present invention. For example, while a valving structure may be described and claimed herein as being located at a “top” of the beverage container, a container having valving structure operably similar to the presently claimed invention would be considered as infringing the claimed invention, even if the infringing container had valving structured located in what would be considered a side of that container.
[0024] When discussing the beverage containers of the present invention, one or more side, top, bottom, end, etc., walls may be referenced. It is to be understood that each of the various distinct walls can be formed from a single piece of material folded, crimped, sealed, or otherwise manipulated to form the various walls. Thus, while multiple walls may be referenced, the walls can be formed from an integral piece of material. Of course, each of the walls can also be formed from distinct pieces of materials as well.
[0025] Various abbreviations are used herein to identify various material types. One of ordinary skill in the relevant art will readily understand the abbreviations used. For the sake of clarity, however, some of the abbreviations used herein are accorded the following meanings: LLDPE refers to linear low density polyethylene; EVOH refers to ethylene vinyl alcohol; LDPE refers to low density polyethylene; EVOH refers to ethylene vinyl alcohol; PE refers to polyethylene; and PP refers to polypropylene; PP refers to polypropylene. It is to be understood that, while various materials may be listed independently in the claims, the invention can include combinations of those listed as well as known variants thereof.
[0026] Reference will now be made to the exemplary embodiments illustrated in the drawings, and specific language will be used herein to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended. Alterations and further modifications of the inventive features illustrated herein, and additional applications of the principles of the inventions as illustrated herein, which would occur to one skilled in the relevant art and having possession of this disclosure, are to be considered within the scope of the invention.
[0027] As illustrated in FIGS. 1A-1C , a stand-alone flexible beverage container, indicated generally at 100 , in accordance with the present invention is shown for containing a beverage illustratively indicated at 120 . The container can be formed of two sheets of flexible material: a front sheet 104 and a rear sheet 102 . While the front and rear sheets are shown in the figures as two distinct sheets of material, it is to be understood that the two sheets can be formed from, or can form a part of, a single sheet of material folded or otherwise manipulated to form a pouch 118 .
[0028] Two generally vertical side seams 106 can be formed by joining the edges of the flexible sheets in a substantially inseparable manner. The flexible sheets can be cut, punched or otherwise dimensioned to form a substantially rectangular shape. A top seam 108 can be formed by further joining the top edged of the flexible or plastic sheets to form a seam. This top seam can include an opening for a closable valve 114 . The closable valve can further include a cap 116 . The closable valve and cap can be similar in many aspects to the valve, cap and “boat” assembly shown in U.S. Pat. No. 6,273,307, which is hereby incorporated herein by reference to the extent it is pertinent hereto, but not to the extent it is inconsistent herewith.
[0029] Between the sheets of flexible material 102 , 104 , and further enclosed by the seams 106 , 108 and valve 114 , a pouch (or pouch area) 118 can be defined for containing a beverage. The combination of seams can provide sufficient structural support to enable the container/pouch to be freestanding through a range of filled conditions. For example, the container can be freestanding when the pouch is substantially filled with a beverage; it can be freestanding when the pouch is only partially filled with a beverage; and can also be freestanding when the pouch is voided of the beverage. In this manner, the present invention provides a container that can be sufficiently flexible so as to be relatively easily compacted when empty, and yet be capable of freestanding when placed on a shelf or other surface when offered for sale. As presenting such beverages for sale in an orderly manner is a significant consideration for vendors, the present invention allows single units of beverages packaged in flexible containers to be presented for sale without undue risk that the containers will tip over under normal storage conditions.
[0030] FIG. 3 includes a series of photographs of a container in accordance with the present invention: shown at 300 in a substantially filled configuration; at 310 in a substantially empty configuration and at least partially collapsed; and at 320 in an empty configuration and rolled into a compacted configuration to minimize the volume of the container that is consumed when discarding the container.
[0031] The vertical seams 106 can overlap a bottom seam 110 in order to form a bottom support structure, or a gusset frame. In the present embodiment of the invention, a supporting bottom 111 can be joined to the two vertical sheets 102 and 104 , to form the bottom seam. The supporting bottom can be in the shape of an elongated hexagon with a fold line 122 longitudinally bisecting the hexagon, as shown in FIG. 1C . The supporting bottom 111 with the elongated hexagonal shape can be joined to the two vertical sheets in an inverted-V fashion, as best shown in FIG. 1B . In this manner, the bottom seam can provide good structural support to the sides, balancing the container 100 and providing stability to the base. When the container is filled with a beverage 120 , the volume of the pouch 118 can increase, narrowing the base width and increasing the base depth. In this manner, a full container can expand the base to give maximum vertical support to the container to provide freestanding capabilities to the container. As the liquid is dispensed from the container (and thus the weight on the bottom seam is reduced), the supporting bottom can reduce in width accordingly. The elongated hexagon-shaped supporting bottom joined in an inverted-V fashion can facilitate ease of collapsibility of the container as the beverage in the container is emptied.
[0032] In one aspect of the invention, the closable valve 114 can be a unidirectional (e.g., “one-way”) valve in order to prevent air or other fluids from flowing into the container 100 as the container is emptied. In this manner, as the beverage is emptied or dispensed from the container, the supporting bottom or gusset frame is pulled inward along the fold line 122 by way of the vacuum created in the container as the beverage in emptied. The container can thus automatically collapse during the process of emptying the beverage from the container. The one-way valve also serves to restrict or prevent contaminants from entering the beverage container, either as the beverage is dispensed from the container, or prior to the container being filled with the beverage.
[0033] As previously discussed, a large volume of waste can be produced by conventional empty beverage containers that retain their shape after use. By incorporating a one-way valve within the present container, a vacuum can be created inside the pouch 118 as it is emptied, which can cause the container to collapse to a small volume while it is emptied. Thus, once the container is emptied, no further manipulation of the container is necessary to collapse or compress the container prior to disposal. Accordingly, the present a container has a less negative impact on the environment due to its low volumetric waste.
[0034] The closable valve 114 can be associated with or bonded to the top seam 108 in a variety of manners. The valve may be part of a fitment that includes a valve, or other sealed valve configurations that will be practical for use with the container. The top seam can be joined to the closable valve using a variety of means, including heat sealing, use of adhesives, plastic welding, etc.
[0035] In one aspect of the invention, the flexible sheets 102 , 104 and supporting bottom 111 , can include multiple layers of material coupled or joined to form a single sheet of flexible material. Currently, a large variety of suitable flexible materials are available in the art to produce multilayered flexible sheets for various purposes. The choice of plastics used in the present invention will vary depending upon the type of beverage contained, the environment in which the containers will be stored, shipped, used, etc. Other considerations that may affect the choice of materials include: reaction tendencies with various adhesives, odor, thickness, material strength, color, clarity, and a variety of other factors. Multiple layers of differing material can be combined to include two or more plastics each having a desired attribute. For example, a strong plastic may be layered with a plastic that has a desired adhesive quality for receiving ink and other printed decorations.
[0036] Typical materials that can be used as layers to create a flexible sheet of plastic include, without limitation, PET, nylon, and Cast Nylon. Typical sealants may include EVOH and EVOH Coex. The corresponding thicknesses for each layer may vary according to their respective combinations. In one embodiment a multiple layered flexible plastic can include a layer of PET joined to a layer of nylon. These layers can be joined by a sealant including, without limitation, EVOH or EVOH Coex sealant. In one embodiment, a multiple layered flexible plastic can include multiple layers of PET joined by an EVOH or EVOH Coex sealant. The manner of joining the various layers can also vary, and can include, without limitation, lamination, adhesives, plastic welding, etc.
[0037] While the present container can be used for a variety of beverages, in one embodiment it is particularly well suited for use as a container for drinking water. Packaging of drinking water in containers generally presents difficulties not often associated with packaging of other beverages such as sports drinks, fruit juices, etc. This is at least in part due the fact that the presence of materials that alter the taste, sight and smell of a beverage can be much more easily detected in drinking water than in other types of beverages that can “mask” the presence of such contaminants.
[0038] It has been found that the problem of contaminating drinking water with matter from the packaging of the container can be greatly exacerbated by heat. That is, when containers storing drinking water are exposed to relatively high degrees of heat, the migration of taste- or appearance-altering matter from packaging materials can be greatly increased. Various embodiments of the present invention have been found to maintain drinking water in an un-contaminated in temperatures approaching the melting point of the packaging materials.
[0039] As illustrated in FIG. 4 , in one aspect of the invention, the material used to form the present container can include multiple layers of materials. In one embodiment, the outer layer 130 of the material can be formed from about 0.48 ga. PET which can provide toughness and clarity to the outside layer of the material. A second layer 132 can be formed of 0.75 ga. nylon and can serve as a barrier to outside flavors entering the beverage. A third layer 134 can consist of printing ink displaying information such as product name, logo, nutritional information, manufacturer's contact information, etc. A fourth layer 136 can be a relatively thin layer of adhesive. An innermost (e.g., the layer in contact with the beverage), fifth layer 138 can be 5.25 EVOH (co-extruded) that can stop flavors from the ink from entering the beverage. While not so limited, an overall thickness of the material can be from about 5.5 mils to about 6 mils.
[0040] In one embodiment of the invention, the structure of the container can be composed of layers of materials as follows:
[0041] 0.48 ga PET/ink/adhesive/1.1 mil Nylon/1.8 mil PE/0.35 EVOH/1.9 mil PE.
[0042] In one embodiment of the invention, the structure of the container can be composed of layers of materials as follows:
[0043] 0.75 ga Cast/Nylon/ink/adhesive/5.25 EVOH Coex.
[0044] In one embodiment, the layers of material can be as follows:
[0045] PET12/PA15/LLPE125, with an OTR value of about 23 cc/m 2 .24 h.
[0046] In one embodiment, the layers of material can be as follows:
[0047] PET12/PA15/(LDPE/EVOH/LLDPE)125, with an OTR value of about 23 cc/m 2 .24 h.
[0048] Turning now to FIG. 2 , in one aspect of the invention, an unfilled flexible plastic beverage container 200 can include a closable valve 114 , a cap 116 , two vertical seams 106 , a top seam 108 , and a bottom seam 110 , and a pouch 216 similar to previously described embodiments. The container can include a substantially rectangular shape, with a container width 204 being at least one-half of the container height 202 . The container depth can be determined by the height of the folded bottom 208 , which can be calibrated to allow a container depth of at least one-half the container width, when filled.
[0049] To provide sufficient structural support to enable the container to be freestanding when the container is at least partially filled, the pouch 216 can be enclosed with two vertical seams 106 , a top seam 108 , and a bottom seam 110 . These seams may be formed as a single seam, or as multiple overlapping seams. The thickness of the seam 206 can affect the strength of the structural support of the container. A thin seam may not provide sufficient support to enable freestanding capabilities, while a relatively thick seam may be bulky, uncomfortable when held, and create excess waste when the container is disposed of. Typical vertical and bottom seam widths can be between 5 mm and 7 mm, but a seam width greater than 7 mm can also be effective. Typical top seam widths can likewise be between 5 mm and 7 mm but may be greater than 7 mm to accommodate incorporation of a valve in the top seam. In one aspect of the invention, the minimum seam width is on the order of 3/16 of an inch, or about 4.75 mm. As shown in FIG. 2 , the sides of the bottom seam can be thicker than the center of the bottom seam, to provide structural support to the container.
[0050] FIGS. 2 and 1 A- 1 C also illustrate features of the invention than can aid in providing a free-standing container. In this embodiment, the container is formed from three pieces of material, sheet 102 , sheet 104 and supporting bottom 111 (shown in detail in FIGS. 1A-1C ). The side sheets 102 and 104 are joined at side seams 106 . These portions of the side seams 106 extend downwardly along the sides of the container and terminate at the approximate location of the fold line 122 . The supporting bottom is then folded and inserted between the side sheets and the side seams are continued downwardly along the sides of the container to the bottommost portion of the container, with each side seam coupling a portion of the side sheets to the supporting bottom 111 . In this manner, the supporting bottom and lower portions of the side sheets form a lower gusset that can expand and contract accordingly to the volume of beverage in the container.
[0051] In one aspect of the invention, one or more compressed areas 212 can be formed, e.g, “stamped,” in either or both of one of the side sheets and the supporting bottom 111 . The compressed areas can serve to add rigidity to the lower portions of the side sheet, supporting bottom, and/or gusset to aid in providing a stand-alone container. Also shown in FIG. 2 is one method by which the lower portions of the side seams (to which the supporting bottom is attached) can be coupled to one another. As will be appreciated, in the areas where the side seams couple the supporting bottom to the side sheets, two finished seams will face each other in the inner portion of the gusset (e.g., the outer edges of the supporting bottom are folded against one another while the inner edges of the supporting bottom are coupled to the inner edges of the side sheets). As it may be difficult to bond or attach the outer portions of the side seams to one another in these locations, the present inventor has found that a crescent shaped void 214 can be left in the outer portions of the supporting bottom such that as the supporting bottom is coupled to the side sheets, a crescent shaped piece of the side sheets is left exposed. In one embodiment, this exposed piece will be formed of EVOH. In order to attach the sides of the gusset to one another, these exposed pieces of EVOH can be pressed or bonded together to attach the sides of the gusset to one another, even in the case where the sides are formed of a finished seam.
[0052] The present invention provides many advantages over conventional beverage container systems. For example, as the containers can be shipped to a filling facility in a reduced volume state (e.g., a generally “flat” configuration), the costs of shipping empty containers can be reduced and the efficiencies can be increased. Also, in the embodiments of the invention in which a unidirectional valve is incorporated into the container, internal portions of the container can be maintained in a clean state from the point in time in which the container is manufactured to the point it is filled with a beverage. In this manner, the present containers need not be cleaned at the filling location, leading to great cost savings at the filling site. The present inventor has found that the filling plant used for the present container can be up to ⅕ smaller than an equivalent plant used for conventional bottles.
[0053] In addition, the present container is generally much easier to transport and store than conventional bottles, as the present container will “form-fit” to a pocket, backpack, purse, glove-box, etc., in which the container is stored.
[0054] Also, label information such as branding, content information, nutritional information, etc., can be applied to the present package at the time of forming the package. This aspect of the invention can completely eliminate the step of applying a label to the container, which is necessary in most conventional processes. Also, as the label information is applied directly to the present package (or within two layers of material), the risk of having the label fall off the packaging, of become illegible, is greatly reduced with the present system.
[0055] The embodiment of the invention illustrated in FIG. 1A includes valving assembly or closable valve 114 that includes an internal gate 140 . The gate portion 120 of the valving assembly can include a flexible membrane 142 , best appreciated from FIGS. 5 , 6 A and 6 B. The membrane can be attached within the gate portion (which can itself be attached within the valving assembly) to regulate flow into and out of the container. As shown in FIGS. 6A and 6B , the membrane can include one or more slits or cuts 142 formed therein that are maintained in a normally closed configuration. The membrane can also include a curvature, as shown in FIG. 5 . The curvature and slits can cooperate to allow flow through the valving assembly when flow is induced from inside the pouch area and out of the container, as the drinking water or beverage applies force to the underside of the membrane and “open” the slits or cuts and pass through.
[0056] However, in the event flow tends toward the pouch area (e.g., if the container were attempted to be filled after the membrane were installed), the curvature and the slits would work toward maintaining the slits closed in response to this “backward” flow, and the valve would resist flow. The membrane is thus one manner in which the containers can be configured to be easily evacuated (as the drinking water or beverage is dispensed), yet be maintained in a substantially collapsed configuration after dispensing (as the entry of air into the empty container is resisted or prevented by the valve).
[0057] It is to be understood that the above-referenced arrangements are only illustrative of the application for the principles of the present invention. Numerous modifications and alternative arrangements can be devised without departing from the spirit and scope of the present invention. While the present invention has been shown in the drawings and fully described above with particularity and detail in connection with what is presently deemed to be the most practical and preferred embodiment(s) of the invention, it will be apparent to those of ordinary skill in the art that numerous modifications can be made without departing from the principles and concepts of the invention as set forth herein.
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A beverage container includes a pair of flexible sidewalls defining therebetween a pouch area for containing a beverage. The flexible sidewalls are comprised of a material having at least two material layers coupled to, or integrated with, one another. The layers include at least an outer layer comprised of an outer barrier material and an inner layer including an inner barrier material. The inner barrier material is operable to be exposed to the beverage contained in the pouch area while resisting migration of contaminants through the sidewalls and into the beverage.
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BACKGROUND OF THE INVENTION
1.Field of the Invention
This invention relates generally to very low flow rate propellant feed systems and, more particularly, to a low power arcjet propellant feed system for delivering propellant to low power arcjets.
2. Discussion of the Related Art
In order to place and maintain spacecraft, such as satellites, in geosynchronous and low earth orbits, various types of thrusters are utilized to perform station keeping, attitude control and delta velocity maneuvers, which are sometimes referred to as reaction control system (RCS) functions. The thrusters used to perform these functions include typical chemical reaction thrusters which generally consume large quantities of propellant or high power arcjet thrusters which extend the performance of chemical reaction thrusters by consuming less propellant.
The high power arcjet thrusters in use today generally operate by decomposing a liquid propellant to form a gaseous propellant. The gaseous propellant is subsequently heated with an electric arc and expanded through a nozzle of the thruster to provide thrust. These high power arcjet thrusters typically operate in a power range of between about 1.0 kilowatts to 25 kilowatts and utilize liquid hydrazine (N 2 H 4 ) as the propellant. The liquid hydrazine is decomposed and the resulting gas propellant, generally consisting of ammonia, hydrogen and nitrogen, is fed to the arcjet thruster at a high flow rate of about 30 grams per second.
These high power arcjets have a higher specific impulse (I SP ) than the typical chemical reaction thruster, which is defined as the thrust developed by an engine per unit of propellant weight flow rate. However, improvements in the next generation arcjet thruster is needed to reduce power while still maintaining specific impulse (I SP ) value much higher than chemical RCS thrusters. By doing this, the operating life of lower power, smaller spacecraft is increased due to conserving propellant consumption well below that of chemical thrusters. Moreover, the size and weight of the spacecraft can also be reduced, thereby reducing launch costs. To achieve these results, the next generation arcjets will be low power and low flow arcjets. The power applied to the arcjet will typically range between 400 to 800 watts and flow rate will typically range between 3 to 50 milligrams per second.
Downsizing of conventional propellant feed systems used in high power arcjets to feed low power arcjets may initially appear to be straightforward. However, after closer inspection, several disadvantages and unforeseen challenges arise. Specifically, use of a conventional high power arcjet feed system in which a gas generator is directly coupled to a low power arcjet exhibits several problems.
First, a typical gas generator is too large and provides a flow rate much greater than that required to run a low power arcjet. Moreover, the size of the gas generator cannot be simply reduced because the useful life of the gas generator is then significantly decreased. Second, the flow rate of gas propellant directly from the gas generator tends to oscillate. This oscillation causes unstable and varying pressure resulting in flow rate fluctuations which ultimately causes uncontrolled fluctuations in thrust out of the arcjet. Third, use of only the gas generator directly coupled to the arcjet causes flow instability at low flow rates, in contrast to the high flow rate used for high power arcjets, which will tend to "unstart" the arcject (or kill the formation of the arc) by suppressing electric conduction of the arc between the electrodes. Fourth, during blow down in a closed system, it is very difficult, if not impossible to provide a steady continuous gas flow rate to a low power arcjet directly from the gas generator. Fifth, low flow rate direct-flow gas generators are very sensitive to any gas bubbles in the upstream liquid feed to the gas generator, which will cause further arcjet erratic behavior and shorten arcjet life. Finally, by simply reducing the flow rate from the gas generator, the feed tubes, as well as the gas generator itself, tend to heat up, which may ultimately cause ignition within the feed system.
What is needed then is a low power arcjet propellant feed system which does not suffer from the above mentioned disadvantages. This will, in turn, provide a steady state unperturbable mass flow rate to the low power arcjet regardless of upstream pressure; provide an optimized flow rate at a controllable pressure to the arcjet independent of the gas generator; eliminate the feed system from heating up or igniting due to low flow rates; and provide a controllable flow rate so that the thrust from the arcjet can be dynamically controlled as required and the electric arc can be stably sustained through a steady conducting medium (i.e., the gas feed). It is, therefore, an object of the present invention to provide such a low power arcjet propellant feed system.
SUMMARY OF THE INVENTION
In accordance with the teachings of the present invention, a low power arcjet propellant feed system for delivering propellant to a low power arcjet is disclosed. The low power arcjet propellant feed system provides a substantially continuous and stable low flow rate of a gaseous propellant to the low power arcjet. This substantially continuous and stable low flow rate enables precision thrust control of the low power arcjet and stable arcjet operation. Moreover, the substantially continuous and stable low flow rate can be controllably adjusted so that the thrust from the low power arcjet can be dynamically varied over a wide range as required.
In one preferred embodiment, a liquid propellant storage chamber stores a liquid propellant. A gas generator in communication with the liquid propellant storage chamber generates a gas propellant upon receipt of the liquid propellant from the storage chamber. A gas plenum in communication with the gas generator accumulates the gas propellant from the gas generator up to a desired pressure. Controllable valves actively control the flow of the liquid propellant into the gas generator and actively control the flow of the resultant gas propellant out of the gas generator into the gas plenum up to the desired pressure. This allows a substantially continuous and stable low flow rate of gas propellant to be delivered to the low power arcjet.
Use of the present invention provides a low power arcjet propellant feed system for delivering propellant to a low power arcjet. As a result, the aforementioned disadvantages associated with utilizing the currently available propellant feed systems have been substantially eliminated.
BRIEF DESCRIPTION OF THE DRAWING
Still other advantages of the present invention will become apparent to those skilled in the art after reading the following specification and by reference to the drawing in which:
FIG. 1 is an overall system block diagram of one preferred embodiment of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The following description of the preferred embodiment concerning a low power arcjet propellant feed system is merely exemplary in nature and is in no way intended to limit the invention or its application or uses. Moreover, while the preferred embodiment is discussed below with reference to a satellite, those skilled in the art would also recognize that the low power arcjet propellant feed system can be incorporated into other types of spacecraft.
Referring to FIG. 1, a low power arcjet propellant feed system 10 is shown in a system environment. The low power arcjet propellant feed system 10 can be incorporated into various types of spacecraft, such as satellites, in order to feed multiple low power arcjet thrusters 12 onboard a satellite 14. The satellite 14 is first placed into low earth orbit or parking orbit using a delivery craft (not shown). Once in parking orbit, the low power arcjet thrusters 12 onboard the satellite 14 are used to position and maintain the satellite 14 within any desired orbit using the available energy onboard the satellite 14.
The low power arcjet propellant feed system 10 includes an unregulated pressurized supply tank 16 used to preferably hold from about a few tens of pounds to hundreds of pounds of a liquid hydrazine (N 2 H 4 ) propellant. This liquid hydrazine propellant is initially held at a pressure of about 400 psia (pounds per square inch absolute) within the supply tank 16 using preferably a nitrogen (GN 2 ) or helium (He) gas. Those skilled in the art would also recognize that other types of liquid propellant and gas may be used within the feed system 10. The pressure in the supply tank 16 is monitored by a control unit 18, discussed in more detail shortly, via a pressure transducer 20.
Upon opening a pair of actively controllable valves 22 and 24, the pressure in the supply tank 16 forces the liquid hydrazine out of the supply tank 16 and through a filter 26. The filter 26 filters out any impurities or contaminants in the liquid hydrazine using a 10 micron absolute filter 26. The pair of valves 22 and 24 are in series and simultaneously opened and closed by a valve driver 28 powered by a power supply 30 and controlled by the power processing unit 18. By using the two valves 22 and 24 in series, a redundant safety feature is provided so that if one valve fails, the power processing unit 18 is still able to inhibit the flow of liquid hydrazine using the other operable valve. Attached to the valve 24 is a thermocouple 32 used to sense the temperature of the liquid hydrazine flowing through the valve 24 in order to insure that the maximum operating temperature of the valves 22 and 24 are not exceeded.
As the liquid propellant passes through the actively controllable valves 22 and 24, the liquid propellant enters a flow limiter 34 having a thermocouple 36. The flow limiter 34 is a fixed flow rate device which provides a fixed flow rate at a given pressure. Thus, by knowing the pressure in the supply tank 16, via the pressure transducer 20, the flow rate into a gas generator 38 is also known. The controlled flow of liquid hydrazine is then distributed over a catalyst bed inside the gas generator 38 which is preferably a Shell 405 catalyst bed. This causes the liquid hydrazine to be decomposed in an exothermic reaction to produce a gaseous propellant of ammonia, hydrogen and nitrogen. The gaseous propellant is then filtered by a 10 micron absolute filter 40 to remove any impurities which may have broken off from the catalyst bed during the exothermic reaction.
The filtered gas propellant is directed along tubular feed lines 42 having an inner diameter of about 0.25 inches to three (3) activately controllable valves 44, 46 and 48. Each valve 44, 46 and 48 uses a valve driver and a power supply (not shown), similar to the valve driver 28 and the power supply 30, and are controlled by the power processing unit 18 which is in turn controlled by a control computer 50. The power processing unit 18 is similar to other power processing units currently used in existing satellites and is built using commercially available off the shelf components known to those skilled in the art.
The power processing unit 18 provides an arc voltage to the arcjet thruster 12 of between about 90 volts to 200 volts which is scalable to between about 400 watts to 4 kilowatts. The power processing unit 18 further performs the overall control and telemetry/status functions for the arcjet thruster 12, via the control computer 50. The power processing unit 18 also provides real time control of the arcjet 12 based on external commands from a ground based satellite controller (not shown), as well as data obtained from the various pressure and temperature sensors located within the low power arcjet propellant feed system 10. A DC to DC converter (not shown) within the power processing unit 18 increases the internal satellite voltage from about 28 volts to the required voltage level to power the system 14.
The power processing unit 18 is controlled by the control computer 50 which preferably utilizes a single digital signal processor (DSP) microcontroller. The control computer 50 provides real time control of the arcjet thruster 12, as well as real time control of the various actively controllable valves throughout the low power arcjet propellant feed system 10 based on the various closed loop feedbacks positioned within the system 10.
Upon opening valve 44, a low pressure plenum 52 is controllably pressurized with the gas propellant up to a desired pressure in the range of between about 35 to 250 psia and preferably to about 50 psia. The low pressure plenum 52 essentially accumulates the gas propellant and holds the gas propellant at a desired pressure until it is subsequently fed on demand to the arcjet thruster 12. The low pressure plenum 52 is controllably pressurized by pulsing the gas generator 38, via the actively controllable valves 22 and 24, in combination with the actively controllable valve 44 which allows the low pressure plenum 52 to be controllably incremented up to the desired pressure. A pressure transducer 54 continuously monitors the pressure of the low pressure plenum 52 and a thermocouple 56 monitors the temperature of the low pressure plenum 52, which typically ranges between about 50° F. to 300° F. The pressure transducer 54 and the thermocouple 56 essentially form a closed loop feedback in order to actively control, in real time, the pressure in the low pressure plenum 52.
By continuously monitoring the pressure and temperature of the low pressure plenum 52 using a real time closed loop feedback, the low pressure plenum 52 can be controlled to hold the desired pressure of about 50 psia ±2 psia, or any other desired pressure. For example, if the low pressure plenum 52 is opened, via valve 58, the pressure in the low pressure plenum 52 will drop only to about 47.9 psia. Since the low pressure plenum 52 is continuously monitored by the pressure transducer 54, upon reaching 47.9 psia, the actively controllable valve 44 will be opened, as well as the gas generator 38 pulsed with additional liquid hydrazine at a known rate, via actively controllable valves 22 and 24, so that the low pressure plenum 52 is again pressurized up to about 52 psia. In other words, the low pressure plenum 52 is actively controlled to hold the gas propellant at the desired pressure while the low pressure plenum 52 supplies the gas propellant to the arcjet thruster 12.
Upon opening valve 58, the gas propellant passes through a sonic orifice 60, which acts as a fixed choke, to provide a very low flow rate of between about 1 to 10 milligrams per second at a given pressure. Therefore, since the pressure of the low pressure plenum 52 can be actively controlled and varied, via the actively controllable valves 22, 24 and 44 and the closed loop feedback, the flow rate can be set to any desired low flow rate, preferably between about 1 to 10 milligrams per second.
The gas propellant having the stable and controlled low flow rate passes through a filter 62 to filter out any additional impurities or contaminants from the gas propellant prior to passing into the arcjet thruster 12. By filtering out any impurities before the gas reaches the arcjet thruster 12, this prevents the impurities from shorting out or sputtering within the electric arc generated within the arcjet thruster 12. A pressure transducer 64 is used to monitor the pressure of the gas feeding the arcjet 12 in order to insure that the arcjet 12 is receiving the proper flow rate of gas. While the arcjet thruster 12 is in operation, an additional pressure transducer 66 and a thermocouple 68 are utilized to ensure that the arcjet thruster 12 is operating and firing properly.
Turning to valve 46, upon opening valve 46, an optional high pressure plenum 70 is controllably pressurized with the gas propellant up to a desired pressure in the range of between about 100 to several hundred psia, similar to the way the low pressure plenum 52 is controllably pressurized. The high pressure plenum 70 is also monitored by a pressure transducer 72 and a thermocouple 74 while an actively controllable valve 76 is used to supply the gas propellant at a high pressure to the arcjet thruster 12 through a sonic orifice 78. The sonic orifice 78 controls the flow rate of the heated gas in the range of 10 to 100 milligrams per second. The high pressure plenum 70 is generally utilized for providing a high pressure start-up pulse to the arcjet thruster 12. The start-up pulse is used when the arcjet thruster 12 is first fired up before being operated in a steady state condition via the low pressure plenum 52.
Turning to valve 48, the valve 48 allows the gas propellant to flow directly from the gas generator 38 through a sonic orifice 80 and into the arcjet thruster 12 or to other thrusters (not shown) positioned onboard the satellite 14. The heated gas passes through the valve 48 and into a high pressure pulse line 82 which is monitored by a pressure transducer 84 to determine the pressure of the gas and the resultant flow rate out of the sonic orifice 80. This high pressure pulse line 82 is generally used when the satellite requires higher thruster power (i.e. high specific impulse, I SP ) to move the satellite greater distances or for start-up conditions of the arcjet thruster 12, similar to the use of the high pressure plenum 70.
By providing multiple feeds, via valves 44, 46 and 48, multiple arcjet thrusters 12 (not shown) can be individually controlled or operated to control the movement of the satellite 14. Moreover, by providing the high pressure pulse line 82 or the high pressure plenum 70, there is no need during start-up of the arcjet thruster 12 to raise the pressure in the low pressure plenum 52 up to the start-up pulse pressure and then subsequently bleed off the pressure within the low pressure plenum 52, via a bleed valve (not shown), before the arcjet 12 is driven in a steady state condition.
In operation, the satellite 14 is first placed into a parking orbit or low earth orbit, via a separate launch vehicle (not shown). Upon being placed in this parking orbit, the satellite 14 is either controlled, via a ground based control center through the control computer 50 and the power processing unit 18 or controlled autonomously to place the satellite 14 into any higher orbit as required for satellite operations. In order to feed the low power arcjet thruster 12, as well as additional arcjet thrusters (not shown), the power processing unit 18 pulses the valve driver 28 which pulses the actively controllable valves 22 and 24 on and off at about a 50% duty cycle where the valves 22 and 24 are opened for about 100 milliseconds and closed for about 100 milliseconds. By doing this, more control is achieved because the gas generator 38 is incrementally pulsed to generate gas which is subsequently supplied to the low pressure plenum 52, via the actively controllable valve 44.
The low pressure plenum 52 is controllably pressurized with the gas propellant from the gas generator 38 using the closed loop feedbacks from the pressure transducer 54 and the thermocouple 56. This is achieved by actively controlling valves 22 and 24, and actively controlling valve 44 in a pulsed manner to controllably increment the pressure in the low pressure plenum 52. The optimized or desired pressure to feed the arcjet thruster 12 is determined and held in the low pressure plenum 52 independent of the pressure in the gas generator 38. To start the arcjet thruster 12, either the high pressure pulse line 82 is utilized or the optional high pressure plenum 70, which is controllably pressurized similar to the low pressure plenum 52. The arejet thruster 12 is pulsed with a high pressure start-up pulse having a flow rate of about 25 milligrams per second at a pressure of about 300 psia to start the low power arcjet thruster 12.
Upon receiving the high pressure pulse, either valve 48 or 76 is actively closed and valve 58 is opened to supply a low pressure, low flow steady state gas propellant to the arcjet thruster 12. This provides a controllable steady state thrust from the low power arcjet thruster 12, independent of what is occurring within the gas generator 38. Moreover, the pressure in the low pressure plenum 52 can be controllably adjusted to any desired pressure, therefore providing a controllably adjusted unperturbable flow rate to the arcjet 12. Thus, the thrust from the arcjet 12 can be dynamically varied over a specific impulse (I SP ) range of about 400 seconds to 550 seconds, irrespective of the pressure in the supply tank 16.
By utilizing the low pressure plenum 52, a robust, long-life gas generator 38 can be utilized in a nontaxing, low duty cycle mode without concerns of flow instability due to the decomposition of the liquid hydrazine within the catalyst bed. As the liquid hydrazine supply is utilized within the supply tank 16 (i.e. blow-down) from about 2.4 to 0.7 MPa (400 to 100 psia), the arcjet thruster 12 can be operated without impacting on the arcjet flow rate from the low constant pressure plenum 52. For example, assuming the tank is 80% full of liquid hydrazine at 400 psia, and is empty at 100 psia, this generates a 4 to 1 blow-down which is not regulated at the supply tank 16. However, the arcjet thruster 12 can be operated at constant feed pressure, while the closed supply tank 16 blows down from the 400 psia to 100 psia range because the low constant pressure plenum 52 operates independent of the gas generator 38 and essentially decouples the fluctuating portion of the supply system 10 from the arcjet thruster 12. In addition, a flow rate tolerance of about ±2% can be maintained without the risk of instantaneous arcjet gas starvation because of the precision flow control, via the low pressure plenum 52, which equates to precision thrust control, via the arcjet thruster 12.
Still further, gas flow rate to the arcjet thruster 12 can be throttled by sending a new command to the control computer 50, which in turn will reduce the pressure in the low pressure plenum 52 by changing the gas generator 38 duty cycle. This condition would occur if the satellite 14 is exhibiting a power loss such that the power applied to the arcjet 12 is reduced. Therefore, the pressure in the low pressure plenum 52 is also reduced to provide the new required flow rate because of the lower power being applied to the low power arcjet thruster 12. Moreover, by using the low pressure plenum 52, gas supply pressure overshoots during ramp-ups and after shutdowns are eliminated or greatly minimized.
The foregoing discussion discloses and describes merely exemplary embodiments of the present invention. One skilled in the art will readily recognize from such discussion, and from the accompanying drawings and claims, that various changes, modifications and variations can be made therein without departing from the spirit and scope of the invention as defined in the following claims.
|
A lower power arcjet propellant feed system for delivering propellant to a low power arcjet. The low power arcjet propellant feed system includes a liquid propellant storage chamber for storing a liquid propellant. A gas generator in communication with the liquid propellant storage chamber generates a gaseous propellant upon receipt of the liquid propellant from the liquid propellant storage chamber. A gas plenum in communication with the gas generator accumulates the gaseous propellant from the gas generator up to a desired pressure. Actively controllable valves actively control the flow of the liquid propellant into the gas generator and actively control the flow of the resultant gaseous propellant out of the gas generator and into the gas plenum up to the desired pressure. A substantially continuous and stable low flow rate of gaseous propellant is then delivered to the low power arcjet.
| 1 |
FIELD OF THE INVENTION
[0001] This invention relates to apixaban pharmaceutical formulations comprising crystalline apixaban particles having a maximum size cutoff; and methods of using them, for example, for the treatment and/or prophylaxis of thromboembolic disorders.
BACKGROUND OF THE INVENTION
[0002] Apixaban is a known compound having the structure:
[0000]
[0003] The chemical name for apixaban is 4,5,6,7-tetrahydro-1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (CAS name) or 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-1-piperidinyl)phenyl]-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide (IUPAC name).
[0004] Apixaban is disclosed in U.S. Pat. No. 6,967,208 (based on U.S. application Ser. No. 10/245,122 filed Sep. 17, 2002), which is herein incorporated by reference in its entirety, has utility as a Factor Xa inhibitor, and is being developed for oral administration in a variety of indications that require the use of an antithrombotic agent.
[0005] The aqueous solubility (40 μg/mL at all physiological pH) of apixaban suggests that the tablets with less than 10 mg apixaban (dose/solubility ratio=250 mL) should not demonstrate dissolution rate limited absorption since dissolution rate limitations are only expected when the dose/solubility ratio is greater than 250 mL. Based on this dose and solubility consideration, the particle size of the compound should not be critical for achieving consistent plasma profiles, according to the prediction based on the Biopharmaceutics Classification System (BCS; Amidon, G. L. et al., Pharmaceutical Research, 12: 413-420 (1995)). However, it was determined that formulations that were made using a wet granulation process as well as those using large particles of apixaban drug substance resulted in less than optimal exposures, which can present quality control challenges.
SUMMARY OF THE INVENTION
[0006] Surprisingly and unexpectedly, it has been found that compositions for tablets comprising up to 5 mg, apixaban particles having a D 90 (90% of the volume) less than 89 microns (μm) lead to consistent in-vivo dissolution in humans (at physiologic pH), hence, consistent exposure and consistent Factor Xa inhibition that will lead to consistency in therapeutic effect. Consistent exposure is defined as that where in-vivo exposure from tablets is similar to that from a solution and not affected by the differences in dissolution rates. The compositions were prepared using a dry granulation process. Accordingly, the invention provides a pharmaceutical composition comprising crystalline apixaban particles having a D 90 equal to or less than about 89 μm as measured by laser light scattering method, and a pharmaceutically acceptable diluent or carrier. It is preferred that the apixaban particles in the composition have a D 90 not exceeding 89 μm. It is noted the notation D X means that X % of the volume of particles have a diameter less than a specified diameter D. Thus a D 90 of 89 μm means that 90% of the volume of particles in an apixaban composition have a diameter less than 89 μm.
[0007] The range of particle sizes preferred for use in the invention is D 90 less than 89 μm, more preferably D 90 less than 50 μm, even more preferably D 90 less than 30 μm, and most preferably D 90 less than 25 μm. The particle sizes stipulated herein and in the claims refer to particle sizes were determined using a laser light scattering technique.
[0008] The invention further provides the pharmaceutical composition further comprising a surfactant from 0.25% to 2% by weight, preferably from 1% to 2% by weight. As regards the surfactant, it is generally used to aid in wetting of a hydrophobic drug in a tablet formulation to ensure efficient dissolution of the drug, for example, sodium lauryl sulfate, sodium stearate, polysorbate 80 and poloxamers, preferably sodium lauryl sulfate.
[0009] The invention further provides a method for the treatment or prophylaxis of thromboembolic disorders, comprising administering to a patient in need of such treatment or prophylaxis a therapeutically effective amount of a composition comprising crystalline apixaban particles having a D 90 equal to or less than about 89 μm as measured by laser light scattering, and a pharmaceutically acceptable carrier.
[0010] The present invention also provides a dry granulation process for preparing a composition comprising crystalline apixaban particles having a D 90 equal to or less than about 89 μm as measured by laser light scattering, and a pharmaceutically acceptable carrier.
[0011] The formulations of this invention are advantageous because, inter alia, as noted above, they lead to consistent human in-vivo dissolution. The invention is surprising in this respect, however, in that exposures are variable even though apixaban has adequate aqueous solubility that would allow the drug to dissolve rapidly. That is, one would expect dissolution rate for a drug that has high solubility (as defined by the Biopharmaceutical Classification System) would not be limited by the particle size. It has surprisingly been found, however, that the particle size that impacts apixaban absorption rate is about a D 90 of 89 μm. Thus apixaban can be formulated in a composition having a reasonable particle size using dry granulation process, to achieve and maintain relatively fine particles to facilitate consistent in vivo dissolution.
[0012] In a relative bioavailabiltiy study where various apixaban formulations were evaluated, it was determined that formulations made using a wet granulation process resulted in lower exposures compared to the exposures obtained from a dry granulation process. Additionally, tablets made using larger particles (D 90 of 89 μm) had lower exposures compared to tablets made using the same process but with particle size of D 90 of 50 μm. In a dry granulation process, water is not used during manufacturing to develop granules containing apixaban and the excipients.
[0013] Formulations according to this invention, when dissolution tested in vitro preferably exhibit the following dissolution criteria. That is, the formulation exhibits dissolution properties such that, when an amount of the drug equivalent to 77% therein dissolves within 30 minutes. Usually the test result is established as an average for a pre-determined number of dosages (e.g., tablets, capsules, suspensions, or other dosage form), usually 6. The dissolution test is typically performed in an aqueous media bufferred to a pH range (1 to 7.4) observed in the gastrointestinal tract and controlled at 37° C. (±1° C.), together maintaining a physilogical relevance. It is noted that if the dosage form being tested is a tablet, typically paddles rotating at 50-75 rpm are used to test the dissolution rate of the tablets. The amount of dissolved apixaban can be determined conventionally by HPLC, as hereinafter described. The dissolution (in-vitro) test is developed to serve as a quality control tool, and more preferably to predict the biological (invivo) performance of the tablet, where invivo-invitro relationships (IVIVR) are established.
[0014] The term “particles” refers to individual drug substance particles whether the particles exist singly or are agglomerated. Thus, a composition comprising particulate apixaban may contain agglomerates that are well beyond the size limit of about 89 μm specified herein. However, if the mean size of the primary drug substance particles (i.e., apixaban) comprising the agglomerate are less than about 89 μm individually, then the agglomerate itself is considered to satisfy the particle size constraints defined herein and the composition is within the scope of the invention.
[0015] Reference to apixaban particles having “a mean particle size” (herein also used interchangeably with “VMD” for “volume mean diameter”) equal to or less than a given diameter or being within a given particle size range means that the average of all apixaban particles in the sample have an estimated volume, based on an assumption of spherical shape, less than or equal to the volume calculated for a spherical particle with a diameter equal to the given diameter. Particle size distribution can be measured by laser light scattering technique as known to those skilled in the art and as further disclosed and discussed below.
[0016] “Bioequivalent” as employed herein means that if a dosage form is tested in a crossover study (usually comprising a cohort of at least 10 or more human subjects), the average Area under the Curve (AUC) and/or the C max for each crossover group is at least 80% of the (corresponding) mean AUC and/or C max observed when the same cohort of subjects is dosed with an equivalent formulation and that formulation differs only in that the apixaban has a preferred particle size with a D 90 in the range from 30 to 89 μm. The 30 μm particle size is, in effect, a standard against which other different formulations can be compared. AUCs are plots of serum concentration of apixaban along the ordinate (Y-axis) against time for the abscissa (X-axis). Generally, the values for AUC represent a number of values taken from all the subjects in a patient population and are, therefore, mean values averaged over the entire test population. C.sub.max, the observed maximum in a plot of serum level concentration of apixaban (Y-axis) versus time (X-axis) is likewise an average value.
[0017] Use of AUCs, C max , and crossover studies is, of course otherwise well understood in the art. The invention can indeed be viewed in alternative terms as a composition comprising crystalline apixaban particles having a mean particle size equal to or less than about 89 μm, as measured by Malvern light scattering, and a pharmaceutically acceptable carrier, said composition exhibiting a mean AUC and/or mean C max which are at least 80% of the corresponding mean AUC and/or C max values exhibited by a composition equivalent thereto (i.e., in terms of excipients employed and the amount of apixaban) but having an apixaban mean particle size of 30 μm. Use of the term “AUC” for purposes of this invention implies crossover testing within a cohort of at least 10 healthy subjects for all compositions tested, including the “standard” 30 μm particle size composition.
[0018] The present invention may be embodied in other specific forms without departing from the spirit or essential attributes thereof. Thus, the above embodiments should not be considered limiting. Any and all embodiments of the present invention may be taken in conjunction with any other embodiment or embodiments to describe additional embodiments. Each individual element of the embodiments is its own independent embodiment. Furthermore, any element of an embodiment is meant to be combined with any and all other elements from any embodiment to describe an additional embodiment. In addition, the present invention encompasses combinations of different embodiment, parts of embodiments, definitions, descriptions, and examples of the invention noted herein.
DETAILED DESCRIPTION OF THE INVENTION
[0019] As previously stated, apixaban in any form which will crystallize can be used in this invention. Apixaban may be obtained directly via the synthesis described in U.S. Pat. No. 6,967,208 and/or US20060069258A1 (based on U.S. application Ser. No. 11/235,510 filed Sep. 26, 2005), herein incorporated by reference.
[0020] Form N-1 (neat) and Form H2-2 (hydrate) of apixaban may be characterized by unit cell parameters substantially equal to the following shown in Table 1.
[0000]
TABLE 1
Form
N-1
H2-2
Solvate
None
Dihydrate
T
+22
+22
a(Å)
10.233(1)
6.193(1)
b(Å)
13.852(1)
30.523(1)
c(Å)
15.806(1)
13.046(1)
α, °
90
90
β, °
92.98(1)
90.95(1)
γ, °
90
90
V(Å 3 )
2237.4(5)
2466.0(5)
Z′
1
1
Vm
559
617
SG
P2 1 /n
P2 1 /n
Dcalc
1.364
1.335
R
0.05
0.09
Sol. sites
None
2 H 2 O
Z′ is the number of molecules per asymmetric unit.
T(° C.) is the temperature for the crystallographic data.
Vm = V(unit cell)/(ZZ′)
[0021] Characteristic X-ray diffraction peak positions (degrees 20±0.1) at room temperature, based on a high quality pattern collected with a diffractometer (CuKα) with a spinning capillary with 2θ calibrated with a NIST suitable standard are shown in Table 2 below.
[0000]
TABLE 2
Form N-1
Form H2-2
10.0
5.8
10.6
7.4
12.3
16.0
12.9
20.2
18.5
23.5
27.1
25.2
[0022] It will be appreciated by those skilled in the art of manufacturing and granulation processes that there are numerous known methods which can be applied to producing apixaban solid dosage forms. The feature of this invention, however, involves processes that produce apixaban dosage forms with an ability to produce primary particles at the site of dissolution with a d90<89 μm. Examples of such methods include as well as dry granulation or wet-granulation by low or high-shear techniques
[0023] The dry granulation process that produces crystalline apixaban particles having a mean particle size equal to or less than about 89 μm, is believed to be novel, and is accordingly provided as a further feature of the invention. Thus, the invention provides a drug product manufacturing process, comprising the steps:
(1) Blend the raw materials required prior to granulation; (2) Granulate the raw materials from Step 1 using a dry or wet granulation process; (3) Blend the sized granules from step 3 with extragranular raw materials; (4) Compress the blend from Step 3 into tablets; and (5) Film coat the tablets from step 4.
[0029] In another embodiment, the invention provides a drug product manufacturing process, comprising the steps:
(1) Blend the raw materials, with apixaban of controlled particle size; (2) Include intragranular portions of binder, disintegrant and other fillers in the mix from step (1); (3) Granulate the materials from step (2) using process (3a) or (3b): (3a) DRY GRANULATION: Delump the intragranular lubricant using a suitable screen or mill. Add the lubricant to the blend from step (2) and blend. Compact the lubricated blend to ribbons of density in the range of 1.0 to 1.2 g/cc and size the compacted ribbons using a roller compactor; or (3b) WET GRANULATION: Wet granulate the composition from step (2) using water to a target end point and optionally, size the wet-granules by passing through a screen/mill. Remove water for granulation by drying in a convection oven or a fluid-bed dryer. Size the dried granules by passing through a screen/mill; (4) Blend the sized granules from step (3) and the extragranular disintegrant in a suitable blender; (5) Delump the extragranular lubricant using a suitable screen/mill and blend with granules from step (4); (6) Compress the blend from (5) into tablets; (7) Film coat the tablets from step (6).
[0040] In a preferred embodiment, a dry granulation process is employed.
[0041] In a preferred embodiment, the surfactant (SLS) in the composition serves as a wetting aid for inherently hydrophobic apixaban drug substance (contact angle=54° with water), further exacerbated as part of air-jet milling process that is used to reduce apixaban particle size to the desired size.
[0042] The amount of apixaban contained in a tablet, capsule, or other dosage form containing a composition of this invention will usually be between 2.5 and 5 mg, usually administered orally twice a day, although amounts outside this range and different frequencies of administration are feasible for use in therapy as well. As previously mentioned, such dosage forms are useful, inter alia, in the prevention and/or treatment of thromboembolic disorders, for example, deep vein thrombosis, acute coronary syndrome, stroke, and pulmonary embolism, as disclosed in U.S. Pat. No. 6,967,208.
[0043] As noted, average particle size can be determined by Malvern light scattering, a laser light scattering technique. In the examples below, the particle size for apixaban drug substance was measured using a Malvern particle size analyzer.
[0044] Upon measurement completion, the sample cell was emptied and cleaned, refilled with suspending medium, and the sampling procedure repeated for a total of three measurements.
[0045] The dissolution test is performed in 900 mL of dissolution medium at 37° C., using USP Apparatus 2 (paddles) method at a rotation speed of 75 rpm. Samples are removed after 10, 20, 30, 45, and 60 minutes from test initiation and analyzed for apixaban by HPLC at 280 nm. 0.1 N HCl or 0.05 M sodium phosphate pH 6.8 with 0.05% SDS solution has been used as dissolution medium during formulation development. While both methods serve the purposes as quality control tests (with adequate discrimination ability), and in establishing IVIVR, the latter was preferred from the standpoint of method robustness. A role of SDS (surfactant) in the latter dissolution medium is as a wetting aid to facilitate complete dissolution of hydrophobic apixaban from tablets, rather than to increase the solubility of apixaban. Dissolution data from both the tests are included in this invention record and unless otherwise specified, the results reported were averages of values from six tablets.
[0046] Blood samples are drawn at predetermined time points following drug administration as specified in the clinical study protocol. Concentrations of the samples are measured using a validated analytical method (Liquid Chromatography with Tandem Mass Spectrometry). Individual subject pharmacokinetic parameters (eg, Cmax, AUC, T-HALF) are derived by non-compartmental methods using Kinetica® software from the time-concentration profiles.
[0047] The invention is further exemplified and disclosed by the following non-limiting examples:
[0048] Table 3 shows apixaban tablet compositions prepared using the drygranulation process that were evaluated in bioequivalence (BE) study.
[0000]
TABLE 3
Dry Granulation
5% w/w Drug
20 mg
Loaded Granulation
Tablet
Ingredients
(% w/w)
(mg/tablet)
Intragranular
Apixaban
5.00
20.00
Lactose Anhydrous
49.25
197.00
Microcrystalline Cellulose
39.50
158.00
Croscarmellose Sodium
2.00
8.00
Magnesium Stearate
0.50
2.00
Sodium Lauryl Sulfate
1.00
4.00
Extragranular
Croscarmellose Sodium
2.00
8.00
Magnesium Stearate
0.75
3.00
Total
100.00 mg
400 mg
Film Coat
3.5
14.0
Total
103.5 mg
414 mg
[0049] Table 4 shows apixaban tablet compositions prepared using the wet granulation process that were evaluated in BE study.
[0000]
TABLE 4
Wet Granulation
5% w/w Drug
20 mg
Loaded Granulation
Tablet
Ingredients
(% w/w)
(mg/tablet)
Intragranular
Apixaban
5.00
20.00
Lactose Monohydrate
70.00
280.00
Microcrystalline Cellulose
5.00
60.00
Croscarmellose Sodium
2.50
10.00
Povidone
4.50
18.00
Purified Water
17.40
69.60
Extragranular
Croscarmellose Sodium
2.50
10.00
Magnesium Stearate
0.50
2.09
Microcrystalline Cellulose
10.00
10.09
Total
100.00
400.00
Film Coat
3.5
14.0
Total
103.5 mg
414.0
[0050] Table 5 and Table 5a show the dissolution data that indicates that having a dry granulation process will result in faster dissolution compared to that from a wet granulation process. As shown in Table 5, the 20 mg tablets made using a dry granulation process had 79% apixaban dissolved in 30 minutes versus 62% apixaban dissolved at 30 minutes for the 20 mg tablets made using a wet granulation process. Dissolution test in 0.1N HCl also indicated a similar behavior of faster dissolution from tablets made using dry granulation process (58% in 30 min), compared to wet granulation process (45% in 30 min).
[0000]
TABLE 5
% apixaban dissolved (USP II, 75 rpm,
0.05% SLS in 50 mM phosphate, pH 6.8)
Time
Wet Granulation
Dry Granulation
(minutes)
20 mg Tablets
20 mg Tablets
10
38
47
20
54
70
30
62
79
45
71
86
60
76
90
API Particle Size
83.8
83.8
D 90 (μm)
[0000]
TABLE 5a
% apixaban dissolved (USP II, 75 rpm, 0.1N HCl)
Time
Wet Granulation
Dry Granulation
(minutes)
20 mg Tablets
20 mg Tablets
10
30
41
20
39
52
30
45
58
45
51
64
60
56
68
90
64
74
API Particle Size
83.8
83.8
D 90 (μm)
[0051] Table 6 and Table 6a provides the dissolution data from tablets made with different manufacturing pprocesses (wet and dry granulation) and drug substance different particle sizes. As shown Table 6, apixaban tablets that had 77% dissolved in 30 minutes or 86% dissolved in 30 minutes both had AUC values that met bioequivalence criteria (Confidence Interval between 80% to 125%) when compared to the tablets that had 89% dissolved at 30 minutes. Similar rank order of the dissolution rates were observed for these tablets (A, B & C) when tested in 0.1N HCl.
[0000]
TABLE 6
% apixaban dissolved (USP II, 75 rpm,
0.05% SLS in 50 mM phosphate, pH 6.8)
Wet Granulation
Wet Granulation
Dry Granulation
2 × 2.5 mg
2 × 2.5 mg
2 × 2.5 mg
Time
Tablets
Tablets
Tablets
(minutes)
(A)
(B)
(C)
10
63
42
70
20
79
64
84
30
86
77
89
45
91
87
94
60
94
93
96
C max (ng/mL)
101.8 (21)
87.8 (24)
108.3 (24)
AUC(INF)
1088 (32)
1030 (25)
1153 (26)
(ng*hr/mL)
Geomean (CV %) are presented for Cmax and AUC(INF)
[0000]
TABLE 6a
% apixaban dissolved (USP II, 75 rpm, 0.1N HCl)
Wet Granulation
Wet Granulation
Dry Granulation
2 × 2.5 mg
2 × 2.5 mg
2 × 2.5 mg
Time
Tablets
Tablets
Tablets
(minutes)
(A)
(B)
(C)
10
44
25
56
20
62
43
71
30
72
54
79
45
80
66
85
60
84
74
88
AUC(INF)
1088 (32)
1030 (25)
1153 (26)
(ng*hr/mL)
Geomean (CV %) are presented for Cmax and AUC(INF)
[0052] The results of clinical studies demonstrated that, for tablets with similar dissolution rates (89% and 86% at 30 min in pH 6.8 phosphate buffer containing 0.05% SLS), Cmax and AUC of the coated Phase 3 tablet (C) relative to the uncoated Phase 2 tablet (A), met bioequivalence criteria. Tablets with different dissolution rates (77% and 86% at 30 min) had similar AUCs, but did not meet equivalence criteria for Cmax. The lower boundary of the 90% confidence interval of ratio of geometric mean Cmax was 0.788, indicating the rate of absorption, as defined by Cmax, was lower for the slower dissolving tablet (77% at 30 min). Since the oral bioavailability from these tablets is shown to be comparable to that from solution (see FIGS. 1 and 2 below), this dissolution rate (77% in 30 min) is defined as the threshold for achieving consistent exposure.
[0053] FIGS. 3 and 4 illustrate the dissolution data that shows that while particle size impacts dissolution, controlling the particle size to less than 89 microns will result in a dissolution rate that will ensure consistent in-vivo exposures. As indicated in FIGS. 3 and 4 , consistent exposures are expected once apixaban tablets have greater than 77% apixaban dissolved in 30 minutes. Since the tablets with 89 microns have >77% dissolved at 30 minutes, these tablets will also exhibit exposures that are equivalent to the exposures from tablets made with smaller particles (such as the tablets with 10 micron particles shown below). Whilst dissolution rate at an apixaban particle size of 119 microns is marginally greater than 77% in 30-min for the 5-mg apixaban tablets ( FIG. 4 ), the particle size threshold claimed is less than 89 microns. This allows for the typical variability (RSD=2 to 3%) in the dissolution results, such that the oral bioavailability from tablets consistently matches that from solution.
|
Compositions comprising crystalline apixaban particles having a D 90 equal to or less than 89 μm, and a pharmaceutically acceptable carrier, are substantially bioequivalent and can be used to for the treatment and/or prophylaxis of thromboembolic disorders.
| 0 |
BACKGROUND OF THE INVENTION
The present invention relates to a zinc oxide-based transparent conductor having zinc oxide as its primary component, and a sputtering target for forming the foregoing transparent conductor. Incidentally, the term “transparent conductor” as used herein includes a transparent conductive film.
Today, the material that is being used most as a transparent electrode of flat panel displays and the like is ITO (Indium Tin Oxide), which is obtained by doping indium oxide with an appropriate amount of tin.
The reason why ITO plays the leading part in a transparent conductor is that the various characteristics of ITO such as low resistivity and high transmittance in the visible light region, which are required in a transparent conductor, are superior in comparison to transparent conductors prepared from other materials.
Nevertheless, In (indium) as the raw material to be used in ITO entails problems in that the cost of the end product will increase because indium is expensive, and the supply of materials may become impossible due to resource depletion because indium is a scarce resource. Although the development of a zinc oxide-based transparent conductor having zinc oxide as its primary component is being actively pursued as the development of the substitute material of ITO, there is still a problem in that the resistivity is significantly high in comparison to ITO.
The reason for this is that the conventional development policy of zinc oxide-based transparent conductive materials was only based on the search of an optimal single dopant. In other words, the foregoing policy is to find an element from a periodical table that will serve as an n-type dopant and emit electrons as a result of doping the zinc oxide as the parent material with such element. Specifically, for example, in most cases, a target doped with a candidate element having an atomic valence that is greater than bivalence, which is the valence of zinc, in an appropriate range of concentration is prepared, and this is subject to sputter-deposition to evaluate the resistivity of the film.
As a result of this development policy, although candidate dopants having an atomic valence of trivalence (refer to Patent Document 1) and tetravalence (refer to Patent Document 2) were discovered, the actual condition is that the resistivity of such candidate dopants is far inferior to ITO.
Meanwhile, it has been reported recently that a zinc oxide-based transparent conductor with low resistivity was developed by applying the so-called co-doping theory (refer to Patent Document 3). The subject matter thereof merely requires that an n-type dopant having a concentration above a specified level is contained in an amount that is greater than a p-type dopant.
As it stands now, there have been no other reports in the past in addition to the foregoing report which actually succeeded in preparing a zinc oxide-based transparent conductor with low resistivity, though they have simply satisfied the foregoing requirement.
In addition, although the foregoing report refers to the Metal Organic Chemical Vapor Deposition (MOCVD) method and Molecular Beam Epitaxy (MBE) method in the examples as the method of manufacturing a zinc oxide-based transparent conductor, both of these methods are inappropriate for preparing a large-area transparent conductive film.
[Patent Document 1] Japanese Patent Laid-Open Publication No. S61-205619
[Patent Document 2] Japanese Patent Laid-Open Publication No. S62-154411
[Patent Document 3] Japanese Patent Laid-Open Publication No. 2002-50229
SUMMARY OF THE INVENTION
As described above, the search for an optimal single dopant in the development of a zinc oxide-based transparent conductor as the substitute material of ITO that does not contain In, which is an expensive raw material with concern of resource depletion, has already reached its limit. Moreover, in the development based on the co-doping theory, the subject matter thereof is ambiguous, and the current status is that the adopted manufacturing methods are unable to manufacture a large-area transparent conductor that is suitable for industrial application.
The present invention was devised in view of the foregoing problems. Thus, an object of the present invention is to provide a zinc oxide-based transparent conductive film with low resistivity that is comparable to ITO and which can be manufactured in a large area.
As a result of intense study to overcome the foregoing problems, the present inventors succeeded in realizing a zinc oxide-based transparent conductive film with low resistivity that is comparable to ITO and which can be manufactured in a large area by setting the type, range of concentration and relative value of concentration of the n-type dopant and the p-type dopant to be within an appropriate range, and further adopting an appropriate doping raw material and doping method. The present inventors thereby conceived the present invention.
The co-doping theory utilizes the effect of lowering the respective impurity levels based on mutual interaction by doping both the n-type dopant and the p-type dopant, and in particular is being reviewed for application to realize p-type zinc oxide which is considered to be difficult to manufacture. In other words, lowering the impurity level of the p-type dopant is to provide numerous holes, which exceeds the effect of normally existing the n-type dopant, and the results lead p-type zinc oxide to be realized.
Meanwhile, the present invention is unique in that it took particular note of n-type impurities. Specifically, since the impurity level of the n-type dopant is also lowered, the theoretical rationale that the present invention can be realized is the application of the foregoing effect to a zinc oxide-based transparent conductor.
The reason why the co-doping theory is considered to be effective in manufacturing an n-type zinc oxide-based transparent conductor is based on the discovery that, by introducing an n-type dopant and a p-type dopant at a ratio of 2:1 to zinc oxide, a compound is formed between the two dopants, the n-type impurity level is lowered further based on mutual interaction, and the activation rate of n-type impurities will increase. Thus, it is possible to reduce the doping amount of n-type impurities for obtaining a certain level of carrier concentration, and reduce the scattering of ionized impurities.
Nevertheless, the co-doping theory is only a theory, and it is hypothecating an ideal condition that is different from the actual condition for calculating the impurity level. In other words, the co-doping theory is based on the premise that the n-type dopant and the p-type dopant are respectively substituted with appropriate atoms and form a prescribed atomic arrangement.
Specifically, for example, in a case where the n-type dopant is gallium and the p-type dopant is nitrogen, in the co-doping theory, calculating the impurity level is based on the assumed ideal condition where the gallium is completely substituted with zinc and the nitrogen is completely substituted with oxygen in a lattice position.
In addition, the co-doping theory merely shows the calculation result of the impurity level once the foregoing substitution is realized, and it does not explain whether this kind of substitution actually occurs, nor does it refer to or suggest any means for realizing such substitution.
In fact, the present inventors identified that there are elements in which the foregoing ideal substitution is difficult such as the dopant getting caught between the lattices, and elements that in which the foregoing ideal substitution can be attained relatively easily, depending on the type, combination and introduction method of the dopants to be introduced.
Specifically, since the ion radius of nitrogen that is suitable as the p-type dopant is larger than that of oxygen, when nitrogen is introduced, zinc oxide will be subject to the influence of strains toward the direction of partially enlarging crystal lattice.
Moreover, since the n-type dopant similarly has an ion radius that is greater than that of zinc to which it is to substitute, and zinc oxide will be further subject to the influence of strains toward the direction in which the crystal lattice is enlarged, when the doping amount is increased, the appropriate substitution of these dopants to the lattice position will no longer be possible, the dopants may get caught between the lattices, and the ideal condition hypothesized under the co-doping theory can no longer be realized.
Thus, when using nitrogen as the p-type dopant, an element having an ion radius that is smaller than the ion radius of zinc is used as the n-type dopant. Consequently, the dopants are substituted at the lattice position based on the alleviation effect of the lattice strain caused by the introduction of the dopants, and the effect of the co-doping theory was thereby realized.
Moreover, the present inventors also discovered that the ratio of the n-type dopant and p-type dopant does not necessarily have to be within the range of 2:1, which is the optimal value of the co-doping theory, and the effect is yielded across a certain range.
Based on the foregoing discovery, the present invention provides:
1) A zinc oxide-based transparent conductor characterized in having zinc oxide as its primary component, containing an element at 1 to 10 atomic % which has a smaller ion radius than the zinc in the zinc oxide and serves as an n-type dopant for the zinc oxide, and containing nitrogen in which the atomicity ratio of nitrogen in relation to the n-type dopant (nitrogen/n-type dopant) is 0.3 to 0.6.
Incidentally, the atomic % of the n-type dopant means the ratio of the number of atoms of the n-type dopant in relation to the total number of atoms of the zinc element as the constituent element other than oxygen and nitrogen in the material, and the n-type dopant (hereinafter the same). Moreover, the atomicity ratio in relation to the n-type dopant of nitrogen is obtained by dividing the number of atoms of nitrogen by the number of atoms of the n-type dopant. Thus, if the atomicity ratio in relation to the n-type dopant of nitrogen is 0.5, this means that the number of atoms of nitrogen is half the number of atoms of the n-type dopant (hereinafter the same).
The present invention additionally provides:
2) The zinc oxide-based transparent conductor according to 1) above, wherein the element to serve as the n-type dopant is contained at 2 atomic % to 8 atomic %; and
3) The zinc oxide-based transparent conductor according to 1) or 2) above, wherein the n-type dopant is gallium and/or aluminum.
The present invention further provides:
4) A sputtering target for forming a zinc oxide-based transparent conductor characterized in having zinc oxide as its primary component, containing an element at 1 to 10 atomic % which has a smaller ion radius than zinc in the zinc oxide and serves as an n-type dopant for the zinc oxide, and containing nitrogen in which the atomicity ratio of nitrogen in relation to the n-type dopant (nitrogen/n-type dopant) is 0.3 to 0.6;
5) The sputtering target for forming a zinc oxide-based transparent conductor according to 4) above, wherein nitrogen is contained as gallium nitride;
6) The sputtering target for forming a zinc oxide-based transparent conductor according to 4) or 5) above, wherein the element to serve as the n-type dopant is contained at 2 atomic % to 8 atomic %; and
7) The sputtering target for forming a zinc oxide-based transparent conductor according to any one of 4) to 6) above, wherein the n-type dopant is gallium and/or aluminum.
The present invention yields the effect of dramatically improving the conductive property by doping zinc oxide with an n-type dopant having a smaller ion radius than the ion radius of zinc and nitrogen as the p-type dopant within an appropriate range of concentration, and thereby obtains resistivity that is equivalent to conventional ITO.
Further, by supplying nitrogen in the form of gallium nitride for doping the zinc oxide, the present invention also yields an effect of being able to prepare a sputtering target that is suitable in manufacturing a large-area transparent conductor.
Accordingly, even without having to use In, which is an expensive raw material with concern of resource depletion, it is possible to provide a new transparent conductor having the necessary characteristics as a transparent conductor such as low resistivity that could not be realized with the conventional methods.
DETAILED DESCRIPTION OF THE INVENTION
The appropriate range of concentration of the transparent conductor of the present invention was sought by preparing a sputtering target by adding a chemical compound to serve as the dopant to zinc oxide in an appropriate amount and sintering the mixture, and measuring the resistivity of the transparent conductor film obtained as a result of sputtering the foregoing sputtering target.
If the concentration of the n-type dopant to be added to zinc oxide is less than 1 atomic %, the concentration of electrons emitted from the dopant will not be a sufficiently high value, and it will not be possible to lower the resistivity.
Meanwhile, if the concentration of the n-type dopant exceeds 10 atomic %, the resistivity of the film will increase due to adverse effects such as the scattered ionized impurities caused by the added dopant, or the impurities not being ionized and remaining neutral and existing in the zinc oxide without contributing to the emission of electrons.
Further, if the atomicity ratio in relation to the n-type dopant of nitrogen is less than 0.3, the effect of lowering the n-type impurity level based on the addition of the p-type dopant is minimal. Contrarily, if the atomicity ratio in relation to the n-type dopant of nitrogen exceeds 0.6, the compensation effect of the n-type dopant based on the addition of the p-type dopant will become great and reduce the number of electrons that contribute to the conduction, and this will also lead to increased resistivity.
Accordingly, by obtaining a zinc oxide-based transparent conductor characterized in having zinc oxide as its primary component, containing an element at 1 to 10 atomic % which has a smaller ion radius than zinc in the zinc oxide and serves as an n-type dopant for the zinc oxide, and containing nitrogen in which the atomicity ratio in relation to the n-type dopant is 0.3 to 0.6, it is possible to obtain a transparent conductor having stable and low resistivity.
As a method of manufacturing a target to be used as the sputtering target, for instance, if the n-type dopant is gallium, the foregoing target can be manufactured by weighing and mixing Ga 2 O 3 powder, GaN powder and ZnO powder in appropriate amounts so that the concentration of the respective elements becomes a prescribed value, and retaining the mixed powder for 2 hours at a temperature of 950° C. and a pressure of 300 kgf/cm 2 according to the hot pressing method.
When using Al 2 O 3 as another n-type dopant, for example, the foregoing target can be manufactured by adding Al 2 O 3 powder in substitute for or in addition to the Ga 2 O 3 powder.
A film that is formed by sputtering the foregoing target will be a film having the same composition as the target, and such film will become a transparent conductive film with low resistivity by setting the composition to be in an appropriate range.
The target may also be formed as an integral sputtering target. In this case, the mosaic targets may be combined or the respective targets of zinc oxide, aluminum oxide, and gallium nitride may be independently formed and arranged to set the film composition as a result of sputtering to be ultimately within a prescribed range.
EXAMPLES
The present invention is now explained in detail with reference to the Examples. These Examples are merely illustrative, and the present invention shall in no way be limited thereby. In other words, various modifications and other embodiments based on the technical spirit claimed in the claims shall be included in the present invention as a matter of course.
Example 1
The respective raw material powders were weighed so that ZnO:Ga 2 O 3 :GaN=98.0:0.5:1.0 (ratio of number of molecules; the total does not necessary add up to 100), a zirconia ball of a diameter of 3 mm φ was used and the raw material powder was pulverized with an attritor for approximately one hour, the slurry raw material having an average grain size of 1 μm or less was screened with a 330 mesh sieve, and thereafter retained in a drying oven at 120° C. for 24 hours to evaporate the moisture.
The dried raw material powder was further screened with a 60 mesh sieve, and mixed with a Waring blender so that the raw material became sufficiently uniform.
Subsequently, 250 g (filling amount) of raw material powder was set in a small die of 85 f, and, while flowing Ar, the temperature was raised from room temperature to 900° C. at a rate of temperature increase of 10° C./min, and from 900 to 950° C. at a rate of temperature increase of 5° C./min, the raw material powder was retained for 30 minutes at 950° C., and thereafter pressurized for 10 minutes by applying pressure from 0 to 300 kgf/cm 2 .
After retaining the raw material powder for 2 hours in a condition of 950° C. and 300 kgf/cm 2 , the application of heat of the furnace was stopped, and the raw material powder was naturally cooled. After the temperature fell below 100° C., pressure was applied for 10 minutes and returned to 0, and the target was removed from the furnace. The removed target was processed to have a diameter of 50 mm and a thickness of 7 mm in order to obtain a sputtering target.
The obtained target was subject to sputter-deposition by adjusting the deposition time so that the film thickness would be approximately 150 nm under the condition of an Ar atmosphere of 0.5 Pa, Ar flow rate of 12 sccm, Corning #1737 glass as the substrate, substrate temperature of 200° C., and distance between the substrate and target of 80 mm. The film thickness of the obtained film was measured, and the film resistivity was evaluated based on Hall measurement. The obtained results are shown in Table 1.
Example 2 to Example 6
With respect to Example 2 to Example 6, only the ratios of the number of molecules of ZnO:Ga 2 O 3 :GaN were respectively different at 95.0:1.75:1.5, 95.0:1.5:2.0, 95.0:1.25:2.5, 95.0:1.0:3.0, and 92.0:2.0:4.0, and the other conditions such as the target manufacture and sputtering conditions were the same as Example 1. The obtained results are similarly shown in Table 1.
Example 7 to Example 12
With respect to Example 7 to Example 12, ZnO, Al 2 O 3 , and GaN were used as the raw material powder, and the ratios of the number of molecules of ZnO:Al 2 O 3 :GaN were respectively set to 98.0:0.5:1.0, 95.0:1.75:1.5, 95.0:1.5:2.0, 95.0:1.25:2.5, 95.0:1.0:3.0, and 92.0:2.0:4.0.
The other conditions such as the target manufacture and sputtering were the same as Example 1. The obtained results are similarly shown in Table 1.
Comparative Example 1 to Comparative Example 6
With respect to Comparative Example 1 to Comparative Example 6, ZnO, In 2 O 3 , and GaN were used as the raw material powder, and the other conditions were the same as Example 1. The obtained results are similarly shown in Table 1. The In material used in the Comparative Examples had an ion radius that is larger than that of Zn.
TABLE 1
n-type
conentration
dopant
rate
nitrogen/Ga + Al
resistivity
Example No.
element
(atomic %)
(atomicity ratio)
(mΩcm)
Example 1
Ga
2
0.5
0.68
Example 2
Ga
5
0.3
0.29
Example 3
Ga
5
0.4
0.21
Example 4
Ga
5
0.5
0.18
Example 5
Ga
5
0.6
0.35
Example 6
Ga
8
0.5
0.85
Example 7
Al and Ga
2
0.5
0.65
Example 8
Al and Ga
5
0.3
0.26
Example 9
Al and Ga
5
0.4
0.19
Example 10
Al and Ga
5
0.5
0.17
Example 11
Al and Ga
5
0.6
0.33
Example 12
Al and Ga
8
0.5
0.83
Comperative
In
2
0.5
2.58
Example 1
Comperative
In
5
0.3
1.55
Example 2
Comperative
In
5
0.4
1.23
Example 3
Comperative
In
5
0.5
0.98
Example 4
Comperative
In
5
0.6
2.83
Example 5
Comperative
In
8
0.5
3.88
Example 6
Summary of Examples and Comparative Examples
As shown above, Example 1 to Example 6 are zinc oxide-based transparent conductive (sputtered films) in which 2 to 8 atomic % of gallium was included as the n-type dopant, and nitrogen was included as N/Ga (atomicity ratio) in a range of 0.3 to 0.6.
The resistivity of these films was within the range of 0.18 to 0.85 mΩcm, and showed superior conductive property. Moreover, the transmittance of all films was in a range of 90% or higher in the visible light region, and preferable zinc oxide-based transparent conductive films were obtained.
Example 7 to Example 12 are zinc oxide-based transparent conductive (sputtered films) in which 2 to 8 atomic % of aluminum and gallium were included as the n-type dopant, and nitrogen was included as N/Ga (atomicity ratio) in a range of 0.3 to 0.6.
The resistivity of these films was within the range of 0.17 to 0.83 mΩcm, and showed superior conductive property. Moreover, the transmittance of all films was in a range of 90% or higher in the visible light region, and preferable zinc oxide-based transparent conductive films were obtained.
Meanwhile, Comparative Examples 1 to 6 are cases where indium having an ion radius that is greater than that of zinc was used as the dopant. The indium content was set to be within the same range as the Examples, and nitrogen was also included as N/Ga (atomicity ratio) in the range of 0.3 to 0.6, but the resistivity was 0.98 to 3.88 mΩcm, and all cases resulted in inferior conductive property in comparison to the Examples.
Accordingly, it is evident that the Examples of the present invention improve the conductive property and are effective as a transparent conductor.
The present invention is extremely effective as a transparent conductor in that a low-resistivity, large-area transparent conductor that could not be realized with conventional methods can be realized without having to use In, which is an expensive raw material with concern of resource depletion, by performing sputter-deposition to a zinc oxide-based target.
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Proposed is a zinc oxide-based transparent conductor characterized in having zinc oxide as its primary component, containing an element at 1 to 10 atomic % which has a smaller ion radius than zinc in the zinc oxide and serves as an n-type dopant for the zinc oxide, and containing nitrogen in which the atomicity ratio of nitrogen in relation to the n-type dopant (nitrogen/n-type dopant) is 0.3 to 0.6. In the development of a transparent conductor that does not contain In, which is an expensive raw material with concern of resource depletion, the limit of the conventional development technique known as the single-dopant method is exceeded, a guide to dopant selection as a specific means for realizing the co-doping theory is indicated, and a transparent conductor having low resistivity is provided.
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BACKGROUND OF THE INVENTION
The present invention relates to a process for crystallizing the adduct of bisphenol A with phenol.
There is an increasing demand for bisphenol A as a raw material for polycarbonate resins and epoxy resins, particularly for engineering plastics. These applications need colorless and high-purity bisphenol A.
Bisphenol A is produced, for example, by reacting phenol with acetone in the presence of an acid catalyst, freeing the product mixture of the catalyst, water, unreacted acetone, and a small amount of phenol, cooling the remaining liquid mixture, thereby crystallizing the adduct of bisphenol A with phenol, separating the adduct crystals from the mother liquor, and removing phenol from the adduct, thereby obtaining bisphenol A.
In the case where the catalyst is hydrochloric acid, the product mixture is heated to 100 to 120° C. under reduced pressure for the removal of hydrochloric acid, unreacted acetone, water, and a small amount of phenol.
The vacuum distillation is usually accomplished by controlling the temperature of the bottom product and thus controlling the concentration of the bottom product, while keeping the operating pressure constant according to the vapor-liquid equilibrium of phenol and bisphenol A. (In this case, the bottom product is regarded as a binary system composed of phenol and bisphenol A.)
A disadvantage of this operating method is that the concentration control by means of the temperature control is practically difficult because the boiling point of the bottom product changes only a little even when the concentration of bisphenol A changes greatly. For example, the boiling point is 107° C., 108° C., 109° C., and 110° C. when the concentration of bisphenol A is 25 wt. %, 30 wt. %, 35 wt. %, and 40 wt. %, respectively, if the distillation pressure is 50 mm Hg. Therefore, it is difficult to keep constant the concentration of bisphenol A in the bottom product.
If the bottom product with fluctuating concentrations is continuously fed to a crystallizer, the amount of crystals that are produced in the crystallizer will fluctuate. This makes the quality of the adduct of bisphenol inconsistnet thereby A with phenol, adversely affecting the quality of bisphenol A.
In addition, the fluctuation of concentration leads to the great fluctuation of particle size. This, in turn, leads to the fluctuation of quality because the crystals carry the mother liquor containing impurities in the solid-liquid separating step, with the amount of the mother liquor carried varying depending on the particle size.
The fluctuating concentration of bisphenol A in the slurry poses another problem. An excessively low concentration leads to low yields. An excessively high concentration leads to an increased slurry viscosity, making the slurry transportation impossible.
A problem associated with the continuous crystallization is the deposit of scale on the inside wall of the crystallizer. The deposit of scale interrupts the operation of the crystallizer, making it impossible to produce crystals of uniform quality in a stable manner.
The crystallization of the adduct of bisphenol A with phenol may be accomplished by a process disclosed in Japanese Patent Laid-open No. 135832/1983. According to this process, heat including the heat of crystallization is removed by adding water and evaporating the water. It is considered that no scale easily deposits on the inside wall of the crystallizer because the heat of crystallization is removed internally. Incidentally, said Japanese patent describes nothing about lagging the crystallizer.
The deposit of scale in the crystallizer is usually prevented by providing the crystallizer with a lagging material or a jacket for hot water circulation. These provisions prevent the degree of supersaturation from excessively increasing on the inside wall. The deposit of scale is also prevented by providing the crystallizer with a scraper which removes the scale from the inside wall, or by adding a solvent which dissolves the scale. (See Chemical Engineering Handbook, 4th edition p. 453, published by the Japanese Chemical Industry Association.)
In the case where the adduct of bisphenol A with phenol is crystallized by adding water, providing the crystallizer with a jacket has a disadvantage that a large amount of vapor is generated when the jacket is kept at an excessively high temperature. This leads to an energy loss and makes it necessary to enlarge the equipment. In addition, this causes the vigorous vaporization and bumping of water, which disturb the crystal growth, resulting in the decreased purity and particle size of the crystallized adduct.
On the other hand, providing the crystallizer with a scraper has a disadvantage that the scraper crushes the crystals, making it difficult to separate the crystals in the subsequent solid-liquid separating step, and resulting in decreased quality (due to the mother liquor remaining on the crystal surface) and decreased yields.
Adding a solvent to prevent the deposit of scale is not economical because an additional apparatus is necessary for solvent recovery. In addition, the solvent added is liable to deteriorate the quality of the product.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a process for crystallizing the adduct of bisphenol A with phenol having a high purity, uniform quality, and uniform particle size in the presence of water, said process being free of the above-mentioned problems.
As a result of our extensive studies, it was found that said object is achieved when the concentration of bisphenol A in the phenol solution of bisphenol A to be fed to the crystallizer is controlled by a proper means and the temperature of the inside wall of the crystallizer is kept higher than that of the solution present in the crystallizer. The present invention was completed on the basis of this finding.
In accordance with the present invention there is provided a process for crystallizing the adduct of bisphenol A with phenol from a phenol solution of bisphenol A in the presence of water, said process comprising the steps of controlling the concentration of bisphenol A in said solution by removing a portion of the phenol from said solution or adding phenol to said solution according to feedback control based on the measurement of solution density to obtain an adjusted solution and feeding the adjusted solution to the crystallizer in which its inside wall is kept at a temperature higher than that of the adjusted solution, provided the temperature difference is smaller than 5° C.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawing is a flowsheet showing an embodiment of the present invention.
DETAILED DESCRIPTION OF THE INVENTION
In the process of the present invention, the starting phenol solution of bisphenol A which has not undergone the adjustment of concentration may be a liquid mixture obtained by reacting phenol with acetone in the presence of an acid catalyst and then removing the catalyst, water, unreacted acetone, and a small amount of phenol from the product mixture. The phenol solution may also be a solution of crude bisphenol A in phenol.
For example, in the case where bisphenol A is synthesized by the aid of a strongly acidic cation-exchange resin as the catalyst, it is necessary to remove part of phenol from the phenol solution for the following reason. The synthesis in this case is usually accomplished by a fixed bed reaction which requires that the molar ratio of phenol to acetone in the starting reaction mixture should be high. (In other words, the reaction needs a large excess of phenol.) Therefore, the phenol solution obtained by removing acetone, water, and a small amount of phenol from the product mixture contains bisphenol A in a low concentration. Thus it is necessary to increase the concentration of bisphenol A by removing part of phenol from the phenol solution.
On the other hand, it is necessary to add phenol to a phenol solution in the case where the adduct of bisphenol A with phenol is dissolved in phenol and recrystallized from the phenol solution for further purification.
The density of a phenol solution of bisphenol A can be conveniently measured with a liquid densimeter of the in-line type. The densimeter should have an accuracy of 0.001 g/cm 3 because the density at 100° C. changes by 0.001 g/cm 3 as the concentration changes by 1 wt. %. For example, the density corresponding to the concentration of bisphenol A of 30 wt. %, 40 wt. %, and 50 wt. % is 1.040, 1.050, and 1.060 g/cm 3 , respectively. This requirement will be met by an oscillating liquid densimeter which is commercially available.
The removal of phenol for the adjustment of concentration of bisphenol A may be accomplished by vacuum distillation which evaporates part of the phenol. In this case, the vacuum distillation should be performed by controlling the amount of steam to heat the reboiler in response, to the density of the bottom product. In other words, the feedback control should be performed by measuring the density of the solution.
The addition of phenol for the adjustment of concentration of bisphenol A may be accomplished by mixing the phenol solution of bisphenol A with phenol in a mixer. The adequate amount of phenol to be added should be established by measuring the density of the resulting mixed solution.
After the adjustment of the concentration, the solution should contain 20 to 50 wt. %, preferably 30 to 45 wt. %, of bisphenol A. With a concentration lower than 20 wt. %, the solution gives the product in low yields. Conversely, with a concentration higher than 50 wt. %, the solution gives a slurry of adduct which has such a high apparent viscosity that it cannot be transported.
After the adjustment of concentration, the phenol solution of bisphenol A is continuously fed to a crystallizer and discharged continuously. In the crystallizer, the solution is slowly stirred and cooled to a temperature in the range of 35 to 70° C., so that the adduct of bisphenol with phenol crystallizes.
This cooling is accomplished by adding water to the crystallizer and evaporating the water and a small amount of phenol to remove heat. The evaporation produces a distillate composed of water and a small amount of phenol. The distillate can be recycled.
The water should be added in an amount sufficient to remove heat by evaporation for cooling the phenol solution of bisphenol A and removing the heat of crystallization which is generated when the adduct crystallizes out. This amount of the water is equivalent to 2 to 20 wt. % of the phenol solution.
The crystallizer should be operated under a constant pressure, preferably 20 to 100 mm Hg. The temperature of the content can be controlled by adjusting the amount of water to be added to the crystallizer.
The inside wall of the crystallizer should be kept at a temperature higher than that of the contents of the crystallizer. This is accomplished by providing the crystallizer with a jacket and passing temperature-controlled hot water through it.
In the case where the crystallizer is of Draft-tube type, it is preferable that the tube also has a jacket.
If the temperature of the hot water is lower than that of the content in the crystallizer, the degree of supersaturation on the inside wall increases to such an extent that the adduct crystallizes on the inside wall. This makes it necessary to remove the scale periodically and prevents the stable operation of the process.
The temperature of the hot water should be controlled such that it does not differ more than 5° C. from that of the content. If the temperature difference is greater than 5° C., water evaporates vigorously at the vapor-liquid interface, and bumping and boiling occurs on the inside wall. These disturb the crystal growth and decrease the purity and particle size of the adduct crystals.
The process of the invention will be described with reference to the flowsheet shown in the accompanying drawing.
The product mixture 1, which has been obtained by reacting phenol with acetone in the presence of hydrochloric acid as the catalyst, is fed to a dehydrochlorination column 2. From the top of the column is discharged a mixture 3 of water, hydrochloric acid, and a small amount of phenol; and from the bottom of the column is discharged a mixture 4 of phenol, bisphenol A, and by-products.
The mixture 4 is fed to a phenol evaporator 5. From the top of the evaporator is discharged phenol 6, and from the bottom of the evaporator is discharged a phenol solution 7 of bisphenol A. In order that the phenol solution 7 of constant concentration is fed to a crystallizer 11, the phenol evaporator 5 is operated such that the density of the phenol solution 7 measured with a liquid densimeter 8 is equal to the set value. This is accomplished by controlling the amount of steam 10 to be fed to the reboiler 9 of the phenol evaporator 5. In deed, this control is accomplished by means of a steam amount controller responsive to the density. In the crystallizer, the adduct of bisphenol A with phenol crystallizes out. Incidentally, the crystallizer 11 is provided with a jacket for hot water.
EXAMPLES
The invention will be described in more detail with reference to the following examples, in which "%" means "wt. %", unless otherwise indicated.
EXAMPLE 1
The synthesis of bisphenol A was performed by blowing hydrogen chloride into a mixture of phenol and acetone at 55° C. for 8 hours. The product mixture was heated under reduced pressure in a dehydrochlorination column for the removal of hydrochloric acid and water formed by the reaction. The dehydrochlorinated solution contained 32 to 38% of bisphenol A, 2 to 5% of by-products and the balance being phenol.
Then, the dehydrochlorinated solution was fed to a phenol evaporator which was operated under a pressure of 50 mm Hg and at the bottom temperature of 110° C. in the phenol evaporator, the dehydrochlorinated solution was concentrated until the concentration of bisphenol A increased to 40% by removing part of phenol.
The removal of phenol was performed in response to feed-back control. In other words, the liquid densimeter (Liquid Densimeter Model 7830, SOLARTRON) was placed in the line between the phenol evaporator and the crystallizer, and the amount of steam to be fed to the reboiler of the phenol evaporator was controlled such that the density of the dehydrochlorinated solution measured with the liquid densimeter was equal to the set value. This control was accomplished by means of a steam amount controller responsive to the density.
From the phenol evaporator was discharged a phenol solution of bisphenol A at 90° C. The phenol solution was then fed at a flow rate of 400 kg/hr to a crystallizer which was operated under a pressure of 50 mm Hg.
The crystallizer was heated with hot water (52° C.) passing through the jacket. To the crystallizer was added water at a flow rate of 40 kg/hr via a separate route. The content in the crystallizer was maintained at a constant temperature of 50° C. The resulting slurry was continuously discharged from the crystallizer and then continuously filtered.
The crystallized adduct of bisphenol A with phenol had an average particle diameter of 0.4 mm and contained 0.05% of by-products. It gave a 50% ethanol solution having a Hazen color of 5 APHA.
During the operation, the concentration of bisphenol A in the dehydrochlorinated solution discharged from the dehydrochlorination column was not constant, whereas the concentration of bisphenol A in the dehydrochlorinated solution (feedstock for crystallization) entering the crystallizer was constant.
The entire process was run stably without any crystal growth on the inside wall of the crystallizer.
COMPARATIVE EXAMPLE 1
The adduct of bisphenol A with phenol was crystallized in the same manner as in Example 1, except that the liquid densimeter was not used (or the concentration of bisphenol A in the feedstock for crystallization was not controlled). Although the phenol evaporator was run under constant conditions, the concentration of bisphenol A in the feedstock for crystallization fluctuated between 35% and 45% because th concentration of bisphenol A in the dehydrochlorinated solution fluctuated. In addition, the temperature of the content in the crystallizer also fluctuated as the concentration of bisphenol A fluctuated.
The crystallized adduct of bisphenol A with phenol had an average particle diameter of 0.2 mm. It gave a 50% ethanol solution having a Hazen color of 20 APHA.
COMPARATIVE EXAMPLE 2
The adduct of bisphenol A with phenol was crystallized in the same manner as in Example 1, except that hot water at 48° C. was passed through the jacket and water was added at a flow rate of 35 kg/hr to the crystallizer. The content in the crystallizer remained constant at 50° C.
After the operation for one week, crystals grew into a large mass on the inside wall of the crystallizer, making continued operation impossible.
COMPARATIVE EXAMPLE 3
The adduct of bisphenol A with phenol was crystallized in the same manner as in Example 1, except that hot water at 57° C. was passed through the jacket and water was added at a flow rate of 50 kg/hr to the crystallizer. The content in the crystallizer remained constant at 50° C.
During the operation, the stirring was disturbed by vigorous water bumping, although no scale deposited.
To keep the level of the content in the crystallizer constant, the slurry was discharged continuously. The slurry contained a large amount of fine crystals having an average particle diameter of 0.2 mm. Upon the continuous filtration, the slurry gave crystals containing 0.2% of by-products.
The crystallized adduct gave a 50% ethanol solution having a Hazen color of 30 APHA.
According to the process of the present invention, it is possible to crystallize the adduct of bisphenol A with phenol in the presence of water in a stable manner. In addtion, the crystallized adduct has a uniform particle size and a high purity.
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A process for crystallizing the adduct of bisphenol A with phenol from a phenol solution in the presence of water comprises controlling the concentration of bisphenol A in said solution by removing portion of the phenol from said solution or adding phenol to said solution according to feedback control based on the measurement of solution density to obtain an adjusted solution, and feeding the adjusted solution to the crystallizer in which its inside wall is kept at a temperature higher than that of the adjusted solution, provided the temperature difference being smaller than 5° C. The crystallized adduct has a uniform particle size and a high purity.
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FIELD OF THE INVENTION
The present invention relates generally to masks used for diving, such as scuba diving or skin diving, and particularly to an improved retainer buckle for attaching the head strap.
BACKGROUND OF THE INVENTION
A variety of underwater, diving masks have been used for many years in such activities as scuba diving or skin diving. The typical mask includes a rigid frame that supports a window or lens through which the diver may view his or her surroundings. A flexible skirt is also mounted to the frame and includes an edge designed to fit along the face of the diver. Typically, the skirt extends along the forehead, around the outside of the eyes and under the nose of the diver to prevent water from entering the space between the lens and the diver's eyes.
The mask is held against the diver's face in this sealing relationship by an elastomeric strap that extends about the back of the diver's head. Many modern masks have a silicone skirt that seals against the diver's face with minimal pressure. However, the mask strap is preferably adjustable to facilitate this sealing engagement with the diver's face without causing undue force against the diver's face or other discomfort. Most mask straps are adjustably mounted to the mask through a buckle assembly. Typically, the strap has a plurality of ridges that interact with a catch to allow the diver to adjust the length of the mask strap.
In certain conventional masks, the buckle assembly is affixed to the frame and includes a roller mounted on a pin. The mask strap extends through the buckle, wraps around the roller and doubles back on itself with the ridges extending outwardly. A spring-loaded catch is pivotably mounted within the frame to interact with a select ridge and hold the mask strap in place against the roller. If the length of the strap must be adjusted, the catch is simply pivoted against the force of the spring to release its engagement with the strap. The length of the strap is then adjusted to a desired length and the catch released. The spring pivots the catch back into engagement with the next selected ridge and holds the strap at that desired length.
This affixed buckle arrangement can be problematic when the diver wants to adjust the orientation of the mask strap about his or her head. Because the buckle does not pivot upwardly or downwardly with respect to the diver's head, the strap must generally be placed about the diver's head in one orientation. The diver may be able to move the strap upwardly or downwardly along the back of his or her head, but this is often less comfortable or less stable i.e. the strap is biased back towards a position in general alignment with the orientation of the buckle.
Attempts have been made to overcome this problem by constructing buckles that are pivotal. This allows the orientation of the mask strap to be adjusted with respect to the mask and the diver's head. For example, some divers may find it more comfortable to orient the mask strap at a slight upward angle and others may find it more comfortable to orient the mask strap at a somewhat downward angle rather than the conventional orientation that is substantially perpendicular to the lens of the mask.
Generally, the pivotal buckles include a plate pivotally mounted within a slot located within the frame of the mask. A roller is mounted at the opposite end of the plate to permit the strap to extend thereabout. A catch is pivotably mounted to the plate via a living hinge and interacts with ridges on the strap to maintain the strap in position. Thus, this type of buckle does not have the positive action of a spring loaded catch to pivot the catch into cooperation with the ridges on the strap. Additionally, the resiliency of the living hinge tends to decline over time with repeated usage.
It would be advantageous to design a pivotal buckle that utilized more dependable components and made possible the use of a spring loaded hinge.
SUMMARY OF THE INVENTION
The present invention features a diving mask assembly. According to a preferred embodiment of the invention, the assembly includes a mask having a frame and a lens mounted within the frame. A skirt is also connected to the frame and configured to fit against the face of the diver to maintain a pocket of air disposed between the lens and the diver's face. The mask also includes a strap retainer mounted to the frame. The strap retainer has a buckle plate pivotably mounted to the frame for pivotal motion about a first axis. A swivel mechanism is pivotably mounted between the frame and the buckle plate for pivotal motion about a second axis, the second axis being disposed in a generally transverse orientation with respect to the first axis.
Additionally, a mask strap is adjustably engaged with the swivel mechanism. The buckle plate cooperates with the swivel mechanism to permit adjustment of the mask strap when the buckle mechanism is appropriately pivoted about the first axis.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will hereafter be described with reference to the accompanying drawings, wherein like reference numerals denote like elements and:
FIG. 1 is a side view of a diver wearing a diving mask assembly according to a preferred embodiment of the present invention;
FIG. 2 is a side view of the retainer strap system illustrated in FIG. 1;
FIG. 3 is a partially broken away view of the retainer strap system of FIG. 2;
FIG. 4 is a cross sectional view taken generally along line 4--4 of FIG. 3;
FIG. 5 is a cross sectional view similar to the cross sectional view of FIG. 4, but showing the strap retainer system in an open position;
FIG. 6 is a cross sectional view taken generally along line 6--6 of FIG. 4;
FIG. 7 is a cross sectional view taken generally along line 7--7 of FIG. 4; and
FIG. 8 is a cross sectional view taken generally along line 8--8 of FIG. 4.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The following description is of a preferred embodiment of the inventive system by which a diving mask is attached to a head strap. However, it should be understood that although the strap retainer is contemplated for use primarily with a diving mask and mask strap of the type used by divers in, for example, scuba or skin diving, the invention has potentially broader application. For instance, the strap retainer system could be used to adjustably secure a wide variety of straps, including tie-downs used to secure a variety of items.
Referring generally to FIG. 1, a diver 10 is illustrated wearing a diving mask assembly 12 constructed according to a preferred embodiment of the invention. Diving mask assembly 12 typically includes a mask 14 connected to a mask strap 16 that extends about the head of diver 10 to secure mask 14 over the eyes and nose. Often, diver 10 may wish to place mask strap 16 about his or her head in different orientations to promote comfort or a better fit of mask 14. For instance, diver 10 may wish to move mask strap 16 upwardly or downwardly along the back of his or her head. Thus, it is helpful when mask strap 16 is able to pivot upwardly and downwardly with respect to mask 14.
Mask 14 typically includes an outer frame 18 and a window or lens 20 sealingly mounted within outer frame 18. Lens 20 may be a single or double lens. A flexible skirt 22, often made of silicone, is also sealingly attached to outer frame 18 and is configured to contact the face of diver 10 along a peripheral sealing area 24. Sealing area 24 is held against the face of diver 10 by mask strap 16 to help prevent water from flowing into the air pocket formed between lens 20 and the face of diver 10. Optionally, mask 14 can include a purge valve 26 which permits diver 10 to clear any water that happens to enter the air pocket between the divers face and lens 20. Simply by exhaling through his or her nose, diver 10 can expel this internal water through the purge valve.
Mask 14 also includes at least one and preferably two strap retainers 28. Each strap retainer 28 is mounted to a side panel 30 of outer frame 18 as illustrated. Each strap retainer 28 is designed to receive and grip mask strap 16. However, the strap retainers 28 are also designed to permit diver 10 to selectively adjust the point at which mask strap 16 is gripped, thereby facilitating adjustment of the length of mask strap 16 to accommodate the head size of diver 10.
Mask strap 16 preferably includes a back portion 32 illustrated along the back of the divers head. A pair of side portions 34 extend forwardly from back portion 32 into cooperation with strap retainers 28. Generally, each side portion 34 loops through a corresponding strap retainer 28 and is doubled back on itself to be held in place by a clip 36. Side portions 34 can also include a plurality of ridges 38, as illustrated, to promote secure retention of mask strap 16 by each strap retainer 28.
Referring generally to FIGS. 2-5, a preferred embodiment of strap retainer 28 is illustrated. In this embodiment, a buckle plate 40 is mounted along its corresponding side panel 30. As illustrated, side panel 30 can be disposed within a recess 42 formed in outer frame 18. Buckle plate 40 is pivotably mounted to outer frame 18, preferably by a pair of buckle plate pins 44 (See FIG. 6) disposed along a pivot axis 46. Pivot axis 46 lies generally along side panel 30, as illustrated, and buckle plate pins 44 are received within a pair of apertures 48 formed in a perimeter wall 50 of recess 42.
As best illustrated in FIGS. 4 and 5, buckle plate 40 includes a first extended portion 52 and a second extended portion 54. Extended portions 52 and 54 are disposed on opposite sides of pivot axis 46. As a result, when first extended portion 52 is moved in a general inwardly direction, second extended portion 54 is pivoted in a generally outward direction with respect to side panel 30.
A resilient member 56 interacts with outer frame 18 and first extended portion 52 to bias buckle plate 40 in a predetermined direction about pivot axis 46. In the illustrated embodiment, resilient member 56 is a coil spring disposed between side panel 30 and first extended portion 52. The coil spring is held in place within a pair of spring recesses 58 and 60 disposed in side panel 30 and first extended portion 52, respectively.
A swivel mechanism 62 is disposed between buckle plate 40 and outer frame 18, and preferably between buckle plate 40 and side panel 30 for pivotable motion about a second pivot axis 64. Second pivot axis 64 is disposed generally transversely to side panel 30 and first axis 46, although the axes preferably do not intersect each other. Swivel mechanism 62 is designed to receive and grip a side portion 34 of mask strap 16. Frame 18, buckle plate 40 and swivel mechanism 62 are disposed in cooperative engagement to selectively permit adjustment of the length of mask strap 16. After adjustment, frame 18, buckle plate 40 and swivel mechanism 62 cooperate to hold or grip the appropriate side portion 34 at a desired point, thereby maintaining the desired length of mask strap 16. Although swivel mechanism 62 could potentially be pivotably mounted to frame 18 or a combination of frame 18 and buckle plate 40, it is preferably pivotably mounted solely to buckle plate 40 as illustrated.
Specifically, a preferred embodiment of swivel mechanism 62 includes an outer swivel component 66 and an inner swivel component 68. Outer swivel component 66 and inner swivel component 68 are pivotably connected together along a third pivot axis 70. As illustrated best in FIG. 7, inner swivel component 68 includes a pair of pins 72 that extend outwardly from a base portion 74 of inner swivel component 68. Outer swivel component 66 includes a pair of corresponding apertures 76 located in a base portion 78 thereof.
Outer swivel component 66 also includes a platform 80 having a pivot aperture 82 therethrough. Platform 80 lies along the inside surface of buckle plate 40 and is held proximate buckle plate 40 by at least one and preferably three extensions 84 having flanged ends 86. Extensions 84 can be pressed through pivot aperture 82 sufficiently far so flanged ends 86 hook platform 80 and prevent it from moving away from buckle plate 40. However, extensions 84 and flanged ends 86 do not prevent the pivoting of outer swivel component 66 along the inside surface of buckle plate 40. This arrangement permits the pivoting of the entire swivel mechanism 62 with respect to frame 18 so diver 10 can adjust the orientation of mask strap 16 along the sides and back of his or her head. In other words, mask strap 16 can be moved upwardly or downwardly along the head of the diver, and swivel mechanism 62 pivots about second pivot axis 64 to prevent undue bending or kinking of mask strap 16.
Inner swivel component 68, on the other hand, includes a pair of legs 88 that extend from base portion 74 towards second pivot axis 64. Legs 88 are spaced to receive a rotatable pin 90. Rotatable pin 90 is disposed a sufficient distance from base portion 74 to permit one of the side portions 34 of mask strap 16 to be wrapped thereabout and doubled back on itself as illustrated best in FIGS. 4 and 5. Thus, side portion 34 can be moved about rotatable pin 90 until mask strap 16 is at a desired length. The side portion 34 can then be squeezed between outer swivel component 66 and inner swivel components 68 to secure the side portion 34 in place. Preferably, a protrusion 92 is disposed on platform 80 to interact with rotatable pin 90 and squeeze the side portion 34 therebetween.
Rotatable pin 90 can have a variety of shapes and configurations, but a preferred embodiment is best illustrated in FIG. 8. In this embodiment, rotatable pin 90 is a unitary plastic pin having a central roller section 94. A pair of narrower neck regions 96 extend outwardly from central roller section 94. Neck regions 96 can be divided into a plurality of axially extending segments 98 that terminate in flanged portions 100. Central roller section 84 and segments 98 are sufficiently flexible to permit rotatable pin 90 to be snapped into appropriately configured receptacles 102 formed in legs 88 of inner swivel component 68. Receptacles 102 include an orifice 104 sized to rotatably support neck regions 96, but smaller than the diameter across flanged portions 100 and central roller section 94. Thus, rotatable pin 90 can be snapped into place and securely held as illustrated in FIG. 8.
The actual operation of strap retainer 28 is best described by referring once again to FIGS. 4 and 5. Diving mask assembly 12 could be constructed with a single strap retainer 28, but it preferably includes a strap retainer 28 on each side of outer frame 18. Thus, the length of mask strap 16 can be adjusted on one or potentially both sides of mask 14.
Initially, the desired side portion 34 is threaded through swivel mechanism 62 around rotatable pin 90. At this point diver 10 adjusts the length of mask strap 16 for maximum comfort and utility. Diver 10 initially depresses first extended portion 52 of buckle plate 40 in the direction of arrow 106 shown in FIG. 5. This action compresses resilient member 56 and pivots swivel mechanism 62 away from side panel 30. It should be rated that swivel mechanism 62 is mounted on the opposite side of first pivot axis 46 from resilient member 56.
Pressing first extended portion 52 permits rotatable pin 90, mounted on inner swivel component 68, to pivot away from protrusion 92 of outer swivel component 66. At this point, rotatable pin 90 is able to freely rotate and side portion 34 can be moved through swivel mechanism 62 until mask strap 16 is at a desired length. First extended portion 52 of buckle plate 40 is then released, and resilient member 56 pivots buckle plate 40 about first pivot axis 46 until second extended portion 54 of buckle plate 40 forces inner swivel component 68 against frame 18, specifically side panel 30.
The force exerted by resilient member 56 is also sufficient to pivot outer swivel component 66 with respect to inner swivel component 68 until protrusion 92 cooperates with rotatable pin 90 to squeeze side portion 34 therebetween. The continued force exerted by resilient member 56 also securely holds side portion 34 between protrusion 92 and rotatable pin 90.
However, because both inner swivel component 68 and outer swivel component 66 are capable of simultaneous pivotable motion about second pivot axis 64, the orientation of side portion 34 may be changed without affecting the length of mask strap 16. As illustrated in FIG. 2 by arrows 108, the orientation of side portions 34 and mask strap 16 can be adjusted upwardly or downwardly by pivoting swivel mechanism 62 about second pivot axis 64 without undesirable kinking or bending of side strap 34.
It will be understood that the foregoing description is of a preferred exemplary embodiment of this invention and that the invention is not limited to the specific form shown. For example, a variety of diving mask designs may be used in combination with the strap container, the swivel mechanism can potentially be rotatably mounted to the frame, the side panel may have a variety of contours, the swivel mechanism have a variety of configurations and the resilient member can take a variety of forms, including plastic and metal compression springs, elastomeric bands or living hinges. These and other modifications can be made in the design and arrangement of the elements without departing from the scope of the invention as expressed in the appended claims.
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A strap retainer system is disclosed. The strap retainer system has particular utility with diving masks and includes a buckle pivotably mounted to a frame. The buckle cooperates with a swivel mechanism to permit selective adjustment of the strap length. Additionally, the swivel mechanism is rotatably mounted to the buckle to permit upward and downward pivoting of the strap along the divers head to promote comfort and fit.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a stability control system for an automotive vehicle.
2. Description of the Related Art
In recent years, there is a strong tendency to control stability of an automotive vehicle by controlling braking force applied to four wheels independently. Braking force is applied to one or more wheels so as to gain actually a target yaw rate or a target slip angle of the vehicle given as a target stability parameter based on a steering angle, a vehicle speed, and a yaw rate and a lateral acceleration of the vehicle. This kind of system of driving stability control is known from, for example, Japanese Unexamined Patent Publication No. 2-151571. The system of driving stability control attracts a great deal of attention as a potential safety technique because of its capability of preventing an occurrence of understeering and/or spinning within a limit of tire gripping or adhesion force.
The system of driving stability control of this kind applies braking force to some of the four wheels to cause a yaw moment in the vehicle independently of braking the vehicle. That is, braking force applied to a specific wheel or wheels through the stability control while the vehicle spins or when the slip angle of the vehicle is large bears no direct relation to braking the vehicle. On the other hand, if the driver steps on a brake pedal with the intention of avoiding spin or bringing a spin to the end during execution of the stability control, a confrontation occurs between demands for braking the vehicle and making the vehicle run stably. If either must take preference, measures have to be taken to prevent an occurrence of confrontation between the two demands. Applying braking force simply distributed among the wheels during an occurrence of spin might encourage the spin.
SUMMARY OF THE INVENTION
It is an objective of the invention to provide a system of driving stability control for an automotive vehicle which achieves both braking the vehicle and making the vehicle run stably on a high level with an effect of avoiding an occurrence of a spin.
The foregoing object of the present invention is achieved by providing a system of driving stability control for a vehicle equipped with a braking system for performing braking control and stability control of the vehicle according to vehicle driving conditions by applying braking force independently to respective wheels. The system of driving stability control causes changes a distributive proportion of a braking force between the braking control and the stability control correspondingly to a step-on pressure with which the brake pedal is stepped on by the driver and restrains the braking control by reducing the distributive proportion of braking force when it is judged based on driving conditions that the vehicle is going to cause a spin.
With the system of driving stability control performs coordinated braking and stabilizing control when the brake pedal is stepped during execution of the stability control. If the vehicle encounters a driving condition leading to a spin during the coordinated braking and stabilizing control, the stability control restrains the braking control to prevent the tendency for the vehicle toward the spin. Allowing a margin of slip angle against an occurrence of a spin provides a broad range of driving conditions in which the coordinated braking and stabilizing control The imposing restraint on the coordinated control is achieved simply by a complementary change in distributive proportion of braking force between the braking control and the stability control. When the steering wheel is additionally turned in the same direction, for example, when the steering wheel is further turned right after having been turned right to a certain extent in such a case where the driver drives the vehicle with the active intention of causing a spin for sporty driving, the stability control may be restrained or suspended, which is easily achieved only by increasing the distributive proportion of braking force allocated to the braking control.
BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing and other objects and features of the present invention will be clearly understood from the following detailed description of preferred embodiments when read in conjunction with the accompanying drawings in which:
FIG. 1 is a schematic illustration showing an automotive vehicle equipped with an system of driving stability control in accordance with an embodiment of the invention;
FIG. 2 is a braking pressure line installed to the automotive vehicle shown in FIG. 1;
FIG. 3 is a block diagram of a stability control unit;
FIG. 4 is a block diagram showing calculations of actual and target parameters;
FIG. 5 is a flow chart illustrating a stability control main routine;
FIG. 6 is a flow chart illustrating a control intervention judging subroutine; and
FIG. 7 is a flow chart illustrating a harmonized control routine.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to the drawings in detail and, in particular, to FIG. 1 showing an automotive vehicle equipped with a system of driving stability control (DSC) in accordance with an embodiment of the invention, the automotive vehicle 1 has an engine 11 to which an automatic transmission 12 is connected and a braking system accompanied by a brake master cylinder 10. This braking system comprises hydraulic brake units 2 installed to right and left, front and rear wheels 21RF, 21LF, 21RR and 21LR, respectively, and a pressure supply unit 3 for generating and supplying hydraulic pressure to each brake unit 2 through a distributor unit 4. The respective brake units 2 are controlled by means of a stability control unit 5 in cooperation with the pressure supply unit 3 and the distributor unit 4 based on incoming signals from wheel speed sensors 6 for detecting rotational speeds of the respective wheels 21RF, 21LF, 21RR and 21LR, an acceleration sensor 7 for detecting lateral acceleration of the vehicle 1, a yaw rate sensor 8 for detecting a yaw rate of the vehicle and an angle sensor 9 for detecting a steering angle. A fuel injection control unit 13 is installed to control the amount of fuel to be injected according to engine speed and load.
Referring to FIG. 2 showing a braking pressure line, the braking system has what is called a cross-piping independent brake arrangement. Specifically, the brake units 2 related to the right front wheel 21RF and the left rear wheel 21LR respectively are connected to the brake master cylinder 10 through a first hydraulic line 22a. Similarly, the brake units 2 related to the left front wheel 21LF and the right rear wheel 21RR respectively are connected to the brake master cylinder 10 through a second hydraulic line 22b. The braking system applies braking force to the wheels 21RF, 21LF, 21RR and 21LR independently according to a strength with which a brake pedal 14 is stepped on by the driver. The step-on strength may be detected by a pressure sensor (not shown) or any other sensor known in the art. The pressure supply unit 3 includes hydraulic pumps 31a and 31b, connected respectively to the first and second hydraulic lines 22a and 22b, shut-off valves 32a and 32b disposed respectively in the first and second hydraulic lines 22a and 22b to connect and disconnect pressure supply between the hydraulic pumps 31a and 31b and the brake master cylinder 10, and hydraulic sensor 33 to detect pressure between the brake master cylinder 10 and the shut-off valve 32a. The stability control unit 5 controls the shut-off valves 32a and/or 32b to close to disconnect the brake master cylinder 10 from the first and second hydraulic lines 22a and 22b and to permit hydraulic pressure developed by the hydraulic pumps 31a and 31b to be applied to the brake units 2 through the distributor unit 4 independently from stepping on the brake pedal 14. The distributor unit,4 includes a brake pressure supply valve 41 and a brake pressure relief valve 43 related to each respective brake unit 2. The brake pressure supply valve 41 delivers hydraulic pressure to the brake unit 2 through the first or second hydraulic line 22a or 22b. The brake pressure relief valve 43 releases hydraulic pressure into a reservoir 42 from the brake unit 2. Hydraulic pressure remaining supplied to the brake unit 2, and hence braking force applied to the wheel, is controlled by regulating the valve opening of the brake pressure supply valve 41 or of the brake pressure relief valve 43 by the stability control unit 5.
The stability control unit 5 determines a cornering attitude of the vehicle 1 based on incoming signals from the sensors 6-9 (which comprise a vehicle state detecting means) and controls operations of the pressure supply unit 3 and the distributor unit 4 based on the determined cornering attitude. The stability control unit 5 further controls operations of the pressure supply unit 3 and the distributor unit 4 based on an incoming signal from the hydraulic sensor 33 which indicates the step-on pressure relating to the brake pedal 14.
As shown in FIG. 3, the stability control unit 5 comprises a microcomputer divided into various functional parts including an attitude variable operation part 51, a target attitude variable operation part 52, a control intervention judging part 53, a control variable operation part 54, vehicle condition judging parts 55a, 55b and 55c, Wand a drive control part 56. The control variable operation part 54 comprises three sub-parts, namely a vehicle attitude control sub-part 54a, a deceleration control sub-part 54b and a critical value operation sub-part 54c. The attitude variable operation part 51 calculates a vehicle slip angle and a running speed of the vehicle 1 as attitude variables, which represent a turning attitude with respect to a running direction of the vehicle 1, based on incoming signals from the sensors 6-9. Similarly, the target attitude variable operation element 52 calculates a target vehicle slip angle and a target yaw rate of the vehicle 1 as target attitude variables for a target running direction intended by the driver. Specifically, these vehicle attitude variables are gained through a calculation process as shown in FIG. 4. A slip angle β of vehicle is calculated as shown at block C2 based on a wheel speed of each wheel detected by the respective wheel speed sensors 6, a vehicle speed Vref calculated based on the wheel speeds as shown at block C1, a lateral acceleration detected by the gravity sensor 7, a yaw rate γ detected by the yaw rate sensor 8 and a steering angle θH of the front wheels 21RF and 21LF. A slip ratio and a slip angle of each wheel 21RF, 21LF, 21RR, 21LR are calculated as shown at block C3 based on the wheel speed, the vehicle speed Vref, the yaw rate γ, the steering angle θH of the front wheels 21RF and 21LF, and the slip angle β. A vertical load exerted on each wheel is calculated based on the wheel speed and the lateral acceleration as shown at block C4. The rate of the present total tire gripping or adhesion force relative to the total rated tire gripping or adhesion force of the wheels is calculated as a tire load factor based on the vertical loads and the slip ratio as shown at block C5. A road surface friction coefficient (which is referred to the coefficient of friction of the tire relative to a road surface) is calculated as shown at block C6. A target yaw rate and a target slip angle are calculated based on the road surface friction coefficient, the front wheel steering angle and the vehicle speed Vref as shown at block C7. The control intervention judging part 53 calculates a deviation of the actual slip angle β from the target slip angle and a deviation of the actual yaw rate γ from the target yaw rate, based on which it is judged whether the stability control must intervene.
The control variable operation part 54 includes the vehicle attitude control sub-part 54a, the deceleration control sub-part 54b and the critical value-,operation sub-part 54c as was previously mentioned. The vehicle attitude control sub-part 54a performs attitude or orientation control of the vehicle 1 by applying braking force to either side of the vehicle 1 so as to produce a yaw moment about the center of gravity of the vehicle 1. The deceleration control sub-part 54b controls braking force applied to the right and left wheels to decelerate the vehicle 1. The critical value operation sub-part 54c changes a judging parameter used in drift-out restraint control which will be described later. Based on the result of the judgement of intervention made in the control intervention judging part 53, the control variable operation part 54 calculates braking force to be applied to the respective wheels 21RF, 21LF, 21RR and 21LR necessary to direct the vehicle 1 to an aimed turning direction meeting to the drivers operation. Further, the control variable operation part 54 opens either one of the shut-off valves 32a and 32b when the hydraulic sensor 33 detects hydraulic pressure P applied as braking force to the brake units 2 higher than the atmospheric pressure, bringing the brake master cylinder 10 into communication with either one of the first and second hydraulic line 22a and 22b.
The vehicle condition judging sub-part 55a detects the degree of understeering and judges whether the tendency for the vehicle 1 toward understeering is too strong to rectify the running direction in the drift-out restraint control. The vehicle condition judging sub-part 55b judges whether the vehicle speed it too high to rectify the running direction. The vehicle condition judging sub-part 55c judges whether there is caused a change in running direction during execution of the drift-out restraint control. The drive control part 56 actuates selectively the shut-off valves 32a and 32b, the brake pressure supply valve 41 and the brake pressure relief valve 43 based on the result of the calculation at the controlling element 54.
The system of driving stability control further performs, in addition to the stability control, anti-skid braking control in which an occurrence of wheel lockup is prevented by controlling braking force applied to the wheels 21RF, 21LF, 21RR and 21LR and traction control in which an occurrence of slippage is prevented by controlling drive torque applied to the wheels 21RF, 21LF, 21RR and 21LR. The stability control system gives top priority to the anti-skid braking control and coordinates the stability control and the traction control in a prescribed manner.
The operation of the system of driving stability control depicted in FIGS. 1 through 3 will be best understood by reviewing FIGS. 5 through 7 which are flow charts illustrating various control sequence routines and sub-routines for the microcomputer of the stability control unit 5.
Referring to FIG. 5, which is a flow chart illustrating the basic control sequence routine, when an ignition switch (not shown) is turned on, the flow chart logic commences and control passes directly to step S101 where various values are initialized. Subsequently, after zero adjustment of the sensors 6-9 and 33, signals from the sensors 6-9 and 33 are input to the stability control unit 5 at step S102. Based on to the incoming signals, calculations are made to obtain a vehicle speed, a vehicle deceleration and vehicle speeds at the respective wheels as vehicle attitude variables commonly necessary for various controls including the anti-skid braking control, the stability control and the traction control at step S103. Thereafter, stability control operation is executed at step S104 which includes substeps S41 through S45. Specifically, calculations are made to find a vehicle speed Vref, a slip angle β of the vehicle, a slip ratio and a slip angle of each wheel, a vertical load of each wheel, a tire load factor and a road surface friction coefficient at step S41 and to find a target yaw rate, a target slip angle and a target deceleration as target vehicle attitude variables at step S42. Subsequently, at step S43, a slip angle deviation and a yaw rate deviation are calculated based on these vehicle attitude variables and target vehicle attitude variables to make a judgement whether there is a necessity for a control intervention. If the control intervention is needed, selection of one or more wheels to be braked and a calculation of braking force to be applied to each selected wheel are made at step S44. The brake pressure supplying valve 41 or the brake pressure relief valves 43 is driven to open so as to meet the braking force for the brake unit 2 relating to the selected wheel at step S45. Subsequently to the stability control operation made at step S104, the anti-skid braking control operation and the traction control operation are consecutively made at steps S105 and S106, respectively. After coordinating the results of operations in the prescribed manner at step S107, the brake pressure applying valve 41 or the brake pressure relief valves 43 is driven to regulate its valve opening so as to provide braking force for each brake unit 2 according to the coordinated result at step S108. At step S109, a fail-safe routine is performed to monitor operations of the sensors 6-9 and 33. The flow chart logic orders return for another sequence routine.
FIG. 6 is a flow chart illustrating the control intervention judgement subroutine made at step S43 in the basic control sequence routine shown in FIG. 5. When the flow chart logic commences and control proceeds directly to a judgement at step S201 where the slip angle deviation x of an actual slip angle β from the target slip angle is compared with an intervention threshold value x1. When the slip angle deviation x is equal to or greater than the threshold value x1, this indicates that the vehicle is going to spin due to an increasing tendency toward oversteering, then, the spin restraint control is executed at step S202. On the other hand, when the slip angle deviation x is less than the threshold value x1, the yaw rate deviation y of an actual yaw rate γ from the target yaw rate is compared with an intervention threshold value y1 at step S203. When the yaw rate deviation y is equal to or greater than the threshold value y1, this indicates that the vehicle is going to drift out due to an increasing tendency toward understeering, then, the drift restraint control is executed at step S204.
FIG. 7 is a flow chart illustrating the sequence routine of the coordinated control of vehicle attitude and braking control which is executed at step S107 in the basic control sequence routine shown in FIG. 5, or otherwise may be executed at regular intervals as an interruption routine. The sequence routine shown by the flow chart in FIG. 7 is programmed on condition that the vehicle attitude control is under execution. When the flow chart logic commences and control proceeds directly to a judgement at step S301 where step-on pressure Ps developed correspondingly to pressure exerted on the brake pedal 14 by the driver is detected. Subsequently, the step-on pressure P is compared to a threshold value Po specified for execution of the coordinated control at step S302. When the step-on pressure Ps is less than the threshold value Po, this indicates that the coordinated control is unnecessary for the purpose of braking the vehicle, then, the flow chart logic returns for another execution of the coordinated control. On the other hand, when the step-on pressure P is greater than the threshold pressure Po, then, at step S303, a judgement is made as to whether the vehicle condition is within a zone for the anti-skid braking control. When the answer is affirmative, this indicates that there is a demand for braking force too strong to disregard a possible occurrence of wheel lockup, then, at step S311, the control is switched to the anti-skid braking control. However, when the answer is negative, a braking pressure distribution ratio x indicating a distributive proportion of braking force necessary to be allocated to the braking control is determined at step S304. The distribution ratio x is taken as a complementary correction value of braking force used in the stability control and increased as the step-on pressure and/or the vehicle speed become higher. As will be described later, as the distribution ratio x becomes large, the distributive proportion of braking force allocated to the braking control increases and the distributive proportion of braking force allocated to the stability control complimentarily reduces.
Subsequently, a judgement is made at step S305 as to whether there is an occurrence of a spin. When the answer is negative, the flow chart logic returns. On the other hand, when the answer is affirmative, a slip angle β is compared with a threshold angle β specified for providing a safety margin against spin at step S306. When the slip angle, β is less than the threshold angle βo, this indicates that, even if a spin occurs resulting from braking, the spin is developed only to the level that it may be disregarded in terms of safety driving, then, at step S307, the distribution ratio x is held as it is. However, when the slip angle β is equal to or greater than the threshold angle βo, this indicates that it is too great to avoid an occurrence of a spin, then, at step S308, either the braking control is abandoned by canceling the distribution ratio x (changing the distribution ratio x to zero %) or executed by distributing the braking force at a reduced distribution ratio x. After execution of the distribution of the braking force at step S307 or S308, a judgement is made at step S309 as to whether the steering wheel is additionally turned in the same direction, for example, whether the steering wheel is further turned right after having been turned right to a certain extent. When the answer is negative, the flow chart logic returns to distribute the step-on braking force to the respective wheels at the distribution ratio x held at step S307 or changed at step S308. However, when the answer is affirmative, it indicates that the steering wheel is operated with the active intention of causing a spin during, for example, sporty driving, then, at step S310, the stability control, which is obstructive to the sporty driving, is suspended. Otherwise, the stability control may be restrained by, for example, reducing a control gain. It can be said that suspension of the stability control is achieved by reducing the control gain to the lowest extremity.
It is to be understood that although the present invention has been described with regard to preferred embodiments thereof, various other embodiments and variants may occur to those skilled in the art, which are within the scope and spirit of the invention, and such other embodiments and variants are intended to be covered by the following claims.
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A system of driving stability control, which is adapted to control valves for opening and closing hydraulic pressure passages between a master cylinder and brake units of wheels and simultaneously controls pressurizing valves and a pressure relief valves so as to supply braking force selectively and independently to the brake units when a specified driving condition is detected, performs the coordinated braking control that, when a specified step-on pressure is detected during execution of the driving stability control, delivers the braking pressure to the brake units according to brake pedal travels as the driving intends simultaneously with reducing the participative degree of the driving stability control so as to ensure gripping force of wheels that brake the vehicle and reduces reduce the participative degree of the driving stability control with an intention of regarding driving stability of the vehicle as important when the vehicle is going to cause a spin.
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BACKGROUND
In order to conserve energy, automobiles are now being engineered to give improved gasoline mileage compared to those in recent years. This effort is of great urgency as a result of Federal regulations recently enacted which compel auto manufacturers to achieve prescribed gasoline mileage. These regulations are to conserve crude oil. In an effort to achieve the required mileage, new cars are being down-sized and made much lighter. However, there are limits in this approach beyond which the cars will not accommodate a typical family.
Another way to improve fuel mileage is to reduce engine friction. The present invention is concerned with this latter approach.
Polyethoxylated oleamide containing an average of 5 oxyethylene units is commercially available under the name "Ethomid" (registered trademark, Armak Company). Reference to its use as a demulsifier in lubricating oil appears in U.S. Pat. No. 3,509,052.
SUMMARY
According to the present invention lubricating oils are provided which reduce friction between sliding metal surfaces in internal combustion engines. The reduced friction results from the addition to the lubricating oil of a small amount of a fatty acid amide or ester of diethanol amine.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
A preferred embodiment of the invention is a lubricating oil composition comprising a major amount of lubricating oil and a minor friction-reducing amount of an oil-soluble additive selected from the group consisting of fatty acid amides of diethanolamine, fatty acid esters of diethanol amine and mixtures thereof.
The additives can be made by forming a mixture of a fatty acid and diethanol amine and heating the mixture to remove water. Optionally, a water immiscible inert solvent such as toluene or xylene can be included to aid in the removal of water.
About 1-3 moles of fatty acid are used per mole of diethanolamine. The reaction proceeds to yield mainly amide according to the following equation ##STR1## wherein R is a hydrocarbon residue of the fatty acid.
Some of the diethanol amine can react to form ester according to the following equation ##STR2##
The components can be separated by distillation and used separately in lubricating oil compositions. Preferably, they are not separated, but are used as mixtures. The mixtures can also contain fatty acid ester-amides of diethanol amine. When equal mole mixtures of fatty acid and diethanol amine are reacted very little ester-acid forms. However, when over one mole of fatty acid is reacted with a mole of diethanol amine increased amounts of ester-amide can form according to the following equations ##STR3## Such ester-amides are within the scope of the invention.
Preferred fatty acids used in making the friction-reducing additive are those containing about 8-20 carbon atoms. Examples of these are caprylic acid, pelargonic acid, capric acid, undecylic acid, lauric acid, tridecoic acid, myristic acid, stearic acid, arachidic acid and the like.
More preferably the fatty acid is an unsaturated fatty acid such as hypogeic acid, oleic acid, elaidic acid, erucic acid, brassidic acid and the like.
More preferably the fatty acid is oleic acid. Thus, the preferred additives are N,N-bis-(2-hydroxyethyl)oleamide, N-(2-hydroxyethyl)aminoethyl oleate and mixtures thereof.
EXAMPLE 1
In a reaction vessel was placed 52.5 gms (0.5 mol) of diethanol amine and 141 gms (0.5 mol) of oleic acid (caution exotherm). The mixture was stirred under nitrogen and heated to 188° C. over a two-hour 13-minute period while distilling out water. The resultant product was mainly N,N-(2-hydroxyethyl)oleamide containing about 35 weight percent N-(2-hydroxyethyl)aminoethyl oleate. These components can be separated by distillation.
EXAMPLE 2
In a reaction vessel was placed 282 gms of oleic acid, 105 gms diethanol amine and a small amount of xylene. The mixture was stirred under nitrogen and heated from 165°-185° C. over a two-hour period while distilling out water and returning xylene. The xylene was then stripped from the mixture under vacuum leaving 363 gms of a viscous liquid product consisting mainly of N,N-bis-(2-hydroxyethyl)oleamide and about 36 weight percent of N-(2-hydroxyethyl)aminoethyl oleate.
Other fatty acids can be substituted for oleic acid in the above examples with good results. Alternatively, the amide can be made by reacting one mole of oleamide with about two moles of ethylene oxide. The additives are used in an amount sufficient to reduce the sliding friction of metal surfaces lubricated by oil containing the additive. An effective concentration is about 0.05-5 weight percent. More preferably, the use concentration is about 0.2-1 weight percent.
The base lubricating oil may be mineral lubricating oil or synthetic lubricating oil. Useful mineral oils include all those of suitable lubricating viscosity. Representative synthetic oils include olefin oligomers such as α-decene trimer and tetramer, alkyl benzenes such as didodecyl benzene, esters such as dinonyl adipate, trimethylol propane tripelargonate, and complex esters made from polycarboxylic acids and polyols with a monocarboxylic acid or monohydric alkanol end group.
Blends of mineral oil and synthetic oil are very useful. For example, a blend of about 80% 150 SUS mineral oil and 20% α-decene trimer gives a very useful base lubricating oil. Likewise, blends of synthetic esters with mineral oil are very useful. For example, a blend of 15 weight percent di-2-ethylhexyl adipate and 85 weight percent 150 SUS mineral oil is a very effective base lubricating oil for use in an engine crankcase.
Improved results are obtained when a zinc dihydrocarbyl dithiophosphate (ZDDP) is used in combination with the present additives. The amount can very over a wide range. It is usually expressed in terms of zinc content of the oil. Formulated oil would include 0.01-0.3 weight percent zinc as ZDDP. A preferred range is about 0.05-0.15 weight percent zinc.
The ZDDP may be aryl type or alkyl type. A representative aryl type ZDDP is zinc di-nonylphenyl dithiophosphate. Preferably, an alkyl type ZDDP is used. Examples of these are zinc isobutyl amyl dithiophosphate, zinc di-(2-ethylhexyl)dithiophosphate and the like.
Other additives may be included such as alkaline earth metal phenates and sulfurized phenates, alkaline earth hydrocarbyl sulfonates such as calcium petroleum sulfonate, magnesium alkyl benzene sulfonate, overbased calcium alkyl benzene sulfonate and the like. Phosphosulfurized terpene and polyolefins and their alkaline earth metal salts may be included. Viscosity index improvers such as the poly-alkyl methacrylate or ethylene-propylene copolymers, ethylene-propylene non-conjugated diene terpolymers are also useful VI improvers in lubricating oil. Antioxidants such as 4,4'-methylenebis-(2,6-di-tert-butylphenol) can be beneficially added to the lubricating oil.
Tests were carried out which demonstrated the friction-reducing properties of the additives. These tests have been found to correlate with fuel economy tests in automobiles. In these tests an engine with its cylinder head removed and with the test lubricating oil in its crankcase was brought to 1800 rpm by external drive. Crankcase oil was maintained at 63° C. The external drive was disconnected and the time to coast to a stop was measured. This was repeated several times with the base oil and then several times with the same oil containing one percent of a mixture prepared as described in Example 2. The base oil was a typical commercial oil formulated for use in a crankcase. The friction-reducing additive was found to increase the coast-down time an average of 4.3%.
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Lubricating oil adapted for use as a crankcase lubricant in internal combustion engines containing a friction-reducing amount of a fatty acid amide or ester of diethanolamine.
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BACKGROUND OF THE INVENTION
This invention provides for the cloning and expression of the human Macrophage Inflammatory Protein-1α (MIP-1α)/RANTES Receptor. This receptor binds two cytokines MIP-1α and RANTES which are pro-inflammatory cytokines. The receptor is useful for assaying the levels of these cytokines in biological specimens. These cytokines play key roles in the inflammatory processes afflicting man.
The chemokine β division of the platelet factor 4 superfamily is comprised of at least six distinct cytokines that regulate trafficking of phagocytes and lymphocytes in mammalian species; at least one of these, MIP-1α also possesses anti-proliferative activity for hematopoietic stem cells. MIP-1α and the related β chemokine, RANTES, induce transient alterations in intracellular Ca 2+ concentration in neutrophils that can be reciprocally and specifically desensitized, suggesting a common receptor. This invention provides both the cDNA and the gene for this receptor. The receptor is a member of the G protein-coupled receptor superfamily. It has .sup.˜ 33% amino acid identity with receptors for the α chemokine, interleukin-8, and may be the human homologue of the product of US28, an open reading frame of human cytomegalovirus.
The platelet factor 4 cytokine superfamily is comprised of structurally and functionally related 8-10 kilodalton peptides that are the products of distinct genes clustered on human chromosomes 4 and 17. The superfamily was named after the first member to be characterized. These peptides have been collectively designated as "chemokines" because of their hybrid activities: they regulate the trafficking and activation of lymphocytes and phagocytes of the mammalian immune system, but in addition, some are able to regulate the proliferative potential of hematopoietic progenitor cells, endothelial cells, and certain types of transformed cells (for reviews see Wolpe and Cerami, FASEB J. 3, 2565-2573 (1989); Oppenheim et al., Immunol. 9, 617-648 (1991); Schall, Cytokine 3, 165-183 (1991)). Thus, the chemokines are thought to play an important role in host defense against infection, in the pathogenesis of chronic inflammatory disorders, and in wound healing.
A structural signature common to all chemokines is the presence of four conserved cysteine residues. The chemokines can be divided into two groups, α and β, by the arrangement of the first two of these cysteines. Members of the chemokine α group all possess a single amino acid of variable identity interposed between the first two cysteines, the so-called "C--X--C" motif. The human chemokine α family includes platelet factor 4, interleukin-8/neutrophil activating peptide-1 (IL-8), GROα/melanoma growth stimulatory activity (GROα/MGSA), neutrophil activating peptide-2 (NAP-2), and other less well-characterized molecules. In general, members of this group are potent chemoattractants for neutrophils in vivo and in vitro; IL-8 and platelet factor 4 also regulate angiogenesis. (Koch et al., Science 258, 1798-1801 (1992); Maione et al., Science 247, 77-79 (1990)). Two human chemokine α receptors, designated IL-8 receptors A and B, have been identified; their structures are 77% identical at the amino acid level. IL-8 receptor B is a receptor for IL-8, NAP-2 and GROα/MGSA (Murphy and Tiffany, Science 253, 1280-1283 (1991); Lee et al., J. Biol. Chem. 267, 16283-16287 (1992)) whereas IL-8 receptor A is more selective for IL-8 (Holmes et al., Science 253, 1278-1280 (1991); Lee et al., J. Biol. Chem. 267, 16283-16287 (1992)). Signal transduction by both receptor subtypes leads to a rapid rise in the intracellular concentration of Ca 2+ .
In contrast, the first two conserved cysteines of all members of the chemokine β group are adjacent, the "C--C" motif. Members of this group attract and activate neutrophils, eosinophils, monocytes, macrophages and lymphocytes with variable selectivity. The human chemokine β family includes MIP-1α (Macrophage Inflammatory Protein-1α), MIP-1β, RANTES (Regulated on Activation, Normal T Expressed and Secreted), MCP-1 (Monocyte Chemoattractant Protein-1), MCP-2, MCP-3 and I-309. Of these, the biological properties of MIP-1α, RANTES and MCP-1 have been the most characterized.
Murine MIP-1 was originally purified from supernatants of endotoxin-activated macrophages as a complex of MIP-1α and MIP-1β which are 67% identical in amino acid sequence (Wolpe et al., J. Exp. Med. 167, 570-581 (1988); Davatelis et al., J. Exp. Med. 167, 1939-1944 (1988); Sherry et al., J. Exp. Med. 168, 2251-2259 (1988)).
In addition to being a chemoattractant for neutrophils (Wolpe et al., J. Exp. Med. 167, 570-581 (1988); Saukkonen et al., J. Exp. Med. 171, 439-448 (1990)), murine MIP-1 is a prostaglandin-independent endogenous pyrogen, has autocrine effects on macrophages, and may be involved in wound healing (Davatelis et al., Science 243, 1066-1068 (1989); Fahey et al., J. Immunol. 148, 2764-2769 (1992); Fahey et al., Cytokine 2, 92-98 (1990)). Many if not all of these effects are due to MIP-1α. In addition, MIP-1α suppresses proliferation of hematopoietic stem cells (Graham et al., Nature 344, 442-444 (1990); Broxmeyer et al., Blood 76, 1110-1116 (1990); Broxmeyer et al., J. Immunol. 147, 2586-2594 (1991); Dunlop et al., Blood 79, 2221-2225 (1992)). For this reason it has been suggested that MIP-1α may be a useful cytoprotective agent for clinical radiotherapy and chemotherapy of neoplastic disease (Dunlop et al., Blood 79, 2221-2225 (1992)). Limited functional information for MIP-1α using the human ligand and human targets is available. High and low affinity binding sites have been reported for human MIP-1α on the human myeloid cell line U937 (Yamamura et ai., Int. J. Hematol. 55, 131-137 (1992)); in contrast, a single class of binding sites for murine MIP-1α was detected on murine T cell and macrophage cell lines (Oh et al., J. Immunol. 147, 2978-2983 (1991)).
RANTES attracts eosinophils, monocytes and "memory" T cells (CD4 + /CD45RO + ). It is a weak chemoattractant for neutrophils (Kameyoshi et ai., J. Exp. Med. 176, 587-592 (1992); Schall et al., Nature 347, 669-671 (1990); Schall, Cytokine 3, 165-183 (1991)). Characterization of binding sites for RANTES has not yet been reported. MCP-1 is a potent and specific chemoattractant and activating factor for monocytes (reviewed in Matsushima and Oppenheim, Cytokine 1, 2-13(1989)). Binding sites have been detected for MCP-1 on human monocytes (Yoshimura and Leonard, J. Immunol. 145, 292-297 (1990)).
SUMMARY OF THE INVENTION
This invention provides for a substantially purified nucleic acid encoding a receptor for macrophage inflammatory protein-1α (MIP-1α) and reduced upon activation normal T expressed and secreted (RANTES) protein said nucleic acid having a sequence substantially identical to a nucleic acid of Sequence I.D. No. 1 or the corresponding RNA. This invention further provides for primers and probes specific for this nucleic acid which comprise at least 12 contiguous nucleotides. Said sequences are then compared with known sequences by computer to determine their specificity in the human genome.
These nucleic acids are useful for expression in recombinant hosts operably linked to a promoter which is part of an expression cassette. The expression typically occurs as part of an expression vector or plasmid. The vector is then transformed into a host cell, preferably a mammalian cell. Functional expression whereby the receptor in an active form is expressed and transported to the plasma membrane of a cell is also described herein.
In addition this invention provides for purified recombinantly produced MIP-1α and RANTES protein from the nucleic acids described herein.
This invention further provides for a method of detecting the presence, absence or amount of cytokines RANTES and MIP-1α in a sample such as a physiological specimen, said method comprising:
(i) transforming a mammalian cell with a nucleic acid encoding a receptor for macrophage inflammatory protein-1α (MIP-1α) and reduced upon activation normal T expressed and secreted (RANTES) protein said nucleic acid having a sequence substantially identical to a nucleic acid of Sequence I.D. No. 1;
(ii) culturing the cell under conditions permitting the expression of the receptor and its transport to the plasma membrane of the cell;
(iii) contacting the cell with a cytokine selected from the group consisting of RANTES and MIP-1α; and,
(iv) detecting the binding of the cytokines to the receptor. In preferred formats the cells are oocytes, the nucleic acid is either cDNA or cRNA and the detection step is by measuring calcium mobilization or direct assay of the cytokine on the plasma membrane.
In another embodiment, the invention provides for assays in which activated neutrophils or any other cell producing the MIP-1α/RANTES receptor are used. Said cells would rely upon endogenous genes for the production of the receptor. The methods for use of endogenous receptor containing cells are as described herein for the recombinantly transformed cells.
BRIEF DESCRIPTION OF THE FIGURES
FIGS. 1A-C. Signal transduction by the receptor. (A) This chart presents evidence that the described cDNA encodes a receptor selective for an intercrine β ligand. (B) This chart provides concentration dependence for MIP-1α calcium mobilizing activity. (C) This chart presents data evidencing that the MIP-1α receptor is also a receptor for RANTES.
FIGS. 2A-B. Binding of 125 I-labeled MIP-1α to oocytes injected with p4 cRNA. (A) Total (closed circles) and non-specific binding (open circles) was determined. (B) Competitive assays involving a MIP-aα radioligand. More specifically, oocyte injected with MIP-1α/RANTES cRNA were incubated with 100,000 cpm 125 I-labeled MIP-1α in the presence or absence of unlabeled MIP-1α.
DEFINITIONS
The phrase "nucleic acid sequence" refers to a single or double-stranded polymer of deoxyribonucleotide or ribonucleotide bases read from the 5' to the 3' end. It includes both self-replicating plasmids, infectious polymers of DNA or RNA and non-functional DNA or RNA.
Nucleic acids, as used herein, may be DNA or RNA. Additionally, substantial nucleic acid sequence identity exists when a nucleic acid segment will hybridize under selective hybridization conditions, to a complement of another nucleic acid strand under stringent hybridization conditions. Thus a given sequence can be varied to a minor degree and without effecting its ability to bind to a predetermined target. Typically a nucleic acid will hybridize to other sequences that are almost identical if the stringency conditions are reduced. The sequences of this invention are considered substantially identical if the sequences are able to bind under the following highly stringent conditions: 68° C. and 0.1× SSC or SSPE. Typically this means that the sequences are at least 75% homologous. However, when the signals are at optimum levels, one is assured that the sequences are essentially identical having about 90% homology. Thus, the invention provides for orthologous non-human MIP-1α/RANTES receptors.
The phrase "calcium mobilization" refers to the release of calcium ions from intracellular stores into the cytoplasm. This is often accompanied by an influx of calcium ions from the extracellular fluid (environment) into the cytoplasm. The final event is the pumping of cytoplasmic calcium into the extracellular fluid which is known as efflux and measured by release of radioactive calcium or by fluorescent means.
The term "complementary" means that one nucleic acid is identical to, or hybridizes selectively to, another nucleic acid. Typically, selective hybridization will occur when there is at least about 55% identity over a stretch of at least 14-25 nucleotides, preferably at least about 65%, more preferably at least about 75%, and most preferably at least about 90%. See, M. Kanehisa Nucleic Acids Res. 12:203 (1984), incorporated herein by reference.
"Isolated" or "substantially pure", when referring to nucleic acids, refer to those that have been purified away from other cellular components or other contaminants, e.g., other cellular nucleic acids or proteins, by standard techniques, including alkaline/SDS treatment, CsCl banding, column chromatography, and others well known in the art. See, F. Ausubel, et aI., ed. Current Protocols in Molecular Biology, Greene Publishing and Wiley-Interscience, New York (1987), incorporated herein by reference.
"Nucleic acid probes" may be DNA fragments prepared, for example, by PCR as discussed above, or synthesized by either the phosphoramidite method described by Beaucage and Carruthers, Tetrahedron Lett. 22:1859-1862 (1981), or by the triester method according to Matteucci, et al., J. Am. Chem. Soc., 103:3185 (1981), both incorporated herein by reference. A double stranded fragment may then be obtained, if desired, by annealing the chemically synthesized single strands together under appropriate conditions or by synthesizing the complementary strand using DNA polymerase with an appropriate primer sequence. Where a specific nucleic acid sequence is given, it is understood that the complementary strand is also identified and included. The complementary strand will work equally well in situations where the target is a double stranded nucleic acid.
A nucleic acid probe is complementary to a target nucleic acid when it will anneal only to a single desired position on that target nucleic acid under conditions described herein. Proper annealing conditions depend, for example, upon a probe's length, base composition, and the number of mismatches and their position on the probe, and must often be determined empirically. For discussions of nucleic acid probe design and annealing conditions, see, for example, Sambrook et al., Molecular Cloning: A Laboratory Manual (2nd ed.), Vols. 1-3, Cold Spring Harbor Laboratory, (1989) or Current Protocols in Molecular Biology, F. Ausubel et al., ed. Greene Publishing and Wiley-Interscience, New York (1987), both of which are incorporated herein by reference.
The term "promoter" refers to a region of DNA upstream from the structural gene and involved in recognition and binding RNA polymerase and other proteins to initiate transcription.
The term "operably linked" refers to functional linkage between a promoter and a second sequence, wherein the promoter sequence initiates transcription of RNA corresponding to the second sequence. Generally, operably linked means that the nucleic acid sequences being linked are contiguous and, where necessary to join two protein coding regions, contiguous and in reading frame.
Techniques for nucleic acid manipulation, such as subcloning nucleic acid sequences encoding polypeptides into expression vectors, labelling probes, DNA hybridization, and so on are described generally, for example in Sambrook et al. (1989) op. cit., or Ausubel et al., ed. (1987) op. cit., both of which are incorporated herein by reference.
"Expression vectors", "cloning vectors", or "vectors" are often plasmids or other nucleic acid molecules that are able to replicate in a chosen host cell. Expression vectors may replicate autonomously, or they may replicate by being inserted into the genome of the host cell, by methods well known in the art. Vectors that replicate autonomously will have an origin of replication or autonomous replicating sequence (ARS) that is functional in the chosen host cell(s). Often, it is desirable for a vector to be usable in more than one host cell, e.g., in E. coli for cloning and construction, and in a mammalian cell for expression.
The phrase, "MIP-1α/RANTES receptor" refers to the gene product encoded by Seq. I.D. No. 1 and includes naturally occurring polymorphic variants in human and non-human populations which would be detectable using the given sequence as hybridization probe. In addition the term includes minor or conservative substitutions, deletions and additions to the primary amino acid sequence which do not significantly alter the biological properties of the native protein. Such changes would include substitutions of amino acids having similar chemical properties such as aspartic acid for glutamic acid or lysine for arginine and the like.
The terms "peptide", "polypeptide" or "protein" are used interchangeably herein. The term "substantial identity", when referring to polypeptides, indicates that the polypeptide or protein in question is at least about 70% identical to an entire naturally occurring protein (native) or a portion thereof, and preferably at least about 95% identical. Thus, the invention embraces orthologous non-human MIP-1α/RANTES receptors.
As used herein, the terms "isolated" and "substantially pure" are used interchangeably and describe a protein that has been separated from components which naturally accompany it. Typically, a monomeric protein is substantially pure when at least about 60 to 75% of a sample exhibits a single polypeptide backbone. Minor variants or chemical modifications typically share the same polypeptide sequence. A substantially purified protein will typically comprise over about 85 to 90% of a protein sample, more usually about 95%, and preferably will be over about 99% pure. Protein purity or homogeneity may be indicated by a number of means well known in the art, such as polyacrylamide gel electrophoresis of a protein sample, followed by visualizing a single polypeptide band on a polyacrylamide gel upon staining. For certain purposes high resolution will be needed and HPLC or a similar means for purification utilized.
A polypeptide is substantially free of naturally-associated components when it is separated from the native contaminants which accompany it in its natural state. Thus, a polypeptide which is chemically synthesized or synthesized in a cellular system different from the cell from which it naturally originates will be substantially free from its naturally-associated components.
DETAILED DESCRIPTION
An isolated nucleic acid sequence, termed MIP-1α/RANTES receptor and the novel polypeptide which it encodes are described herein. Under stringent hybridization conditions, the intact isolated nucleic acids of this invention, particularly seq. I.D. No. 1, can be used as a probe to identify other mammalian MIP-1α/RANTES receptors. Under these conditions, the sequence does not cross-hybridize to non MIP-1α/RANTES receptor genes.
The nucleic acid compositions of this invention, whether RNA, cDNA, genomic DNA, or a hybrid of the various combinations, may be isolated from natural sources or may be synthesized in vitro. The preferred source for the MIP-1α/RANTES receptor gene is a human genomic library such as from livers, as available from Stratagene (La Jolla, Calif.).
The nucleic acids claimed may be present in transformed or transfected whole cells, in a transformed or transfected cell lysate, or in a partially purified or substantially pure form.
Nucleic acid probes are also included in the claimed invention. Such probes are useful for detecting the presence of MIP-1α/RANTES receptor in physiological samples, and as primers for gene amplification. The nucleic acid probes will usually be at least about 20 nucleotides in length, more typically they will be more than 500 nucleotides in length.
A method of isolating the MIP-1α/RANTES receptor is also described herein. Briefly, the nucleic acid sequences can be isolated by probing a DNA library which is comprised of either genomic DNA or cDNA. Libraries may be either from commercial sources or prepared from mammalian tissue by techniques known to those skilled in the art. The preferred cDNA libraries are human cDNA libraries derived from B cells or neutrophils which are available from commercial sources. These receptors are also found in non-human species, e.g. mammals. For non-human orthologous receptors, one probes the appropriate library.
The DNA libraries can be probed by plaque hybridization using nucleic acid probes of at least 20 base pairs which are complementary to unique sequences of the MIP-1α/RANTES receptor gene. A preferred probe is about 626 bases binding to base 259 to base 884 of Seq. I.D. No.1. The probes are labeled to facilitate isolation of the hybridized clones. Labeling can be by any of the techniques known to those skilled in the art. Typically the longer probes are labeled with 32 P using Klenow.
Alternatively, using the sequences provided herein, those of skill may use polymerase chain reaction technology (PCR) to amplify nucleic acid sequences of the MIP-1α/RANTES receptor gene directly from mRNA, from cDNA, from genomic libraries or cDNA libraries. Polymerase chain reaction (PCR) or other in vitro amplification methods may also be useful, for example, to clone nucleic acid sequences that code for proteins to be expressed, to make nucleic acids to use as probes for detecting the presence of MIP-1α/RANTES receptor in physiological samples, for nucleic acid sequencing, or for other purposes. Appropriate primers and probes for identifying MIP-1α/RANTES receptor from alternative mammalian tissues are generated from comparisons of the sequences provided herein. For a general overview of PCR see PCR Protocols: A Guide to Methods and Applications. (Innis, M, Gelfand, D., Sninsky, J. and White, T., eds.), Academic Press, San Diego (1990), incorporated herein by reference.
In summary, the MIP-1α/RANTES receptor gene can prepared by probing or amplifying selected regions of a mixed cDNA or genomic pool using the probes and primers generated from the sequences provided herein.
Through the use of recombinant DNA techniques one may express the MIP-1α/RANTES receptor gene in yeast, filamentous fungal cells, insect (especially employing baculoviral vectors), mammalian cells, and in bacterial systems. For this purpose, the natural or synthetic nucleic acids included in the invention will typically be operably linked to a promoter (which is either constitutive or inducible), and may be incorporated into an expression vector.
The isolated nucleic acid sequences can then be inserted into a cloning vector suitable for replication and integration in either prokaryotes or eukaryotes. The cloning vectors contain transcription and translation terminators, initiation sequences, and promoters useful for regulation of the expression of the MIP-1α/RANTES receptor gene. The vectors are comprised of expression cassettes containing at least one independent terminator sequence, sequences permitting replication of the plasmid in both eukaryotes and prokaryotes, i.e., shuttle vectors, and selection markers for both prokaryotic and eukaryotic systems.
Methods for the expression of cloned genes in bacteria are well known. To obtain high level expression of a cloned gene in a prokaryotic system, it is essential to construct expression vectors which contain, at a minimum, a strong promoter to direct mRNA transcription. The inclusion of selection markers in DNA vectors transformed in E. coli is also useful. Examples of such markers include genes specifying resistance to ampicillin, tetracycline, or chloramphenicol. See Sambrook for details concerning selection markers and promoters for use in E. coli.
It is expected that those of skill in the art are knowledgeable in the expression systems chosen for expression of the MIP-1α/RANTES receptor gene and no attempt to describe in detail the various methods known for the expression of proteins in eukaryotes will be made.
Suitable eukaryote hosts may include plant cells, insect cells, mammalian cells, yeast, filamentous fungi, or preferably, bacteria (e.g., E. coli or B. subtilis).
The protein encoded by the MIP-1α/RANTES receptor gene which is produced by recombinant DNA technology may be purified by standard techniques well known to those of skill in the art. Standard techniques include selective precipitation with such substances as ammonium sulfate, column chromatography, immunopurification methods, and others. See, for instance, R. Scopes, Protein Purification: Principles and Practice, Springer-Verlag: New York (1982), incorporated herein by reference.
Alternatively and preferably, fusion proteins produced by the above method may be purified by a combination of sonication and affinity chromatography. Subsequent digestion of the fusion protein with an appropriate proteolytic enzyme releases the desired polypeptide.
The MIP-1α/RANTES receptor gene appears in the human population in various forms. By following the methods disclosed herein, one can evaluate the polymorphisms. The invention describes a single sequence encoding MIP-1α/RANTES receptor. Polymorphic forms are also intended to be included. These forms are obtained by using the given sequence as probe under stringent conditions to assay a genomic library. Polymorphic variants of the MIP-1α/RANTES receptor genes are obtained by comparing the sequences of other genes hybridizing to the original sequence.
The present invention also provides methods for detecting the presence or absence of MIP-1α/RANTES receptor in a physiological specimen.
One method involves a Southern transfer and is well known to those of skill in the art. Briefly, the digested genomic DNA is run on agarose slab gels in buffer and transferred to membranes. Hybridization is carried out using the probes discussed above. Visualization of the hybridized portions allows the qualitative determination of the presence or absence of MIP-1α/RANTES receptor.
Similarly, a Northern transfer may be used for the detection of MIP-1α/RANTES receptor in samples of RNA. This procedure is also well known in the art. See, Maniatis, et al., Molecular Cloning: A laboratory manual, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. (1982). In brief, the mRNA is isolated from a given cell sample using an acid guanidinium-phenol-chloroform extraction method. The mRNA is then electrophoresed to separate the mRNA species and the mRNA is transferred from the gel to a nitrocellulose membrane. As with the Southern blots, labeled probes are used to identify the presence or absence of the MIP-1α/RANTES receptor transcript.
An alternative means for determining the level of expression of the MIP-1α/RANTES receptor gene is in situ hybridization. In an in situ hybridization cells are fixed to a solid support, typically a glass slide. If DNA is to be probed the cells are denatured with heat or alkali. The cells are then contacted with a hybridization solution at a moderate temperature to permit annealing of MIP-1α/RANTES receptor specific probes that are labelled. The probes are preferably labelled with radioisotopes or fluorescent reporters. In situ hybridization assays are well known and are generally described in Angerer, et al., Methods Enzymol., 152:649-660 (1987).
In addition to the detection of MIP-1α/RANTES receptor using nucleic acid hybridization technology, one can use immunoassays to detect the MIP-1α/RANTES receptor gene product. Immunoassays can be used to qualitatively and quantitatively analyze the MIP-1α/RANTES receptor gene product. A general overview of the applicable technology can be found in Harlow and Lane, Antibodies: A Laboratory Manual, Cold Spring Harbor Pubs., N.Y. (1988). In brief, the gene product or a fragment thereof is expressed in transfected cells, preferably bacterial cells, and purified as generally described above and in the examples. The product is then injected into a mammal capable of producing antibodies. Either monoclonal or polyclonal antibodies specific for the gene product can be used in various immunoassays. Such assays include ELISA, competitive immunoassays, radioimmunoassays, western blots, indirect immunofluorescent assays and the like.
Finally, the MIP-1α/RANTES receptor can be functionally expressed on the surface of mammalian cells and these cells used to directly assay for MIP-1α or RANTES in biological samples. The quantitation of MIP-1α or RANTES is useful for monitoring the levels of these cytokines in a patient. Such measurements are useful in following the anti-inflammatory effects of drugs and prospective usefulness of new anti-inflammatory agents.
Functional expression of eukaryote proteins is well known. The methods are as followed in typical transection protocols such as described in Sambrook. In brief, such assays are produced by transforming cells such as COS cells, 293 cells, 3T3 fibroblast cells, and yeast cells. Alternatively oocytes, typically from frogs can be microinjected with synthetic RNA (copy RNA). The cells are transformed with a suitable expression vector or a suitable amount of synthetic or copy RNA to effect expression of the MIP-1α/RANTES receptor on the cell's plasma membrane. The cells are then exposed to labelled MIP-1α or RANTES and the amount of binding assayed either by fluorescent microscopy or autoradiography. Alternatively, binding of MIP-1α or RANTES to the cells will result in a calcium efflux and this can be measured as described below.
Fluid samples from patients suffering from inflammatory diseases are taken using standard methods. These fluids include plasma, synovial fluid, abscess fluid, bronchopulmonary lavage fluid and the like. For example, synovial fluid from an arthritic joint could be assayed for the presence of elevated amounts of MIP-1α or RANTES. As the disease progresses or is abated by drug therapies, the relative amount of MIP-1α or RANTES will change and the concentration changes would be reflected in the binding assays described above.
The following examples are provided by way of illustration only and not by way of limitation. Those of skill will readily recognize a variety of noncritical parameters which could be changed or modified to yield essentially similar results.
EXAMPLES
Example 1: Screening a Genomic Library for the MIP-1α/RANTES Receptor
i. PCR Amplification of a MIP-1α/RANTES Probe
The DNA sequence encoding the MIP-1α/RANTES receptor may be isolated from a human genomic or cDNA library using a DNA probe specific to a portion of that sequence. A preferred probe encoding a 626 base pair portion of the coding block of the MIP-1α/RANTES receptor gene may be amplified by polymerase chain reaction (PCR) from human genomic DNA using a pair of primers corresponding to sequences from base 259 to 275 and from base 868 to 884 of sequence I.D. No. 1. The PCR reaction solution consists of 67 to 71 μl of water, 10 μl of 10× buffer, 8 μl dNTPs (10 mM stock concentration each for dATP, dCTP, dGTP, dTTP in a master mix, final concentration=2 mM each, Perkin-Elmer Cetus, Emeryville, Calif.), 5 μl each of 20 μM sense and antisense primer (final concentration each=1 μM), 1-5 μl DNA, and 1 μl Taq DNA polymerase (Boehringer-Mannheim, Indianappolis) to provide a total volume of 100 μl. The PCR conditions are 95° C. for 5 min; 30 cycles of 94° C. for 20 sec then 55° for 20 sec, and 72° C. for 1 min. Cycling occurs in a GeneAmp Thermocycler from Perkin Elmer/Cetus.
ii. Screening a Genomic Library
Using the above described probe, a human fetal liver genomic library (Stratagene, La Jolla, Calif.) is screened by plaque hybridization with a 32 P-labeled probe specific to a segment of the DNA encoding the MIP-1α/RANTES receptor. Hybridization occurs in a buffer containing 50% formamide, 5× SSPE, 0.5% SDS, 50 μg/ml denatured salmon sperm DNA and 10 6 cpm/ml of labeled probe at 37° C. for 20 hours. The filters are washed in 5× SSPE at 45° C. for 1 hour. Positive clones are then purified and their sequences verified in comparison with Seq. I.D. No. 1.
Example 2: Synthesis of MIP-1α/RANTES Receptor Protein cRNA
In our laboratory, the given sequence was identified and cloned without pre-knowledge of the actual sequence. From this sequence a copy RNA was produced and its ability to generate a suitably sized protein checked by in vitro synthesis. The cRNA was synthesized by in vitro transcription with T3 RNA polymerase of a Bluescript construct that had been cleaved with Xho I.
Example 3: Functional Expression and Calcium Efflux Assay
The materials and methods used for the calcium efflux assay were as described in Murphy, et al., J. Immunol. 145:2227-2234 (1990). Adult female laboratory bred Xenopus laevis (Nasco, Fort Atkinson, Wis.) were maintained at 19° C. to 22° C. in a light-dark cycle of 12 h per phase. The frogs were anesthetized and ovarian lobes were resected and defolliculated in OR2 solution (82.5 mM NaCl, 1 mM MgCl 2 , 2.4 mM KCl, 5 mM HEPES, pH 7.5) containing 2 mg/ml collagenase for 2 h on a rotary shaker. Stage V-VI oocytes were transferred to ND96 solution (96 mM NaCl, 2 mM KCl, 1.8 mM CaCl 2 , 1 mM MgCl2, 2.4 mM sodium pyruvate, penicillin 100 U/ml, streptomycin 100 μg/ml, 5 mM HEPES, pH 7.4 to 7.5).
After 1-2 days, oocytes were microinjected with RNA samples in a total volume of 50 nl per oocyte and were then incubated in ND96 solution at 20° C. to 23° C. for 3 to 5 days. Oocytes were then incubated in 500 μl of OR2 medium containing 45 Ca 2+ [50 μCi/ml (ICN Biomedicals, Costa Mesa, Calif.)] for 3 hours at 20° C. After ten washes with ND96 medium, individual oocytes were stimulated with ligand in wells of a 96-well tissue culture plate containing 100 μl of ND96 medium. Three 100 μl samples of the incubation medium were collected and analyzed by liquid scintillation counting: a) the final 100 μl wash (20 min) before application of ligand; b) fluid containing the stimulus, removed after a 20 min incubation with the oocyte; and c) the oocyte solubilized in SDS (1%) in medium 20 min after stimulation. Data are presented as the mean±standard error of the mean (SEM) of the percent of loaded 45 Ca 2+ that was released by individual oocytes in response to the stimulus, or [(b-a)÷(b+c)]×100.
Ligands were all human recombinant material obtained from the following sources: MIP-1α (R and D Systems, Minneapolis, Minn.); IL-8, RANTES, and MCAF (Genzyme, Cambridge, Mass.); NAP-2 (Bachem Bioscience, Philadelphia, Pa.); GRO-α (a gift from M. P. Beckmann, S. Lyman and D. Cerretti). MIP-1α and MIP-1β used in a ligand screen was a gift of U. Siebenlist (NIAID, Bethesda, Md.) and were used as a diluted supernatant of Sf9 insect cells expressing immunoreactive recombinant human MIP-1α (from clone pAT464) or MIP-1β (from clone pAT744) that was prepared as described in Zipfel et al. J. Immunol. 142:1582-1590 (1989) and Zipfel et al. Lymph. Cyto. Res. 11:141-148 (1992). All proteins were diluted from aqueous stock solutions or culture supernatants into ND96 oocyte media (96 mM NaCl, 1 mM KCl, 1 mM MgCl 2 . 1/8 mM CaCl 2 , pH 7.45) containing 0.1% bovine serum albumin.
Oocytes injected with cRNA acquired responsiveness to MIP-1α and RANTES, but not to MIP-1β, MCP-1, IL-8, GROα, or NAP-2 (FIG. 1).
More specifically the data presented in FIG. 1 demonstrates that a signal transduction is associated with the MIP-1α/RANTES receptor. (A) The MIP-1α/RANTES receptor cDNA encodes a receptor selective for an intercrine β ligand. Five days after injection with 10 ng of either MIP-1α/RANTES receptor cRNA (closed bars) or IL-8 receptor B cRNA (open bars), oocytes were stimulated with recombinant human IL-8, GRO-α or NAP-2 at 500 nM, or a 1:5 dilution of an Sf9 supernatant containing recombinant human MIP-1α or MIP-1β. Prostaglandin E2, histamine, C5a, f-met-leu-phe, ATP, UTP and platelet activating factor were also tested and were inactive. Neither MIPα nor MIP-1β activated the IL-8 receptor B. (B) Concentration dependence for MIP-1α calcium mobilizing activity. Oocytes injected with 50 ng HL-60 RNA (closed circle) or 10 ng of MIP-1α/RANTES receptor cRNA (open circle) were stimulated with the indicated concentration of recombinant human MIP-1α. (C) The MIP-1α receptor is also a receptor for RANTES. Oocytes were injected with either HL-60 RNA (open bars) or MIP-1α/RANTES receptor cRNA (closed bars) and stimulated with the indicated ligand at 250 nM. In panels A-C, the data derive from 5-8 replicate determinations per point. Basal amounts of calcium efflux and calcium uptake were similar for all experimental conditions.
From our studies, the EC 50 for RANTES was approximately 50 nM. The oocyte response to MIP-1α had two phases, one that appeared to saturate at 100 NM MIP-1α, and a second that did not reach a plateau at 5000 nM MIP-1α.
Example 4: Radioligand Binding Assay
Carrier free recombinant human MIP-1α 10 μg (Genzyme, Cambridge, Mass.) was labeled using 5 mCi Na 125 I (Amersham, Arlington Heights, Ill.) in 100 μl 0.2M sodium phosphate, pH 7.2 and 50 μl reconstituted Enzymobeads (BioRad, Richmond, AC). The reaction was started using 25 μl 1% β-D-glucose and allowed to continue for 20 minutes. Labeled sample was separated from the free iodine using a NAP-5 column (Pharmacia LKB, Piscataway, N.J.) which had been previously rinsed with 1% bovine serum albumin in 0.2M sodium phosphate, pH 7.2. Labeled material was collected from the column and analyzed on a 14% acrylamide gel. Single oocytes were incubated with 125 I-MIP-1α for 30 min on ice in 10 μl of binding buffer (Hanks' balanced salt solution with 25 mM HEPES, 1% bovine serum albumin, pH 7.4). Unbound ligand was removed by centrifugation of the oocyte through 300 μl of F50 silicone fluid (General Electric, Waterford, N.Y.). The tubes were quickly frozen and gamma emissions from the amputated tips were counted.
The results of the binding assays are presented in FIG. 2. Binding of 125 I-labeled MIP-1α to oocytes injected with MIP-1α/RANTES receptor cRNA. (A) Total (closed circles) and non-specific binding (open circles) was determined by incubating oocytes injected with MIP-1α/RANTES receptor cRNA with the indicated concentration of 125 I-labeled MIP-1α in the absence or presence of a 100 fold molar excess of unlabeled MIP-1α, respectively. Non-specific binding was subtracted from total binding to determine specific binding (open squares). Specific binding of 125 I-labeled MIP-1α to oocytes expressing IL-8 receptor B was undetectable. (B) Oocytes injected with MIP-1α/RANTES receptor cRNA were incubated with 100 nM 125 I-labeled MIP-1α in the presence or absence of the indicated concentration of unlabeled MIP-1α. One hundred percent represents a mean of 6401 cpm. Data are derived from triplicate determinations per point.
The threshold for detection of specific binding of 125 I-MIP-1α to oocytes injected with the MIP-1α/RANTES receptor cRNA was the same as that required for stimulation of calcium efflux. 125 I-MIP-1α did not bind specifically to oocytes expressing human IL-8R B.
__________________________________________________________________________SEQUENCE LISTING(1) GENERAL INFORMATION:(iii) NUMBER OF SEQUENCES: 2(2) INFORMATION FOR SEQ ID NO:1:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 2156 base pairs(B) TYPE: nucleic acid(C) STRANDEDNESS: single(D) TOPOLOGY: linear(ii) MOLECULE TYPE: DNA (genomic)(ix) FEATURE:(A) NAME/KEY: primer.sub.-- bind(B) LOCATION: 259..275(ix) FEATURE:(A) NAME/KEY: primer.sub.-- bind(B) LOCATION: complement (868..884)(ix) FEATURE:(A) NAME/KEY: CDS(B) LOCATION: 63..1128(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:GGCACGAGCCCAGAAACAAAGACTTCACGGACAAAGTCCCTTGGAACCAGAGAGAAGCCG60GGATGGAAACTCCAAACACCACAGAGGACTATGACACGACCACAGAG107MetGluThrProAsnThrThrGluAspTyrAspThrThrThrGlu151015TTTGACTATGGGGATGCAACTCCGTGCCAGAAGGTGAACGAGAGGGCC155PheAspTyrGlyAspAlaThrProCysGlnLysValAsnGluArgAla202530TTTGGGGCCCAACTGCTGCCCCCTCTGTACTCCTTGGTATTTGTCATT203PheGlyAlaGlnLeuLeuProProLeuTyrSerLeuValPheValIle354045GGCCTGGTTGGAAACATCCTGGTGGTCCTGGTCCTTGTGCAATACAAG251GlyLeuValGlyAsnIleLeuValValLeuValLeuValGlnTyrLys505560AGGCTAAAAAACATGACCAGCATCTACCTCCTGAACCTGGCCATTTCT299ArgLeuLysAsnMetThrSerIleTyrLeuLeuAsnLeuAlaIleSer657075GACCTGCTCTTCCTGTTCACGCTTCCCTTCTGGATCGACTACAAGTTG347AspLeuLeuPheLeuPheThrLeuProPheTrpIleAspTyrLysLeu80859095AAGGATGACTGGGTTTTTGGTGATGCCATGTGTAAGATCCTCTCTGGG395LysAspAspTrpValPheGlyAspAlaMetCysLysIleLeuSerGly100105110TTTTATTACACAGGCTTGTACAGCGAGATCTTTTTCATCATCCTGCTG443PheTyrTyrThrGlyLeuTyrSerGluIlePhePheIleIleLeuLeu115120125ACGATTGACAGGTACCTGGCCATCGTCCACGCCGTGTTTGCCTTGCGG491ThrIleAspArgTyrLeuAlaIleValHisAlaValPheAlaLeuArg130135140GCACGGACCGTCACTTTTGGTGTCATCACCAGCATCATCATTTGGGCC539AlaArgThrValThrPheGlyValIleThrSerIleIleIleTrpAla145150155CTGGCCATCTTGGCTTCCATGCCAGGCTTATACTTTTCCAAGACCCAA587LeuAlaIleLeuAlaSerMetProGlyLeuTyrPheSerLysThrGln160165170175TGGGAATTCACTCACCACACCTGCAGCCTTCACTTTCCTCACGAAAGC635TrpGluPheThrHisHisThrCysSerLeuHisPheProHisGluSer180185190CTACGAGAGTGGAAGCTGTTTCAGGCTCTGAAACTGAACCTCTTTGGG683LeuArgGluTrpLysLeuPheGlnAlaLeuLysLeuAsnLeuPheGly195200205CTGGTATTGCCTTTGTTGGTCATGATCATCTGCTACACAGGGATTATA731LeuValLeuProLeuLeuValMetIleIleCysTyrThrGlyIleIle210215220AAGATTCTGCTAAGACGACCAAATGAGAAGAAATCCAAAGCTGTCCGT779LysIleLeuLeuArgArgProAsnGluLysLysSerLysAlaValArg225230235TTGATTTTTGTCATCATGATCATCTTTTTTCTCTTTTGGACCCCCTAC827LeuIlePheValIleMetIleIlePhePheLeuPheTrpThrProTyr240245250255AATTTGACTATACTTATTTCTGTTTTCCAAGACTTCCTGTTCACCCAT875AsnLeuThrIleLeuIleSerValPheGlnAspPheLeuPheThrHis260265270GAGTGTGAGCAGAGCAGACATTTGGACCTGGCTGTGCAAGTGACGGAG923GluCysGluGlnSerArgHisLeuAspLeuAlaValGlnValThrGlu275280285GTGATCGCCTACACGCACTGCTGTGTCAACCCAGTGATCTACGCCTTC971ValIleAlaTyrThrHisCysCysValAsnProValIleTyrAlaPhe290295300GTTGGTGAGAGGTTCCGGAAGTACCTGCGGCAGTTGTTCCACAGGCGT1019ValGlyGluArgPheArgLysTyrLeuArgGlnLeuPheHisArgArg305310315GTGGCTGTGCACCTGGTTAAATGGCTCCCCTTCCTCTCCGTGGACAGG1067ValAlaValHisLeuValLysTrpLeuProPheLeuSerValAspArg320325330335CTGGAGAGGGTCAGCTCCACATCTCCCTCCACAGGGGAGCATGAACTC1115LeuGluArgValSerSerThrSerProSerThrGlyGluHisGluLeu340345350TCTGCTGGGTTCTGACTCAGACCATAGGAGGCCAACCCAAAATAAGCAGGCGT1168SerAlaGlyPhe355GACCTGCCAGGCACACTGAGCCAGCAGCCTGGCTCTCCCAGCCAGGTTCTGACTCTTGGC1228ACAGCATGGAGTCACAGCCACTTGGGATAGAGAGGGAATGTAATGGTGGCCTGGGGCTTC1288TGAGGCTTCTGGGGCTTCAGTCTTTTCCATGAACTTCTCCCCTGGTAGAAAGAAGATGAA1348TGAGCAAAACCAAATATTCCAGAGACTGGGACTAAGTGTACCAGAGAAGGGCTTGGACTC1408AAGCAAGATTTCAGATTTGTGACCATTAGCATTTGTCAACAAAGTCACCCACTTCCCACT1468ATTGCTTGCACAAACCAATTAAACCCAGTAGTGGTGACTGTGGGCTCCATTCAAAGTGAG1528CTCCTAAGCCATGGGAGACACTGATGTATGAGGAATTTCTGTTCTTCCATCACCTCCCCC1588CCCCCGCCACCCTCCCACTGCCAAGAACTTGGAAATAGTGATTTCCACAGTGACTCCACT1648CTGAGTCCCAGAGCCAATCAGTAGCCAGCATCTGCCTCCCCTTCACTCCCACCGCAGGAT1708TTGGGCTCTTGGAATCCTGGGGAACATAGAACTCATGACGGAAGAGTTGAGACCTAACGA1768GAAATAGAAATGGGGGAACTACTGCTGGCAGTGGAACTAAGAAAGCCCTTAGGAAGAATT1828TTTATATCCACTAAAATCAAACAATTCAGGGAGTGGGCTAAGCACGGGCCATATGAATAA1888CATGGTGTGCTTCTTAAAATAGCCATAAAGGGGAGGGACTCATCATTTCCATTTACCCTT1948CTTTTCTGACTATTTTTCAGAATCTCTCTTCTTTTCAAGTTGGGTGATATGTTGGTAGAT2008TCTAATGGCTTTATTGCAGCGATTAATAACAGGCAAAAGGAAGCAGGGTTGGTTTCCCTT2068CTTTTTGTTCTTCATCTAAGCCTTCTGGTTTTATGGGTCAGAGTTCCGACTGCCATCTTG2128GACTTGTCAGCAAAAAAAAAAAAAAAAA2156(2) INFORMATION FOR SEQ ID NO:2:(i) SEQUENCE CHARACTERISTICS:(A) LENGTH: 355 amino acids(B) TYPE: amino acid(D) TOPOLOGY: linear(ii) MOLECULE TYPE: protein(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:MetGluThrProAsnThrThrGluAspTyrAspThrThrThrGluPhe151015AspTyrGlyAspAlaThrProCysGlnLysValAsnGluArgAlaPhe202530GlyAlaGlnLeuLeuProProLeuTyrSerLeuValPheValIleGly354045LeuValGlyAsnIleLeuValValLeuValLeuValGlnTyrLysArg505560LeuLysAsnMetThrSerIleTyrLeuLeuAsnLeuAlaIleSerAsp65707580LeuLeuPheLeuPheThrLeuProPheTrpIleAspTyrLysLeuLys859095AspAspTrpValPheGlyAspAlaMetCysLysIleLeuSerGlyPhe100105110TyrTyrThrGlyLeuTyrSerGluIlePhePheIleIleLeuLeuThr115120125IleAspArgTyrLeuAlaIleValHisAlaValPheAlaLeuArgAla130135140ArgThrValThrPheGlyValIleThrSerIleIleIleTrpAlaLeu145150155160AlaIleLeuAlaSerMetProGlyLeuTyrPheSerLysThrGlnTrp165170175GluPheThrHisHisThrCysSerLeuHisPheProHisGluSerLeu180185190ArgGluTrpLysLeuPheGlnAlaLeuLysLeuAsnLeuPheGlyLeu195200205ValLeuProLeuLeuValMetIleIleCysTyrThrGlyIleIleLys210215220IleLeuLeuArgArgProAsnGluLysLysSerLysAlaValArgLeu225230235240IlePheValIleMetIleIlePhePheLeuPheTrpThrProTyrAsn245250255LeuThrIleLeuIleSerValPheGlnAspPheLeuPheThrHisGlu260265270CysGluGlnSerArgHisLeuAspLeuAlaValGlnValThrGluVal275280285IleAlaTyrThrHisCysCysValAsnProValIleTyrAlaPheVal290295300GlyGluArgPheArgLysTyrLeuArgGlnLeuPheHisArgArgVal305310315320AlaValHisLeuValLysTrpLeuProPheLeuSerValAspArgLeu325330335GluArgValSerSerThrSerProSerThrGlyGluHisGluLeuSer340345350AlaGlyPhe355__________________________________________________________________________
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This invention provides for the cloning and expression of the human Macrophage Inflammatory Protein-1α (MIP-1α)/RANTES Receptor. This receptor binds two cytokines MIP-1α and RANTES which are pro-inflammatory cytokines. The receptor is useful for assaying the levels of these cytokines in biological specimens. These cytokines play key roles in the inflammatory processes afflicting man.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a process for removing elemental sulfur from fluids, particularly fuels such as gasoline, jet fuel, diesel, kerosene and fuel additives such as ethers (e.g., MTBE) transported in pipelines which are usually used to transport sour hydrocarbons.
2. Description of the Related Art
It is well known that elemental sulfur and other sulfur compounds contained in hydrocarbon streams are corrosive and damaging to metal equipment, particularly copper and copper alloys. Sulfur and sulfur compounds may be present in varying concentrations in refined fuels and additional contamination may take place as a consequence of transporting the refined fuel through pipelines containing sulfur contaminants resulting from the transportation of sour hydrocarbon streams such as petroleum crudes. The sulfur has a particularly corrosive effect on equipment such as brass valves, gauges and in-tank fuel pump copper commutators.
Various techniques have been reported for removing elemental sulfur from petroleum products. For example U.S. Pat. No. 4,149,966 discloses a method for removing elemental sulfur from refined hydrocarbon fuels by adding an organo-mercaptan compound and a copper compound capable of forming a soluble complex with said mercaptan and said sulfur and contacting said fuel with an adsorbent material to remove the resulting copper complex and substantially all the elemental sulfur.
U.S. Pat. No. 4,908,122 discloses a process for sweetening a sour hydrocarbon fraction containing mercaptans by contacting the hydrocarbon fraction in the presence of an oxidizing agent with a catalytic composite, ammonium hydroxide and a quaternary ammonium salt other than hydroxide.
U.S. Pat. No. 3,185,641 describes a method for removing elemental sulfur from a liquid hydrocarbon which comprises contacting with solid sodium hydroxide a hydrocarbon stream having dissolved therein at least 7.6 parts by weight of water per part of sulfur contained therein to yield both a hydrocarbon phase and an aqueous phase. The method is claimed to be effective and convenient for treating gasoline containing from trace to more than 25 ppm sulfur employing temperatures as high as about 140° F. (60° C.).
U.S. Pat. No. 4,011,882 discloses a method for reducing sulfur contamination of refined hydrocarbon fluids transported in a pipeline for the transportation of sweet and sour hydrocarbon fluids by washing the pipeline with a wash solution containing a mixture of light and heavy amines, a corrosion inhibitor, a surfactant and an alkanol containing from 1 to 6 carbon atoms.
U.S. Pat. No. 5,160,045 discloses a process for removing elemental sulfur from fluids such as gasoline, diesel fuel, jet fuel or octane enhancement additives such as ethers (MTBE), which pick up sulfur when transported through pipelines which are otherwise used for the transport of sour hydrocarbon streams. In that patent the sulfur containing fluid is contacted with an aqueous solution containing caustic, sulfide and optionally elemental sulfur to produce an aqueous layer containing metal polysulfides and a clear fluid layer having a reduced elemental sulfur level. Preferably an organo mercaptan is also mixed with the fluid to accelerate the removal of elemental sulfur. This patent also recites that alcohol such as methanol, ethanol, propanol, ethylene glycol, propylene glycol, etc., may be added to the aqueous caustic mixture which is contacted with the fluid to be treated. The amount of alcohol used may vary within wide limits. In the case of methanol the patent recites that from 0 to about 90 volume percent of the water may be replaced with alcohol.
U.S. Pat. No. 5,199,978 discloses a process for removing elemental sulfur from fluids such as gasoline, diesel fuel, jet fuel or octane enhancement additives such as ethers (MTBE) which pick up sulfur when transported through pipelines which are otherwise used for the transport of sour hydrocarbon streams. In that patent the sulfur containing fluids are mixed with an inorganic caustic material, an alkyl alcohol and an organo mercaptan or inorganic sulfide compound capable of reacting with sulfur to form a fluid insoluble polysulfide salt reaction product at ambient reaction temperatures. The treated fluid is then contacted with an adsorbent or filtered to remove the insoluble salt leaving a fluid product of very low residual sulfur content.
U.S. Pat. No. 4,248,695 is directed to a process for desulfurizing a sulfur containing fuel comprising contacting the fuel with a lower primary alkanol solution containing an alkali metal hydrosulfide at a temperature and pressure from ambient up to the critical temperature of the alkanol solvent, the water content of said solution being below that which will cause said hydrosulfide to decompose into K 2 S hydroxide, and separating said fuel from said alkanol solution now containing the corresponding high sulfur content alkali metal polysulfide with the proviso that the volume ratio of said alkanol solution to said fuel is determined by the gram mols of sulfur present in the fuel divided by 11/2 gram mols of sulfur, when sodium is the alkali metal, times the molecular weight of sodium hydrosulfide divided by the number of grams of sodium hydrosulfide per milliliter of the alkanol solution and the volume ratio of said alkanol solution to said fuel is determined by the gram mols of sulfur present in the fuel divided by 2 gram mols of sulfur, when potassium is the alkali metal, times the molecular weight of potassium hydrosulfide per milliliter of the alkanol solution. The process can further include the step of adding 10% water to said separated alkanol solution when the alcohol is below boiling temperature to separate the alcohol and the polysulfide from the fuel. As an additional step water in an amount of not more than one half of the volume of the alkanol can be added to dissolve the alkali metal polysulfide to form a concentrated solution in water which separates from the fuel.
U.S. Pat. No. 5,618,408 is directed to a process for reducing the amount of elemental sulfur picked up by a hydrocarbon fluid being transported in a pipeline by reducing or controlling the amount of dissolved oxygen present in the hydrocarbon fluid prior to fluid being introduced into the pipeline. This is accomplished by isolating the fluid from air or oxygen so as to prevent the fluid from becoming contaminated with dissolved oxygen, or, if the fluid is already contaminated with dissolved oxygen, treating the fluid so as to reduce the dissolved oxygen content of the fluid down to about 30 wppm dissolved O 2 or less, preferably about 10 wppm dissolved O 2 or less. The dissolved O 2 content is reduced by washing the O 2 contaminated fluid with an oxygen adsorbed such as sodium sulfite or hydrazines or by using sodium sulfite, clay or hydrotalcites as an O 2 adsorbent bed.
SUMMARY OF THE INVENTION
The present invention is a process for removing sulfur from hydro-carbonaceous fluids by contacting the sulfur contaminated fluid with layered double hydroxide (or hydrolalcite) Mg 2 AlNO 3 ; mH 2 O or Mg 3 AlNO 3 ; mH 2 O where m is the number of waters of hydration. Alternatively fluids contaminated with elemental sulfur can have added to them a quantity of hydrocarbyl mercaptan or conversely fluids contaminated with mercaptans can have added to them a quantity of elemental sulfur, to form a mixture and subsequently the mixture is contacted with an adsorbent selected from the group consisting of alumina, bayerite, brucite, and hydrotalcites of the formula:
M.sub.x.sup.2+ M.sub.y.sup.3+ (OH).sub.2x+3y-z (NO.sub.3).sub.z.mH.sub.2 O
wherein M 2+ is magnesium, M 3+ is aluminum, x, y and z are values from 1 to 6 and m is the number of waters of hydration, and mixtures thereof, to thereby remove the sulfur and mercapto compounds from such fluids.
DETAILED DESCRIPTION OF THE INVENTION
The fluids which are treated in accordance with the invention include fluids containing elemental sulfur or mercaptans where the elemental sulfur or mercaptans is (are) detrimental to the performance of the fluid. The invention is particularly applicable to those liquid products which have become contaminated with elemental sulfur as a result of being transported in a pipeline previously used to transport sour hydrocarbon streams such as petroleum crudes.
The fluids treated in accordance with the invention include a wide variety of petroleum fuels and particularly refined hydrocarbon fuels such as gasoline, jet fuel, diesel fuel and kerosene.
Other fluids include ethers used to improve the octane ratings of gasoline. These ethers are typically dialkyl ethers having 1 to 7 carbon atoms in each alkyl group. Illustrative ethers are methyl tertiary-butyl ether, methyl tertiary-amyl ether, methyl tertiary-hexyl ether, ethyl tertiary-butyl ether, n-propyl tertiary-butyl ether, isopropyl tertiary-amyl ether. Mixtures of these ethers and hydrocarbons may also be treated in accordance with the invention.
Still other fluids which can be so treated include liquefied petroleum gas (LPG) and solvents.
The above fluids, when contaminated with elemental sulfur, will have added of them, in accordance with the present invention, a quantity of organo mercaptan sufficient to produce in the fluid a mercaptan to elemental sulfur ratio of about 0.2:1 to 5:1 moles mercaptan to moles of elemental sulfur, preferably 0.2:1 to 2:1 moles mercaptan to moles of elemental sulfur.
Organo mercaptans include alkyl, aryl, alkenyl, cycloalkyl, cyclo-alkenyl, aryl alkyl or alkyl aryl mercaptans. Alkyl groups can contain from 1 to 16 carbon, alkenyl groups can contain 2-16 carbons. Aryl, alkyl aryl and aryl alkyl groups contains 6 to 16 carbons, as appropriate, while cycloalkyl and cycloalkenyl groups contains 5 to 16 carbons, in total.
In those instances in which the hydrocarbon fluid is contaminated with mercaptan, such fluid can be treated by the present invention by addition thereto of sufficient elemental sulfur to produce a final mercapto to elemental sulfur ratio within the above recited limits.
The hydrocarbon fluid containing the elemental sulfur and mercaptan as described above, is contacted with an adsorbent for the removal of the sulfur species (element sulfur and mercaptan).
The adsorbent used is selected from the group consisting of alumina, bayerite, brucite, other anionic materials containing hydroxyl groups, hydrotalcites of the formula
M.sub.x.sup.2+ M.sub.y.sup.3+ (OH).sub.2x+3y-z (NO.sub.3).sub.z.mH.sub.2 O
where M 2+ is magnesium, M 3+ is aluminum, x, y and z are numbers from 1 to 6 and m is the number of waters of hydration present, and mixtures thereof, preferably alumina, bayerite, brucite and the above described hydrotalcites.
The amount of adsorbent used ranges from about 100 mg to 100 g of adsorbent per liter of hydrocarbonaceous fluid being treated, preferably 500 mg to 20 g of adsorbent per liter of fluid.
The fluid to be treated can be contacted with the absorbent in many different ways, i.e., the adsorbent can be mixed with the fluid, then filtered, or permitted to settle with the supernatant fluid being decanted, the fluid can be passed through a bed of adsorbent, with the adsorbent being in any convenient form, i.e., pellets, powders, performed open grids, etc.
The treating conditions which may be used to carry out the present invention are conventional. Contacting the fluid to be treated is effected at ambient temperature conditions, although higher temperatures up to 35° C. may be employed. Depending upon the volume of fuel to be treated, flow rate, e.g., through a one kilogram adsorbent bed can vary from 0.1 to 3 L per minute. Contact times may vary widely depending on the fluid to be treated, the amount of elemental sulfur therein and the adsorbent materials used. The contact time will be chosen to effect the desired degree of sulfur removal. Contact times under batch treating conditions ranging from 30 seconds to 24 hours more usually 2 to 60 minutes will be usually adequate.
Contacting times under continuous process treating conditions in the absence of added organic mercaptan using a column, expressed as liquid hourly space velocity (LHSV in hour -1 ), of from 0.2 to 3 LHSV, hour -1 , preferably 1 to 2 LHSV hour -1 , will be adequate. As demonstrated in Example 4, below, however, in the presence of added organo mercaptan to remove elemental sulfur contaminates (or conversely, in the presence of added elemental sulfur to remove mercaptan contaminants) a higher throughput can be employed, e.g., a rate of 150 to 180 or higher LHSV, hour -1 can be used.
EXAMPLES
The following example describes the general procedure for the production of hydrotalcite materials useful in the present invention.
Synthesis of Mg 6 Al 2 (OH) 16 (NO 3 ) 2 4H 2 O
A solution of Mg(NO 3 ) 2 6H 2 O (2.4 moles) and Al(NO 3 ) 3 9H 2 O (0.8 mole) in 1.28 L of distilled water was slowly added under nitrogen during 90 minutes at room temperature, under a vigorous agitation, to a solution containing sodium nitrate (NaNO 3 , 0.8 mole) and NaOH 50% (8.19 moles) in 1.6 L of distilled water. At the end of the addition, the reaction mixture was in a gel form. It was then heated to 65-70° C. during 18 hours, washed and vacuum-dried at 125° C.
Gasoline containing 30 mg/L of elemental sulfur was used in the following examples.
The experimental procedure was identical for examples 1 to 3 that follow. 100 mg of powdered adsorbent material was dispersed in 20 mL of gasoline. The mixture was covered and stirred for 18 hours, then, centrifuged. The supernatant was decanted and elemental sulfur content determined by a polarographic method.
The following examples are illustrative of the invention:
Example 1
The following results show that Attapalgus clay, molecular sieve 5 Å, silica gel, alumina, bayerite, tetraphenylphosphonium-montmorillonite, Kao-EG.9.4 Å, Kao-tetraethylene glycol, Al 13 pillared montmorillonite, tetramethylammonium-montmorillonite, tetrahexylammonium-montmorillonite, sodium-montmorillonite, palygorskite-PFl-s, Kaolinite KGa-I, Kao cellosolve and Iron (III) thiomontmorillonite are ineffective in removing elemental sulfur. However, the hydrotalcites Al 2 LiCl, Mg 2 AlNO 3 , Mg 2 FeNO 3 , Mg 3 FeNO 3 , Mg 3 AlNO 3 were particularly effective as shown highlighted in the box below:
______________________________________ S.sup.0, mg/L in fuelAdsorbent after treatment______________________________________Molecular sieve 5Å 30Attapalgus clay 30Silica gel 29Alumina 28Bayerite 29Tetraphenylphosphonium-Montmorillonite 35Kao-EG 9.4Å 31Kao-tetraethylene glycol 30Al.sub.13 pillared Montmorillonite 32Tetramethylammonium-Montmorillonite 32Tetrahexylammonium-Montmorillonite 34Sodium-Montmorillonite 32Palygorskite-PF1-s 30Kaolinite KGa-1 30Kao cellosolve 30Iron (III) Thiomontmorillonite 331 #STR1##______________________________________
Example 2
This example shows that not all the hydrotalcites have the same effectiveness in removing elemental sulfur from fuel. Ineffective hydrotalcites were Zn 2 AlNO 3 and Mg 2 AlCO 3 , shown in the box below:
______________________________________Hydrotalcite S.sup.0, mg/L in fuel______________________________________2 #STR2##Al.sub.2 LiCl 12Mg.sub.3 FeNO.sub.3 20Mg.sub.2 FeNO.sub.3 13Mg.sub.3 AlNO.sub.3 6Mg.sub.2 AlNO.sub.3 5______________________________________
Example 3
This example shows that for the same adsorbent, addition of 106 PrSH:S° (1.39:0.94) mg/L of n-propyl mercaptan to the above fuel significantly improved the elemental sulfur removal. Some adsorbents that were previously ineffective in Example 1 (in box below) were now rendered effective, and the hydrotalcite Mg 3 AlNO 3 gave exceptionally improved S° removal.
______________________________________Adsorbent n-PrSH mg/L S.sup.0, mg/L in fuel______________________________________3 #STR3##Brucite 0 22Brucite 106 4Mg.sub.2 AlCO.sub.3 0 29Mg.sub.2 AlCO.sub.3 106 26Mg.sub.2 AlNO.sub.3 0 5Mg.sub.2 AlNO.sub.3 106 <1Mg.sub.3 AlNO.sub.3 0 6Mg.sub.3 AlNO.sub.3 106 <1______________________________________
Example 4
This example shows that the removal of elemental sulfur from the gasoline can be achieved by adsorption through a column packed with the adsorbent.
In this example, 500 mg of Mg 2 AlNO 3 (occupying a 0.4 mol volume) was packed in a mini-glass column (0.5 cm internal diameter×2 cm length). 20 ml of gasoline containing 30 mg/L elemental sulfur was percolated through the column. Passage of the entire gasoline sample through the column took about 20 minutes for a LHSV, hr -1 of 150. Addition of 106 mg/L n-propyl mercaptan improved significantly the elemental sulfur removal.
______________________________________Hydrotalcite n-PrSH mg/L S.sup.o, mg/L in fuel______________________________________Mg.sub.2 AlNO.sub.3 0 25Mg.sub.2 AlNO.sub.3 106 (1.39:0.94 moles to moles) 0______________________________________
As is evident, the very high liquid hourly space velocity (LHSV, hour -1 of about 150) resulted in a reduced efficiency in elemental sulfur removal using the Mg 2 AlNO 3 in the absence of any added n-propyl mercaptan, as compared to the level of sulfur removal obtained using the same adsorbent again in the absence of nPrSH, but in the batch contacting made of the Examples above. Thus, to achieve high levels of sulfur removal under continuous process treating conditions (as compared against batch contacting conditions) requires that the fluid to be treated have a relatively long contact time, i.e., a low throughput ratio. It is desirable, therefore, that the throughput rate, expressed as liquid hourly space velocity be on the order of about 0.2 to 3 LHSV, hour -1 . When organo mercaptan is added, higher space velocities can be employed, e.g., as high as 150 to 180 LHSV, hour -1 or higher.
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Elemental sulfur present in fluids such as refined petroleum products, e.g., gasoline, jet, diesel, kerosene or fuel additives such as ethers, is removed from such fluids by contacting the contaminated fluid with an adsorbent of Mg2AlNO3 or Mg3AlNO3 or by adding to the fluids a quantity of hydrocarbyl mercaptan and passing the resulting mixture through an adsorbent selected from the group consisting of alumina, bayerite, brucite and hydrotalcite like materials of the formula M x 2+ M y 3+ (OH) 2x+3y-z (NO 3 )mH 2 O wherein M 2+ is Magnesium, M 3+ is aluminum, and x, y and z are values from 1 to 6 and m is the number of waters of hydration.
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BACKGROUND OF THE INVENTION
It is generally known that poultry such as chickens, geese, turkeys, quail, pheasants and the like are particularly susceptible to poor productivity (reduced growth rate, feed efficiency, egg shell quality and high mortality) during periods of environmental heat distress (high ambient temperatures and high relative humidity). It is also generally well known that these heat distress effects are greatly exacerbated if the anticoccidial agent nicarbazin (Nicarb) is administered during such heat distress periods.
Heat distress substantially reduces the growth rate of broiler chicks. Diets have been altered to reduce this problem via reducing the heat increment of the diet with fat supplementation (H. L. Fuller et al; "Effect of Heat Increment of the Diet on Feed Intake and Growth of Chicks Under Heat Stress", Proc. Maryland Nutr. Conf., pp 58-664, 1973) and improved the amino acid balance (P. W. Waldroup et al; "Performance of Chicks Fed Diets Formulated to Minimize Excess Levels of Essential Amino Acids", Poultry Sci., 55:243-253, 1976). It has also been suggested that the decline in growth rate results directly from reduced feed intake (R. L. Squibb et al; "Growth and Blood Constitutients of Immature New Hampshire Fowl Exposed to Constant Temperatures of 99° C. for 7 Days", Poultry Sci., 38:220-221, 1959). It has been demonstrated that the growth rate of heat stressed broilers can be increased by force feeding at a level exceeding ad libitum feed intake (M. O. Smith et al; "Feed Intake and Environmental Temperature Effects Upon Growth, Carcass Traits, Ration Digestibility, Digestive, Passage Rate and Plasma Parameters in Ad Libitum and Force-Fed Broiler Chicks" Poultry Sci., 62:1504 abstr., 1983).
SUMMARY OF THE INVENTION
This invention is concerned with the alleviation of heat distress symptoms and mortality which occur with the administration of nicarbazin to poultry. More particularly, this invention is concerned with the administration of phenothiazine to poultry which are also being administered nicarbazin during periods of heat distress in order to eliminate the toxicity caused by the combination of heat distress and nicarbazin. Thus, it is an object of this invention to describe such a method to reduce these effects. A further object is to describe the feed and water compositions containing nicarbazin and phenothiazine for administration to poultry. A still further object is to describe the amounts of penothiazine and nicarbazin which are found in the feed and water compositions used for the administration of the drugs. Further objects will become apparent from a reading of the following description.
DESCRIPTION OF THE INVENTION
It has been unexpectedly discovered that the well known toxic effects of nicarbazin upon poultry subject to heat distress, that is prolonged periods of high ambient temperature and/or relative humidity, can be alleviated or eliminated if phenothiazine, a known insecticide and anthelmintic agent, is administered during the period of nicarbazin treatment which occurs during periods of heat distress. The typical symptoms of nicarbazin heat distress toxicity of reduced weight gain, reduced feed effiency and death are all significantly reduced when phenothiazine is used to counteract nicarbazin heat distress toxicity.
The toxic effects of nicarbazin will begin to be observed during summertime conditions when the daily high temperature, as measured inside the poultry building, exceeds 28° C. The toxic effects of the combination of high temperature, humidity and nicarbazin will vary with age of the bird, the genetic make-up and the previous exposure of the bird to high temperatures. A brief exposure to temperatures in excess of 30° C. may have only a moderate toxic effect upon the bird while a longer exposure at 28° C. could have a more severe effect. The method of this invention will reduce the heat induced toxicity in both cases. Since poultry will generally rely on the mechanism of panting to help dissipate body heat, higher levels of relative humidity will reduce the efficiency of panting as a cooling mechanism and will increase the toxic effect of nicarbazin/heat distress combination.
Nicarbazin is generally administered to poultry such as chickens, geese, turkeys, ducks, quail, pheasant, and the like at levels of from 100 to 150 ppm in the feed, preferably about 125 ppm. Because it is highly insoluble in water, nicarbazin is generally not administered in poultry drinking water.
When phenothiazine is added to the poultry feed in amounts of from 160 to 10,000 ppm under heat stress conditions, the toxic effects of nicarbazin were completely reversed and phenothiazine tested birds were essentially indistinguishable from the control birds. Preferably the phenothiazine is administered at from 160 to 625 ppm and most preferably at about 320 ppm.
Phenothiazine, being a basic compound, is capable of forming pharmaceutically acceptable acid addition salts with increased water solubility. Thus, the phenothiazine can also be readily administered as a part of the poultry drinking water. The phenothiazine is generally administered in the water ration at levels of from 50 to 1000 ppm. Preferably the phenothiazine is administered at from 100 to 500 ppm and most preferably at about 250 to 300 ppm.
The preferred acid addition salts of phenothiazine are those derived from hydrohalic acids, preferably hydrochloric, or other mineral acids such as nitric, sulfuric, phosphoric and the like. Organic acids such as acetic acid are also suitable.
Specifically, tests were carried out wherein chickens were subjected to temperatures with a daily variation of from 24° to 35° C. with temperatures exceeding 32° C. for about 6 hours per day. In addition, the relative humidity was maintained at from 35 to 50%. In such tests, nicarbazin was administered at 0 (control) and 125 ppm and phenothiazine was administered at from 0 to 2500 ppm. The addition of nicarbazin decreased the number of birds surviving the study by 47%; decreased the weight gain by 19%; and decreased feed efficiency by 47%. The addition of phenothiazine at all doses of about 160 ppm and higher, produced survivability, weight gain and feed effiency which were indistinguishable from the control birds.
The compounds of this invention are orally administered to poultry for the control of nicarbazin induced heat stress. Any number of conventional methods are suitable for administering the compounds of this invention to poultry, as for example, they may be given in the poultry feed.
Of the various methods of administering the compounds of this invention to poultry, they are most conveniently administered as a component of a feed composition. The novel compounds may be readily dispersed by mechanically mixing the same in finely ground form with the poultry feedstuff, or with an intermediate formulation (premix) that is subsequently blended with other components to prepare the final poultry feedstuff that is fed to the poultry. Typical components of poultry feedstuffs include molasses, fermentation residues, corn meal, soybean meal, fish meal, ground and rolled oats, wheat shorts and middlings, alfafa, clover and meat scraps, together with mineral supplements such as bone meal and calcium carbonate and vitamins and amino acid supplementation.
The following examples are provided that the invention might be more fully understood. They should not be contrued as limitations of the inventions.
EXAMPLE 1
Trials utilizing 1920 birds have been conducted according to the following protocol. Nicarbazin (125 ppm) addition to the basal ration decreased (P<0.01) live weight gain (18.6%), survivability (47%), and feed efficiency (47%). Feed efficiency values were reduced by nicarbazin primarily as a result of its effect upon mortality. Phenothiazine addition (312.5, 625, 1250, 2500 ppm) to nicarbazin containing rations returned (P>0.1) all production parameters (gain, survival, feed efficiency) to control values. No difference was detected (P>0.1) between the 312.5 ppm and the 2500 ppm phenothiazine levels for any of the parameters evaluated.
Phenothiazine was tested for efficacy to ameliorate nicarbazin toxicity according to the following treatments.
______________________________________TRT. Nicarbazin (ppm) Phenothiazine (ppm)______________________________________Control 0 01 125 02 125 312.53 125 6254 125 12505 125 2500______________________________________
Birds were allotted to treatment such that individual treatment groups contained 16 replicates of 6 chicks per replicate.
Environment: The enviromental chamber was set to oscillate between 24° C. and 35° C. in a manner simulating a typical summer day. Hours in excess of 32° C. averaged approximately 6 hours per day. Relative humidity was maintained between 35 and 50%.
Parameters/Statistical Analysis: Parameters monitored included live weight gain, feed consumption, water consumption, feed efficiency and mortality. Live weight gain was estimated by the difference between initial and final body weights. Feed consumption was recorded for each replicate while water consumption was tallied over 8 replicates within a treatment group (2 observations/trt). Feed efficiency was estimated by dividing total weight of birds surviving the study in each replicate by the total feed consumed. No effort was made to adjust feed efficiency for mortality as it was anticipated that the mortality effects on feed efficiency would be significant, adversely affected by treatment and of economic importance to the poultry industry. All data were subjected to analysis of variance using the General Linear Model of the statistical analysis system. When a significant F statistic was indicated by the analysis of variance for treatment, means were separated by least squares analyses utilizing the model which accounted for the greatest variation in the most efficient manner.
OBJECTIVE
The objective of the experiment described herein is to refine the dose titration of 125 ppm nicarbazin with 4 graded levels of phenothiazine.
MATERIALS AND METHODS
Test Animals: Vantress X Arbor Acre male chicks, numbering 1,300 were raised on rice hull litter and fed starter ration during the first 3 weeks posthatching. This pre-experimental time period was necessary in order to bring birds to the age at which they become susceptible to heat distress. On the first day of the 4 th week, following an overnight fast, 960 chicks were selected at random, weighed and randomly allotted to treatment groups.
______________________________________STARTER AND GROWER RATIONSINGREDIENT STARTER GROWER______________________________________Corn 53.7 56.75Soybean meal 40.0 36.0Tallow 1.8 3.0Dicalcium Phospha 2.35 2.35Calcium Carbomate 1.2 0.9Salt 0.4 0.5Vitamin Supplement 0.3 0.3Trace Minerals 0.1 0.1d1-Methionine 0.15 0.1 100.0 100.0______________________________________
Management: At all times, save for the overnight fast at experiment initiation (4 weeks post-hatching), both feed and water were available for ad libitum consumption. Rations utilized were formulated to provide at least 105% of the requirement for essential nutrients specified by the Nutrient Requirement Council with the exception that energy mimicked current industry standards. The energy standards established by the NRC were used to establish nutrient/calorie ratios.
Test Drugs: The phenothiazine available to the agricultural industry has an 8μ particle size. However, a 3μ particle size is also available by special order and was utilized in this study. The smaller particle size may be more desirable for enhanced absorption and a lowered effective dosage rate.
The addition of nicarbazin to the basal ration decreased (P<0.01) survival (40%), live weight gain (27%) and feed efficiency (46%). Survivial in this study for chicks receiving nicarbazin in the absence of phenothiazine averaged 40% while survival for heat distressed chicks not fed nicarbazin averaged 92% Nicarbazin effects on live body weight gain have been mixed in other studies with results ranging from no effect to significant reductions. This variation is likely due to the birds previous exposure to heat distress and the severity of the stress encountered. In this study the birds had no prior exposure to heat distress and were subsequently exposed to a significantly elevated ambient temperature with the result that weight gains were reduced by 27%. Feed efficiency for birds consuming the nicarbazin supplemented ration without phenothiazine was reduced (P<0.01) by 46% which is a reflection of both the depressed weight gain and survival. No effort was made to adjust feed efficiency values for mortality, therefore the feed efficiency values are producer oriented.
The phenothiazine by nicarbazin interaction as well as the quadratic effect of phenothiazine within this interaction was significant (P<0.01) for survival, gain and feed efficiency. This interaction may be attributed to the slight effect of phenothiazine on the broiler parameters monitored in contrast to the large phenothiazine effect in the presence of nicarbazin.
Phenothiazine additions (312.5, 625, 1250, and 2500) to the basal ration containing 125 ppm nicarbazin returned all production parameters to control values. No significant differences (P>0.1) were detected between the phenothiazine doses in rations containing nicarbazin for survival, live weight gain and feed efficiency. Phenothiazine addition to the basal ration in the absence of nicarbazin tended (P<0.1) to increase survival at the 1250 ppm supplementation level, but only numerically increased survival at 2500 ppm. Phenothiazine tended (P<0.1) to enhance growth rate in rations without nicarbazin at the 2500 ppm supplementation, level, but only numerically enhanced growth rate at the other levels. Feed efficiency values parallel survival. Averaging phenothiazine supplementation levels over nicarbazin indicated a non-significant F statistic for survival, body weight gain, and feed efficiency.
Conclusion
The capability of phenothiazine to reduce nicarbazin's toxic effects in male broilers during heat distress is sufficient to reduce nicarbazin induced heat stress toxicity to control levels. The lowest effective phenothiazine dose necessary to elicit a maximal response was not detected suggesting that it is equal to or less than 312.5 ppm.
EXAMPLE 2
Summary
One trial utilizing 960 birds was conducted to further refine the dose titration of nicarbazin (125 ppm) with graded phenothiazine levels (0, 80, 160, 320, 640 ppm). All rations evaluated in the study contained nicarbazin. Linear effects of phenothiazine supplementation were significant (P<0.01) as phenothiazine increased survival from 28% for birds consuming ration supplemented with 0 ppm to 60.2% for the 640 ppm supplementation level. The 320 ppm phenothiazine level was similar (P=0.948) to the 640 ppm level with bird survival at 59.9 and 60.2% respectfully. Some signs of toxicity were observed at the 160 ppm dose indicating that the minimal effective dose for full heat distress protection, lies within the 160 and 320 ppm phenothiazine inclusion levels. Results are consistent with Example 1 where the 312.5 and 625 ppm phenothiazine levels were judged similar. Gain was not affected by phenothiazine level (P>0.1) while feed efficiency paralleled bird survival. The high mortality observed in this study occurred on day 4 of the assay when the relative humidity increased to 72% as the result of a defective humidistat. A nicarbazin free control treatment group was not included in this experiment so that treatment replication could be maximized. The data do indicate that phenothiazine has efficacy under extremely stressful environments and that the minimal effective dose is likely between 160 and 320 ppm.
Objective
The purpose of this trial was to further refine the dose titration of 125 ppm nicarbazin with graded levels of phenothiazine in heat distressed broilers.
MATERIALS AND METHODS
Test Animals: Vantress X Arbor Acre male chicks, numbering 1,300, were raised on rice hull litter and fed starter ration during the first 3 weeks posthatching. This time period was necessary to bring birds to the age at which they become susceptible to heat distress. On the first day of the 4 th week, following an overnight fast, chicks were weighed and randomly allotted to treatment groups.
Management: At all times, save the overnight fast at experiment initiation, both feed and water were available for ad libitum consumption. Rations utilized were formulated to provide at least 105% of the requirement for essential nutrients specified by the Nutrient Requirement Council with the exception that energy mimicked industry standards. The energy standards established by the NRC were used to establish nutrient/calorie ratios.
Test Drug: The phenothiazine marketed to the agricultural industry has an 8μ particle size. However, a 3μ particle size is also available by special order and was utilized in this study. The smaller particle size may be desirable for enhanced absorption and a lowered dosage rate with maximal efficacy.
Treatments and Allocation: Treatment groups consisted of the following nicarbazin-phenothiazine combinations:
______________________________________TRT. Nicarbazin (ppm) Phenothiazine (ppm)______________________________________1 125 02 125 803 125 1604 125 3205 125 640______________________________________
Birds were allotted to treatment such that individual treatment groups contained 32 replicates of 6 chicks per replicate. The treatment groups evaluated did not include birds fed a nicarbazin free ration in order that replication could be maximized to separate phenothiazine supplementation levels.
Environment: The environmental chamber was set to oscillate between 24° C. and 35° C. in a manner simulating a typical summer day. Hours in excess of 32° C. averaged approximately 6 hours per day. It was intended that relative humidity be regulated between 45 and 50%. However, on day 4 of the experiment a defective humidistat remained in the "on" position with the result that relative humidity soared to 72%. This high level of relative humidity constituted an extremely acute heat distress environment with the result that mortality was massive. Based upon one previous experience in the environmental chamber where relative humidity rose to over 80% with an ambient temperature of just 31° C., it would be expected that mortality for birds not consuming nicarbazin to also have been dramatically elevated.
Parameters/Statistical Analysis: Parameters monitored included live weight gain, feed consumption, feed efficiency and mortality. Live weight gains were estimated by difference between initial and final body weights. Feed consumption was recorded for each replicate. Feed efficiency was estimated by dividing total weight of birds surviving the study, for each replicate, by the total feed consumed. No effort was made to adjust feed efficiency for mortality as the mortality effects on feed effiency were significant and adversely affected by treatment. All data were subjected to analysis of variance using the General Linear Model of the statistical analysis system. When a significant F statistic was indicated by the anaylsis of variance for treatment, means were separated by least squares analyses utilizing the model which accounted for the greatest variation in the most efficient manner detected.
Discussion
Data collected in this study were consistent with numerous other studies where phenothiazine has been observed to ameliorate nicarbazin toxicity occurring in broilers during heat distress. In contrast to other experiments where the phenothiazine doses evaluated exceeded 300 ppm the linear effects of phenothiazine supplementation were significant (P<0.01). Phenothiazine increased survival from 28% for birds consuming ration supplemented with 0 ppm to 60.2% for the 640 ppm supplementation level. The 320 ppm phenothiazine level was similar (P=0.948) to the 640 ppm level with bird survival at 59.9 and 60.2% respectfully. Specifically, this observation is consistent with Example 1 where the 312.5 and 625 ppm phenothiazine levels were also judged similar. Survival, however; was some what reduced (P<0.01) in this study for the 80 and 160 ppm doses indicating that the minimal effective dose for full heat distress protection likely lies within the 160 and 320 ppm phenothiazine inclusion levels. Gain was not affected by phenothiazine level (P> 0.1) while feed efficiency paralleled bird survival. The high mortality observed in this study occurred on day 4 of the assay when the relative humidity increased to 72% as the result of a defective humidistat. A nicarbazin free control treatment group was not included in this experiment in order that treatment replication could be maximized. However, based upon previous experience this type of acute heat distress would be expected to also significantly increase the mortality of birds consuming nicarbazin free rations.
Conclusion
Data collected in this study indicate that phenothiazine efficacy under extremely stressful environments and that the minimal effective dose for full heat distress protection is likely within the 160 and 320 ppm levels.
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There is disclosed a method for the reduction of a toxicity resulting from the use of nicarbazin in fowl during periods of high heat distress. The method involves the administration of phenothiazine during periods of high ambient temperature and/or relative humidity which are concurrent with periods of nicarbabin treatment. The use of phenothiazine during periods of potential heat induced toxicity caused by the administration of nicarbazin results in reduced mortality, higher feed efficiency and higher weight gain than is observed without the use of phenothiazine.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation of U.S. patent application Ser. No. 11/281/151, filed Nov. 17, 2005, which is a continuation of U.S. patent application Ser. No. 10/678,774, filed Oct. 3, 2003, now abandoned, which is a continuation of U.S. patent application Ser. No. 10/201,112, filed Jul. 22, 2002, now abandoned, which is a continuation of U.S. patent application Ser. No. 09/668,067, filed Sep. 22, 2000, now U.S. Pat. No. 6,425,887 issued Jul. 30, 2002, which is a divisional of U.S. patent application Ser. No. 09/457,844, filed on Dec. 9, 1999, now U.S. Pat. No. 6,592,559 issued Jul. 15, 2003, which claims the benefit of U.S. Provisional Patent Application Ser. Nos. 60/111,624, filed Dec. 9, 1998 and 60/130,597 filed Apr. 22, 1999, each of which is hereby incorporated herein by reference.
TECHNICAL FIELD
[0002] This invention relates generally to medical devices and more particularly to needles that are curved for indirect infusion access within the body.
BACKGROUND
[0003] Medical procedures involving the vertebrae are typically complicated because of the preciseness required to avoid both neural damage and injury to major blood vessels, as well as the indirect path that is usually required to access the treatment site.
[0004] This is certainly the case when performing a vertebroplasty, a procedure whereby bone cement, most commonly methyl methacrylate, is injected into a vertebral body to provide stabilization and/or pain relief in selected patients having a spinal condition such as osteolytic metastasis and myeioma, painful or aggressive hemangiome (benign lesions of the spine), or painful osteoporotic vertebral collapse.
[0005] Standard treatment practice depends on the region of the spine being treated. For the cervical vertebrae, anterolateral access is used with a 15 gauge needle. The large vessels adjacent to the vertebra are laterally manipulated by the radiologist to provide an access site between the vessels and the pharyngolarynx. An upward access route is required because the needle must be introduced below the mandible.
[0006] When accessing the thoracic or lumbar vertebrae, typically a large 10 gauge needle is used following a transpedicular or posterolateral approach. The transpedicular route is preferred to avoid spinal nerve injury and to decrease the probability of the cement leaking into tissues adjacent to the vertebral body.
[0007] To obtain complete fill of a damaged vertebral body, it is often required that a second transpedicular access be made from the opposite side. A single infusion usually cannot fill the entire target area because the needle tip cannot be redirected from the original plane of entry. Continued infusion of cement from the first access site will usually not result in an adequate infusion due to the tendency of the material to set before it fills all of the affected area, thereby becoming a baffle to itself. Furthermore, the thick density of the marrow and structures, such as veins, usually acts to impede free flow of the cement within the vertebral body.
[0008] Another concern during the procedure is accidental puncture of the these veins. Because vertebral veins lead directly to the lungs, there is a significant risk of pulmonary embolism if cement is accidentally introduced therein.
[0009] The inability to adequately maneuver the needle cannula tip within a body or around structures is a major limitation of the straight needle. Additional needle sticks to complete a medical procedure result in discomfort to the patient and additional risk of leakage and other complications.
[0010] To sufficiently access a vertebral body for complete infusion of cement, the needle tip must be capable of being deflected at significantly large angles from the original axis. This would require that the needle have a distal bend so that the needle could be rotated to selectively direct the material.
[0011] Rigid curved needles are well known for suturing applications; however, adding anything more than a slight bend to an infusion needle limits its access path and ability to deeply penetrate tissue, especially bone. For example, a rigid curved needle is unsuitable for use in a vertebroplasty procedure where the needle cannula must be driven through the bone and deep into the vertebral body using a relatively straight approach and maintained in place to avoid additional damage to the entry site. While the initial needle access must be done with a straight needle of sufficient strength to penetrate bone, the ideal approach would be to direct a lateral infusion of cement following needle penetration, and then to withdraw the needle along its original path.
[0012] Accomplishing this is problematic. The tissue density and resistance of the tissue to penetration at the treatment site can require that the inner infusion member be nearly as stiff as the outer piercing cannula. A certain degree of needle rigidity is required in order to be able to maneuver the needle and accurately direct flow of material.
[0013] While stainless steel needles having a slight distal bend are known, the amount of needle curvature necessary to provide adequate lateral infusion is not possible—the needle plasticly deforms once inside the outer restraining cannula and hence is unable to return resiliently to its preformed shape. Thus, a second needle access would still be required to provide adequate filling.
[0014] Other medical procedures present similar problems when a single straight needle is used. One example is tumor ablation where percutaneous ethanol injection is used to treat carcinoma of the liver and kidney. Originally introduced as a palliative treatment for inoperable hepatocellular carcinoma of the liver, ethanol injection has now been shown to have curative potential comparable to resection in many patients, especially for smaller tumors.
[0015] Practice has been to inject ethanol directly into masses using a straight needle and to allow the ethanol to infuse from one or more side holes into the tissue. The problem is that the infusion may not penetrate any deeper than the needle tract; thus portions of the tumor are not effectively treated. It is desirable to provide a device for more effective infusion of ethanol into the tumor mass.
SUMMARY OF THE INVENTION
[0016] The foregoing problems are solved and a technical advance is achieved in an infusion needle made of rigid superelastic material and having at least one performed bend along the distal portion of its length. The needle is used as an inner cannula coaxially with a second hollow cannula for restraining the inner needle cannula in a substantially straight orientation during percutaneous introduction to the target site, whereby the inner needle cannula is deployed to resiliently return to its preformed configuration.
[0017] The ability of the preformed inner needle cannula to deflect laterally upon exiting the outer cannula allows the inner needle cannula to infuse or aspirate material at multiple points within different planes in the body as the inner infusion needle rotates about its longitudinal axis. This helps to reduce or eliminate the need for additional “sticks” with the outer cannula; it also allows the operator to make an entry from one direction, then to deploy the curved inner cannula to reach a site that cannot be accessed directly, such as where another structure lies along the access path, thereby blocking the target site.
[0018] The preferred material for the inner cannula is a superelastic, shape memory alloy such as sold under the trademark Nitinol (Ni—Ti); however, there are other non Ni Ti alloys that may be used. A Nitinol alloy is desirably selected that has properties whereby the temperature at which the martensitic to austenitic phase change occurs is lower than the working temperature of the device (i.e. room temperature).
[0019] As described in U.S. Pat. No. 5,597,378, incorporated herein by reference, a permanent bend may be heat set in a superelastic Nitinol cannula by maintaining the cannula in the desired final shape while subjecting it to a prescribed high temperature for a specific time period. The resulting cannula can be elastically manipulated far beyond the point at which stainless steel or other metals would experience plastic deformation. Nitinol and other superelastic materials when sufficiently deformed undergo a local phase change at the point of stress to what is called “stress-induced martensite” (SIM). When the stress is released, the material resiliently returns to the austenitic state.
[0020] A second method of imparting a permanent bend to the needle material is by a process commonly known as “cold working.” Cold working involves mechanically overstressing or overbending the superelastic cannula. The material within the bending region undergoes a localized phase shift from austenite to martensite and does not fully return to its original shape. In the case of the cold-worked cannula, the result is a permanent curve about the bending zone which has been locked in to at least a partial martensitic crystalline state.
[0021] In contrast, when heat treating is used, the entire heat-annealed cannula is in a austenitic condition, even in the curved region, and is only temporarily transformed to martensite under sufficient bending stresses. Therefore, the flexural properties of the annealed cannula vary little across its length.
[0022] Conversely, the bend of a cold-worked cannula, which contains martensite, has increased resistance to deformation and therefore holds its shape better than the more flexible bend of the pure austenitic cannula This increased rigidity can be an advantage for certain clinical applications.
[0023] In one aspect of the invention, an introducer trocar or stylet is used with either the outer or inner needle cannula, depending on the luminate size of the needle, to facilitate access to tissue and/or prevent coring tissue into the distal tip of the needle device. The infusion needle or inner cannula is introduced through the outer cannula after access has been established and the trocar or stylet is removed.
[0024] Depending on the size of the cannulas, the degree of the preformed bend, or the method used to form the bend, the inner cannula or needle may slightly deform the outer cannula as the preformed bend present in the inner needle or cannula is constrained within the outer cannula. As a result, the outer cannula may be deflected a few degrees from its normal longitudinal axis at a point corresponding to the bend of the inner cannula. As the inner cannula is deployed from the outer cannula, the inner cannula deflects laterally until the entire region of the bend is unsheathed. The distal opening of the inner cannula is oriented at a large angle (preferably within the range of 60-90°) from the original longitudinal axis when the inner needle is fully deployed.
[0025] The ability of the inner cannula to deflect at a significant angle from the original longitudinal axis has great utility in a number of applications where straight access is required followed by redirection of the distal opening. This deflection permits access to a different site without the necessity of withdrawing and reintroducing the needle.
[0026] A primary example of such a procedure is vertebroplasty in which infusion of the stabilizing cement with a straight needle often requires a second stick to provide complete filling to stabilize the vertebral body while avoiding damage to delicate structures such as veins. As with the standard single-needle procedure involving the thoracic or lumbar regions of the spine, a transpedicular approach is normally used whereby the larger outer needle cannula, such as a coaxial Jamshldi-type needle, is introduced into the damaged or diseased vertebral body. The outer needle includes an inner introducer trocar which is then replaced with a inner curved needle for infusion of the cement.
[0027] The ability of the curved needle to deflect laterally and rotate to reach multiple planes gives it a significant advantages over straight needles which have a limited range of movement. Because of this additional range of movement, the curved needle can usually complete the vertebroplasty procedure with a single access of the vertebral body. This avoids additional discomfort and risks to the patient, which include complications from leakage of cement or inadvertent infusion into non-target areas.
[0028] In addition to using the coaxial needle for infusion of cement as above, the device can also be adapted for aspirating material or serving as a conduit for the introduction of other devices. The apparatus may be used for a percutaneous corpectomy, a procedure which involves fusion and decompression of two or more vertebrae by first aspirating tissue from the damaged vertebral bodies, then introducing a prosthesis having a carbon fiber composite cage packed with bone graft material to serve as scaffolding for the affected vertebrae. Once the cage is properly positioned, methyl methacrylate or another suitable material is infused into the vertebral bodies to secure the prosthesis. The percutaneous corpectamy offers less trauma, and with the reinforcement cage, provides superior rigidity over a conventional corpectomy utilizing bone graft material alone.
[0029] In another aspect of the invention, the coaxial needle can be adapted for paraspinal use to inject medicaments within the neural canal or epidural space as part of management and/or diagnosis of pain. Preferably, the outer cannula has a tip adapted for piercing soft tissue. This outer needle cannula, preferably about twenty-one (21) gauge, is introduced percutaneously parallel to the spinal column along with an internal stylet with matched bevel to prevent coring tissue into the distal opening. The stylet is removed and the curved needle, about twenty-five (25) gauge, is inserted into the outer cannula. The needle assembly is then maneuvered to contact a nerve root during a diagnostic procedure to help recreate pain symptoms of the patient. The inner infusion needle also includes a stylet which is situated within the passageway of the needle as it is directed to the target site. The stylet is then removed from the infusion needle and medicaments, commonly steroids such as celestone (injected with lidocaine), kenalog, or methylprednisone are introduced to the treatment site. The inner needle is then withdrawn into the outer sheathing cannula and both are withdrawn from the patient.
[0030] Another use of the smaller gauge paraspinal needle is for diskography which consists of injecting a contrast agent (preferably nonionic contrast media) directly into the patient's disk to delineate the extent of any malformation or injury to the vertebral body.
[0031] Yet another aspect of the invention solves the problem of infusion of ethanol into a tumor mass by utilizing a plurality of curved needle cannulae deployed within an cannula introduced into the tumor where the curved needle cannulae radiate outward into an umbrella-shaped configuration. Infusion can take place at multiple points within the tumor to provide wider dispersion of the ethanol. Following treatment, the curved needle cannulae are withdrawn into the cannula and the device is removed from the patient.
[0032] In a related aspect, one or more needle cannulae are located proximal to the distal end of the infusion needle. These proximally-located cannulae allow infusion of medicaments at different points along the length of the device. By having multiple sets of needles arranged in the umbrella configuration, the volume of tissue treated is increased. The coaxial outer cannula includes a plurality of side apertures that allow the proximally-located needle cannulae to deploy after the infusion needle is placed at the desired location in the body and the outer cannula is withdrawn. An outer sheath over the coaxial outer cannula selectively exposes the side apertures to permit the appropriate alignment of needle cannulae and apertures when there are multiple rows of each.
[0033] The invention has applicability in any clinical situation where a straight approach is dictated and there is a need to avoid an obstructing structure (a large vessel, bowel loop, etc.) in the entry path, or the need to redirect the approach to a more lateral pathway to infuse medicaments or aspirate, such as to drain an abscess.
[0034] In addition to infusion or aspiration, the invention can provide a conduit for introducing and/or directing the path of other medical devices within the body such as radio-frequency ablation catheters or wire guides. This would allow a straight approach to a critical juncture whereafter the curved infusion needle can be deployed to precisely proceed to the desired anatomical site, especially in situations such as a luminal bifurcation or when access to an ostium is required.
[0035] Another use of the invention is to place the infusion needle in a bronchoscope or colonoscope which can serve as the outer constraining device. Under visualization, the inner needle then can be directed to perform a biopsy or other type of procedure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0036] FIG. 1 is an isometric view of an illustrative embodiment of the curved needle inner cannula;
[0037] FIG. 2 is a top view of an outer needle cannula with an introducer trocar and the inner curved needle cannula;
[0038] FIG. 3 is a top view of the assembly of the inner curved needle cannula inside the outer needle cannula;
[0039] FIG. 4 is an exploded isometric view of a second embodiment of the inner and outer cannula;
[0040] FIG. 5 depicts a pictorial view of the inner cannula of FIG. 4 with an introducer stylet;
[0041] FIG. 6 is a side view of the inner cannula of FIG. 4 being initially deployed from the outer cannula;
[0042] FIG. 7 is a side view of the inner cannula of FIG. 4 being further deployed from the outer cannula;
[0043] FIG. 8 is a side view of the inner cannula of FIG. 4 being still further deployed from the outer cannula;
[0044] FIG. 9 is a partially sectional view depicting the apparatus of FIG. 2 being introduced into a vertebral body;
[0045] FIG. 10 is a partially sectional view similar to FIG. 9 , depicting of the apparatus of FIG. 2 infusing cement into a vertebral body.
[0046] FIG. 11 is a broken, partially sectioned view similar to FIGS. 9 and 10 , depicting of the apparatus of FIG. 2 infusing additional cement into a vertebral body.
[0047] FIG. 12 is an isometric view of a third embodiment of the apparatus;
[0048] FIG. 13 is a side view of the multi-directional infusion needle illustrated in of FIG. 12 ;
[0049] FIG. 14 is a broken, side view of the needle of FIG. 13 partially showing the needle deployed;
[0050] FIG. 15 is a side view of a trocar introducer used with the embodiment of FIG. 12 ;
[0051] FIG. 16 is a side view of the proximal assembly portion of the apparatus illustrated in FIG. 12 ;
[0052] FIG. 17 is a side view of a fourth embodiment of the apparatus;
[0053] FIG. 18 is a broken, partially-sectioned side view of the apparatus illustrated in FIG. 17 prior to deployment;
[0054] FIG. 19 is a transverse cross-sectional view of coaxial outer cannula depicted in FIG. 17 ;
[0055] FIG. 20 depicts cross-sectional views of two embodiments of coaxial outer cannula depicted in FIG. 17 ;
[0056] FIG. 21 is an isometric view of a fifth embodiment of the present apparatus; and
[0057] FIG. 22 is an isometric view similar to that of FIG. 21 showing the apparatus fully deployed.
DETAILED DESCRIPTION
[0058] FIG. 1 depicts a needle assembly 10 comprising an infusion needle 11 with a preformed bend 16 for lateral infusion or aspiration of medicaments and other materials. As defined herein, the “needle assembly 10 ” can comprise infusion needle 11 alone or infusion needle 11 in combination with other components. The “infusion needle 11 ” as defined herein comprises one or more needle cannulae having a preformed bend 16 .
[0059] The infusion needle 11 of FIG. 1 is comprised of a superelastic alloy needle cannula 13 , preferably the alloy sold under the trademark Nitinol, that is soldered or otherwise affixed to a well-known needle hub 14 using one of a selected number of well-known techniques, including that of Hall described in U.S. Pat. No. 5,354,623 whose disclosure is expressly incorporated herein by reference, and a flange 23 which has a first tapered or pointed end 24 whose shape is readily distinguishable from the second, squared end 42 .
[0060] First end 24 corresponds to the direction of preformed bend 16 in needle cannula 13 of infusion needle 11 . Bend 16 is formed in the Nitinol needle cannula 13 by either the well-known process of deforming the cannula under extreme heat for a prescribed period of time, which produces a cannula entirely in the austenitic state, or by cold working the cannula, which involves applying a large amount of mechanical stress to deflect the 15 cannula well beyond the desired amount of permanent bend. Cold working permanently locks a crystalline structure in the bending zone into at least a partial martensitic condition while the unstressed portions of the cannula remain in the austenitic state.
[0061] Cold worked Ni—Ti alloys are discussed in “Linear Superelasticity In Cold-Worked Ni—Ti”, (Zadno and Duerig) pp. 414 to 419, in Engineering Aspects of Shape Memory Alloys, Butterworth-Heineman, Boston, Mass. (Duerig et al, editors) which is incorporated herein by reference. In addition to Nitinol, superelastic or pseudoelastic copper alloys, such as Cu—Al—Ni, Cu—Al—Zi, and Cu—Zi, are available as alternative needle cannula materials. Flexible polymeric materials with sufficient rigidity for both deployment and shape memory to assume a desired curve may also be used in certain applications, either alone or in combination with reinforcing metal components such as a metal braid or tip.
[0062] Preformed bend 16 of infusion needle 11 forms a distal portion of needle cannula 13 , preferably close to about 25% of the length of needle cannula 13 in the embodiment shown in FIG. 1 . The large size of the infusion needle, preferably 10 to 18 gauge, makes this particular embodiment suitable for penetrating a vertebral body to perform a vertebroplasty or percutaneous corpectomy procedure. A more preferred range is 12 to 17 gauge, with the most preferred cannula size being 13 to 15 gauge.
[0063] With regard to a vertebroplasty and corpectomy procedures, the larger gauge cannula has both the strength to penetrate dense bone material as well as a sufficient lumen diameter to aspirate material from the vertebral body and to infuse highly viscous bone cement, such as methyl methacrylate. The preferred preformed bend 16 of the infusion needle 11 has a constant radius. For the embodiment of FIG. 1 , the preferred radius of distal bend 16 is approximately 3.0 cm for a 13 gauge needle, and approximately 2.5 cm for a 14 gauge needle. Although the illustrative embodiment has a constant bend radius, an increasing or decreasing radius bend could be employed for certain clinical applications. Furthermore, it is possible to introduce more than one bend into the superelastic cannula for applications requiring a special needle configuration.
[0064] The primary purpose of using a Nitinol or other superelastic alloy cannula is that the cannula can be constrained into one shape during passage to the treatment site, then deployed into the preformed configuration without experiencing any plastic deformation.
[0065] FIG. 2 depicts a pair of needles to be used coaxially in that manner, including the infusion needle 11 of FIG. 1 and a coaxial outer cannula 12 for maintaining inner infusion needle 11 in a substantially straight configuration while being introduced to the treatment site. The embodiment depicted in FIG. 2 is Jamshidi-type needle (Manan Inc., Northbrook, Ill.) which is a two-part needle assembly 43 , and is most commonly used for accessing dense, hard tissue such as bone, fibrous material, etc. Thus, it is well suited for penetrating the wall of a vertebral body wherein the infusion needle 11 can be deployed.
[0066] The two-part needle assembly 43 includes a coaxial outer cannula 12 having a stainless steel cannula 19 with an inner passageway 21 that is sufficiently large to accommodate inner infusion needle 11 . For example, the standard 11 gauge Jamshidi-type needle suitable for accessing a vertebral body would be used with thirteen (13) gauge inner curved needle. Stainless steel cannula 19 is affixed proximally to a handle 26 and a connector hub 31 (shown in FIG. 3 ). The connector hub 31 receives the second part of the two-part needle assembly 43 , the coaxial outer cannula introducer 52 which preferably comprises a trocar 25 . The trocar hub 27 locks into handle 26 of coaxial outer cannula 12 . The beveled tip 30 of trocar 25 extends approximately 5 mm beyond the distal tip 22 of coaxial outer cannula 12 and assists in penetration. Trocar 25 also serves to prevent the coaxial outer cannula 12 from coring a sample of bone or other material during access.
[0067] After outer needle assembly 43 has been directed to the target site, trocar 25 is removed from coaxial outer cannula 12 and infusion needle 11 is inserted into passageway 21 of the coaxial outer cannula 12 , as shown in FIG. 3 . To maintain openness of the infusion needle passageway 15 and to prevent tissue coring during deployment, an inner needle introducer stylet 46 can be introduced coaxially inside the infusion needle. Inner needle introducer stylet 45 includes a handle 83 and a shaft 46 which is made of a flexible, high-tensile. polymeric material such as polyetherethylketone (PEEK) to allow stylet 45 to assume the contour of preformed bend 16 after deployment.
[0068] Inner infusion needle 11 straightens as it is loaded into coaxial outer cannula 12 . As the portion including preformed bend 16 of infusion needle 11 extends out from tip 22 of coaxial outer cannula 12 as depicted in FIG. 3 , infusion needle 11 assumes the preformed shape due to the superelastic properties of needle cannula 13 . For infusion, inner needle introducer stylet 52 , which helps prevent coring of tissue into passageway 21 of coaxial outer cannula 12 , is removed. The tapered or “arrow” end 24 of flange 23 of proximal hub 14 corresponds with the deflection plane 29 of infusion needle 11 .
[0069] By maneuvering flange 28 , the inner curved needle 13 can be rotated in either direction 28 to reorient the plane of deflection 29 and place the tip opening 17 at multiple locations within the area being treated.
[0070] In FIG. 3 , tip 17 is deflected at an angle 44 of approximately 60° to 70° from the device longitudinal axis 18 . This gives, for example, with a thirteen (13) gauge infusion needle 11 , a lateral reach, measured from tip 17 to longitudinal axis 18 , of nearly thirty (30) millimeters in any direction.
[0071] While the degree of deflection required is determined by the application and desired lateral reach of the device, it is also limited by the size of the cannula if the permanent bend is cold worked into the material. Cold working provides a stiffer bend which can be advantageous in certain applications such as vertebroplasty and biopsy of dense tissue; it is more difficult to permanently deform a larger gauge Nitinol cannula without application of extreme heat. For the embodiments contemplated, the angle of deflection 44 can encompass a range of 30° to 110°, with a preferred range of 40 to 90° for most applications.
[0072] FIG. 4 depicts a second version of the inner curved needle and sheathing outer needle adapted for use in the injection of medicaments, contrast media, or other non-viscous agents. The infusion needle 11 is comprised of a smaller gauge needle cannula 13 , preferably around twenty-five (25) gauge, mounted to a proximal hub 14 . The preformed bend 16 of individual needle cannula 13 has a slightly tighter radius than that illustrated in FIGS. 1 through 3 .
[0073] Still referring to FIG. 4 , the coaxial outer cannula 12 includes a correspondingly sized needle cannula 19 , preferably around twenty-one (21) gauge, attached to a standard needle hub that is adapted to receive proximal hub 14 of infusion needle 11 . The embodiment of FIG. 4 is used with a plurality of stylets that are inserted within both the inner and outer needles during their respective introduction into the body. The first is an outer cannula introducer stylet 52 that is inserted into the passageway 21 of coaxial outer cannula 12 . The coaxial outer cannula 12 and outer cannula introducer stylet 52 are inserted together into the patient. The stylet, which is preferably a stainless steel stylet wire 46 with an attached standard plastic needle hub 47 , prevents the coaxial outer cannula 12 from coring tissue into passageway 21 at distal tip 22 .
[0074] Once coaxial outer cannula 12 is in position, outer cannula introducer stylet 52 is withdrawn from coaxial outer cannula 12 and infusion needle 11 and second introducer stylet 45 are inserted together into outer needle passageway 21 . The inner needle introducer stylet 45 , which is longer than outer cannula introducer stylet 52 in order to fit the longer infusion needle 11 , serves a similar function to the outer cannula introducer stylet 52 by preventing coring of tissue when infusion needle 11 is deployed from coaxial outer cannula 12 .
[0075] As illustrated in FIGS. 4 and 5 , proximal hub 14 of infusion needle 11 is adapted such that hub 53 of inner needle introducer stylet 45 locks together with proximal hub 14 to keep the two in alignment. This locking mechanism includes a molded protuberance 49 on hub 53 that fits within a recess 50 on proximal hub 14 . The purpose of maintaining alignment of hub 53 and proximal hub 14 is to match the beveled surface 51 at the tip of the inner needle introducer stylet 45 , shown in FIG. 5 , with the beveled edge at the tip 17 of infusion needle 11 .
[0076] FIGS. 6 through 8 depict the deployment of infusion needle 11 from within outer needle cannula 12 . FIG. 6 shows infusion needle 11 during initial deployment from coaxial outer cannula 12 . The preformed bend 16 of the infusion needle 11 is constrained by the cannula 19 ; however, as illustrated in FIG. 6 , preformed bend 16 may be of sufficient stiffness to slightly deform outer cannula 19 while infusion needle 11 is inside coaxial outer cannula 12 . Despite this slight deformation, coaxial outer cannula 12 is still substantially straight.
[0077] As depicted in FIG. 7 , stress preformed bend 16 places on outer cannula 19 relaxes as infusion needle 11 is further deployed and the angle of deflection 44 (measured from longitudinal axis 18 of coaxial outer cannula 12 to the opening at tip 17 of infusion needle 11 ) is increased. As infusion needle 11 is further deployed as depicted in FIG. 8 , fully exposing preformed bend 16 to produce the largest angle of deflection 44 , the unstressed outer cannula returns to a straight configuration.
[0078] The phenomenon depicted in FIGS. 6 through 8 is most noticeable when using smaller gauge cannulae, such as shown in FIGS. 4 and 5 . The larger gauge outer cannula of FIGS. 1 to 3 is more resistant to deformation than that of FIGS. 4 and 5 . Naturally, the tendency of the stressed outer cannula to deform is also very much dependent on the stiffness and radius of the preformed bend 16 as well as the thickness of the cannula wall and material used. To eliminate this deformation during introduction of the device into the body, stylet 45 , as depicted in FIG. 5 , can be used as a stiffener until removed immediately before the portion having preformed bend 16 is deployed.
[0079] FIGS. 9 through 11 depict the use of the device illustrated in FIG. 3 to perform a vertebroplasty procedure on a pathological vertebral body 33 using a transpedicular approach. As depicted in FIG. 9 , coaxial outer cannula 12 with introducer trocar 25 is introduced through the wall 38 and into the marrow 37 of the vertebral body 33 . The transpedicular route of access places the needle between the mammillary process 34 and accessory process 35 of the vertebral arch 55 . The vertebral arch 55 is attached posteriorly to the vertebral body 33 and together they comprise the vertebra 54 and form the walls of the vertebral foremen 36 .
[0080] Once coaxial outer cannula 12 and inner introducer trocar 25 are within the internal region or marrow 37 of the vertebral body, trocar 25 is withdrawn from the coaxial outer cannula 12 and infusion needle 11 is inserted in its place. FIG. 10 depicts infusion needle 11 infusing bone cement 41 , commonly methyl methacrylate, into vertebral body 33 to provide it with improved structural integrity. As depicted in FIG. 11 , infusion needle 11 can be partially withdrawn or rotated to obtain more complete filling or to avoid the network of vertebral veins. Even though the vertebral body may not need to be completely filled, the density of marrow 37 would still necessitate a second transpedicular stick in the absence of the instant apparatus infusing cement within multiple planes within vertebral body 33 . Upon completion of the procedure, infusion needle 11 is withdrawn back into coaxial outer cannula 12 and both are removed from vertebral body 33 .
[0081] The utility of the hollow, curved superelastic needles is certainly not limited to procedures involving the spine. Such needles are useful at many sites within the body that might require straight access by a needle, followed by indirect or lateral infusion, aspiration, or sampling. For example, the inner needle could be adapted to take biopsy samples from dense tissue, such as a breast lesion, especially where indirect access is might be desirable.
[0082] FIG. 12 is an isometric view of hollow, curved superelastic needles in which needle assembly 10 comprises a multiple needle assembly 70 useful in infusion of ethanol or other medicaments into a tumor. In FIG. 12 , needle assembly 10 comprises an infusion needle 11 , which includes a multiple needle assembly 70 comprising a plurality of needle cannulae 13 , each having a preformed bend 16 , a proximal assembly 58 for constraining the multiple needle assembly 70 , and a coaxial outer cannula 12 for introducing the multiple needle assembly 70 to its anatomical target.
[0083] The multiple needle assembly 70 in FIG. 13 includes a base cannula 56 affixed to a proximal hub 14 such as a standard female luer fitting. A plurality of needle cannulae 13 are manifolded into base cannula 56 , preferably evenly spaced in an umbrella configuration 75 , and affixed in place with a solder joint 57 . In the structure illustrated in FIG. 12 , five needle cannulae 13 are used; from two to as many as appropriate for the given cannula size can be used. As with the other versions, needle cannulae 13 are preferably made of Nitinol that is either annealed or cold-worked to produce the preformed bend 16 . In the structure illustrated in FIG. 12 , the coaxial outer cannula 12 has an outer diameter of approximately 0.072 inches and an inner diameter of around 0.06 inches, while the individual curved needle cannulae 13 have an outer diameter of 0.02 inches and an inner diameter of about 0.12 inches. As shown in FIG. 14 , the tips 17 of the needle cannulae 13 may be beveled to better penetrate tissue.
[0084] Deployment of curved needle cannulae 13 of multiple needle assembly 70 is depicted in FIG. 14 . Needle cannulae 13 are restrained by coaxial outer cannula 12 until multiple needle assembly 70 is advanced, exposing the distal end portions of needle cannulae 13 at distal end 22 of coaxial outer cannula 12 , whereby they radiate outward to assume, when fully advanced, the umbrella configuration 75 shown in FIG. 13 .
[0085] FIG. 15 depicts a side view of an outer needle assembly comprising a coaxial outer cannula 12 and outer cannula introducer stylet 52 used in placement of the multiple needle assembly 70 of FIGS. 12 through 14 . The outer cannula introducer stylet 52 is inserted into passageway 21 of coaxial outer cannula 12 with the male proximal hub 47 of the outer cannula introducer stylet 52 fitting into the female proximal hub 20 of coaxial outer cannula 12 when the outer cannula introducer stylet 52 is fully advanced. Outer cannula introducer stylet 52 includes a sharp tip 63 , such as the diamond-shape tip depicted, for penetrating tissue.
[0086] The outer cannula introducer stylet 52 and coaxial outer cannula 12 may be introduced percutaneously into the liver or kidney and placed at the desired treatment location. The outer cannula introducer stylet 52 is then removed. The proximal assembly 58 with the preloaded multiple needle assembly is then advanced into the coaxial outer cannula 12 which remains in the patient. In the version illustrated in FIGS. 12 through 15 , the coaxial outer cannula preferably has an outer diameter of about 0.095 inches and an inner diameter of about 0.076 inches, while the outer diameter of the inner stylet is preferably about 0.068 inches.
[0087] FIG. 16 a side view of the proximal assembly 58 shown of FIG. 12 . The Proximal assembly 58 includes a distal male adaptor 60 connected to an intermediate cannula 59 that is sufficiently large to accommodate multiple needle assembly 70 . At the proximal end of the intermediate cannula 59 is proximal assembly female adaptor 61 which is connected proximally to a proximal assembly hub 62 , such as a Tuohy-Borst adaptor. Proximal assembly hub 62 is utilized by the physician during manipulation of the device.
[0088] The multiple needle assembly 70 of FIG. 13 is loaded into lumen 64 at the proximal end 65 of the proximal assembly hub 62 , with the needle cannulae 13 remaining within intermediate cannula 59 . Distal end 66 of proximal assembly 58 with preloaded multiple needle assembly 70 is then inserted into proximal hub 20 of the coaxial outer cannula as depicted in FIG. 12 . The multiple needle assembly 70 is then advanced from the proximal assembly 58 into the coaxial outer cannula 12 where it is deployed as depicted in FIGS. 12 to 14 . Ethanol is infused into multiple needle assembly 70 via the proximal hub 14 of the infusion needle 11 . Following treatment, the multiple needle assembly 70 is withdrawn into coaxial outer cannula 12 and the entire needle assembly 10 is removed from the patient.
[0089] FIGS. 21 and 22 depict a variation of needle assembly 10 of FIG. 12 in which infusion needle 11 and coaxial outer cannula 12 are connected to a coaxial handle 76 used to advance and deploy multiple needle assembly 70 releasably from constraint of coaxial outer cannula 12 . As shown, coaxial handle 76 comprises a stationary outer component 77 that fits over base cannula 56 of multiple needle assembly 70 and attaches to proximal hub 20 . A slidable inner component 78 further comprises a thumb piece 79 used by the physician to advance or retract the coaxial outer cannula 12 as the slidable inner component 78 retracts into stationary outer component 77 .
[0090] In FIG. 21 , the needle assembly is depicted in the introducer position with the thumb piece 79 advanced fully forward within a slot 80 in outer slidable component 77 .
[0091] FIG. 22 depicts the deployment state of needle assembly 10 in which thumb piece 79 has been moved to the most proximal position within slot 80 . In this position, coaxial outer cannula 12 is retracted to fully expose the plurality of needle cannulae 13 which can assume their unconstrained configuration with the preformed bends 16 .
[0092] This type of handle can be used with both the multiple and single infusion needle where a introducer trocar or stylet is not required. Other well-known types of coaxial handles 76 include, but are not limited to, screw-type, rachet-type, or trigger-activated handles which allow coaxial outer cannula 12 to be longitudinally displaced relative to infusion needle 11 . To reduce the need for a trocar or stylet for facilitating tissue penetration, distal tip 22 of coaxial outer cannula 12 can be shaped into a needle point such as depicted, or into a non-coring point to help maintain an open outer cannula passageway 21 .
[0093] A syringe or other reservoir container can be attached to proximal hub 14 as an infusate source or for collection of aspirated material. In addition, a reservoir, such as a syringe, can be incorporated internally within coaxial handle 76 of needle assembly 10 or integrally attached thereto.
[0094] Another version of multiple needle assembly 70 is depicted in FIGS. 17-20 whereby there are one or more groupings of proximally-located needles 73 in addition to the distally-located needles 74 that are similar to those illustrated in of FIG. 12 . By locating the additional needle cannulae 13 proximal to those at the distal end, wider dispersal and coverage is attained for infusion of medicaments.
[0095] In the version illustrated in FIG. 17 , there is an arrangement of four needle cannulae comprising the distally-located needles 74 , while at least one other group comprising proximally-located needles 73 located along the length of infusion needle 11 provides for simultaneous infusion in a more proximal location. The needle cannulae 13 of the proximally-located and distally-located needles 73 , 74 can vary in configuration, length, number, and how they are attached to a base cannula 56 such as that shown in FIG. 13 . For example, individual needle cannulae 13 within an umbrella configuration 75 or between proximally-located and distally-located needles 73 , 74 can be longer, or have a different radius than others, to vary the distribution pattern of the infusate.
[0096] As depicted in FIGS. 17 and 18 , each pair of oppositely-disposed needle cannulae 13 within a grouping of four proximally-located needles 73 are longitudinally offset with respect to the adjacent pair located ninety degrees (90°) therefrom, as are the side apertures 67 from which they emerge. With regard to attachment, possibilities include, but are not limited to, having all needle cannulae 13 attaching to a single base cannula 56 ; dividing base cannula 56 such that a separate portion extends distally from the proximally-located needles 73 to join the distally-located needles 74 , or eliminating the base cannula 56 such that needle cannulae 13 of multiple needle assembly 70 are separate and run the length of infusion needle 11 .
[0097] To constrain needle cannulae 13 for introduction along a single pathway into the body, a coaxial outer cannula 12 is used that has side apertures 67 in the cannula to permit the proximally-located needles 73 to deploy outward therethrough for lateral infusion. FIG. 18 shows a sectioned view of the needle assembly of. FIG. 17 in which the needle cannulae 13 are constrained in the introduction position. An introducer cannula 68 is used to selectively expose side apertures 67 in versions where the arrangement of needles is such that individual needle cannulae 13 may prematurely exit a non-designated hole or row, preventing or delaying proper deployment of the multiple needle assembly 70 . By maintaining the introducer sheath over side apertures 67 until distally-located needles 73 are deployed, proper deployment of all needle cannulae 13 is easier.
[0098] FIGS. 19 and 20 illustrate intraluminal guides 69 to help facilitate proper alignment of needle cannulae 13 with a designated side aperture 67 . In FIG. 19 , a series of ridges 71 within passageway 21 of coaxial outer cannula 12 guide the needle cannulae 13 to align with a designated side aperture 67 . FIG. 20 depicts an alternative intraluminal guide 69 in which the needle cannulae 13 travel longitudinally within grooves 72 formed in the inner wall of passageway 21 .
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A needle assembly 10 compromising an infusion needle 11 that includes a needle cannula 13 made of a superelastic material such as Nitinol. The needle cannula is cold-worked or heat annealed to produce a preformed bend 16 that can be straightened within passageway 21 of a coaxial outer cannula 12 for introduction into the body of a patient. Upon deployment from the outer cannula, the needle cannula substantially returns to the preformed configuration for the introduction or extraction of materials at areas lateral to the entry path of the needle assembly. The needle assembly can compromise a plurality of needle cannulae than can be variably arranged or configured for attaining a desired infusion pattern.
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This application is a continuation-in-part of application Ser. No. 349,291, filed Feb. 16, 1982.
FIELD
This invention relates to a method for the high-speed metal plating of plastics. More specifically, it is directed toward the high-speed plating of plastics in the same mold in which the plastics are formed. Moreover, the bonding of the plating to the plastic occurs simultaneously with the formation of the plastic article in the mold.
BACKGROUND
A need to use light-weight components as a means to achieve better fuel economies has existed in the automotive and aircraft industries for several years. In addition, there is a growing need to shield out electromagnetic and radio frequency emissions from car radios, truck skid-control braking systems, ignition equipment, microprocessor-based engine-control systems, and systems found in the communication, aerospace, computer, and medical industries. One method for solving these weight and electromagnetic and radio frequency shielding problems is through the electrodeposition of a metallic coating on plastics, commonly called metal electroplating, metal plating, or simply plating. However, metal plating of plastics, as it is currently practiced, involves a long series of time, material, and labor consuming preplating steps as well as a lengthy set of plating steps.
Typically the part to be plated is removed from a forming mold; cleaned thoroughly to remove dirt, fingerprints, particles, die lubricants, etc.; preconditioned to allow for a uniform etch; etched (involving one or more etching and rinsing steps) to afford better metal to plastic adhesion; neutralized of the residues from etching; treated with a catalyst to make the surface more receptive to the deposition of a thin conductive metallic coating on the plastic; treated with an accelerator to promote the effectiveness of the catalyst; coated with a metallic preplate to give the necessary conductivity for the electroplating steps; and plated with copper for 10-20 minutes. The cycle time for the preplating and plating steps is typically in the range of 45 to 60 minutes. Moreover, the etching step necessary to afford metal-plastic adhesion often requires the use of etchable plastics or the addition of etchable materials to the plastic. See, for example, "Plastics Engineering Handbook," 4th edition, 1976, Joel Frados, editor, po. 742-749.
Although the plating of surfaces and the subsequent adhesion of materials to the electroplate to produce metal-clad materials is known (as in Canada Patent 473,507, R. N. Sabee, et. al., May 8, 1951; U.S. Pat. No. 3,649,474, B. E. Blakeslee, et. al., Mar. 14, 1972; U.S. Pat. No. 3,689,729, G. E. Neward et. al., Sept. 5, 1972; IBM Technical Disclosure Bulletin, 1, 14, 60 (June 1971)), problems of long plating times, additional steps, and poor electroplate to material retention have precluded this methodology from gaining widespread acceptance and replacing the aforementioned state of the art. Long plating times have been especially troublesome and rather than use this technique, it has been found that it is more efficient to mold a large number of plastic articles and then plate all of them in a batch process. Coating of surfaces by methods other than electroplating, with the subsequent adhesion of materials to the coating to form coated articles also is known (U.S. Pat. No. Re. 28,068, J. H. Lemelson, July 9, 1974).
High-speed electroplating has been described (U.S. Pat. Nos. 4,053,370, K. Yamashita, et. al., Oct. 11, 1977; 4,080,268, S. Suzuki, et. al., Mar. 21, 1978; 4,119,516, S. Yamaguchi, Oct. 10, 1978; and Plating and Finishing, 7, 68, 52-55 (July 1981)), but it has not been used in conjunction with the high-speed production of metal-clad molded articles.
OBJECTS
It is an object of this invention to provide a method for the rapid metal plating of plastics which can be accomplished in a few steps and in a very short time.
Another object of this invention is to provide a process wherein the metal electroplate is formed first and subsequently the plastic is simultaneously bonded to the metal electroplate and molded to the desired shape.
Another object of this invention is to provide a process wherein many of the aforementioned steps associated with the present state of the art are eliminated, thereby significantly reducing the time, labor and materials required to obtain a metal-plated plastic.
A further object of this invention is to broaden the range of materials which can be used in conjunction with the metal electroplate, e.g. glass-filled polymers can now be effectively plated.
A further object is to provide a process in which the metal plate contains a surface with nodular growths so as to strengthen the adhesion of the metal plate to the plastic.
A further object of this invention is to provide an improved process wherein the metal can be plated in a very short time so as to allow the various steps in the process to be automated and repeated in rapid succession on a large number of articles.
A further object is to provide a process wherein an electrode is used for plating which contains interior channels so as to promote a more effective turbulent electroplating solution flow, which allows for the use of higher current densities and as a result, decreases the plating time.
Another object of the invention is to provide a process wherein an electrode is used for plating which conforms to the shape of the surface to be plated in order to achieve a metal electroplate of uniform thickness.
SUMMARY
A typical process according to the present invention comprises the steps of rapidly electroplating a metallic electroplate layer onto the surface of a metallic mold through the use of high current densities and a turbulent flow of electroplating solution between the anode and the mold surface, contacting a plastic with the electroplated metallic layer such that the plastic material adheres more strongly to the electroplated layer than the electroplated layer adheres to the surface of the mold, and then separating the mold from the molded plastic article leaving the metallic layer bonded to the molded plastic article. The rapid electroplating step can be carried out in a time short enough to allow it to be combined with the other steps of the process and to allow for the repeated automation of the entire process.
Typically, the current density and the electroplating solution flow rate are maintained so as to produce an initial smooth layer of electroplate. After a smooth layer of electroplate is formed, variables which affect metal electroplate characteristics such as electroplating solution flow rate, current density, temperature, and electroplating solution concentration are varied so as to produce an electroplate surface containing nodular growths. These nodular growths are particularly effective in promoting the adhesion of the plastic to the metal electroplate.
The electrode which is used to plate the mold used for the plastic molding typically contains interior channels to promote the turbulent flow of electroplating solution between the anode and the mold surface to be plated and is shaped to conform to the surface of the mold. These features allow for the use of higher current densities to decrease plating times and better control of the metal plate surface characteristics and thickness uniformity.
An additional coating may be placed on the electroplate surface of the completed plastic article. This may be an additional electroplate layer or other suitable coating such as paint or laquer. It may be for desired decorative, structural, or corrosion resistant purposes.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a front sectional view of the electroplating apparatus positioned over a mold member used for plastic molding in the present invention.
FIG. 2 is a top sectional view of a portion of the electroplating apparatus and the mold member of FIG. 1 taken in the plane 2--2 of FIG. 1.
FIG. 3 is an end view of the electrode shown in FIG. 1.
FIG. 4 is a front sectional view of the electroplated mold member of FIG. 1 assembled with a second unplated mold member so as to form a mold cavity.
FIG. 5 is a perspective sectional view of a plastic article after it has been molded and removed from the apparatus shown in FIG. 4.
DETAILED DESCRIPTION
This invention is directed to a process in which plastic articles are given a metallic coating by first rapidly electroplating all or portions of the molding surfaces of a mold and then molding a plastic article in the electroplated mold so as to transfer the electroplate from the mold to the surface of the plastic article.
In FIG. 1, which illustrates a typical arrangement for the electroplating of a member of a mold, an electroplating apparatus 10 is mounted over a mask 11 and a mold member 12. The electroplating apparatus 10 is held in place over the mold member 12 by means of alignment pins 13. The electroplating apparatus 10 comprises an electrode 14 with interior channels 14' through which flows an electroplating solution, an alignment fixture 15 to hold the electrode 14 in position over the mold member 12, and the electrical conductors 22 and 23 by means of which the electrode 14 and the mold member 12 are connected to a source of positive and negative electrical potential (not shown). A metal electroplate 16 is deposited on the mold surface 17 of the mold member 12 by the application of a potential difference between the electrode 14 and mold member 12 (typically grounded at 23) while simultaneously turbulently flowing an electroplating solution between the electrode 14 and the mold member 12.
FIG. 2 helps to illustrate the general shape of the mold member cavity 21 and the position of the alignment fixture 15. The alignment fixture 15 is positioned over the mold 12 so as to form a space 15' (FIG. 1) that is open at both ends to allow the electroplating solution to flow from the electroplating apparatus 10 after the electroplating solution has been pumped though the electrode channels 14' and caused to turbulently flow between the electrode 14 and the mold surface 17.
FIG. 3 illustrates a typical arrangement of the lower ends of the internal channels 14' in the electrode 14. Such an arrangement allows a turbulent flow of electroplating solution to be maintained over all parts of the mold surface 17 being electroplated. As seen in FIG. 1 and FIG. 3, the shape of the electrode 14 conforms to the shape of the mold surface 17 being electroplated in order to achieve a metal electroplate 16 of relatively uniform thickness. The electrode 14 is an insoluble-type anode, typically comprising alloys of lead with tin or antimony, platinum, platinized titanium, or the like.
Although this invention is illustrated with a single anode 14 which contains interior channels 14' to obtain turbulent electrolyte flow in the plating step, multiple electrodes and other means for achieving turbulent flow such as stirring, use of nozzles, and the like may be used. The number, arrangement, and shape of the electrodes and means to achieve turbulent flow largely depend on the shape and size of the article to be plated.
FIG. 2 illustrates two alignment holes 18 which are used in conjunction with the alignment pins on a second mold member 12A so as to align the two mold members 12 and 12A when they are fitted together to form a mold cavity 19 as shown in FIG. 4. Molding material can be poured, injected, or otherwise caused to enter the mold cavity 19 through the inlet port or opening 12'. FIG. 4 illustrates a mold arrangement wherein only one side and half an edge of a plastic article 26 will be plated with metal. When the upper part of the article 26 is to be plated also, the upper mold member 12A may be provided with a metal deposit similar to the deposit 16 on the lower mold member 12. Other variations and patterns may be obtained by selectively masking various portions of the mold members 12 and 12A.
FIG. 5 illustrates the plated plastic article 26 after it has been removed from the mold illustrated in FIG. 4. FIG. 5 illustrates the selective plating of half of the plastic article 26 achieved by plating only one mold member 12 and also illustrates the surface at the junction 24 of the plastic body 20 and the metal electroplate 16.
Rapid electroplating of the mold surface 17 is carried out using high current densities and a turbulent flow of electrolyte solution between the electrode 14 and the mold surface 17. The following conditions are typical of those used to obtain a metal electroplate 16.
______________________________________Current Density 20-600 A/dm.sup.2Flow Velocity 0.1-10 m/sec(between anode andmold surface)Gap, between anode and 1-4 mmmold surfaceElectroplating SolutionCopper Sulfate 1-2 moles/literSulfuric Acid 0.5-0.8 moles/literTemperature 30-60° C.______________________________________
Selection of appropriate conditions requires a balance among, (1) current density, (2) flow velocity, (3) temperature, and (4) copper ion in solution. With a satisfactory balance, it is possible to obtain a satisfactory electroplate 16 in about 15 sec. Although the invention is described herein with a copper electroplate, other electroplates such as nickel, iron, cobalt, zinc, brass, and the like may be used.
In one mode of operation, the mold 12 is enclosed in masking material 11 except for that portion of the mold surface 17 which is to be plated. The electroplating apparatus 10 is mounted over the mask 11 and the mold 12. The entire apparatus shown in FIG. 1 is then submerged in a container of electroplating solution. The electroplating solution is pumped from the container, through the electrode channels 14' in the direction of the arrows, and returned to the container of electroplating solution through the submerged openings at either end of the cavity 15'.
In a variation of FIG. 1, the cavity 15' is enclosed except for a small exit port to which is attached a piece of tubing through which the exiting electroplating solution can flow to a container of electroplating solution which is away from the electroplating apparatus 10 and from which electroplating solution is continuously pumped to the electrode channels 14'.
The above variations of the electroplating apparatus 10 serve only to show two of the many possible variations in the electroplating apparatus 10 which may be used with this invention. The shape and design of the electroplating apparatus 10 will in large part depend on the shape of the mold 12 to be plated and also on the molding equipment to be used. This is especially true if automated plating and molding equipment is used.
The mold surface 17 usually is polished to a smooth finish in order to provide a smooth and pore free electroplate coating 16 on the finished article 26. The presence of pores through the metal electroplate 16 could allow the molding plastic to contact the mold surface 17 and thus could cause the metal electroplate 16 to stick to the mold 12 or could result in a residue of plastic molding material on the surface of the metal plate 16 after the finished article 26 has been removed from the mold 12,12A. Such residue would interfere with the next plating cycle.
The mold surfaces 17 which are exposed to the electroplating solution typically comprise corrosion-resistant materials such as 304 Stainless or other austenitic steel. Mold surfaces 17 of materials such as carbon steel corrode quickly under the conditions used in rapid electroplating. When corrosion occurs on the mold surface 17, the metal electroplate 16 has a tendency to stick to the mold surface 17 rather than to the molded plastic 20.
Adhesion of the metal electroplate 16 to the mold surface 17 can be reduced by treating the mold surface 17 with such adhesion-reducing agents as graphite, chromate wash, and the like according to usual practices.
Adhesion of the molded plastic 20 to the metal electroplate 16 can be improved by the formation of nodular growths on the electroplate surface 25 during the last part of the electroplating process. Nodular growth is achieved by varying either or both the current density and the electroplating solution agitation in the region of the plating process. Increasing the current density while maintaining the same solution agitation or decreasing the solution agitation while maintaining the same current density will produce nodular growth. Nodular growth also can be obtained by increasing both the solution agitation and the current density such that the increase in current density is in greater proportion than the increase in solution agitation. For automated assembly-line operations, the time of the electroplating step for plating both the smooth and the nodular metal can be reduced to a value corresponding to the time of the molding sequence by increasing both solution agitation and current density.
The following conditions are typical of those used to obtain nodular growth on copper.
______________________________________ Reduced Increased Flow Velocity Current Density______________________________________Current Density 20-300 A/dm.sup.2 300-600 A/dm.sup.2Flow Velocity 0.1-1 m/sec 1-2 m/sec(between anode andmold surface)Gap, between anode and 1-4 mm Samemold surfaceElectroplating SolutionCopper Sulfate 1-2 moles/liter SameSulfuric Acid 0.5-0.8 moles/liter SameTemperature 30-60° C. Same______________________________________
The mold members 12 and 12A are of the kinds designed for use in injection molding. However, the process is also suitable for other molding techniques such as pour molding, reaction injection molding, transfer molding, compression molding, roto casting, and the like.
Greater adhesion between the plastic body 20 and the metal electroplate 16 can be achieved by adding coupling agents such as A-1100, a silane made by Union Carbide, to the molding formulation before it is injected into the mold cavity 19.
Shrinkage of the plastic material 20 during the molding process can be alleviated by the addition of materials such as chopped glass fibers to the molding composition.
Molding compositions 20 may comprise such materials as high density polyethylene, polycarbonate, ethylene vinyl acetate, and the like. Specific materials will depend on the end application of the metal-coated article 26.
Additional coatings may be applied to the metal-clad article 26 after it is removed from the mold 12,12A for such purposes as decoration, corrosion inhibition, and strength. Such additional coatings may include additional layers of electroplate such as bright nickel and chromium, laquers, paint, and the like.
The rapid electroplating of the mold member 12 allows the electroplating time to be reduced from the normal plating time of 10-20 minutes to about 20 sec. A plating time of 20 sec allows the electroplating step to be incorporated sequentially with the molding step and both steps automated by the use of automation equipment such as the 4 oz New Britain Injection Molder manufactured by New Britain Plastics Machine of New Britain, Conn.
EXAMPLE A
A stainless steel mold member 12 (304 alloy) with a 51 mm diameter and 1.5 mm deep mold cavity 21 was masked with a plating resist 11 leaving exposed only the mold cavity surface 17. The mold member 12 was fit with a conforming anode 14 of 93% lead-7% tin with about 3 mm clearance from the mold cavity surface 17. The disk-like anode 14 had a cluster of nine holes 14', each 3 mm diameter and about 6 mm center to center distance, for flow of electrolyte between the anode 14 and the die mold surface 17. Plating conditions used were:
______________________________________Current Density 250 A/dm.sup.2Flow Volume (radial) 60 liters/minFlow Velocity (peripheral 2.0 m/secminimum)Plating Rate, average copper 47 μm/minGap between anode and mold 3 mmTime 15 secTotal Current 50 ACopper Sulfate 1.5 moles/literSulfuric Acid 0.5 moles/literTemperature 50° C.______________________________________
On completion of the initial plating, the flow velocity was decreased to 0.75 m/sec and plating continued for another 2 sec to obtain nodular copper on the surface 17 of the electroplate 16.
The electroplating apparatus 10 was removed and the mold member 12 fitted with a second mold member 12A to form a complete mold. The assembled mold 12,12A was placed in a 1 oz Watson Stillman Injection Molder. The molding composition was formulated by mixing Ultrathene UE631, an ethylene vinyl acetate polymer manufactured by the U.S. Industrial Chemicals Company of New York, N.Y. A-1100, a silane coupling agent manufactured by Union Carbide (2 parts in 100 parts resin) and 1/4 in. chopped glass fibers (6 parts in 100 parts resin). After mixing, the materials were ground in an Abbe mill to facilitate molding. The molding material was injected into the mold 12,12A at a melt temperature of 320° F. and a hydraulic pressure of about 2000 psi. Parts were molded in typical cycle times of 2-5 sec injection time, 10 sec hold time, and 15-30 sec cooling time for a total cycle time of 30-45 sec.
An additional decorative coating of about 1 mil of bright nickel and about 0.01 mil of bright chromium was applied to the copper-clad article. The copper surface was first cleaned in a proprietary cleaner compounded for cleaning non-ferrous metals (ENBOND 160 made by Enthone, Inc. of New Haven, Conn.), then rinsed and dipped into 3N sulfuric acid to remove any oxides, rinsed again, then nickel plated using the PERGLOW plating process (Harshaw Chemical Co. of Cleveland, OH). Plating conditions for the proprietary nickel solution were 140° F. and 5 A/dm 2 for about 25 minutes. The plating was rinsed and chromium plated in a solution containing 250 g/liter CrO 3 and 2.5 g/liter H 2 SO 4 , for about 2 minutes at 115° F. and 20 A/dm 2 .
EXAMPLE B
A metal electroplate 16 of copper in mold cavity 21 was produced as in Example A and several samples of metal-clad article 26 were produced using a variety of plastic compositions including high density polyethylene, polycarbonate, fluoroethylenepropylene, polyformaldehyde, polyetherimide, polyphenylene oxide, polyether ether ketone, polyphenylene sulfide, polyolefins, or acrylonitrilebutadiene-styrene polymers.
EXAMPLE C
The electroplating apparatus 10 as in Example A was used to produce a metal electroplate 16 of nickel using a typical "Watts-type" nickel electroplating solution. Plating conditions used were:
______________________________________Current Density 25 A/dm.sup.2Flow Volume (radial) 6 liters/minFlow Velocity (peripheral 0.2 m/secminimum)Gap, between anode and mold 3 mmTime 300 secTotal Current 5ANickel Sulfate 0.91Nickel Chloride 0.17Boric Acid 0.48pH 2.8Temperature 52° C.______________________________________
On completion of the initial plating, the current density was increased to 75 A/dm 2 for another 180 sec to obtain nodular nickel on the surface 17 of electroplate 16.
EXAMPLE D
The electroplating apparatus 10 as in Example A was used to produce a metal electroplate 16 of zinc. Plating conditions used were:
______________________________________Current Density 50 A/dm.sup.2Flow Volume (radial) 6 liters/minFlow Velocity (peripheral 0.2 m/secminimum)Gap, between anode and mold 3 mmTime 5 minTotal Current 10 AZinc Sulfate 1 mole/literpH 3.5Temperature 32° C.______________________________________
EXAMPLE E
A stainless steel mold member 12 (304 alloy) with a 51 mm and 1.5 mm deep mold cavity 21 was masked with a plating resist 11 leaving exposed only the mold cavity surface 17 as in Example A. The mold member 12 was fit with a solid conforming anode (i.e. interior channels 14' were eliminated). The alignment fixture 15 was modified so that solution entered one side of the fixture and exited from the opposite side with unidirectional flow in the gap between the anode 14 and die mold surface 17. Plating conditions used were:
______________________________________Current 150 A/dm.sup.2Flow Volume (transverse) 12 liters/minFlow Velocity (average) 2.5 m/secGap, between anode and mold 1.6 mmTime 25 secTotal Current 30Copper Sulfate 1.5 moles/literSulfuric Acid 0.5 moles/literTemperature 50° C.______________________________________
On completion of the initial plating, the flow velocity was decreased to 0.6 m/sec and plating continued for another 5 sec to obtain nodular copper on the surface 11 of the electroplate 16.
Although, the invention is described herein with acid electroplating solutions, other commonly used electroplating solutions, such as neutral and alkaline solutions, may be used.
While the forms of the invention herein disclosed constitute presently preferred embodiments, many others are possible. It is not intended herein to mention all of the possible equivalent forms or ramificiations of the invention. It is to be understood that the terms used herein are merely descriptive rather than limiting, and that various changes may be made without departing from the spirit or scope of the invention.
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A die used for plastic injection molding is masked on its inner surface with a plating resist to leave only a selected area exposed. A conforming anode is fit into the die leaving a small clearance between the die cavity surface and the anode. A metal layer is electroplated onto the exposed mold surfaces of the die in less than a minute by using a high current density and a turbulent flow of electroplating solution. The die is then assembled with a second die to form a mold. A plastic molding composition is injected into the mold cavity and comes in contact with and adheres to the metal electroplate more tightly than the metal electroplate adheres to the surface of the mold member. As the mold is separated, the metal electroplate remains bonded to the plastic molding composition to form a metal-clad plastic article. Adhesion between the metal electroplate and the plastic can be improved by forming nodular growths on the metal electroplate. This is done by varying the current density and/or the electroplating solution flow-rate near the end of the electroplating process. The electroplating and molding steps may be sequentially combined into an automated process for the continuous production of metal-clad articles.
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CROSS-REFERENCES TO RELATED APPLICATIONS
The present application is a continuation of U.S. patent application Ser. No. 14/135,695, filed Dec. 20, 2013, which is a divisional of U.S. patent application Ser. No. 12/109,921, filed Apr. 25, 2008, now U.S. Pat. No. 8,623,038, issued Jan. 7, 2014, which claims the benefit of U.S. Provisional Application No. 60/914,179, filed Apr. 26, 2007, all of which are incorporated herein in their entirety by reference.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to a planning device generating control data for a treatment apparatus for refraction-correcting ophthalmic surgery, said apparatus using a laser device to separate a corneal volume, which is to be removed for correction, from the surrounding cornea by at least one cut surface in the cornea. The invention further relates to a treatment apparatus for refraction-correcting ophthalmic surgery, said apparatus comprising a planning device of the aforementioned type.
The invention further relates to a method of generating control data for a treatment apparatus for refraction-correcting ophthalmic surgery, which apparatus uses a laser device to separate a corneal volume, which is to be removed for correction, from the surrounding cornea by at least one cut surface in the cornea.
Finally, the invention also relates to a method for refraction-correcting ophthalmic surgery, wherein a corneal volume, which is to be removed for correction, is separated from the surrounding cornea by at least one cut surface formed in the cornea by a treatment apparatus comprising a laser device.
2. Background
In the prior art, the most diverse treatment methods aiming to correct refraction of the human eye are known. The aim of said surgical methods is to selectively modify the cornea so as to influence the refraction of light. Various surgical methods are employed for this purpose. The most common method is presently the so-called laser in situ keratomileusis, also abbreviated as LASIK, wherein a corneal lamella is first detached on one side and folded aside. The detachment of said lamella can also be effected using a mechanical microkeratome or a so-called laser keratome as distributed, for example, by Intralase Corp., Irvine, USA. Once the lamella has been detached and folded aside, the LASIK operation provides for the use of an excimer laser which ablates the corneal tissue thus exposed under the lamella. After a volume located beneath the corneal surface has been evaporated in this manner, the corneal lamella is folded back in its original place.
The application of a laser keratome for exposing the lamella is advantageous as compared to a mechanical knife, because it reduces the risk of infection while improving the cut quality. In particular, the lamella may be produced with a much more constant thickness if laser radiation is used. Also, the cut is generally smoother, which reduces the risk of subsequent optical impediments by this boundary surface which still remains after surgery. However, this method has the disadvantage of requiring the use of two different treatment apparatuses, namely the laser keratome for exposing the lamella, on the one hand, and the laser evaporating the corneal tissue, on the other hand.
These disadvantages are overcome by a method recently implemented by Carl Zeiss Meditec AG and abbreviated by the term FLEX. In this method, a femtosecond laser is used to form such a cut geometry in the cornea that a corneal volume (a so-called lenticle) is separated within the cornea. This corneal volume is then removed manually by the surgeon. The advantage of this method is, on the one hand, that the cut quality is further improved by the use of the femtosecond laser. On the other hand, only one treatment apparatus is required because the excimer laser is no longer employed.
When generating cut surfaces in the cornea by laser radiation, the optical radiation effect is usually taken advantage of to generate an optical breakthrough. It is also known to introduce individual pulses, whose energy is below a threshold value for an optical breakthrough, into the tissue or the material in a superimposed manner such that a separation of material or tissue is also achieved thereby. This concept of cut generation in the corneal tissue allows a great variety of cuts.
The result of treatment remaining in these described laser-surgical methods is a cut in the cornea, and although it is no longer visible to the naked eye after a short time, it never heals due to the particular nature of the cornea, because the cornea is “dead” tissue in this respect. Due to the cut, the parts of tissue above the cut are no longer fixedly connected to the parts of tissue below the cut.
However, a need for re-treatments may arise, namely if either the result of the previous operation is not yet satisfactory in terms of the correction of refraction, or if the previous operation was not sufficiently completed for any reason (e.g. due to termination of the operation).
In the case of an insufficient refractive correction, it is known for the excimer laser-based LASIK operation to lift off the corneal lamella again and to remove additional corneal tissue for re-treatment.
However, this approach is impractical for the FLEX method, because it would not allow a re-treatment to be carried out by the same device as for the previous operation, so that it would be mandatory to keep an extra device ready merely for re-treatments.
For terminated laser-based FLEX operations, in fact, no useful or safe solution is known at all.
SUMMARY OF THE INVENTION
Therefore, it is an object of the invention to provide a planning device for generating control data, a treatment apparatus for refraction-correcting ophthalmic surgery, as well as a method of generating control data for such treatment apparatus or a method for refraction-correcting ophthalmic surgery, which simply enables re-treatment without ablation of corneal tissue or continuation of a terminated treatment, respectively.
According to the invention, this object is achieved by a planning device of the above-mentioned type. The planning device comprises an interface for receiving corneal data including information on pre-operative cuts which were generated in a previous ophthalmic operation and computing means for defining a corneal cut surface. The computing means confines the corneal volume to be removed and defines the corneal cut surface on the basis of the corneal data, then generates a corneal cut surface control dataset for control of the laser device.
The object is further achieved by a treatment apparatus for refraction-correcting ophthalmic surgery. This treatment apparatus comprises an interface, a laser device, and a planning device. The interface supplies the corneal data including information on pre-operative cuts which were generated in a previous ophthalmic surgery. The laser device separates a corneal volume, which is to be removed, from the surrounding cornea by at least one cut surface formed in the cornea by laser radiation according to control data. The planning device may be of the type just mentioned, which generates the control data.
The object is finally also achieved by a method of generating control data according to the above-mentioned type, said method comprising: accessing corneal data, which include information on pre-operative cuts generated in a previous ophthalmic operation; defining a corneal cut surface, which confines the corneal volume to be removed, on the basis of the corneal data, and generating a control dataset for the corneal cut surface for control of the laser device.
Finally, the object is also achieved by a method of refraction-correcting ophthalmic surgery, which comprises: accessing corneal data, which include information on pre-operative cuts generated in a previous ophthalmic operation; defining a corneal cut surface, which confines the corneal volume to be removed, on the basis of the corneal data, and generating a control dataset for the corneal cut surface; transmitting the control data to the treatment apparatus, and generating the cut surfaces by control of the laser device using the control dataset.
The object is further achieved by the use of a treatment apparatus for a refraction-correcting ophthalmic operation, said treatment apparatus comprising a laser device, which forms a cut surface in cornea by pulsed laser radiation in order to isolate in the cornea a corneal volume which is to be removed for correction, said ophthalmic operation being effected as a re-treatment of a previous operation which left cuts in the cornea.
Because the inventors realized that such an apparatus can be applied in a surprisingly unproblematic manner to cases in which cuts have already been made pre-operatively in the cornea, this concept provides for a re-treatment using an apparatus known for the FLEX method.
Thus, the invention quite generally provides for generating at least one additional cut surface in the cornea, which cut surface isolates a corneal volume whose removal results in the desired refractive correction. In the state of the art, such corneal volume is also referred to as a lenticle, because it is lenticular in most cases.
By taking into consideration the pre-operative cuts, i.e., those cuts already existing as a result of the previous operation, a re-treatment can now be carried out both in cases where a residual correction of refraction is still required and in cases where the previous operation was not duly completed, i.e., terminated. Particularly in the latter cases, there has been no suitable means whatsoever in the prior art to achieve a correction of refraction by an ophthalmic method.
A re-treatment is advantageously carried out such that the corneal cut surface defined by the planning device, by the planning method, the corneal cut surface generated by the treatment apparatus, or the treatment method does not intersect the pre-operative cuts. This has the advantage of avoiding any undesired isolation of volumes in the cornea which are possibly removed from the cornea along with the removal of the actually intended volume and lead to an unpredictable alteration of the corneal surface. Further, this also avoids undesired weakening when folding aside the lamella isolated during re-treatment or undesired folding aside of further parts of the cornea, in a manner not intended, which folding could occur due to an insufficiently considered pre-operative cut.
Such negative occurrences during re-treatment can be avoided in a particularly reliable manner if the computing means of the planning device or the corresponding planning method, respectively, define the cut surface in the cornea such that the corneal volume to be removed is located completely posterior to the pre-operative cuts generated, completely anterior to the pre-operative cuts, or encloses the pre-operatively generated cuts.
The first or second variant are particularly suitable in cases where the previous operation went according to plan, but a residual eyesight defect still has to be corrected. The third variant is suitable in cases where the previous operation—for whatever reasons—was terminated, because the remaining pre-operative cuts, whose position may possibly not be determined with absolute precision, are removed from the cornea when removing the corneal volume isolated by the re-treatment.
On the other hand, if the position of the pre-operative cuts is, or can be determined, with sufficient precision, an alternative of the invention allows the corneal cut surface to be defined as a continuation of the pre-operative cuts.
Because the existing pre-operative cuts have to be taken into consideration, the planning of the corneal cut surface is of particular importance in the case of a re-treatment. This planning is facilitated for the surgeon if a display device for visual representation of the cornea and of the existing pre-operative cuts, preferably in a superimposed representation, is provided.
It is a particular advantage that specific data can be used for planning and execution of the re-treatment. These may be data of the previous operation, which are stored in the apparatus; diagnostic data of the eye to be treated, which were acquired after the previous operation and prior to the re-treatment; or data of the eye to be treated, which were acquired intra-operatively, i.e. during re-treatment. Advantageously, such corneal data can be generated on the basis of a measurement of the eye and can be supplied to the planning device, in which case a measurement device is used which optionally comprises one or more of the following devices: autorefractor, refractometer, keratometer, aberrometer, wavefront measurement device, OCT, confocal corneal microscopy, Scheimpflug camera, and topographic measurement.
If a re-treatment is carried out due to a residual need for correction, i.e. if the previous operation was completed according to plan, a particularly important detail is, of course, the eyesight defect to be corrected and/or the thickness and/or diameter of a pre-operatively generated corneal lamella which can be folded aside.
A re-treatment can be carried out more easily or precisely when accurate knowledge of the pre-operatively existing cut is available. Therefore, it is advantageous, quite generally and independently of the realization of the re-treatment, if a laser-surgical treatment apparatus for refractive ophthalmic surgery comprises a device which logs the progress of the generated cuts during an operation. If the treatment apparatus uses pulsed laser radiation, said logging may include the position and the energy of each laser radiation pulse focused into the cornea. The relative position of the cornea (or the eye, respectively) and of the apparatus is also logged. Such logging is unknown in the prior art. In fact, such logging goes far beyond the usual extent of available information which comprises information on the patient, the need for correction of refraction and, at best, the cut surface geometry used. Accordingly, the data storage volume is advantageous, even though considerable in volume, when a re-treatment is required, especially if the previous operation was not completed. If so, simple and precise continuation of the terminated cut surface generation is then possible.
For re-treatment, the invention provides for the defined or used cut surfaces to be geometrically arranged such that either no intersection occurs at all with the pre-operative, already existing cut or that this cut is suitably supplemented or continued.
Several cases are distinguished. In the case of a subsequent refractive correction by which the previous method is duly completed, the additional cuts can be arranged such that they are located less deeply below the corneal surface than the pre-operatively existing cut which was generated to fold the corneal lamella aside. As an alternative, it is possible to arrange the corneal cut surface at a greater depth than the pre-operatively existing cut. The lenticle to be removed is then removed from a corneal region which is located below the pre-operatively generated corneal lamella. By contrast, the lenticle may be located within the corneal lamella in the first-mentioned case.
These variants, as with the variant in which the corneal volume encloses the pre-operatively existing cut, are based on the concept that the corneal volume to be removed, usually in the shape of a lenticle, is generated without re-using the pre-operative cuts, e.g. by a separate flap cut as well as a separate lenticle cut.
As an alternative, it is possible to use the already existing pre-operative cut and to define the corneal cut surface such that the corneal cut surfaces supplement or utilize the pre-operative cut when isolating the corneal volume to be removed by re-treatment. The lenticle is then limited by the pre-operatively existing cut as well as by the defined corneal cut surface. Cut surfaces are thus generated more quickly. However, this protocol requires precise knowledge of the pre-operative cut. Supplementing may accordingly be effected above the pre-operative cut, i.e. through the corneal lamella or below the pre-operative cut, i.e. towards the inner surface of the cornea.
In the case of a re-treatment preceded by a previous operation that was not completed, there is always the problem that, depending on how the pre-operative cut was generated, there may exist only incomplete cut surfaces. For example, a lenticle cut intended to posteriorly limit the corneal volume that should have been removed by the previous operation may have been carried out completely or partially. However, there may possibly be also a partial or even nearly complete flap cut which was intended to limit the lenticle anteriorly. There may also be a case in which the peripheral cut, which allows the corneal lamella to be folded aside, is the only cut which has not been completed. In each case, it is often adequate to continue these cuts if the pre-operatively generated cuts are precisely known. The continuation may also be such that the cut surface includes part of the pre-operative cut already generated, i.e. generating the re-treatment cut surface is begun in a region in which a pre-operative cut is already expected. An overlap ensures continuous separation of tissue by the combined effect of the pre-operative cut and of the cut surface generated during re-treatment. If it is not desired to continue the pre-operative cuts, e.g. because their positions are not sufficiently precisely known or the quality of these cuts is not satisfactory, the cut surface for isolation of the corneal volume to be removed is often conveniently defined such that it is either completely anterior to the pre-operative cuts, completely posterior to the pre-operative cuts, or confines the pre-operative cuts in the corneal volume to be removed.
As the discussion of the re-treatment shows, it may be important to determine the position of the pre-operative cut in order to position the corneal cut surfaces as exactly as possible. Alternatively,
1. The position of the pre-operative cut is measured by diagnostic methods prior to carrying out the re-treatment. The diagnostic methods may comprise confocal microscopy of the cornea, optical coherence tomography, or the use of a slit lamp with a measurement camera connected thereto.
2. Position data of the pre-operative cuts can be derived from internal data from the apparatus by which the previous operation was conducted. Thus, in planning the re-treatment, input data used to plan the previous operation and/or data acquired during execution of the previous operation may be used. Examples of data which can be acquired during execution of the previous operation include: data from an intra-operative measurement of the residual stroma thickness, data concerning the time at which the operation was terminated and/or data concerning the real position of the cuts generated by the previous operation.
3. Position data concerning the pre-operatively generated cuts during the re-treatment can also be determined by a measurement system provided in the apparatus for the re-treatment. Stated otherwise, the position data concerning the pre-operatively existing cuts may be intraoperatively determined. Such a measurement system may use a confocal sensor or optical principles of coherence tomography. It is also possible to execute a test cut using the treatment apparatus and to derive the position of the pre-operatively existing cut from the data of an observation camera.
Describing the position of the pre-operatively existing cut generally requires the complete indication of the function z(x,y) for all pairs of coordinates (x,y) of the cut area. However, a considerable reduction of parameters is possible, e.g. for a circular flap of homogeneous thickness. In this case, it is sufficient to determine flap thickness, flap diameter, and the position of the flap's center.
During execution of a laser-surgical operation carried out using pulsed laser radiation, the position of the laser focus follows a previously computed trajectory {right arrow over (s)}(t):=R 1 →R 3 , with tεI=[0,T]⊂R, for the purpose of generating a two-dimensional cut surface S:=R 2 →R 3 . R is the quantity of real numbers and R n is the n th dimension Euclidian vector space.
Individual partial cut surfaces S j ⊂S are sequentially represented by {right arrow over (s)}(t), i.e. for each partial cut surface S j , there is exactly one interval I j =[t 1 ,t 2 ] j from which the trajectory {right arrow over (s)}(t) of S j comes. Due to the strict sequencing of the cut surfaces S j in the trajectory {right arrow over (s)}(t), the individual intervals are disjoint, i.e.
∃! I j ⊂I|∀tεI j |{right arrow over (s)} ( t )ε S j ^∀i≠j|I i ∩I j =Ø
holds true.
The trajectory {right arrow over (s)}(t) can be computed, for a specific laser therapy, together with the corresponding set of disjoint intervals I j . During laser therapy, the parameter t passes through the interval I=[0,T]. The therapy is complete as soon as t=T or at least
∀
k
∈
⋃
j
I
j
|
t
≥
k
.
If the therapy is terminated at t=t int , the intervals I j determine at which cut surface the termination took place, or how far this cut surface has been completed. A partial cut surface S j is complete when ∀kεI j |k≦t int holds true. Thus, in order to determine the location where the therapy was terminated, it is sufficient to determine the time at which it was terminated. It is possible here to determine the time within a certain tolerance, i.e. for example at a resolution of 1% of T.
Determining the termination time makes logging easier and safer. Therefore, it is advantageous to simplify logging such that it does not involve logging the position of each laser radiation pulse emitted into the cornea, but merely the logging of parameters of the emission of laser radiation pulses (e.g. frequency of the pulses), of focus deflection (e.g. deflection speed), as well as indicating the exact time of any termination of the operation and cut geometry data.
It is not decisive for the invention how the pre-operative cuts were generated. Thus, in principle, they may also have been generated using a mechanical microkeratome or the like.
It will be appreciated that the above-mentioned features and those yet to be explained below can be employed not only in the combinations indicated, but also in other combinations or alone, without departing from the scope of the present invention.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be explained in more detail below with reference to the enclosed drawings, which also disclose features essential to the invention and wherein:
FIG. 1 shows a schematic representation of a treatment apparatus comprising a planning device for a re-treatment in connection with ophthalmic correction of refraction;
FIG. 2 shows a schematic representation of the effect of the laser radiation used in the treatment apparatus of FIG. 1 ;
FIG. 3 shows a further schematic representation of the treatment apparatus of FIG. 1 with respect to the introduction of the laser radiation;
FIG. 4 shows a schematic sectional view of the cornea, illustrating the removal of the corneal volume in connection with the ophthalmic correction of refraction;
FIG. 5 shows a schematic representation relating to the construction of the treatment apparatus of FIG. 1 with particular reference to the planning device present;
FIG. 6 shows a schematic sectional view of the cornea in connection with the ophthalmic correction of refraction in a re-treatment for correction of a residual eyesight defect;
FIG. 7 shows a schematic sectional view of the cornea in connection with the ophthalmic correction of refraction in a re-treatment for continuation of a terminated previous operation;
FIG. 8 shows a further schematic sectional view of the cornea in connection with the ophthalmic correction of refraction in a re-treatment for continuation of a terminated previous operation by continuing the existing cut surface; and
FIG. 9 shows a further schematic sectional view of the cornea in connection with the ophthalmic correction of refraction in a re-treatment for correction of a residual eyesight defect, using the existing cut surface.
DETAILED DESCRIPTION
A treatment apparatus for ophthalmic correction of refraction is shown in FIG. 1 and generally indicated at 1 . The treatment apparatus 1 is provided for re-treating correction of refraction to the eye 2 of a patient 3 . For this purpose, the treatment apparatus 1 comprises a laser device 4 , which emits a laser beam 6 from a laser source 5 , said beam being directed as a focused beam 7 into the eye 2 or into the cornea. The laser beam 6 is preferably a pulsed laser beam having a wavelength of between 400 nanometers and 10 micrometers. Further, the pulse duration of the laser beam 6 is in the range of between 1 femtosecond and 10 picoseconds, with pulse repetition frequencies of from 1 to 1000 kilohertz and pulse energies of between 0.01 microjoules and 0.01 millijoules being possible. Thus, the treatment apparatus 1 generates a cut surface in the cornea of the eye 2 by deflection of the pulsed laser radiation. For this purpose, the laser device 4 or its laser source 5 , respectively, also includes a scanner 8 as well as a radiation intensity modulator 9 .
The patient 3 is lying on a table 10 , which is shiftable in three spatial directions in order to align the position of the eye 2 with the incidence of the laser beam 6 . In a preferred construction, the table 10 is shiftable by a motor drive.
Control may be effected, in particular, by a control device 11 , which generally controls the operation of the treatment apparatus 1 and is connected to the treatment apparatus via suitable data links, for example connecting lines 12 , for this purpose. This communication may, of course, be effected also via other paths, e.g. by light guides or by radio. The control device 11 performs the corresponding settings, time control of the treatment apparatus 1 , in particular of the laser device 4 , and thus performs corresponding functions of the treatment apparatus 1 .
The treatment apparatus 1 further comprises a fixing device 15 which positionally fixes the cornea of the eye 2 with respect to the laser device 4 . This fixing device 15 may comprise a known contact glass 45 with which the cornea is placed in contact by a vacuum and which imparts a desired geometrical shape to the cornea. The person skilled in the art is familiar with such contact glasses from the prior art, for example from DE 102005040338 A1. The disclosure of this document is fully incorporated herein by reference as far as the description of a construction of the contact glass 45 usable for the treatment apparatus 1 is concerned.
The control device 11 of the treatment apparatus 1 further comprises a planning device 16 , which will be explained in more detail below.
FIG. 2 schematically shows the effect of the incident laser beam 6 . The laser beam 6 is focused and is incident in the cornea 17 of the eye 2 as the focused laser beam 7 . Schematically indicated optics 18 are provided for focusing. They effect a focus in the cornea 17 , in which focus the laser radiation energy density is so high that, in combination with the pulse duration of the pulsed laser radiation 6 , a non-linear effect appears in the cornea 17 . For example, each pulse of the pulsed laser radiation 6 in the focus 19 may produce an optical breakthrough in the cornea 17 , which in turn initiates a plasma bubble indicated only schematically in FIG. 2 . When the plasma bubble forms, the tissue layer separation comprises an area larger than the focus 19 , although the conditions for producing the optical breakthrough are achieved only in the focus 19 . In order for an optical breakthrough to be generated by each laser pulse, the energy density, i.e. the fluence of the laser radiation, must be above a certain pulse duration-dependent threshold value. This connection is known to the person skilled in the art, for example, from DE 69500997 T2. Alternatively, a tissue-separating effect can also be achieved by pulsed laser radiation in that several laser beam radiation pulses are emitted in a region where the focus spots overlap. In this case, several laser radiation pulses cooperate to achieve a tissue-separating effect.
However, the type of tissue separation used by the treatment apparatus 1 is not really relevant to the following description; it is only essential that a cut surface is generated in the cornea 17 of the eye 2 .
Now, in order to perform an ophthalmic correction of refraction, a corneal volume is removed from a region within the cornea 17 by means of the laser radiation 6 , separating tissue layers therein which isolate the corneal volume and enable the removal of the latter then. For isolation of the corneal volume to be removed, the position of the focus 17 of the focused laser radiation 7 in the cornea 17 is shifted, for example in cases where pulsed laser radiation is introduced. This is schematically shown in FIG. 3 . The refractive properties of the cornea 17 are selectively modified by removal of the volume so as to achieve the correction of refraction. Therefore, said volume is lenticular in most cases and is referred to as a lenticle. The removal of the corneal volume is effected here as a re-treatment. It was either preceded by an ophthalmic correction of refraction, which left a residual need for correction, or is even an ophthalmic correction of refraction terminated during the operation, wherein the cut surfaces were generated incompletely. Of course, this also creates a need for correction.
FIG. 3 shows the elements of the treatment apparatus 1 only insofar as they are required in order to understand how the cut surfaces are produced. As already mentioned, the laser beam 6 is bundled in a focus 19 in the cornea 17 , and the position of the focus 19 in the cornea is shifted such that focused energy from laser radiation pulses is introduced into the tissue of the cornea 17 at different locations so as to produce cut surfaces. The laser radiation 6 is preferably provided as pulsed radiation by the laser source 5 . The scanner 8 has a two-part design in the construction of FIG. 3 and consists of an xy-scanner 8 a , which is realized, in one variant, by two galvanometer mirrors with substantially orthogonal deflection. The scanner 8 a two-dimensionally deflects the laser beam 6 coming from the laser source 5 , so that a deflected laser beam 20 is present downstream of the scanner 8 . Thus, the scanner 8 a causes shifting of the position of the focus 19 substantially perpendicular to the main direction of incidence of the laser beam 6 in the cornea 17 . For shifting of the depth position, a z-scanner 8 b , preferably in the form of an adjustable telescope, for example, is provided in addition to the xy-scanner 8 a in the scanner 8 . The z-scanner 8 b ensures that the z-position of the focus 19 , i.e. its position along the optical axis of incidence, is changed. The z-scanner 8 b may be arranged preceding or following the xy-scanner 8 a.
It is not essential for the functional principle of the treatment apparatus 1 how the individual coordinates are assigned to the spatial directions nor that deflection by the scanner 8 a is effected along mutually orthogonal axes. On the contrary, any scanner may be used which can shift the focus 19 in a plane in which the axis of incidence of the optical radiation is not located. Further, any non-Cartesian coordinate systems whatsoever can be used for deflection or control of the position of the focus 19 . Examples include spherical coordinates or cylindrical coordinates.
The position of the focus 19 is controlled by the scanners 8 a , 8 b under the control of the control device 11 , which performs suitable settings of the laser source 5 , of the modulator 9 (not shown in FIG. 3 ) as well as of the scanner 8 . The control device 11 ensures suitable operation of the laser source 5 as well as the three-dimensional focus shift described here as an example, thus finally producing a cut surface which isolates a determined corneal volume that is to be removed for correction of refraction.
The control device 11 works according to predetermined control data, which are predefined, for example, in the laser device 4 described here merely as an example, as target points for focus shifting. The control data are usually compiled in a control dataset, which provides geometrical parameters for the cut surface to be formed, e.g. the coordinates of the target points as a pattern. In this embodiment, the control dataset then also includes concrete set values for the focus position shifting mechanism, e.g. for the scanner 8 .
FIG. 4 shows an example of how to produce the cut surface using the treatment apparatus 1 . A corneal volume 21 is isolated in the cornea 17 by shifting the focus 19 , into which the focused beam 7 is bundled. For this purpose, cut surfaces are formed, which are provided here, by way of example, as an anterior flap cut surface 22 as well as a posterior lenticle cut surface 23 . These terms are to be understood here merely as examples and are intended to establish a relation to the conventional LASIK or FLEX methods, for which the treatment apparatus 1 is provided, as already described. It is only essential here that the cut surfaces 22 and 23 as well as peripheral cuts, which are not referred to in detail and which make the cut surfaces 22 and 23 converge at their peripheries, isolate the corneal volume 21 . By means of an opening cut 24 , a corneal lamella anteriorly limiting the corneal volume 21 can further be folded aside so as to allow removal of the corneal volume 21 .
FIG. 5 schematically shows the treatment apparatus 1 , by reference to which the planning device 16 shall be explained in more detail. In this variant, the treatment apparatus 1 comprises at least two devices or modules. The laser device 4 already described emits the laser beam 6 onto the eye 2 . As already described, operation of the laser device 4 is effected fully automatically by the control device 11 , i.e., the laser device 4 starts generating and deflecting the laser beam 6 in response to a corresponding start signal and, thus, generates cut surfaces, which are structured as described, in order to remove the corneal volume 21 . The laser device 5 receives the control signals required for operation from the control device 11 , to which corresponding control data have been provided before. This is effected by the planning device 16 , which is shown in FIG. 6 merely by way of example, as part of the control device 11 . Of course, the planning device 16 may also be provided separately and may communicate with the control device 11 either in a wire-bound or wireless manner. It is then only essential to provide a corresponding data transmission channel between the planning device 16 and the control device 11 .
The planning device 16 generates a control dataset which is provided to the control device 11 to carry out the ophthalmic correction of refraction. In doing so, the planning device uses measurement data relating to the cornea of the eye. In the presently described embodiment, these data come from a measurement device 28 , which has previously measured the eye 2 of the patient 2 . Of course, the measurement device 28 may have any design whatsoever and may transmit the corresponding data to the interface 29 of the planning device 16 .
Now, the planning device assists the user of the treatment apparatus 1 in defining the cut surface for isolation of the corneal volume 21 . This may even include a fully automatic definition of the cut surfaces, which may be effected, for example, by the planning device 16 using the measurement data to determine the corneal volume 21 to be removed, whose boundary surfaces are defined as cut surfaces, and generating therefrom suitable control data for the control device 11 . At the other end of the degree of automation, the planning device 16 may provide input means by which a user inputs the cut surfaces in the form of geometrical parameters, etc. Intermediate steps provide suggestions for the cut surfaces, which the planning device 16 generates automatically and which can then be modified by an operator. Basically, all the concepts already explained in the above, more generic part of the description, can be applied here in the planning device 16 .
In order to perform a re-treatment, the planning device 16 generates control data for cut surface production, which are then used in the treatment apparatus 1 . FIG. 6 shows an example of the possible location of the cut surfaces, wherein the cut surfaces corresponding to those of FIG. 4 bear the same reference symbols. Now, the essential difference to the situation of FIG. 4 is that there already is an older cut 30 in the cornea 17 , which cut resulted from a previous operation, e.g. from an operation according to the FLEX method. In FIG. 6 as well as in the subsequent figures, the older cut 30 is indicated by a dot and dash line. For distinction from the older cut 30 , the cut surfaces intended for re-treatment are indicated by a dashed line.
As FIG. 6 shows, the control data are defined such that the re-treatment cut surfaces eliminating the residual need for correction are all located beneath the older cut 30 . Thus, with respect to the older cut 30 , the corneal volume 21 to be removed is generated posteriorly, for example by a lenticle cut 23 and by a flap cut 22 , including a lateral opening cut 24 . This avoids any undesired interference with the older cut 30 .
In a modification (not shown) of the cut surfaces of FIG. 6 , all the cut surfaces provided or used for re-treatment may also be located within the corneal lamella 31 which has been generated between the older cut 30 and the anterior surface of the cornea 17 .
FIG. 7 shows a further variant which is applicable, in particular, if there is no sufficiently exact knowledge about the extent to which the older cuts were carried out. The re-treatment cut surface, e.g. comprising a lenticle cut 23 and a flap cut 22 , is now defined such that the older cuts 30 (again indicated by a dot and dash line) are located completely within the corneal volume 21 being removed for correction. This approach has the advantage that the number of boundary surfaces remaining in the cornea after the operation is small.
FIG. 8 shows a possibility which is applicable, in particular, if the positions of the older cuts are particularly well known. The re-treatment cut surfaces are then provided as continuations of the older cut 30 . This is applicable, of course, where the previous operation was unintentionally terminated.
A further method of using older cuts is shown in FIG. 9 , wherein the corneal volume 21 to be isolated is defined by both older cuts 30 and cut surfaces produced during re-treatment. As an example, the use of the older cut 30 as a flap cut is shown here, which is supplemented by a lenticle cut 23 generated in the re-treatment. This is to be understood as an example, of course, and it is also possible to use a cut extending into the lamella 31 as a supplement in the re-treatment.
In addition, it should also be noted that the treatment apparatus 1 or the planning device 16 , respectively, also specifically realizes the method which was generally explained above.
A further embodiment of the planning device exists in the form of a computer program or of a corresponding data carrier comprising a computer program and realizing the planning device on a suitable computer so that the measurement data or the transplantation material data are input to the computer by suitable data transmission means and the control data are transmitted from this computer to the control device 11 , for which purpose data transmission means known to the person skilled in the art are, in turn, suitable.
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A planning device generating control data for a treatment apparatus for refraction-correcting ophthalmic surgery is provided, said apparatus using a laser device to separate a corneal volume, which is to be removed for correction, from the surrounding cornea by at least one cut surface in the cornea of an eye, said planning device comprising an interface for receiving corneal data including information on pre-operative cuts which were generated in a previous ophthalmic operation, and computing means for defining a corneal cut surface which confines the corneal volume to be removed, said computing means defining the corneal cut surface on the basis of the corneal data and generating a control dataset for the corneal cut surface for control of the laser device.
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This application claims the benefit of U.S. patent application Ser. No. 09/561,999 filed May 1, 2000, now U.S. Pat. No. 6,419,843 which claimed the benefit of provisional patent application No. 60/135,476 filed May 24, 1999.
FIELD OF USE
The invention relates generally to applications whereby it is desirous to introduce or reintroduce gas with liquid flowing through pipes, and/or mix two fluids within a pipe. In particular, this method can be used, but is not so limited, to mix and entrain air and other odorous gas emissions into sewage to reduce odorous gas emissions and to reduce hydrogen sulfide corrosion and abrasive wear in waste water conveyance, collection and treatment systems.
BACKGROUND OF THE INVENTION
Throughout past decades, sewers have been utilized to efficiently transport waste water or sewage from locations where it was generated to waste water treatment plants and other destinations. These sewers consist generally of pipelines locate below ground level and oriented with a slight downward grade in the direction of the sewage flow. Gravity acts upon the sewage to cause it to flow within the pipelines toward its ultimate destination. These pipelines are sometimes interconnected by “drop structures” that allow the sewage to flow from one line into the drop structure, drop vertically therewithin, and then to flow out of the drop structure into additional pipes or other structures.
One problem that occurs during the transport of sewage is the release of sulfides from the sewage. Sulfides form as a result of bacterial reduction of sulfates within the sewage in an anaerobic environment. As sewage ages, the level of sulfides increases. Drop structures within a sewer system can provide a beneficial aeration of the sewage flow by introducing additional dissolved oxygen into the flow. The dissolved oxygen reacts with the sulfides, resulting in less chemical volatility in the sewage. This aeration is particularly beneficial where the sewage is fresh and contains a relatively small amount of dissolved sulfides, such as hydrogen sulfide (H 2 S).
Unfortunately, in most practical applications, sewage contains a significant amount of potentially volatile dissolved molecular hydrogen sulfide gas. Turbulence within the sewage flow can cause this dissolved gas to be released into the surrounding air. Significant sources of turbulence in sewage flow, and hence the emission of hydrogen sulfide gas in a sewer, occur in drop structures such as interceptor drop maintenance holes, joint structures, forcemain discharges and wet well drops in sewer pumping stations. Thus, while drop structures can reintroduce dissolved oxygen into the sewage flow, lowering the level of hydrogen sulfide gas, they can also cause the release of hydrogen sulfide gas. The hydrogen sulfide emissions often cause corrosion with the drop structures and adjacent sewer lines, and cause odor problems even the most elegant, pristine neighborhoods.
One known type of drop structure comprises an influent line, a maintenance hole and an effluent line. The influent line runs almost horizontally at a relatively shallow depth below the ground surface in the form of a pipe. The maintenance hole is located below the street level maintenance hole manhole cover. The maintenance hole is generally cylindrical in shape with a vertical longitudinal axis. The effluent line is another almost horizontal pipe that exits slightly above the bottom of the maintenance hole. Turbulent waste water flow is created when the sewage, which has a substantial amount of potential energy, exits from the influent line near the top of the maintenance hole and tumbles down like a waterfall to the side wall and base of the maintenance hole. Then the sewage pools and eventually flows out the effluent line. This turbulent action releases hydrogen sulfide gas into the air. To reduce the problem of gas release, while still allowing beneficial aeration of the sewage, the potential and kinetic energy in the sewage must be dissipated.
One known method is to create a wall hugging spiral flow down the maintenance hole to dissipate the energy by friction. The spiral flow is generated by the insertion of a vortex form connected to the influent line near the top of the maintenance hole. The vortex form is generally helical in shape and is placed directly below the manhole cover near the top of the maintenance hole. The vortex form channels and diverts the flow from its languid state into a spiral flow descending down the cylindrical wall of the maintenance hole. The vortex form can be made of concrete with applied protective coating, or made of a noncorrosive material, metal or plastic, such as PVC, High Density Polyethylene (HDPE) or other like materials. The vortex form may be manufactured at the factory or on-site.
Two problems remain to be solved when applying this known method of using a vortex form in a drop structure for sewage flows. First, the upstream flow velocities within the influent line are usually not large enough to create a stable spiral flow on the vertical wall of a typical maintenance hole. Thus, the flow, rather than continuing to spiral down the cylindrical wall of the maintenance hole, will generally revert to a turbulent descending flow similar to waterfall, losing the effective energy dissipation of the spiral flow and releasing significant amounts of hydrogen sulfide gas into the air. Second, quite often the maintenance hole is used for additional lateral influent connections at elevations lower than the main influent pipe. Consequently, the lateral influent connections disrupt the spiral flow and create a turbulent waterfall of sewage to the bottom of the maintenance hole, again releasing significant amounts of hydrogen sulfide gas into the air. The additional influent pipe may run in any direction, but at a lower depth than the main influent pipe.
SUMMARY OF INVENTION
It, therefore, is an object of this invention to provide a method for reducing gas emissions of a fluid through the entraining and mixing of gas with the liquid.
It is also an object of this invention to provide a method for mixing gas with one or more fluids in a conduit.
Another object of this invention is to provide a method for use in sewer drop structures that significantly reduces odorous gas emissions from the sewer.
A further object of the invention is to reduce hydrogen sulfide corrosion in waste water conveyance, collection and treatment systems.
A benefit of this invention is the improved way in which the method helps to protect conveyance or collection systems from abrasive wear.
Another benefit is the way the invention in particular improves the quality of wastewater by wastewater aeration.
The foregoing objects and benefits of the present invention are provided by a method for reducing gas emission and for entraining and mixing gas with liquids. The method comprises channeling a fluid flow though one or more pipes, introducing the flow from the pipe(s) into a conduit or chamber through the use of spiral flows of predetermined radii, reducing such radii to increase centrifugal forces acting upon the flow, introducing gas into the reduced radius flow and continuing the reduced radius flow within the conduit until the gas is substantially entrained within the flow. This method can be implemented through the use of a maintenance hole and an influent line for carrying liquid to the maintenance hole, a vortex form which accepts the liquid from the influent line, the vortex form comprising a spiral channel of decreasing radius disposed substantially within the maintenance hole, and a conduit also disposed within the maintenance hole and fluidly connected to the vortex form and extending substantially downwardly from the vortex form to a flow exit near the maintenance hole base. The fluid flowing from the influent line enters the vortex form and is channeled by the vortex form into a spiral flow with a radius smaller than the maintenance hole wall radius. The reduction in the radius of the channel outer wall causes the centrifugal forces acting upon the fluid flow to increase, forcing the flow to continue in intimate contact with the outer wall of the channel. The fluid then flows from the reduced radius of the vortex channel into the conduit and, aided by gravity and the flow's acquired rotational velocity, continues its spiral descent towards the maintenance hole base, in substantially intimate contact with the conduit wall. The spiral flow then exits the conduit near the maintenance hole base into an energy dissipating pool.
The method creates an accelerated fluid flow sufficient to create substantial intimate contact with the vortex form and conduit wall throughout the fluid flow's descent in the maintenance hole. This intimate contact creates frictional forces that reduce the kinetic energy of the flow and inhibit turbulent flow. The reduction in turbulent flow in turn reduces the release of gases, including hydrogen sulfide. In addition, the spiral flow in the conduit creates an air core with reduced pressure in the center of the conduit, inhibiting the escape of any hydrogen sulfide gas into the environment and encouraging the reintroduction of any escaped gas back into the spiral flow and the energy dissipating pool.
In another embodiment of the invention, two influent lines may be used to channel the same or separate flows into the same conduit at two different but proximate locations. The influent lines can originate from a single line or from two distinct lines and may contain the same or different fluids. The flows are then introduced into the conduit through reducing-radius vortices in opposing rotational direction.
In certain embodiments of the invention, it may be advantageous to utilize a vortex form channel with a downwardly sloping base sufficient to create an accelerating spiral flow. The method may also utilize a vortex form incorporating an entrance flume designed to accept the fluid flow from the influent line and more gently direct the flow into the vortex channel. This entrance flume may also incorporate a slope to create an accelerating flow into the vortex channel.
The invention also contemplates utilizing in certain applications of the invention various conduit base configurations for allowing the fluid flow to exit the conduit into the energy dissipating pool. These flow exit paths vary based on the desired fluid flow rates, the energy dissipating pool depth, and the existence and configuration of any effluent lines running from the conduit.
While this invention is particular useful in wastewater conveyance systems, it is not so limited, and can be applied to any system where one desires to mix and entrain one or more gases, including air, into one or more fluid flows within a conduit. Additional applications for the present invention include aeration and/or purification of water in wastewater treatment plants, fishery basins, and natural streams, lakes and bays, and heat transfer in power plant cooling basins. This invention may also be applied to mix food and beverage liquids; to mix constituents in pharmaceutical applications, including applications to suspensions and emulsions; and to mix construction materials including insulation materials, fillers, and high-air concentration mortars and concrete. Thus, the particular embodiments discussed below are not exhaustive and are not intended to limit the scope of this invention.
BRIEF DESCRIPTION
Other objects, features, and advantages of the present invention will become more fully apparent from the following detailed description of certain embodiments, the appended claims, and the accompanying drawings in which:
FIG. 1 is a side elevation, cross-sectional, view of one embodiment of the present invention with a portal-type flow exit;
FIG. 2 is the cross-sectional view A—A of the embodiment illustrated in FIG. 1;
FIG. 3 is perspective view of another embodiment of the present invention with a flow exit comprising a plurality of legs;
FIG. 4 is a side elevation view of an additional embodiment of the present invention with a suspended flow exit;
FIG. 5 is a top plan view of a portion of an influent line and a vortex form;
FIG. 6 is a perspective view of one embodiment of the vortex form;
FIG. 7 is a perspective view of another embodiment of the present invention using two vortex forms from a single influent line;
FIG. 8 is a perspective view of another embodiment of the present invention using two vortex forms from two influent lines.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 illustrates in a side elevation view one embodiment of a sewer apparatus 10 constructed in accordance with the present invention. Referring to FIG. 1, the sewer apparatus 10 includes an influent line 12 , a vortex form 20 , a maintenance hole 30 , a conduit 40 , a flow exit 50 , and an effluent line 60 .
The maintenance hole 30 in which the vortex form 20 is disposed may be identified from street level as being below a manhole cover 32 . FIG. 1 shows the maintenance hole 30 as being cylindrical in shape and oriented vertically. A lateral line 33 for inputting additional city sewer flowage into the maintenance hole 30 may be disposed below the influent line 12 . The base 34 and walls 36 of the maintenance hole 30 are generally concrete. An energy dissipating pool 72 , comprised of sewage, forms at the base 34 of the maintenance hole 30 . An effluent line 60 is connected to the maintenance hole 30 near the top level of the energy dissipating pool 72 .
As illustrated in FIG. 1, sewage flows from the influent line 12 into the vortex form 20 near the top of a maintenance hole 30 . The influent line 12 is generally a cylindrical pipe running slightly below the ground surface. To create an accelerated flow of sewage, a portion of the influent line 12 can be set at a predetermined downward sloping orientation. Such an orientation is shown in FIG. 3 . The slope necessary to create a constant or accelerating velocity is known as the critical or supercritical slope, respectively. A critical slope in which the velocity of the sewage flow would remain constant is identified as having a Froude Number (Fr) equal to one. A supercritical slope in which the sewage flow is accelerating is identified as having a Froude Number greater than one (Fr>1). The Froude Number is calculated using the formula Fr=V/(g*d){fraction (1/2,)} where V represents average sewage flow velocity, d represents flow depth and g represents acceleration due to gravity, approximately 32.2 feet per second squared. Each of these factors can effect the critical slope of the influent line 12 . While the critical slope will generally occur around one to three percent, it is envisioned that the desired slope could vary anywhere from one percent or more. In the embodiment illustrated in FIG. 3, the influent line 12 descends at a supercritical slope of about ten percent slope to create an accelerated flow.
Referring again to FIG. 1, the influent line 12 connects to the vortex form 20 and maintenance hole 30 near the top of the maintenance hole 30 . The vortex form 20 is disposed within the maintenance hole 30 for receiving the sewage from the influent line 12 and is generally shaped to create a descending spiral flow. FIG. 2 presents the cross-sectional view A—A of FIG. 1, illustrating the vortex form in further detail. Referring to FIG. 2, the vortex form 20 includes a vortex channel 24 , and may in certain embodiments also include an entrance flume 22 . In the embodiment of the present invention shown in FIG. 1, the entrance flume 22 is fluidly connected to the influent line 12 . The entrance flume 22 can take on any shape capable of transporting the sewage from the influent line 12 to the vortex channel 24 . In the embodiment illistrated in FIG. 1, the entrance flume 22 consists of a base 21 and side walls 23 . The vortex channel 24 is fluidly connected to the entrance flume 22 and comprises a base 25 , an outer wall 26 , and an inner wall 27 . While the specific vortex channel shown utilizes a flat base 25 with substantially vertical side walls 26 and 27 , it is envisioned that these structures could take on any shape capable of transporting the sewage in a spiral flow.
The vortex form 20 may be made of concrete with applied protective coating, or made of a noncorrosive material, metal or plastic, such as PVC, High Density Polyethylene (HDPE) or other like materials . The vortex form 20 may be made in advance at the factory or on-site. As shown in FIGS. 3 and 4, the entrance flume 22 and/or vortex channel 24 may be manufactured and oriented with their bases having a supercritical slope, allowing the sewage to accelerate as it flows through the vortex form 20 . The selected slopes of the influent line 12 , the entrance flume base 21 , the vortex channel base 25 will not necessarily be the same. In the embodiment illustrated in FIG. 1, the influent line 12 is substantially horizontal, while the entrance flume base 21 and the vortex channel base 25 have a supercritical slope of about ten percent.
As noted, while the embodiment shown in FIGS. 1 and 2 illustrate a vortex form containing an entrance flume 22 , other embodiments of the present invention may fluidly connect the vortex channel 24 directly to the influent line 12 , omitting the use of the entrance flume 22 . Examples of such embodiments are shown in FIGS. 3, 4 , and 5 .
Referring to FIG. 2, the vortex channel 24 directs the sewage flow into a substantially spiral flow. The vortex channel 24 also reduces the radius of this spiral flow in order to increase the centripetal forces acting upon the flow. This is accomplished through the reduction in radius of the outer wall 26 , which will increase the centripetal forces applied by the outer wall 26 on the spiral flow. In the embodiment shown in FIG. 2, a radius transition section 28 supports the outer wall 26 and reduces the radius of the spiral flow created by the vortex channel 24 (shown in FIG. 2 as R 1 ) to the radius of the conduit 40 (shown as R 2 ). The radius transition section 28 also aids in directing the flow from the vortex channel 24 into the conduit 40 . The radius transition section 28 is generally made of a noncorrosive metal or plastic with concrete or a foam fill material.
To allow the sewage flow to enter the conduit 40 , inner wall 27 must include a height transition section 29 (identified on FIGS. 2, 4 , and 6 as section A-B) which allows the sewage flow to enter the conduit 40 . It is envisioned that this transition section could take many forms, including a sharp vertical cut or a gradual decrease in wall height. It has been found to be advantageous, however, to fabricate inner wall 27 such that its height profile reflects an axial flow velocity distribution. This type of cut is illustrated in FIG. 6 .
Referring again to FIG. 1, conduit 40 is disposed within maintenance hole 30 and fluidly connected to vortex channel 24 . Conduit 40 comprises a pipe wall 45 having a radius smaller than maintenance hole 30 and extending substantially downwardly from vortex form 20 . Conduit 40 further comprises a base 46 , and a flow exit path 50 near said maintenance hole base. The upper portion of the pipe wall 45 may be constructed integrally with inner wall 27 .
Still referring to FIG. 1, the sewage spirals and falls from vortex channel 24 into conduit 40 , along the inner surface 47 of pipe wall 45 . This flow continues to descend along the inner surface 47 of pipe wall 45 in a substantially spiral fashion until the sewage nears the conduit base 46 . The conduit base 46 is disposed below the surface of the energy dissipating pool 72 and at or above the base 34 of the maintenance hole 30 to create a flow exit path 50 . The sewage flow accumulates in the conduit base where it eventually flows through the flow exit path 50 , located at or near the conduit base 46 , into the energy dissipating pool 72 near the bottom of the maintenance hole 30 .
The flow exit path 50 may comprise any structure that allows the sewage flow to exit the conduit 40 at a predetermined flow rate. One example of a flow exit path is shown in FIG. 1, comprising a portal 56 in the conduit base 46 . The portal 56 allows the sewage flow that has accumulated in the conduit base 46 to exit into the energy dissipating pool 72 . Additional embodiments of the flow exit path 50 are shown in FIGS. 3 and 4. In FIG. 3, the flow exit path 50 comprises a plurality of legs 52 connected to and supporting the conduit base 46 . The plurality of legs 52 are themselves supported by the maintenance hole base 34 . The plurality of legs 52 allows the sewage flow within the conduit base 46 to be fluidly connected to the energy dissipating pool 72 and allows the sewage flow to exit the conduit base 46 at a predetermined flow rate. In FIG. 4, the flow exit path 50 comprises a suspended conduit support 80 . The suspended conduit support 80 includes a conduit anchor 82 and a vortex form base support 84 . The vortex form base support 84 is connected to both the maintenance hole side wall 36 and the maintenance hole base 34 , and supports the vortex form 20 and conduit 40 in a suspended fashion. The conduit anchor 82 , comprising a rigid structure capable of securing the conduit 40 , is connected to the maintenance hole side wall 36 and provides horizontal support for the conduit 40 . The conduit support 80 allows the conduit 40 to be suspended above the maintenance hole base 34 , thus allowing the sewage flow to exit the conduit 40 at the conduit base 46 and enter the energy dissipating pool 72 .
Once the flow has reached the energy dissipating pool 72 , it may be drawn away for further transport though an effluent line 60 , as shown in FIG. 1 . In another embodiment, shown in FIG. 4, the sewage flow may be drawn into a treatment pool 62 for further treatment.
As illustrated in FIG. 3, the present invention may utilize an air relief 70 to equalize substantially the air pressure within the maintenance hole 30 above the vortex form 20 with the air pressure within the maintenance hole 30 below the vortex form 20 and within the effluent line 60 . Air relief 70 comprises a pipe connecting the top portion of the effluent line 60 with the maintenance hole 30 above the vortex form 20 . The air relief 70 substantially equalizes the air pressures in the upper influent line 12 and the lower effluent line 60 , drawing the air from the higher pressure influent line 12 downward to the lower pressure effluent line 60 . This pressure equalization, by drawing the air through the air relief 70 into the effluent line 60 , further prevents the leakage of noxious gases not absorbed by the sewage flow within the maintenance hole 30 . These gases, dragged by the influent flow and not consumed by the spiral flow, would otherwise rise and emit from the improved sewer apparatus into the neighborhood. As illustrated in FIG. 5, in another embodiment the air relief 70 comprises a pipe extending through the vortex form, providing a path for the air to travel from the higher pressure area above the vortex form 20 to the lower pressure area below the vortex form 20 . The air relief 70 of this embodiment acts in the same fashion as the previously described embodiment to prevent the leakage of noxious gases not absorbed by the sewage flow within the maintenance hole 30 .
Referring to the embodiment illustrated in FIG. 1, in operation, incoming sewage at a small slope enters the vortex form 20 at the entrance flume 22 and descends through the vortex channel 24 . The supercritical slope of the entrance flume 22 and the vortex channel 24 provides rising flow velocities with a partial potential energy transition into kinetic energy. Even though sewage flow encounters a narrowing of the cross-section of the entrance flume 22 , the water level generally does not rise due to the flow acceleration created by the supercritical slope of the base 21 . The flow is then directed within the vortex channel 24 by the radius transition section 28 and the height reduction section 29 of the inner wall 27 into a smaller radius conduit 40 .
The sewage flow then spirals downwardly against the inside wall of the conduit 40 , creating a low pressure air core running longitudinally in the center of the conduit 40 . The low pressure air core draws air from the maintenance hole 30 above the vortex form 20 into the conduit 40 . Some of the oxygen in the air core mixes with and becomes entrained in the sewage flow, reacting with the potentially volatile dissolved hydrogen sulfide gas (H 2 S) in the liquid sewage to produce hydrogen sulfate (H 2 SO 4 ) in the solution. This reaction prevents hydrogen sulfide gas from being released into the air and then onto sewer surfaces where corrosion can occur or into the above ground neighborhood as a foul gas. The conduit 40 also helps to dissipate the high velocities and kinetic energy of the sewage flow by friction between the descending spiral flow and the conduit wall 45 . This energy reduction through friction reduces flow turbulence and thus hydrogen sulfide gas emission from the waste water liquid into the surrounding air. Without losing the flow's integrity, the gravity flow is transformed into a flow with combined gravity and centrifugal forces.
The sewage flow completes its downward spiral near the conduit base 46 , where the most intensive processes of flow mixing and aeration occur. The sewage air-flow mixture then flows out of the conduit base 46 through a flow exit 50 into an energy dissipating pool 72 for further internal mixing and friction. At the top surface of the energy dissipating pool 72 is a generally tranquil flow that leaves the maintenance hole 30 via the effluent line 60 .
As shown in FIGS. 7 and 8, other embodiments of the invention can also be used to mix and entrain gas in fluid flow within a conduit 120 . In FIG. 7, flow is channeled through influent line 12 into separate vortex forms 102 and 112 . Influent line 12 is generally a cylindrical pipe, but can take any cross-sectional shape. Depending upon the flow acceleration desired in the vortex forms 102 and 112 , the influent line 12 and the vortex forms 102 and 112 can be oriented at a variety of slopes. In addition, fluid flow pumps (not shown), known in the prior art, can be utilized to accelerate the flow within the influent line 12 . In FIG. 7, the influent line 12 is shown substantially horizontal.
The influent line 12 is fluidly connected to both vortex forms 102 and 112 . Each vortex form 102 and 112 is positioned to receive a portion of the flow from influent line 12 and each is generally shaped to create a spiral flow about the centerline 122 of conduit 120 . Vortex form 112 is positioned proximate to and downstream of vortex form 102 . In practice, it is beneficial to direct the spiral flow of vortex form 112 in a direction opposing the spiral flow created in vortex form 102 . As described in the previous embodiments, the vortex form 102 directs the fluid into a spiral of a predetermined radius (shown as R 3 ) greater than the radius (shown as R 7 ) of the conduit 120 and subsequently reduces the radius of the spiral flow (shown as R 4 ) to be equal to or less than radius R 7 of the conduit 120 to increase the centrifugal forces acting upon the fluid. Vortex form 112 directs the flow in a similar manner, creating spiral flow of predetermined radius (shown as R 5 ) and reducing the radius of a that spiral flow (shown as R 6 ).
Conduit 120 is fluidly connected to vortex forms 102 and 112 and extends downstream away from the vortex forms 102 and 112 . The downstream extension of conduit 120 may be oriented in any position from substantially horizontal to downwardly vertical, depending upon the application. Conduit 120 may also extend upstream of vortex form 102 . Conduit 120 includes an air intake 124 upstream of vortex form 102 that allows air or other gases to enter into conduit 120 and mix with flows delivered by vortex forms 102 and 112 within conduit 120 . In FIG. 7, the air intake 124 is a pipe, but could in other embodiments take any form allowing the flow of air or gases into the conduit 120 upstream of vortex form 102 . The spiral flows created by vortex forms 102 and 112 create a column of air or gas that is drawn through the air intake 124 and causes a portion of the air or gas to mix with and become entrained in the fluid flow. The conduit 120 must extend far enough downstream to allow such mixing and entrainment.
The embodiment in FIG. 8 also uses vortex forms 102 and 112 to create two spiral flows. However, in FIG. 8, each vortex form 102 and 112 receives fluid from separate influent lines 130 and 132 . The influent lines 130 and 132 may deliver the same or different fluids, and the densities of each fluid may differ. Conduit 126 is disposed within conduit 120 about centerline 122 , and receives flow from vortex form 102 . Conduit 126 can be formed separate from or integral with vortex form 102 . Conduit 126 ends proximate to vortex form 112 . Gas mixes with the spiral flow from vortex form 102 within conduit 126 . The spiral flow and gas within conduit 126 then empty into conduit 120 and mix with the spiral flow created by vortex form 112 . It is again beneficial to direct the spiral flows from vortex forms 102 and 112 in opposing directions to enhance the mixing and entrainment of the gas and fluids.
This description is intended to provide specific examples of individual embodiments which clearly disclose the present invention. By way of example only, and without limitation, the present invention could find use in drop structures having other than a circular or cylindrical configuration, thus freeing designers to construct such structures according to need. This invention can also be used in non-sewer applications where one seeks to mix gas and fluid within a conduit. Accordingly, the invention is not limited to the described embodiments, or to the use of the specific elements described therein. All alternative modifications and variations of the present invention which fall within the spirit and broad scope of the appended claims are covered.
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A method for entraining and mixing gas with liquids within a conduit or drop structure, comprising the channeling of one or more liquid flows into spiral flows of predetermined radius (radii), reducing the predetermined radius (radii) to increase the centrifugal forces acting upon the spiral flow(s) as the spiral flow(s) enter the conduit, and allowing gas access to the conduit to mix with and entrain within the spiral flow within the conduit or drop structure. The method can facilitate the mixing of gas with one or more fluid flows and/or reduce the release of gas emissions from the fluid(s) into the surrounding environment.
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FIELD OF THE INVENTION
The present invention relates to “active implantable medical devices” as such devices are defined by the Jun. 20, 1990 Directive 90/385/CEE of the Counsel of the European Community, and more particularly to implants that allow continuous monitoring of the cardiac rhythm and deliver to the heart, if necessary, the electrical pulses required to ensure a joint and permanent pacing of the right and left ventricles in order to resynchronize them, which technique is known as “CRT” (Cardiac Resynchronization Therapy) or “BVP” (Bi-Ventricular Pacing).
BACKGROUND OF THE INVENTION
As an alternative or in addition to the treatment of the cardiac rhythm disorders, a biventricular pacing has been proposed for some myocardium contraction disorders observed in patients suffering from heart failure, which disorders are spontaneous or induced by a traditional pacing technique. One can refer, for example, to a study from J. C. Daubert et coll., Stimucoeur, 25, #3, pp. 170-176 which gives a global overview of the topic. This therapy often induced spectacular results for patients suffering from class III heart failure and not improved by traditional treatments.
A CRT pacemaker is, for example, disclosed in the EP 1 108 446 A1 (and its counterpart U.S. Pat. No. 6,556,866 B2) (ELA Medical), which describes a device able to establish a variable interventricular delay between the two ventricles, tuned so as to resynchronize the ventricle contractions with fine optimization of the patient Haemodynamic.
Many currently used CRT devices are “multi-site” prostheses in which coils are implanted in a plurality of distinct sites, including at least one atrial site in addition to the right and left ventricle sites, as in the so-called “triple chamber” (dual ventricular pacing and sensing/pacing of the right atrium) or “quadruple chamber” (dual ventricular pacing and dual sensing/pacing of the atriums) devices. There are also multi-site devices where one of the ventricle leads is implanted in the right ventricular apex and the other in a position chosen to optimize the ventricular resynchronization.
One can define “pacing sites” as the physical location where the intra-cardiac electrodes are in the myocardium. Those sites can be chosen during the implant procedure by an appropriate positioning of the electrodes. When the device comprises several electrodes in a same cardiac cavity, a modification of the pacing site is then possible by an internal switching inside the device.
The notion of “pacing sequence” is related, on one hand, to the order in which the pacing pulses are delivered to the heart (for example: atrium first, then left ventricle, then right ventricle) and, on the other hand, to the timings between the application of these various successive pulses. The pacing sequence is defined at implant and can be, if necessary, subsequently changed by appropriate internal switches of the device and by adjustments of the pacing sequence parameters.
One can define the “pacing configuration” as the combination of the characteristics related to the “pacing sites” and of those related to the “pacing sequence”.
It is necessary to evaluate the relevancy of the selected pacing configuration, for this impacts the efficiency of the bi-ventricular pacing therapy. Furthermore, the positive effects procured by this therapy can lead, in the long term, to re-evaluate the initial configuration to eventually change the sites and/or the pacing sequence parameters.
The ultrasound-based evaluation techniques that shall be implemented in the hospital environment by a qualified personnel are expensive and can not be used as often as necessary without interfering with the daily life of the patient.
A solution described in the aforementioned patent EP 1 108 446 A1 concerns in evaluating the degree of synchronization of the right and left ventricle contractions by an intra-cardiac bio-impedance measurement. This data are indeed representative of the cardiac flow and, therefore, of the ejection fraction, considered as being the reference Haemodynamic parameter.
The present invention is based on another approach of the optimization of the bi-ventricular pacing, implementing an analysis of the endocardiac acceleration, and more precisely an analysis of the endocardiac acceleration peaks.
Indeed, clinical studies have indicated that the endocardiac acceleration is a parameter that provides very comprehensive information of the myocardium functional state, in the case of a normal functioning as well as in a deficient one: the endocardiac acceleration, which is measure by an accelerometer directly in contact with the cardiac muscle (generally, but not exclusively, at the right ventricle apex, sometimes in the right atrium) very precisely reflects, in real time, the converging phenomenon of the mechanical functioning of the heart.
More precisely, the EP 0 515 319 A1 (and its counterpart U.S. Pat. No. 5,304,208) (Sorin Biomedica Cardio SpA) teaches a useful manner to collect the endocardiac acceleration signal by means of an endocardiac lead equipped with a distal pacing electrode implanted in the ventricle and integrating a micro-accelerometer allowing to measure the endocardiac acceleration. The endocardiac acceleration signal collected during a cardiac cycle presents two peaks, corresponding to the two major sounds that it is possible to identify in each cycle of a healthy heart:
the first endocardiac acceleration peak (“PEA1”) corresponds to the closing of the mitral and tricuspid valves, at the beginning of the iso-volumetric ventricular contraction (systole). The variations of this first peak are narrowly linked to the pressure variations in the ventricule (the amplitude of the PEA1 peak being, more precisely, correlated to the positive maximum value of the pressure variation dP/dt in the left ventricle) and can therefore constitute a representative parameter of the myocardium contractility, which is linked to the activity level of the sympathetic system; the second endocardiac acceleration peak (“PEA2”) corresponds to the closing of the aortic and pulmonary valves, at the moment when the iso-volumetric ventricular relaxation occurs. This second peak, induced by the rapid deceleration of the blood mass moving in the aorta is a representative parameter of the protodiastolic blood pressure in the beginning of the diastole.
The EP 0 655 260 A1 (and its counterparts U.S. Pat. No. 5,693,075 and U.S. Pat. No. 5,496,351) (Sorin Biomedica Cardio SpA) describes a useful manner to process the endocardiac acceleration signal delivered by the sensor located in the end of the lead to deliver two values linked to those respective endocardiac acceleration peaks. These values are notably useful for the detection of cardiac rhythm disorders and whether or not to trigger a defibrillation therapy.
The EP 1 736 203 A1 (and its counterpart FR 2 887 460 A1 and U.S. patent application Ser. No. 11/425,668 filed Jun. 21, 2006) (ELA Medical) describes an application specific to bi-ventricular implantable pacemakers, using the parameters linked to the endocardiac acceleration to determine an optimal pacing configuration for the patient, during implant or after. Various measurements are performed to characterize the PEA signal and are combined to give a composite performance indication, the final pacing configuration chosen being the one that maximizes this performance indication.
OBJECTS AND SUMMARY OF THE INVENTION
The starting point of the present invention is the recognition by the inventor that one can use the endocardiac acceleration data collected by the known device and processed by the implant for an additional purpose, namely to evaluate at any given moment, the clinical status of the patient, that is to say the response of the patient to the cardiac resynchronization therapy. An indication of the clinical status will allow following the patient's ventricular function in the long term, preferably to evaluate the risks that a heart failure episode occurs.
In other words, the present invention proposes to use certain data already calculated by the implant in connection with optimizing the pacing configuration (preferably in the manner described in the already cited EP 1 736 203 A1 (and corresponding FR 2 887 460 A1 and U.S. patent application Ser. No. 11/425,668 filed Jun. 21, 2006). This data are then processed, in a manner described hereafter to produce an indication of the clinical status of the patient.
In one embodiment, the invention can be implemented by the use of an external device such as a programmer of the kind used by physicians during routine patient follow-up visits to interrogate and optionally change the parameters of the implant. But other solutions can be implemented. For example, in a preferred embodiment, inside the implant, the clinical data can be processed and used to trigger an alarm designed to warn the patient and/or to be transmitted to a distant call center in charge of ensuring the patient's follow-up based on the remotely transmitted data collected.
In a particular implementation, the present invention uses one of the techniques described in EP 1 736 203 A1 (FR 2 887 460 A1; U.S. Ser. No. 11/425,668), that obtains for each pacing configuration a PEA/AVD characteristic by executing a sweeping of the AV Delay (AVD) while recording the variations of the Peak Endocardiac Acceleration (PEA), generally the first peak, PEA1. This characteristic can be obtained by periodic activation, for example, in a test mode triggered by the implant. The collected results are, according to the invention, used during the test to determine an indication of the clinical status of the patient, in addition to the verification of the selected pacing configuration.
Thus, broadly, the present invention is directed to a medical device that can characterize a cardiac status of a patient equipped with an active implant that delivers a cardiac resynchronization therapy by bi-ventricular pacing. The implant collects an endocardiac acceleration signal and searches for an optimal pacing configuration. This latter tests a plurality of different pacing configurations and delivers for each tested configuration parameters derived from the endocardiac acceleration peak (PEA). The device derives a patient clinical status from those parameters, the indication being representative of the patient's response to the cardiac resynchronization therapy. Those parameters include: the possibility to automatically get or not a valid optimal AV Delay among all the biventricular pacing configurations; a factor indicating the character sigmoid of the PEA/AVD characteristic; the average value of the PEA for the various configurations; and the PEA signal/noise ratio. Control software for executing the functionality and method steps are provided for an active implantable medical device and/or a remote programmer.
One such device is an implant of the general type disclosed in aforementioned EP 1736203 A1 (FR 2887460 A1; U.S. Ser. No. 11/425,668) that is able to deliver biventricular cardiac resynchronization therapy, including:
means for bi-ventricular pacing at selected ones of a plurality of pacing sites; means for collecting an endocardiac acceleration signal (EA); means for testing a plurality of different pacing configurations by changing at least one of (i) the selected sites, (ii) a pacing pulse sequence applied to the selected sites and (iii) a time interval between the application of the pacing pulses to the selected sites; means for searching for an optimal pacing configuration using said testing means for each tested pacing configuration, delivering a plurality of parameters derived from one of the two endocardiac acceleration peaks (PEA1, PEA2) that appear respectively during the iso-volumetric and during the iso-volumetric ventricular relaxation; and means for characterizing a patient cardiac status comprising:
means for analyzing said plurality of parameters to derive a corresponding plurality of different respective specific indications, and means for combining said specific indications in a composite indication of the patient clinical status representative of the patient response to the cardiac resynchronization therapy.
In one embodiment, the device includes a sweeping means for varying an AV Delay (AVD) between an atrial sensed or paced event and a consecutive ventricular pacing event, and the characterizing means analyzes a PEA/AVD characteristic, giving successive endocardiac acceleration PEA peaks as a function of the AV Delay. More preferably, the characterizing means determines an optimal AV Delay (OAVD) by analysis of the PEA/AVD characteristic for a plurality of different biventricular pacing configurations, and the composite clinical status indication depends on whether or not a valid optimal AV Delay has been reached, among all of the different biventricular pacing configurations,
Further, the characterizing means may include means for modeling said PEA/AVD characteristic in three segments, having two plateaus from one side and a central segment with a negative slope, and wherein said composite clinical status indication is a function of the relative position of those three segments.
In an alternate embodiment, the characterizing means operates to determine a representative factor of a sigmoid character of the PEA/AVD characteristic for a plurality of different biventricular pacing configurations, and the clinical status composite indication is a function of the determined sigmoid factor. More preferably, the composite clinical status indication is also a function of the number of configurations, among all the different biventricular pacing configurations, for which the corresponding sigmoid factor is above a predetermined threshold.
In yet another embodiment, the characterizing means includes means for calculating an amplitude average value of the detected endocardiac acceleration peaks for a plurality of different pacing configurations, wherein the clinical status composite indication is a function of the average value.
Yet another embodiment provides the characterizing means as including means for quantifying the signal/noise ratio of the detected endocardiac acceleration peak, wherein the composite clinical status indication is a function of the result of the signal to noise quantification.
Preferably, the characterizing means includes means for comparing each of the specific indications to predetermined respective criteria, and a Boolean table that provides a corresponding value of the composite indication in response to the comparison. The comparison may be comparing first level (A 1 ) specific indications derived from a PEA/AVD characteristic and including:
A first specific indication indicating whether at least one optimal AV Delay has been reached or not, and A second specific indication representative of the sigmoid factor of said PEA/AVD characteristic.
The comparison also may include comparing a second level (A 2 ) specific indications including:
A third specific indication derivate from an average value of the endocardiac acceleration peaks, and A fourth specific indication derivate from a quantification of the endocardiac acceleration peak signal/noise ratio.
In addition, the characterizing means preferably includes:
means for analyzing an evolution versus time of at least two successive values of said composite clinical status indication, and means for deriving from said analysis an indication of the patient evolution indicator and of the risk that a heart failure episode occurs.
BRIEF DESCRIPTION OF THE DRAWINGS
Further features, advantages and characteristics of the present invention will be apparent to a person of ordinary skill in the art based on the following detailed description of a preferred embodiment of the invention, made with reference to the attached drawings, in which the same numerical references designate from one drawing to another identical or functionally similar elements, and in which:
FIG. 1 is a chronogram showing, during three consecutive cardiac cycles the variations of the endocardiac acceleration, as well as those of the electrogram and those of the surface electrocardiogram;
FIG. 2 shows a PEA/AVD characteristic giving the variation of the endocardiac acceleration peak as a function of the AV Delay, and explains how to model this characteristic in three consecutive segments;
FIGS. 3 a and 3 b respectively show a PEA/AVD characteristic with a satisfactory convergence and a not sufficient convergence;
FIG. 4 shows the various levels of the endocardiac acceleration peak when successively testing all the possible pacing configurations in a same patient and the average value of the same parameter;
FIGS. 5 a and 5 b are homologous to FIG. 4 , to illustrate the collected parameters at a three month interval in a same patient;
FIG. 6 shows a manner to determine the signal/noise ratio of the endocardiac acceleration peak value;
FIG. 7 is a flow-chart showing a manner by which the indication of the clinical status of the patient is determined from the different parameters measured by the implant; and
FIGS. 8 and 9 show, for two clinical cases given as an example, the evolution with time of a calculated indication of the invention, compared to a clinical evolution determined by traditional means by a physician.
DETAILED DESCRIPTION OF THE INVENTION
With reference to the drawings, a preferred embodiment of a device in accordance with the present invention will be described. With reference to FIG. 1 , the upper curve illustrates the variations of the endocardiac acceleration (EA) measured by a sensor similar to the one described in EP 0 515 319 A1 and U.S. Pat. No. 5,304,208, integrated in an endocardiac lead implanted in the bottom of the ventricle. Also displayed are Electrogram (EGM) curves, that is: the electrical signal collected through the distal electrode of the same sensor, and a corresponding surface electrocardiogram (ECG), during three consecutive cardiac cycles. As explained above, the curve of the acceleration shows two complexes or successive endocardiac acceleration peaks (PEA), the amplitude and the duration of which can be determined by an appropriate signal delivered by the acceleration sensor processing. This is described in EP 0 655 260 A1 (by “peak amplitude”, one means the maximum and minimum values of the acceleration signal separating two positive and negative extremes, corresponding to the PEA1 and PEA2 indicated on the chronogram of FIG. 1 ; by “peak duration”, one means the timing interval between the beginning and the end of the complex).
The already cited EP 1 736 203 A1 and U.S. Ser. No. 11/425,668, to which one can refer for additional details, which is incorporated by reference herein in its entirety, describes a manner to use certain parameters linked to the endocardiac acceleration and collected to automatically determine an optimal pacing configuration for the patient, at the time of implant as well as later on. Various parameters can be used for this, notably: the PEA1 amplitude and/or the PEA2 amplitude, the PEA1 duration and/or the PEA2 duration, the timing between the PEA1 and the consecutive associated PEA2, the timing interval between the PEA2, and the consecutive PEA1 of the next cycle.
In the following description, when referring to “PEA”, one will essentially mean the parameters linked to the first peak (PEA1), which is generally, the most significant. But this characteristic is not limitative, and it should be understood that the invention can also be implemented based on data relative to the second peak (PEA2), or based on a combination of data from PEA1 and PEA2.
As described in EP 1 736 203 A1, during a specific phase the purpose of which is to evaluate and optimize the pacing configuration, the implant tests the possible pacing configurations and preferably measures the amplitudes of the PEA in each of these configurations. Another function implemented in this test algorithm and process concerns, for a given configuration, making the AV Delay vary and collecting the corresponding PEA amplitude values. The algorithm then allows adjusting the AVD on an optimal value of the AV Delay (OAVD), once a particular pacing configuration is selected.
The results collected during these tests are, according to the present invention, used to determine an indication of the clinical status of the patient. In the following example, this indication is determined from among the four following parameters:
convergence of the AVD search algorithm (optionally to determine an optimal AVD), sigmoid character of the PEA/AVD characteristic; average value of the PEA amplitudes in the various possible pacing configurations, and (optionally) quantification of the PEA signal/noise ratio.
Convergence of the AVD Research Algorithm
A PEA/AVD characteristic, similar to characteristic 10 on FIG. 2 , can be obtained by making the AVD vary and collecting the PEA amplitudes (generally the PEA 1 ). The PEA amplitude has a sigmoid appearance when the AVD varies between two extremes, typically between 30 and 200 ms. One can interpret this curve considering that the decreasing amplitude of the PEA as the AV delays increase is determined by two main factors, which are:
“the contractility reserve” of the myocardium, corresponding to the level of the baseline (limit value of the PEA for long AV Delays), and “the noise” produced by the cardiac valves, mainly the mitral valve, which determine the elevation of the amplitude level above this baseline, for the shortest AV Delays.
In order for the second component to be significantly present, it is necessary that the first one is present, because the myocardium contractility is the “driving force” for the entire mechanical phenomenon that occurs during the cardiac cycle.
This PEA/AVD characteristic collected during the test phase is analyzed by an algorithm designed to determine an optimal value of the AVD, hereafter described as OAVD. Clinical studies have demonstrated that the ability of this algorithm to calculate such an OAVD value (convergence of the algorithm) is a major indication of good ventricular condition of the patient. Essentially, it is possible to get an OAVD (i.e., to make the algorithm converge) if the PEA/AVD characteristic shows a tidy sigmoid appearance, with a significant slope between the short and long values of AVD. Clinical studies in particular have demonstrated a good correlation between the middle point of this curve and the optimal AV Delay provided by traditional echocardiography techniques.
We will now describe an example of algorithm and process that may be implemented in control software allowing one to obtain an optimal OAVD value of the AV Delay. The characteristic 10 provided when collecting the PEA amplitude signals is modelled by means of three successive continuous segments, with a horizontal plateau 12 corresponding to small AV Delays, a central inclined segment 14 corresponding to intermediate AV Delays and an horizontal plateau 16 corresponding to large AV Delays.
The algorithm researches, among the lower values of AVD, the one that provides the maximum value of PEA; this value is referenced 18 on the example illustrated in FIG. 2 . All the PEA values collected for an AVD below this maximum value are then replaced by this maximum value, which defines the level of the upper plateau 12 .
The two other segments 14 and 16 are then determined by linear regression, in a manner which is already known, so as to determine the narrowest adjustment between the three segments 12 , 14 and 16 and the real characteristic 10 . The adjustment between the three segment curve and the characteristic 10 is evaluated by mean of a convergence indication (IC), based on the linear regression, which minimises the sum of the square tests:
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The best adjustment is the one considered being the one that provides the maximum value of the IC convergence indication. The optimal OAVD of the AV Delay is considered as the one located in the middle 20 of the slopping central segment 14 .
The algorithm validates this optimal OAVD, by verifying a certain number of criteria. It considers that an optimal AV Delay OAVD is “valid” if the three following conditions are cumulatively fulfilled:
IC convergence indication greater than or equal to a given threshold, for example 0.76 (value that reflects a good adjustment of the modeled curved to the real characteristic); OAVD delay value greater than a given minima threshold, for example, OAVD greater than or equal to 55 ms; Difference of levels, between upper plateau 12 and lower plateau 16 , greater than or equal to 0.15 g (or 10% of the average value of the PEA amplitude of the characteristic)
The above values are, of course, only given as representative examples; they result from clinical studies performed to validate the invention, but do not have any limitative characteristic and other values could be employed within the spirit and scope of the present invention.
Sigmoid Nature of the PEA/AVD Characteristic
This parameter allows discriminating, among the several characteristics collected, those which have a really significant sigmoid nature, which is a central segment with a significant slope, compared to “flatter” curves from which one can not collect significant indications. To make this distinction, a parameter known as “sigmoid factor” or “SF” is calculated, from average values of the PEA amplitude from left and right sides of the characteristic (it should be understood that the term “sigmoid” in its most comprehensive meaning, including, in particular, the situations where the characteristic is assimilated, like it sometimes happens, to be a simple straight line with a negative slope. These indications are graphically illustrated on FIGS. 3 a and 3 b , respectively for a characteristic that shows a significant sigmoid characteristics, and for a much flatter characteristic.
Indeed, in the case of a bi-ventricular pacing, an efficient pacing configuration is synonymous with an accentuated PEA/AVD characteristic for short AV Delays, as illustrated on FIG. 3 a . On the contrary, in case of heart failure, when the myocardium contractility reserve is minimal, the reduction of the ventricular filling for the shortest AV Delays provokes a contractility decrease resulting from the Frank-Starling's law. For short AV Delays, a much lower increase of the PEA amplitude induced by the cardiac valve “noises” is obtained than on healthy patients, as shown on FIG. 3 b , this increase being sometimes hardly visible.
The determination of the sigmoid factor SF is made by comparing the average levels referenced respectively as 22 and 26 on those figures. The calculation is made by the following formula:
SF = 1 + ∑ i = 2 3 Pea i - ∑ i = 5 6 Pea i ∑ i = 2 3 Pea i + ∑ i = 5 6 Pea i
A SF value lower than 1 corresponds to a reversed curve, a SF value of around 1 corresponds to a flat curve, and a SF value higher than 1 corresponds to a searched sigmoid, decreasing curve. The higher the SF is, the stronger the sigmoid characteristic is (in this way, the two examples illustrated in FIGS. 3 a and 3 b correspond to sigmoid values of respectively SF=1.3831 and SF=1.0176). A statistical evaluation performed during clinical studies shows that a threshold superior or equal to 1.12 corresponds to a significant value, with a sensitivity of 79% and a specificity of 81%.
The algorithm performs this analysis of the sigmoid characteristic of the PEA/AVD characteristic for all the possible pacing configurations and determines, for each of them, if the SF factor is above the predetermined threshold or not. The higher the number of characteristics is, the higher the probability to optimize the pacing is (selection of the configuration and AVD adjustment), with, as a consequence, higher chances that the patient satisfactory responds to the cardiac resynchronization therapy.
Average Values of the PEA Amplitudes
Another parameter taken into account by the algorithm is the average value of the PEA for all the possible pacing configurations. FIG. 4 illustrates a result of this measurement for nine possible configurations, designated as L (left ventricle pacing only), LR48 (biventricular pacing with a 48 ms delay left-right) . . . BIV0 (synchronous bi-ventricular pacing) . . . RL48 (bi-ventricular pacing with a 48 ms delay right-left) and R (right ventricular pacing only). For each of the nine configurations, the device measures the average value of the first PEAL peak, represented in 28 on FIG. 4 . The average value of these nine values is then calculated, corresponding to the amplitude level illustrated in 30 on FIG. 4 .
This parameter is considered as a good indication of the contractility state of the ventricles and also as a optional defect signal of the sensor (in case the amplitude value of the PEA is small or equal to zero on all or portions of the configurations). In this way, FIGS. 5 a and 5 b , homologous of FIG. 4 , show the specificity of the parameter of that average PEA amplitude level for two different clinical examples. On those figures, the “S” letter indicates the configurations for which the characteristic profile has been considered as showing a satisfactory sigmoid factor. One can see that, for a given patient (the example illustrated in FIG. 5 a ), despite an important number of sigmoid profiles obtained, the average level of the PEA ( 30 ) is below the one from another patient for which the number of characteristic presenting a satisfactory sigmoid factor is lower ( FIG. 5 b ).
Peak Endocardiac Acceleration Signal/Noise Ratio
An additional—and optional—parameter is obtained by quantifying the first PEAL peak signal/noise ratio, so as to get an indication of the signal quality compared to the mechanical and/or electrical noises.
As illustrated in FIG. 6 , the PEAL value is measured based on the peak to peak amplitude of the first component of the endocardiac acceleration signal, detected during the iso-volumetric contraction phase of the ventricles, inside a first window (WEA1). The noise level (N1) is measured during the same cycle, in the interval separating the end of the WEA1 window and the beginning of the WEA2 window corresponding to the component of the second PEA2 peak. The noise can also be measured in N2, after the end of the WEA2 window.
The signal/noise ratio is given by:
SNR PEA 1 ( n ) = PEA 1 ( n ) 2 · σ noise ( n ) ,
σ noise (n) being characteristic of the noise variability during the n cycle.
In the example of FIG. 6 , the following signal/noise value is obtained: SNR=16.30 for a PEA1 peak=0.397 g.
Determination of the clinical status of the Patient
From the different parameters explicated above, the algorithm determines the clinical status of the patient using a Boolean table explicated by the flow-chart on FIG. 7 . The analysis is performed on two successive levels A 1 and A 2 . The first level—A 1 —is based on the results of the PEA/AVD characteristic analysis: achievement or not of an optimal AV Delay (algorithm convergence) and number of profiles showing among the various configurations a sigmoid factor.
The algorithm checks first (test 40 ) that at least one optimal AVD (OAVD) has been automatically obtained by the algorithm and then verifies the number of profiles having a sigmoid factor greater than the predetermined threshold (SF≧1, 2). The evaluation is satisfactory if, for the nine different configurations, at least three of the characteristics have such a sigmoid profile. It is “insufficient” otherwise (test 42 , 42 ′).
The second level of analysis—A 2 —is designed to evaluate the general level of contractility, from a PEA amplitude average value and (optionally) from the PEA signal/noise ratio. The average value of the PEA is considered as “satisfactory” when it is ≧0.25 g (tests 44 , 44 ′ and 44 ″) and “insufficient” in the contrary (bad ventricular contractility or sensor default). The signal/noise ratio (“SNR”) will be considered as “satisfactory” if SNR (PEA1)≧6, and “insufficient” on the contrary (which reflects a bad capacity or an insufficient reliability of the pacing configuration optimization algorithms).
The patient status is considered as “good” (result # 50 ) for a patient presenting a complete optimization (optimal AV Delay found automatically, at least three curves with a sigmoid factor, and with PEA1 and signal/noise ratio satisfactory levels). The “average” status (result # 52 ) will be attributed to a patient for whom the optimization is only partial, that is for whom only one of the two conditions for the A1 level analysis are satisfied. This “average” status is also attributed (result # 54 ) to a patient that has a complete optimization (the two A1 level analysis criteria are satisfied) but with signals whose amplitude or whose PEA signal quality is too poor, reflecting a bad cardiac contractility level or signals whose reliability is not sufficient. The “bad” status (result # 56 ) will be attributed to a patient for which none of the two conditions of the A1 analysis level is verified. Such a patient probably does not have an efficient response to the resynchronization therapy and has, therefore, a high risk that his pathology deteriorates.
Finally, if the average level of the PEA amplitude is very low, this situation corresponds to non exploitable data or, eventually, an issue such as a sensor failure (result # 58 ).
Evolution Versus Time of the Clinical Status of the Patient
Once, the clinical status of the patient corresponding to his situation at a given moment is defined in the manner described above, it will be appreciated that one can study the evolution of this status versus time. In particular, it is interesting to consider the evolution between two successive executions of the pacing configuration optimization algorithm, for example at T=0 during implantation, and during the follow-up visits at T=3 months and/or T=6 months.
FIGS. 8 and 9 show, for two different clinical cases, the evolution of these different parameters. Those figures illustrate, in the upper part, the PEAL peak amplitude levels in the various pacing configurations (corresponding to the examples of FIGS. 5 a and 5 b ), with—for each of them—an indication of the presence or not of a recognized sigmoid profile for the PEA/AVD characteristic: the “S” letter indicates that this criteria is verified, the “+” symbol indicates those of the pacing configurations which has been selected as the best one by the optimization algorithm and the symbol “˜” indicates configurations considered as roughly equivalent to the best configurations selected by the algorithm.
The following lines indicate, at T=0, T=3 months and T=6 months, the clinical status determined according to the invention (status according to PEA) as well as its evolution: “stable”, “deteriorated” or “improved”. According to a preferred embodiment of the invention, the patient status is considered as:
“improved” if, between two pacing configuration optimization phases, the clinical status indication has changed from: “bad” to “average” or from “average” to “good”; “stable” if the indication has not changed and stayed at an “average” or a “good” level “deteriorated” (or “still bad”) if the indication has changed from “average” to “bad”, from “good” to “average” or has remained “bad”.
It is eventually possible to attribute an “improved” situation if, despite a same clinical status, the analysis reveals an increase number of characteristics presenting a sigmoid curve and/or an increased number of configurations for which it is possible to automatically get an optimal AV Delay (convergence of the algorithm).
The resulting evolution from the endocardiac acceleration analysis is compared on FIGS. 8 and 9 to the evaluation from a physician clinical examination, which is not necessarily the same. Indeed, in the example of the FIG. 8 , between T=0 and T=3 months, according to the data issued from the analysis made according to the invention only, the patient status remained “stable”, whereas the physician diagnosis was a deterioration (false positive) following a patient hospitalization (noted as HOS), in fact not in correlation with his cardiac pathology. In the example illustrated in FIG. 9 , however, the analysis made according to the invention, allowed to detect a deterioration at T=6 months, not diagnosed by the traditional clinical examination (false negative). In this way, the invention provides a prediction of a heart failure episode (noted HF) that could possibly occur after the test performed at T=6 month.
One skilled in the art will appreciate that the present invention can be practiced by other than the embodiments disclosed herein, which are presented for purposes of illustration and not of limitation.
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A medical device for characterizing the cardiac status of a patient equipped with a bi-ventricular pacing active implant device. The implant collects an endocardiac acceleration signal and searches for an optimal pacing configuration. This latter tests a plurality of different pacing configurations and delivers for each tested configuration parameters derived from the endocardiac acceleration peak (PEA). The device derives a patient clinical status from those parameters, the indication being representative of the patient's response to the cardiac resynchronization therapy. Those parameters include: the possibility to automatically get or not a valid optimal AV Delay among all the biventricular pacing configurations; a factor indicating the character sigmoid of the PEA/AVD characteristic; the average value of the PEA for the various configurations; and the PEA signal/noise ratio. The active implantable medical device includes control software and processes for executing the characterizing functionality described.
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FIELD OF THE INVENTION
[0001] This invention relates to the treatment of sickle cell anemia, using blockers of NMDA.
BACKGROUND OF THE INVENTION
[0002] The N-methyl D-aspartate receptor (NMDAR) is an ionotropic receptor for glutamate. Blockers of NMDAR have been used as anesthesia and for treatment of traumatic brain injury, stroke, and neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's.
[0003] This invention focuses on the treatment of sickle cell anemia, a genetic disease characterized by red blood cells that assume an abnormal, rigid, sickle shape. Acute complications of Sickle cell anemia are treated symptomatically with analgesics and transfusions. A prophylactic treatment of sickle cell crisis is long term application of hydroxyurea. Further treatment options are very desirable.
SUMMARY OF THE INVENTION
[0004] The present invention relates to a method of treating sickle cell anemia, using blockers of the NMDAR. Furthermore the invention relates to blockers of the NMDAR for use in the treatment of sickle cell anemia.
[0005] The invention further relates to a method of screening for a compound effective in the treatment of sickle cell anemia, comprising contacting a candidate compound with the NMDAR and choosing candidate compounds which selectively reduce activity of the NMDAR. The invention further relates to compounds selected by these methods of screening.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] FIG. 1 : Samples 1-3 are from three patients with sickle cell anemia. Shown is the specific staining against the NR1 subunit of the NMDA receptor (NRX) and the loading control (LC) of the light (L), middle (M) and high density (H) sub-populations of erythrocytes.
[0007] FIG. 2 : Potassium and calcium fluxes through the NMDA receptor in erythrocytes of healthy donors (C) and patients with sickle cell anemia (H). A: Unidirectional K + influx measured in chloride-free Na-methane sulfate medium in the presence of 100 μM ouabain, the inhibitor of Na,K-ATPase. Conditions corresponding to the numbers at the X axis: (1) control; (2) 50 μM memantine chloride (Sigma-Aldridge); (3) 100 μM NMDA; (4) NMDA+memantine chloride; (5) 2 μM prostaglandine E2 (PGE2); (6) PGE2+memantine chloride. * denotes p<0.05 compared to the corresponding values in healthy donor's erythrocytes, # stands for p<0.05 compared to the corresponding non-treated control. Data are means±SEM for 6-7 individuals. B: Unidirectional Ca 2+ influx in erythrocytes of a single HbSS patient measured on 3 different occasions and in three healthy donors. Conditions indicated in numbers at the X axis are: (1) non-treated control; (2) 100 μM NMDA; (3) 100 μM NMDA and 50 μM MK-801. * denotes p<0.05 compared to the corresponding health donors' samples.
[0008] FIG. 3 : The examples of morphological changes in erythrocytes caused by agonists and antagonists of the NMDA receptor depending on the receptor availability and HbSS presence. Sample 1 is a sample from a sickle cell patient, sample 2 is from a person with high levels of NMDA receptors and reticulocytosis and sample 3 is from a person with low levels of receptors. Treatment 1 denotes administration of 50 μM memantine (sample 2) or MK-801 (sample 3), treatment 2 stands for 1 mM NMDA addition, treatment 2 shows morphological changes in the cells pre-treated with memantine/MK-801 and then exposed to 1 mM NMDA.
DETAILED DESCRIPTION OF THE INVENTION
[0009] The present invention relates to a method of treating sickle cell anemia, comprising administering blockers of the NMDAR, and the use of such blockers in said treatment and in the manufacture of medicaments for treating sickle cell anemia.
[0010] The action of the NMDAR can be blocked by administration of antibodies or antibody fragments directed against the NMDAR, of molecules that affect the protein or mRNA expression of the NMDAR (sRNA; miRNA), as well as of small molecules that interfere with the binding of ligands to the NMDAR (e.g. blocking the binding site of the neurotransmitter glutamate or the glycine site; or inhibiting NMDAR by binding to allosteric sites or blocking the ion channel by binding to a site within it). A further way to prevent binding to the NMDAR is to use soluble NMDAR or fragments thereof.
[0011] Examples of NMDAR blockers according to the invention are disclosed in the following. However, the invention is not restricted to the blockers disclosed therein, but extends to all blockers of NMDAR.
[0012] Preferred blockers of NMDAR according to the invention are:
Soluble NMDAR or fragments thereof Antibodies that bind to NMDAR, antigen binding fragments of an antibody (e.g. Fab fragments) or antibody-like molecules (e.g. repeat proteins) which by binding to NMDAR block its biological activity. Antibodies against NMDAR are known in the art and include the well characterized antibody NMDA NR 1 Pan Antibody, mouse monoclonal, Novus biologicals, NB 300-118. Virus-like particles loaded with NMDAR or fragments thereof and therefore inducing an antibody response directed against NMDAR with the effect to block its biological activity Antisense molecules for downregulation of NMDAR. These antisense molecules are approximately 12-50 nucleotides in length and encode a given sequence found in the exons or introns of NMDAR. Moreover, antisense molecules containing a sequence of the NMDAR promoters and binding within the promoter region may be used. Finally, antisense molecules binding in the 3′ UTR-non translated regions of NMDAR are contemplated Small molecules that block the biological activity of NMDAR. Small molecules contemplated are synthetic compounds up to a molecular weight of approximately 1000 which have suitable physiological activity and pharmacological properties making them useful for the application as medicaments. Such small synthetic molecules are, for example, found by the screening method of the present invention described below. Alternatively, such small molecules are designed by molecular modelling taking into account possible binding sites of NMDAR. Proteins and protein analogs which bind NMDAR and thereby inhibit its biological activity, for example, synthetic proteins or protein analogs which mimic the variable region of binding and/or neutralizing antibodies, or antibodies that mimic a binding pocket of the NMDAR. Likewise small molecules could be applied, which mimic the variable region of binding and/or neutralizing antibodies, or that mimic a binding pocket of the NMDAR.
[0019] Particularly preferred blockers are:
Amantadine (Novartis, Actavis, Pharmascience) Dextromethorphane, Dextrorphan (e.g. Johnson & Johnson) Ibogaine Ketamine (e.g. Javeline Pharmaceuticals) Nitrous oxide Phencyclidine Riluzole (Sanofi-Aventis) Tiletamine Memantine (Allergan, Daiichi Sankyo, Forest Laboratories, Lundbeck) Dizocilpine (MK-801) Aptiganel (Cerestat, CNS-1102) Remacimide HU-211, an enantiomer of the potent cannabinoid HU-210 7-Chlorokynurenate DCKA (5,7-dichlorokynurenic acid) Kynurenic acid, a naturally occurring antagonist 1-Aminocyclopropanecarboxylic acid (ACPC) Lacosamide AP7 (2-amino-7-phosphonoheptanoic acid) APV (R-2-amino-5-phosphonopentanoate) CPPene (3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid) flupirtine (Adeona Pharmaceuticals, Inc.) orphenadrine (Actavis, Akorn) Neu2000KL (Amkor Pharma, Neurotech) AZD6765 (Astra-Zeneca) AM-101 (Auris Medical) Indantadol (Chiesi Farmaceutici, Vernalis) C-10003 (Concert Pharmaceuticals) EVT101, EVT102, EVT103 (Evotec) Radiprodil (Forrest Laboratories) Gacyclidine (1-[(1R,2S)-2-methyl-1-thiophen-2-yl-cyclohexyl]piperidine; Neureva) CNS 5161 (2-(2-chloro-5-methylsulfanyl-phenyl)-1-methyl-1-(3-methylsulfanyl-phenyl)guanidine; Paion) Dexanabinol and other dextrocannabinoid compounds (Pharmos) CR3394 (Rottapharm) Felbamate ((3-carbamoyloxy-2-phenyl-propyl) carbamate; Schering-Plough) TXT0300 (Traxion Therapeutics) AV101 (7-chloro-4-oxo-1H-quinoline-2-carboxylic acid; VistaGen Therapeutics) YT1006 (Yaupon Therapeutics)
[0058] Most preferred blockers are:
Memantine (Allergan, Daiichi Sankyo, Forest Laboratories, Lundbeck) Dizocilpine (MK-801)
[0061] One aspect of the invention relates to a method of preventing and treating sickle cell anemia, comprising administering blockers the NMDAR as defined hereinbefore in a quantity effective against sickle cell anemia to a mammal in need thereof, for example to a human requiring such treatment. For the administration, the blocker is preferably in the form of a pharmaceutical preparation comprising the blocker in chemically pure form and optionally a pharmaceutically acceptable carrier and optionally adjuvants. The blocker is used in an amount effective against sickle cell anemia. The dosage of the active ingredient depends upon the species, its age, weight, and individual condition, the individual pharmacokinetic data, and the mode of administration. In the case of an individual having a body-weight of about 70 kg the daily dose administered is from approximately 0.001 mg/kg to approximately 10 mg/kg, preferably from approximately 0.05 mg/kg to approximately 1 mg/kg, of a blocker of NMDAR. If memantine hydrochloride is applied in humans, a maximal daily dose of 20 mg is administered in adults. To avoid adverse effects a starting dose of 5 mg daily is recommended. The dosage should be increased weekly by 5 mg a day till the maximal dosage (20 mg daily) has been reached. In case of moderate renal insufficiency (Creatinin-Clearance 40-60 ml/min/1.73 m2) the maximal dosage should be reduced to 10 mg daily.
[0062] Pharmaceutical compositions for enteral administration, such as nasal, buccal, rectal or, especially, oral administration, and for parenteral administration, such as subcutaneous, intravenous, intrahepatic or intramuscular administration, are especially preferred. The pharmaceutical compositions comprise from approximately 1% to approximately 95% active ingredient, preferably from approximately 20% to approximately 90% active ingredient.
[0063] For parenteral administration preference is given to the use of solutions of the blockers of NMDAR, and also suspensions or dispersions, especially isotonic aqueous solutions, dispersions or suspensions which, for example, can be made up shortly before use. The pharmaceutical compositions may be sterilized and/or may comprise excipients, for example preservatives, stabilizers, wetting agents and/or emulsifiers, solubilizers, viscosity-increasing agents, salts for regulating osmotic pressure and/or buffers and are prepared in a manner known per se, for example by means of conventional dissolving and lyophilizing processes.
[0064] For oral pharmaceutical preparations suitable carriers are especially fillers, such as sugars, for example lactose, saccharose, mannitol or sorbitol, cellulose preparations and/or calcium phosphates, and also binders, such as starches, cellulose derivatives and/or polyvinylpyrrolidone, and/or, if desired, disintegrators, flow conditioners and lubricants, for example stearic acid or salts thereof and/or polyethylene glycol. Tablet cores can be provided with suitable, optionally enteric, coatings. Dyes or pigments may be added to the tablets or tablet coatings, for example for identification purposes or to indicate different doses of active ingredient. Pharmaceutical compositions for oral administration also include hard capsules consisting of gelatin, and also soft, sealed capsules consisting of gelatin and a plasticizer, such as glycerol or sorbitol. The capsules may contain the active ingredient in the form of granules, or dissolved or suspended in suitable liquid excipients, such as in oils.
[0065] Transdermal/intraperitoneal and intravenous applications are also considered, for example using a transdermal patch, which allows administration over an extended period of time, e.g. from one to twenty days.
[0066] Intravenous or subcutaneous application are particularly preferred.
[0067] Another aspect of the invention relates to the use blockers of NMDAR as described hereinbefore in the treatment of sickle cell anemia, and in the manufacture of medicaments for treating these diseases.
[0068] Medicaments according to the invention are manufactured by methods known in the art, especially by conventional mixing, coating, granulating, dissolving or lyophilizing.
[0069] The blockers of NMDAR can be administered alone or in combination with one or more other therapeutic agents, possible combination therapy taking the form of fixed combinations of a blocker NMDAR and one or more other therapeutic agents known in the treatment of sickle cell anemia, the administration being staggered or given independently of one another, or being in the form of a fixed combination.
[0070] Possible combination partners considered are vitamins B9 and B12 and other medicaments minimizing plasma homocysteine levels. One more group of compounds that could be considered as possible partners are blockers of Gardos channels (such as ICA-17043, see Blood. 2003; 101:2412-2418) and inhibitors of the K+—Cl− cotransporter including magnesium salts.
[0071] The invention further relates to a method of screening for a compound effective in the treatment of sickle cell anemia comprising contacting a candidate compound with NMDAR and choosing candidate compounds which selectively reduce the activity of the NMDAR. The invention further relates to compounds selected by these methods of screening.
[0072] Blockers of NMDAR activity are identified by contacting the NMDAR with a candidate compound. A control assay with the corresponding NMDAR in the absence of the candidate compound is run in parallel. A decrease in activity in the presence of the candidate compound compared to the level in the absence of the compound indicates that the candidate compound is a NMDAR blocker. NPC-16 Patchliner or Syncropatch 96 (Nanion Technologies GmbH) is optimal for screening of the candidate NMDAR blockers specifically on human erythrocytes.
[0073] Antibodies against the NMDAR can be generated e.g. by immunization of mice.
[0074] Concepts and Evidence Behind the Invention
[0075] In vitro studies showed that erythrocytes of patients with sickle cell anemia contain more NMDA receptor than that of healthy donors and that these receptors are predominantly retained in the cell fraction prone or already undergoing sickling (uncontrolled irreversible shrinkage). This cell population looses cell water and K + due to the high permeability of the cell membrane to Ca 2+ mediated by the NMDA receptor. This leads to the conclusion that blocking the NMDA receptor may prevent irreversible shrinkage of erythrocytes of patients with sickle cell anemia.
[0076] Experiments Performed
[0077] The following experiments were conducted using fresh-isolated human erythrocytes of HbSS patients and healthy subjects.
[0078] Experiment 1
[0079] Localization of the NMDA receptors in erythrocytes of patients and healthy subjects was studied using immunoblotting ( FIG. 1 ) and in cells treated with a selective irreversible blocker of the NMDA receptor 3H-MK-801. The number of the MK-801 binding sites per erythrocyte was assessed in sub-populations of cells with different densities (potential age groups). To do so the erythrocyte suspensions in the medium containing (mM) 145 NaCl, 4KCl, 1CaCl 2 , 0.15 MgCl 2 , 10 sucrose, 10 glucose, 10 Tris-HCl (pH 7.4) were incubated at room temperature for 30 min in the presence of 3H-MK-801. Thereafter the cells were washed from external radioactivity and separated on the Percoll density gradient (see Lutz et al., Biochim Biophys Acta Mar. 5, 1992; 1116(1):1-10). Cell sub-populations of different densities were then isolated, washed and lysed with distilled water. Membranes were then collected by centrifugation, dissolved in the scintillation fluid (Quicksafe A, Zinsser Analytic) and the amount of 3H-MK-801 assessed by beta counter and normalized to the amount of cells. Receptors were equally distributed between reticulocytes and young cells (8±1 receptors per cell), mature cells (8±3) dense senescent cell population (7±2). In patients with HbSS the number of receptor copies per cell was higher in all cell populations (50±2, 17±5 and 19±10 receptors per cell in young, mature and senescent sub-populations respectively). When blocker-free the young cells were the first to undergo sickling and shrinkage as the receptor is predominantly present in the dense population (cells prone to sickling).
[0080] Experiment 2
[0081] Fluxes via the nonselective cation channel of the NMDA receptor were assessed using radioactive tracer kinetics. 86Rb was used as a radioactive tracer for K + and 45Ca as a tracer for Ca 2+ . Fluxes through the red cell membrane were measures in the medium containing (mM) 145 Na-methane sulfate, 4 K-gluconate, 1 Ca-gluconate, 10 sucrose, 10 glucose and 10 HEPES-Tris (pH 7.4) in the presence of 100 μM L-arginine and 100 μM ouabain. Details of the flux measurement may be found elsewhere (e.g. Bogdanova et al., J Membr Biol. 2003; 195(1):33-42). Erythrocytes of the HbSS patients showed higher passive K + and Ca 2+ fluxes that may be blocked by MK-801 (50 μM) or the reversible inhibitor of the NMDA receptor used in treatment of Alzheimer disease, memantine (50 μM). Fluxes of both cations are further stimulated by NMDA (100 μM) or prostaglandine E2 (2 μM). Both NMDA- and PGE2-sensitive increase in fluxes could be blocked by MK-801 or memantine. Fluxes through the NMDA receptors were significantly higher in patients with sickle cell anemia during the flue incidents which corresponded to the anemic crisis and hospitalization.
[0082] Experiment 3
[0083] High levels of the NMDA receptors and sensitization of HbSS patients' erythrocytes to NMDA treatment was shown. There was no direct correlation of the abundance of receptors in red cells and the amount of reticulocytes (routine blood status analysis), but rather with specific hematological disorders such as sickle cell anemia. Functional activity of the receptors was assessed by measuring K+(86Rb) influx through the receptor channels and 3H-MK-801 finding studies. Routine screening of control individuals for the receptor expression in erythrocytes revealed that one of them with abnormally high number of receptor copies had beta-thalassemia minor.
[0084] Experiment 4
[0085] Abnormally high sensitivity of the HbSS erythrocytes to NMDA treatment can be followed microscopically as changes in cell morphology. Shown in FIG. 3 are the cells of healthy donors and HbSS patients exposed to 1 mM NMDA with and without pre-treatment with 50 μM of MK-801/memantine.
[0086] Clinical Study, Treatment of Patients with Sickle Cell Anemia with NMDAR Blocker (Suggested Study)
[0087] A prospective phase II clinical feasibility study in human sickle cell patients with a NMDAR blocker can be performed as follows: It starts with an oral treatment with memantine hydrochloride. The maximal daily dose is analogous to the clinical experiences in Alzheimer disease, i.e. 20 mg with a starting dose of 5 mg daily and if tolerability is good a weekly increase of 5 mg a day till the maximal tolerable dosage has been reached. In case of moderate renal insufficiency (Creatinin-Clearance 40-60 ml/min/1.73 m2) the maximal dosage is reduced to 10 mg daily. The treatment with memantine hydrochloride will be continued for one year and during this time all adverse events due to sickle cell anemia and possible side effects of the treatment are monitored. These data are compared with the history of the patient under best supportive care during the year before inclusion in the study. Endpoints of the study are severity and frequency of adverse events due to sickle cell anemia and tolerability of the treatment with memantine hydrochloride.
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Sickle cell anemia is a genetic disease characterized by red blood cells that assume an abnormal, rigid, sickle shape. Acute complications of Sickle cell anemia are treated symptomatically with analgesics and transfusions, and a prophylactic treatment of sickle cell crisis is long term application of hydroxyurea. According to the present invention, an N-methyl D-aspartate receptor (NMDAR) blocker is used for the treatment of sickle cell anemia and for manufacture of a medicament for the treatment of sickle cell anemia. Moreover, a method for screening for a compound effective in the treatment of sickle cell anemia comprises contacting a candidate compound with the NMDAR and selecting said candidate compound as effective if it is found to selectively reduce activity of the NMDAR.
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BACKGROUND AND SUMMARY OF THE INVENTION
The present invention relates to a hand labelling apparatus which in a working cycle imprints and dispenses pressure-sensitive labels adhering to a carrier tape, comprising a feed means which under the control of an operating lever pivotal between a rest position and a working position draws the carrier tape stepwise about a peel edge at which in each working cycle a pressure-sensitive label on feeding in a forward direction detaches from the carrier tape and moves into a dispensing position, and a printing mechanism which in each working cycle at a printing zone remote from the peel edge oppositely to the forward direction produces an imprint on a pressure-sensitive label.
In an apparatus of this type known from DE-PS No. 2,345,249 the imprinting of the pressure-sensitive labels takes place in a printing zone which is two label lengths away from the peel edge in a direction opposite to the forward direction of the carrier tape. This means that the pressure-sensitive label which is brought in an operating cycle into the dispensing position in which it can be applied to an article has already been imprinted in the previous operating cycle. Thus, after the application of the label to an article, before the start of the next operating cycle a label provided with an imprint is already present in the apparatus. If the imprint to be applied is changed this label must be removed from the apparatus so that only labels provided with the changed imprint are applied to articles. Since the imprints on the labels are usually sales prices the presence of a label with an old price imprint is highly undesirable because articles can be marked with the wrong price if the operator forgets to remove the already imprinted label from the apparatus after a price change.
The objective of the present invention is to provide an apparatus of the type outlined at the beginning which is such that even with a relatively large distance between the peel edge and the printing zone after completion of an operating cycle there is no already imprinted but undispensed pressure-sensitive label in the apparatus.
According to the invention this objective is achieved in that the feed means comprises a tape feed mechanism which is driven by the operating lever and which on the movement of the operating lever from the rest position to the work position moves the carrier tape in the return direction opposite the forward direction through at least a distance which is equal to the distance of the peel edge from the printing zone and which on the return of the operating lever from the working position to the rest position moves the carrier tape in the forward direction through the same distance plus one label length. In the apparatus according to the invention the carrier tape with the pressure-sensitive labels adhered thereto is moved in each operating cycle in a so called pilgrim step movement which means that the label disposed at the peel edge is first brought back to the printing zone, whereupon after the printing operation it is again transported in the forward direction to the peel edge and beyond into the dispensing position. This means that in each operating cycle only one pressure-sensitive label is imprinted which is then also the label which is brought in the same operating cycle into the dispensing position and can be attached to an article. If the imprint to be produced on the label is changed, because of the construction of the hand labelling apparatus according to the invention the next label dispensed already bears the new imprint. The removal of labels already provided with the old imprint in previous operating cycles is thus not necessary and consequently there is no danger of applying incorrectly imprinted labels.
BRIEF DESCRIPTION OF DRAWINGS
FIG. 1 is a side view of the apparatus according to the invention,
FIG. 2 is a schematic side view of the drive members essential to the transport of the carrier tape in the basic position,
FIG. 3 is a view similar to FIG. 1 but the drive members are in the position immediately prior to start of the synchronous carrier tape movement in the return direction,
FIG. 4 is a section through the feed roll along the line 3--3 of FIG. 2,
FIG. 5 is a partially sectioned view of the feed roll viewed as indicated by the arrows A and B in a position of the feed roll as in FIG. 2 and
FIG. 6 is a similar view to FIG. 4 but with the feed roll assuming the position of FIG. 3.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 illustrates a hand labelling apparatus 1 with the aid of which pressure-sensitive labels adhering to a carrier tape can be imprinted and dispensed for application to an article. The apparatus 1 comprises an operating lever 2 which is pivotally mounted about a shaft 4 fixedly connected to the apparatus housing 3 between the rest position illustrated in FIG. 1 and a working position in which said lever is squeezed against the grip 5 fixed with respect to the housing.
A well 6 disposed at the housing upper side serves to accommodate a carrier tape supply roll 7. From the supply roll 7 the carrier tape with its pressure-sensitive labels adhering thereto passes to a peel edge which is at the bottom left in the illustration of FIG. 1 and at which in each operating cycle, i.e. on pivoting the operating lever 2 from the rest position to the working position and then back into the rest position, a pressure-sensitive label detaches from the carrier tape and moves into a dispensing position in which it can be applied to an article. In FIG. 1 a pressure-sensitive label 8 is illustrated in the dispensing position.
In FIG. 2 the parts of the labelling apparatus 1 required for transport of the carrier tape 17 are shown diagrammatically. Also illustrated diagrammatically is the operating lever 2 which is pivotal about the axis 4 and which comprises a toothed segment 9 with the aid of which its pivot movement can be utilised for the drive of the actual transport members. The toothed segment 9 is in engagement with a pinion 10 which is non-rotatably mounted on a shaft 11. Also non-rotatably connected to said shaft 11 is a toothed wheel 12 and thus pinion 10, shaft 11 and toothed wheel 12 rotate as a whole. Wheel 12 meshes with a toothed segment 14 rigidly connected to the type wheel 13 of a rotary printing mechanism. The type wheel 13 and the toothed segment 14 are pivotally mounted about a shaft 14a.
The type wheel 13 comprises a print segment 15 in which the print types are disposed which are to produce an imprint in a printing zone on a pressure-sensitive label 8 on the carrier tape 17. The print types may be numbers, letters, or, if a bar code is to be printed, bar-like types of different width. The type wheel 13 is composed of a plurality of discs provided at their peripheral surface with print types. By rotation of the individual discs about the axis 14a the individual print types can be moved to the print segment and consequently at said print segment print types of adjacent discs can be assembled in any desired manner.
The carrier tape 17 with the pressure-sensitive labels 8 adhering thereto is led from the supply roll 7 via a spring metal plate 18, which holds the carrier tape 17 tight, to a roller 19 which presses said tape under the action of a spring 20 against the peripheral surface of the type wheel 13. In the region of the type wheel periphery which adjoins the print segment 15 in the anticlockwise direction a guard plate 21 is arranged so that the roller 19 does not press the carrier tape 17 with the pressure-sensitive labels 8 directly against the type wheel peripheral surface but against the guard plate 21 disposed at said region of said peripheral surface.
The carrier tape 17 is led further between a pressure roller 22 engaging the type wheel 13 via a tooth connection and the type wheel 13 and then passes to a peel edge 23. When the carrier tape 17 is drawn about the peel edge 23 in the forward direction indicated by the arrow 24 the pressure-sensitive labels 8 detach from the carrier tape so that they move into the peel position. A pressure-sensitive label 8 disposed in the peel position is illustrated in FIG. 2 in dashed line.
The carrier tape 17 then runs further to a feed roll 25 about which it is led with a relatively large wrap angle. The feed roll 25 is provided with projections 26 which engage in slit-like recesses in the carrier tape 17. The slits in the carrier tape 17 are arranged at a distance apart which corresponds to the length of a pressure-sensitive label 8. The projections 26 on the feed roll 25 are arranged exactly with the spacing of the slits in the carrier tape 17 so that in the course of the individual operating cycles of the apparatus the carrier tape 17 assumes an exactly defined position when the projections 26 are in engagement with the slits in the carrier tape 17.
To hold the carrier tape 17 reliably in engagement with the peripheral surface of the feed roll 25 coil springs 27 are provided which are led over rollers 28, 29, 30 and 31 and engage round the feed roll 25 as well as the carrier tape 17. The carrier tape is thereby led between the peripheral surface of the feed roll 25 and the worm springs 27.
Associated with the feed roll 25 is a return stop 32 which is fixedly connected to the apparatus housing 3 and which assumes the position illustrated in FIGS. 2 and 3. The return stop 32 includes a return detent member 33 which consists of a spring-loaded ball. Said spring-loaded detent member 33 cooperates with detent teeth 34 which are disposed on an inwardly directed peripheral surface of the feed roll 25. As is apparent, the return stop 32 permits a rotation of the feed roll 25 clockwise but because of the detent teeth 34 opposes a rotation in the anticlockwise direction. The feed roll 25 can only be rotated in the anticlockwise direction when the spring force exerted on the return detent member 33 has been overcome. The return detent member 33 then practically jumps over the detent tooth 34 so that the feed roll 25 can further rotate freely until the next detent tooth 34 comes into engagement with the return detent member 33.
A drive wheel 36 is rotatably mounted on the shaft 35 on which the feed roll 25 is rotatably mounted and is illustrated in FIG. 4. Remembering that in FIGS. 2 and 3 the feed roll 25 is viewed in the direction of the arrow 37 indicated in FIG. 4, then the drive wheel 36 in the illustrations of FIGS. 2 and 3 is at the back of the feed roll 25.
The drive wheel 36 can be rotated via the tooth wheel 12 and the toothed segment 9 by pivoting the operating lever 2. The connection between the drive wheel 36 and the feed roll 25 is formed by a directional ratchet mechanism which includes forward pawls 38 rigidly connected to the drive wheel 36 and cooperating with forward detent teeth 39 on the feed roll 25. This ratchet mechanism permits the feed roll 25 when the drive wheel 36 is held stationary to rotate clockwise in the view of FIGS. 2 and 3, preventing a rotation in the anticlockwise direction. It should be noted that these rotational directions are reversed in the views of FIGS. 5 and 6 because in these Figures the feed roll is observed from the back with respect to FIGS. 2 and 3. Thus, in FIGS. 5 and 6 the ratchet mechanism permits a relative rotation of the feed roll 25 with respect to the drive wheel 36 in the counterclockwise direction but prevents a rotation in the clockwise direction.
It is apparent from FIGS. 5 and 6 that not only the forward pawls 38 are rigidly connected to the drive wheel but also a return pawl 40 which cooperates with drive teeth 41 on an inner peripheral surface of the feed roll 25. As apparent from FIG. 6 the feed roll 25 is driven by means of the return pawl 40 in the clockwise direction when in the course of the rotation of the drive wheel 36 the return pawl 40 comes against a return drive tooth 41.
According to FIG. 4 the feed roll 25 is mounted between two walls 42 and 43 which are fixedly connected to the apparatus housing 3. In the wall 42 an opening 44 is formed whose periphery is described by a circle round the axis 35 of the feed roll 25 with the exception of a limited peripheral region. As can be seen from FIGS. 5 and 6 the periphery of the opening 44 differs in its lower peripheral region from the circular form and forms a control face 45 whose spacing from the axis 35 is less than at the remaining regions of the opening periphery. The function of this control face 45 is apparent on consideration of FIG. 4 in conjunction with FIGS. 5 and 6.
According to FIG. 4 the return pawl 40 projects in the lateral direction from the right end face of the feed roll 25. When the drive wheel 36 assumes the position illustrated in FIG. 5 the portion of the return pawl 40 projecting at the end face of the feed roll 25 bears on the control face 45 so that the return pawl 40 cannot come into engagement with a return drive tooth 41 on the feed roll 25. Only when the drive wheel 36 and the return pawl 40 rigidly connected thereto have rotated to such an extent that the return pawl 40 is no longer supported by the control face 45 can the return pawl 40 act on a drive tooth 41 on the feed roll 25. Such a position of the drive wheel 36 is illustrated in FIG. 6. On further rotation of the drive wheel 36 the return pawl 40, by acting on the return drive tooth 41, drives the feed roll 25 in the clockwise direction in the illustration of FIG. 6.
After this description of the drive components necessary for the carrier belt movement, their respective positions and their individual effects, the operations will now be described which take place in the course of an operating cycle, i.e. on pivoting of the operating lever out of the rest position into the working position and back again into the rest position.
At the start of an operating cycle the drive members assume the basic positions illustrated in FIG. 2. The basic positions of the forward pawls 38 and the return pawl 40 are shown in FIG. 5. As soon as the operating lever 2 is squeezed against the grip 5 the toothed segment 9 moves anticlockwise about the axis 4 so that the pinion 10, which is in engagement with the toothed segment 9, rotates in the clockwise direction in the view of FIG. 2. In the same manner the toothed wheel 12 fixed in rotation with the shaft 11 of the pinion rotates in the clockwise direction so that the type wheel 13 is thereby also rotated anticlockwise by means of the toothed segment 14 rigidly connected thereto.
The toothed wheel 12 also rotates the drive wheel 36 in the illustration of FIG. 2 anticlockwise (clockwise in the illustration of FIG. 5) and as a result the forward pawls 38 in the illustration of FIG. 5 begin to move away in the clockwise direction from the forward detent teeth 39. Since due to the action between the roller 19 and the guard plate 21 disposed at the type wheel periphery the carrier tape is frictionally entrained in the return direction, i.e. in the direction towards the carrier tape supply roll 7, this tensile force also moves the feed roll 25 anticlockwise in FIG. 2. This means in practice that the feed roll 25 follows the rotation of the drive wheel 36. The relative position of the forward pawls 38 and of the drive wheel 36 with respect to the feed roll 25 is thus not changed. The feed roll 25 can however follow the movement of the drive wheel 36 only until the return detent member 33 comes into engagement with the next detent tooth 34. In the example of embodiment illustrated the rearwardly directed movement of the carrier tape 17 continues until the leading --considered in the return direction--edge 46 of the pressure-sensitive label 8 adjoining the peel edge 23 has been pulled back to the printing zone 16. With the respective dimensions indicated in FIG. 2 the rearwardly directed travel in this initial phase is about half the label length.
The type wheel 13 also rotates via a toothed connection the pressure roller 22 which comprises a peripheral portion 47 of larger radius and a peripheral portion 48 of smaller radius. The larger radius is so dimensioned that it is exactly equal to the distance of the axis 49 of rotation of the pressure roller 22 from the periphery of the type wheel. The shaft 49 of the pressure roller 22 is biased in the direction towards the type wheel by a spring which is not illustrated when the peripheral portion 47 is in engagement with the type wheel periphery. The spring is however ineffective when the peripheral portion 48 with smaller radius is opposite the type wheel 13 so that in this case the carrier tape 17 can move freely between the pressure roller 22 and the type wheel periphery. FIG. 2 shows that the carrier tape, immediately after the start of the rotation of the type wheel 13 anticlockwise and thus after the start of the rotation of the pressure roller 22 clockwise, can be freely drawn between the pressure roller 22 and the type wheel 13.
When the return detent member 33 has come into engagement with the detent tooth 34 a further rotation of the feed roll 25 is prevented. The entraining force produced by friction between the roller 19, the carrier tape 17 and the guard plate 21 at the type wheel 13, which acts as pulling force on the carrier tape 17 in the direction towards the carrier tape supply roll 7, is not large enough to move the feed roll 25 past the detent tooth 34, overcoming the detent force exerted by the return detent member 33. Thus, on continued rotation of the type wheel 13 a slipping occurs between the guard plate 21 and the carrier tape 17 with the pressure-sensitive labels 8 disposed thereon so that the carrier tape is not pulled back any further.
In this operating phase, in which the carrier tape is stationary due to the feed roll 25 held fixed by the return detent member 32, the type wheel 13 and thus also the pressure roller 22 driven thereby move further into the positions illustrated in FIG. 3. The print segment 15 reaches a position adjoining the printing zone 16 and the pressure roller 22 also starts to press the carrier tape against the type wheel because its peripheral portion 47 now comes into engagement with the type wheel. In this operating phase the drive wheel 36 also moves further so that the return pawl 40 moves into the position illustrated in FIG. 6 relatively to the stationary feed roll 25. FIG. 6 shows the return pawl 40 in the position in which it just comes into engagement with the return drive tooth 41. If the drive wheel 36 is now further rotated (anticlockwise in FIG. 3 and clockwise in FIG. 6) by the toothed wheel 12 due to the further movement of the operating lever 2 the feed roll 25 is further rotated by the return pawl 40 due to the action thereof on the return drive tooth 41, overcoming the detent force exerted by the return detent member 33 on the detent tooth 34, and as a result the carrier tape 17 can now again move as in the initial phase in the return direction. At the same time, the carrier tape 17 with the pressure-sensitive label 8 disposed thereon is pressed by the peripheral portion 47 of the pressure roller 22 against the type wheel 13 so that in the printing zone 16 the types present in the printing segment 15 roll on the pressure-sensitive label 8 to produce an imprint. Since the pressure roller 22 is driven via a tooth connection by the type wheel 13 the movement of the carrier tape now taking place is in the return direction exactly synchronously with the movement of the type wheel 13 and of the pressure roller 22 because the carrier tape 17 is entrained during the rolling of the peripheral surfaces. From the start of the renewed transport of the carrier tape 17 in the return direction onwards the carrier tape is further moved in the return direction until the entire printing segment 15 has rolled over the pressure-sensitive label 8 in the printing zone 16. The operating lever 2 has then reached its working position in which it is completely squeezed against the grip 5. In the example of embodiment illustrated the carrier tape 17 had thus moved a total of about one and a half label lengths in the return direction.
When the operating lever 2 is now released and again returns under the action of a spring between said lever and the grip 5 into its rest position illustrated in FIG. 1, the directions of rotation of all the drive members described are reversed. To be exact, this means that the toothed segment 9 now rotates clockwise about the axis 4 which results in a rotation of the pinion 10 and the toothed wheel 12 anticlockwise. Accordingly, the type wheel 13 also moves clockwise and thus drives the pressure roller 22 anticlockwise. The drive wheel 36 rotates in the illustration of FIGS. 2 and 3 clockwise and consequently due to the engagement of the forward pawls 38 on the forward detent teeth 39 entraines the feed roll 25. The return stop 32 presents no obstacle to such a rotation of the feed roll 25 because the return detent member 33 can readily overrun the detent teeth 34 in the case of this direction of rotation of the feed roll 25.
At the start of the rotation of the type wheel 13 clockwise the printing segment 15 again rolls over the pressure-sensitive label 8 since the latter again moves between the type wheel 13 and the pressure roller 22.
The transmission ratios between the toothed segment 9, the pinion 10, the toothed wheel 12 and the drive wheel 36 are so chosen that during the return of the operating lever 2 from the working position to the rest position the carrier tape 17 is moved in the forward direction indicated by the arrow 24 through a distance which is equal to the distance of the peel edge 23 from the printing zone 16 plus one label length. Because of this dimensioning the label 8 which was directly behind the peel edge 23 before the start of the operating cycle assumes after completion of said cycle the dispensing position defined by the label 8 indicated in dashed line in which it is detached from the carrier tape 17 and can be applied to an article.
The differing travel in the return direction and in the forward direction is achieved in that the return means slips in defined manner with respect to the carrier tape so that not all the pivot movement of the operating lever 2 from the rest position to the working position is converted into a travel of the carrier tape in the return direction. The opposite direction of movement of the operating lever 2 from the working position to the rest position is however completely converted to a travel of the carrier tape in the forward direction. To ensure that the difference between the travel in the return direction and the travel in the forward direction corresponds exactly to one label length, after the feed roll 25 becomes stationary the drive wheel 36 is further rotated relatively thereto until engagement of the return pawl 40 on the return drive tooth 41 through an angle which corresponds on the periphery of the feed roll 25 to an arc having the length of a pressure-sensitive label.
The pressure-sensitive label 8 disposed directly at the peel edge 23 in the basic position of the hand labelling apparatus 1 illustrated in FIG. 2 is not imprinted because, as apparent from the above outline of the operating cycle, it is imprinted only in the course of the rearwardly directed travel in an operating cycle when it moves into the printing zone 16. The imprint produced on the pressure-sensitive label 8 can thus readily be changed without any danger of a label provided with an unchanged imprint being applied to an article which should bear a label with the new imprint. It is thus not possible with the apparatus described to dispense a label bearing an imprint not corresponding to the print types set at the printing segment of the type wheel.
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In a hand labelling apparatus for printing and dispensing labels from a label strip including a carrier tape where the labels are adhered to the tape, a tape feed mechanism for stepwise feeding the label strip in a forward direction to a peel edge at which point the labels are substantially separated from the carrier tape, a printing mechanism having changeable type where the distance between the printing zone of the printing mechanism and the peel edge exceeds the length of each of the labels, a return member for feeding the label strip in a return direction opposite to the forward direction, an operating lever pivotable between a rest position and a working position where the operating lever is connected to the return member and the tape feed and printing mechanisms so that, during movement of the operating lever from the rest position to the working position, the return member feeds the labels in the return direction to the print zone where one of them is printed, a return stop member for disabling the return member for a predetermined portion of the movement of the operating lever between its rest and working positions so that the label strip movement in the forward direction exceeds that in the return direction by an amount equal to the length of one label so that no printed labels remain in the labelling apparatus even though the distance between the peel edge and the printing zone exceeds the length of each label.
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BACKGROUND OF THE INVENTION
[0001] Lepidium meyenii or maca is an herbaceous, biennial plant or annual plant (some sources say a perennial plant) native to the high Andes of Bolivia and Peru. It is grown for its fleshy hypocotyl (actually a fused hypocotyl and taproot), which is used as a root vegetable and a medicinal herb. Its Spanish and Quechua names include maca-maca, maino, ayak chichira, and ayak willku. Maca is cultivated in the Andean region, especially Peru, where it is a food staple. As reported in Dini et al., (Dini A., Miguliuolo G, Rastrelli L, et al. Chemical composition of Lepidium meyenii , Food Chemistry 1994; 49:347-9) and Walker (Walker M, Effect of Peruvian Maca on hormonal functions. Townsend Letter for Physicians 1998; November: 18-21), the tuber is also used in folk medical traditions as a mood enhancer, as an antidepressant, and to promote wound healing. Dini et al. also reports that the chemical composition of Maca includes a balanced protein compared to carrot and potato protein.
[0002] Maca also contains a variety of trace minerals, including iron, copper and iodine as well as saponins and alkaloids.
[0003] A synopsis of a book by Gloria Chacon de Popivici, “La importanica de Lepidium peruvianum Chacon (Maca) en la Alimentacion y Salud del ser Humano y Animal 2,000 Ados Antes y Despues de Cristo y en el Siglo XXI”, describes an experiment in which rats given Maca powdered root had higher sperm production and motility rates than in control groups. The author is quoted as saying the alkaloids of Maca affect the pituitary and hypothalamus, and it acts on adrenals, pancreas and thyroid. Along these lines, anecdotal information is available suggesting that Maca alleviates perimenopausal and post menopausal symptoms, male impotence erectile dysfunction, and female and male sterility, healing bone fractures, osteoporosis, premature aging, and chronic fatigue.
[0004] Several books and reports describe Andean roots and tubers as crops and sources of food and beverage. See Soensen et al., (Soensen M, Gruneberg W J, Orting B et al. Andean Roots and Tubers: ahipa, arracacha, maca and yacon. Centro Internaciojoal de la Papa, Lima Peru, 1997—Abstract); Condesan, (Pocket guide to nine exotic Andean roots and tubers. Lima, Peru. 1997. Abstract); Comas et al, (Comas M, Miquel X, de la Torre M C, Arias G. Estudio bromatoglogico de la maca o paca ( Lepdium meyenii ). Alimentaria 1997, no. 286:85-90. Abstract); Toledo et al., (Toledo J, Dehal P, Jarrin F et al. Genetic variability of Lepidium meyenii and other Andean Lepidium species assessed by molecular markers. An. Botany 1998; 82:523-30. Abstract). However, based on the information in the Abstracts, none of these references discuss the response of male hormone levels to ingestion of Maca.
[0005] In addition to sugars and proteins, Maca contains uridine, malic acid and its benzoyl derivative, and the glucosinolates, glucotropaeolin and m-methoxyglucotropaeolin. The methanol extract of Maca tuber also contained (1R,3S)-1-methyltetrahydro—carboline-3-carboxylic acid, a molecule which is reported to exert many activities on the central nervous system (Piacente, Sonia; Carbone, V., Plaza, A., Zampelli, A. & Pizza, C. (2002). “Investigation of the Tuber Constituents of Maca ( Lepidium meyenii Walp.)”. Journal of Agricultural and Food Chemistry 50 (20): 5621-5625. PMID 12236688). The nutritional value of dried Maca root is high, similar to cereal grains such as rice and wheat. It contains 60% carbohydrates, 10% protein, 8.5% dietary fiber, and 2.2% fats. Maca is rich in essential minerals, especially selenium, calcium, magnesium, and iron, and fatty acids including linolenic acid, palmitic acid, and oleic acids, and 19 amino acids, as well as polysaccharides (Muhammad, I; Zhao J., Dunbar D. C. & Khan I. A. (2002). “Constituents of Lepidium meyenii ‘maca’”. Phytochemistry 59 (1): 105-110. PMID 11754952). Maca's reported beneficial effects for sexual function could be due to its high concentration of proteins and vital nutrients (Chacón de Popovici, G. (1997). La importancia de Lepidium peruvianum (“ Maca ”) en la alimentacion y salud del ser humano y animal 2,000 anos antes y desputes del Cristo y en el siglo XXI . Lima: Servicios Gráficos “ROMERO”), though Maca contains a chemical called p-methoxybenzyl isothiocyanate, which reputedly has aphrodisiac properties.
[0006] Yohimbine, also known under the antiquated names quebrachin, aphrodin, corynine, yohimvetol and hydroergotocin, is the principal alkaloid of the bark of the West-African evergreen Pausinystalia yohimbe Pierre (formerly Corynanthe yohimbe ) family Rubiaceae (Madder family). There are 31 other yohimbane alkaloids found in Yohimbine. In Africa, yohimbine has traditionally been used as an aphrodisiac.
[0007] Yohimbine is a selective, competitive, alpha2-adrenergic receptor antagonist that is sometimes used as an alternative treatment for erectile dysfunction (National Institutes of Health). The alpha2 receptor is responsible for sensing adrenaline and noradrenaline and telling the body to decrease its production as part of a negative feedback loop. Yohimbine supposedly acts as antagonist, or a blocker, by binding to alpha2 receptors, but not activating them. This in turn increases adrenal gland production of adrenaline and noradrenaline. Yohimbine also antagonizes several serotonin receptor subtypes: 1A (inhibitory, behavioral control), 1B (inhibitory, vasoconstriction), 1D (inhibitory, vasoconstriction), and 2B (smooth muscle contraction). Since yohimbine is an antagonist, it will decrease the effects of these receptors, thus causing excitation, vasodilation, and smooth muscle relaxation. Yohimbine is also said to increase dopamine and have some actions as an MAOI, although these mechanisms are unknown.
[0008] Higher doses of oral yohimbine may create numerous side effects such as rapid heart rate, high blood pressure, and overstimulation. Yohimbine might produce anxiety, and is thought to cause insomnia and sleeplessness in some users.
[0009] Some internet shops sell expensive formulations of yohimbine for transdermal delivery to effect a local reduction of adipose tissue, although there is no evidence that it is effective. Demand for products of this kind is frequently found in the bodybuilding community.
[0010] Yohimbine chloride, a standardized form of yohimbine, is a prescription medicine that has been used to treat erectile dysfunction (National Center for Complimentary and Alternative Medicine). Controlled studies suggest that it is not always an effective treatment for impotence, and evidence of increased sex drive (libido) is anecdotal only (http://pharmrev.aspetjournals.org/cgi/content/ful/53/3/417#SEC4 — 4 — 6 — 2). It has significant side effects such as anxiety reactions. According to the Mayo Clinic, yohimbine can be dangerous if used in excessive amounts.
[0011] Serenoa repens , or saw palmetto, is the sole species currently classified in the genus Serenoa . It has been known by a number of synonyms, including Sabal serrulatum , under which name it still often appears in alternative medicine. It is a small palm, normally reaching a height of around 2-4 m. Its trunk is sprawling, and it grows in clumps or dense thickets in sandy coastal lands or as undergrowth in pine woods or hardwood hammocks. Erect stems or trunks are rarely produced, but are found in some populations. It is endemic to the southeastern United States, most commonly along the Atlantic and Gulf coastal plains, but also as far inland as southern Arkansas. It is extremely slow growing, and long lived, with some plants, especially in Florida, being over 700 years old.
[0012] Saw palmetto is a fan palm (Arecaceae tribe Corypheae), with the leaves having a bare petiole terminating in a rounded fan of about 20 leaflets. The petiole is armed with fine, sharp teeth or spines that give the species its common name. The leaves are light green inland, and silvery-white in coastal regions. The leaves are 1-2 m in length, the leaflets 50-100 cm long. They are similar to the leaves of the palmettos of genus Sabal . The flowers are yellowish-white, about 5 mm across, produced in dense compound panicles up to 60 cm long. The fruit is a large reddish-black drupe and is an important food source for wildlife. The plant is used as a food plant by the larvae of some Lepidoptera species including Batrachedra decoctor (which feeds exclusively on the plant).
[0013] The genus name honors American botanist Sereno Watson.
[0014] The fruits of the Saw Palmetto are highly enriched with fatty acids and phytosterols, and extracts of the fruits have been the subject of intensive research for the treatment of urinary tract infections.
[0015] Saw palmetto extract is an extract of the fruit of Serenoa repens . It is rich in fatty acids and phytosterols, and has been shown to be effective in the management of benign prostatic hyperplasia (Wilt T J et al (1998). “Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review”. JAMA 280: 1604-1609).
[0016] Native Americans used the fruit for food, but also in the treatment of a variety of urinary and reproductive system problems. The European colonists learned of the use of Saw Palmetto. It was used as a crude extract for at least 200 years for various conditions including asthenia (weakness), recovery from major illness, and urogenital problems. For instance, the Eclectic physician H. W. Felter wrote of it, “Saw palmetto is a nerve sedative, expectorant, and a nutritive tonic, acting kindly upon the digestive tract. Its most direct action appears to be upon the reproductive organs when undergoing waste of tissue.” (Felter's Complete Text: http://www.henriettesherbal.com/eclectic/felter/serenoa.html).
[0017] The Eclectics knew Saw Palmetto as more than a prostate herb. King's American Dispensatory, in 1898 claims:
It is also an expectorant, and controls irritation of mucous tissues. It has proved useful in irritative cough, chronic bronchial coughs, whooping-cough, laryngitis, acute and chronic, acute catarrh, asthma, tubercular laryngitis, and in the cough of phthisis pulmonalis. Upon the digestive organs it acts kindly, improving the appetite, digestion, and assimilation. However, its most pronounced effects appear to be those exerted upon the urino-genital tracts of both male and female, and upon all the organs concerned in reproduction. It is said to enlarge wasted organs, as the breasts, ovaries, and testicles, while the paradoxical claim is also made that it reduces hypertrophy of the prostate. Possibly this may be explained by claiming that it tends toward the production of a normal condition, reducing parts when unhealthily enlarged, and increasing them when atrophied (King's American Dispensatory 1898: http://www.henriettesherbal.com/eclectic/kings/serenoa.html).
[0019] In modern times, much research has been done on extract made from the fruits, which are highly enriched with fatty acids and phytosterols. This research has been the subject of a thorough meta-analysis published in the Journal of the American Medical Association and has been shown to be effective for the treatment of men with symptomatic benign prostatic hyperplasia (enlargement of the prostate) compared to placebo and the two major categories of drugs used for men with this condition (Wilt T J et al (1998). “Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review”. JAMA 280: 1604-1609). There are also small, positive clinical trials published on the use of Saw Palmetto extracts topically and internally for male-pattern baldness. In 2005, a long-term, placebo-controlled trial showed that a combination of Saw Palmetto fruit and nettle root extracts were effective in treating urinary tract symptoms in older men (Lopatkin N et al (2005). “Long-term efficacy and safety of a combination of sabal and urtica extract for lower urinary tract symptoms—a placebo-controlled, double-blind, multicenter trial”. World Journal of Urology 23 (2): 139-146). However, in February 2006, a large, blinded placebo-controlled study published in the New England Journal of Medicine showed no reduction of symptoms from enlarged prostate by taking Saw Palmetto, as compared to placebo (Bent S et al (2006). “Saw Palmetto for Benign Prostatic Hyperplasia”. NEJM 354: 557-56). Designers of the latest study questioned whether the differently flavored placebos in previous studies were adequately blinded. Critics of the latest study questioned whether a sufficient dosage of active ingredients was given (Allison Aubrey. Morning Edition: Study Casts Doubt on Saw Palmetto as Prostate Remedy [Audio recording]. National Public Radio). An earlier single case study on saw palmetto concluded that searching for information on a herbal medicine using MEDLINE alone was insufficient, and expanded their search to “alternative” databases, including AGRICOLA, EMBASE, IBIS, and Cochrane, plus a manual search of unindexed herbal journals (McPartland J M, Pruitt P L. (2000). “Benign prostatic hyperplasia treated with saw palmetto: a literature search and an experimental case study”. JAOA 100 (2): 89-96).
[0020] Other research has shown that the herb works by multiple mechanisms, including inhibiting 5alpha-reductase, interfering with dihydrotestosterone binding to the androgen receptor, by relaxing smooth muscle tissue similarly to alpha antagonist drugs, and possibly by acting as a phytoestrogen (Di Silverio F et. al (1998). “Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia”. Prostate 37 (2): 77-83), (Plosker G L, Brogden R N (1996). “ Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia”. Drugs Aging 9 (5): 379-95).
[0021] Because the fruit is the part used, and a prolific quantity is produced by an adult Saw Palmetto plant, this herbal medicine is considered ecologically sustainable.
[0022] Though in vitro studies suggest Saw Palmetto has properties that might make it useful against prostate cancer cells or to reduce prostatitis, clinical trials are lacking.
[0023] David Winston RH (AHG) describes a variety of conditions where Saw Palmetto extract is useful for men and women, using both research and ethnobotanical uses (David Winston (1999). Saw Palmetto for Men & Women: Herbal Healing for the Prostate, Urinary Tract, Immune System and More ( Medicinal Herb Guide ). Storey Publishing, LLC. ISBN 978-158017206).
[0024] Though men taking Saw Palmetto may develop mild nausea, reduced libido, or erectile dysfunction, the rate of such problems is clinically and statistically far less common than in men taking drugs to treat BPH symptoms, based on the JAMA meta-analysis cited above. There are no known drug interactions. It should generally be avoided in pregnancy and lactation and in small children due to lack of experience and knowledge in these populations and because of the purely theoretical risk of hormonal interference.
[0025] While Saw Palmetto is generally considered safe, one of its primary active ingredients, beta-sitosterol, is chemically similar to cholesterol. High levels of sitosterol concentrations in blood have been correlated with increased severity of heart disease in men who have previously suffered from heart attacks (Assmann G, et. al (2006). “Plasma sitosterol elevations are associated with an increased incidence of coronary events in men: results of a nested case-control analysis of the Prospective Cardiovascular Munster (PROCAM) study”. Nutr Metab Cardiovasc Dis 16 (1): 13-21).
[0026] For some people, an increase in libido has been reported through usage. As with other nutrients and herbs, various people will have different responses based on their chemical and biological make up.
[0027] Since Saw Palmetto has been known to have side effects, men taking it may develop mild nausea, reduced libido, or erectile dysfunction, it would be unobvious to combine it in a formula to enhance libido in men. This is a critical fact from the prior, which builds a case for one of the unobvious inventive steps of the present invention.
[0028] The side effect of causing flaccidity in the penis is expected since Saw Palmetto enhances urinary flow. Thus any substance that aided in urinary flow would not be put in an aphrodisiac mixture for men, since it would promote erectile dysfunction as opposed to enhancing the libido.
[0029] Omega-3 fatty acids are a family of polyunsaturated fatty acids, which have in common a carbon-carbon double bond in the ω-3 position.
[0030] Important nutritional essential omega-3 fatty acids are: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). For a more complete list see List of omega-3 fatty acids. The human body cannot synthesize omega-3 fatty acids de novo, but it can form 20- and 22-carbon unsaturated omega-3 fatty acids from the eighteen-carbon omega-3 fatty acid, α-linolenic acid. These conversions occur competitively with omega-6 fatty acids, which are essential closely related chemical analogues that are derived from linoleic acid. Both the omega-3 α-linolenic acid and omega-6 linoleic acid are essential nutrients, which must be obtained from food. Synthesis of the longer omega-3 fatty acids from linolenic acid within the body is competitively slowed by the omega-6 analogues. Thus accumulation of long-chain omega-3 fatty acids in tissues is more effective when they are obtained directly from food or when competing amounts of omega-6 analogs do not greatly exceed the amounts of omega-3.
[0031] Omega-6 fatty acids are fatty acids where the term “omega-6” signifies that the first double bond in the carbon backbone of the fatty acid, occurs in the omega minus 6 position; that is, the sixth carbon from the end of the fatty acid.
[0032] The biological effects of the ω-6 fatty acids are largely mediated by their interactions with the ω-3 fatty acids.
[0033] Linoleic acid (18:2), the shortest chain omega-6 fatty acid is an essential fatty acid. Arachidonic acid (20:4) is a physiologically significant n-6 fatty acid and is the precursor for prostaglandins and other physiologically active molecules.
[0034] Some medical research has suggested that excessive levels of omega-6 acids, relative to omega-3 fatty acids, may increase the probability of a number of diseases and depression. Modern Western diets typically have ratios of omega-6 to omega-3 in excess of 10 to 1, some as high as 30 to 1. The optimal ratio is thought to be 4 to 1 or lower (http://www.csuchico.edu/agr/grsfdbef/health-benefits/ben-o3-o6.html).
[0035] Omega-9 fatty acids are a class of unsaturated fatty acids which have a C═C double bond in the ω-9 position. Some ω-9's are common components of animal fat and vegetable oil.
[0036] Two commercially important co-9 fatty acids are:
Oleic acid (18:1 ω-9), which is a main component of olive oil and other monounsaturated fats. Erucic acid (22:1 ω-9), which is found in rapeseed, wallflower seed, and mustard seed. Rapeseed with high erucic acid content is grown for commercial use in paintings and coatings as a drying oil.
[0039] Unlike ω-3 and ω-6 fatty acids, ω-9 fatty acids are not classed as essential fatty acids (EFA). This is both because they can be created by the human body from unsaturated fat and are therefore not essential in the diet, and because the lack of an ω-6 double bond keeps them from participating in the reactions that form the eicosanoids.
[0040] Under severe conditions of EFA deprivation, mammals will elongate and desaturate oleic acid to make mead acid, (20:3 ω-9). (Lipomics) This also occurs to a lesser extent in vegetarians and semi-vegetarians. (Phinney, 1990)
[0041] The fatty acids are not known to have any aphrodisiac effects on humans.
[0042] Hemp oil is from the seed of the hemp plant that contains between 25-35% oil by weight, which is high in essential fatty acids. Cold-pressed, unrefined hemp oil is light green, with a nutty, grassy flavor.
[0043] Refined hemp oil is clear with little flavor. It is widely used in body care products, lubricants, paints and industrial uses. Antimicrobial properties make it a useful ingredient for soaps, shampoos and detergents. The oil is of high nutritional value because its 3:1 ratio of omega-6 to omega-3 essential fatty acids matches the balance required by the human body (InnVista, November 2005). It has also received attention in recent years as a possible source of bio-diesel (Agua Das (Nov. 16, 1997). Hemp Oil Fuels & How to Make Them. HempFarm.com). There are a number of organizations that promote the production and use of hemp oil (http://www.hempworld.com/pstindex0.htm).
[0044] Hemp oil is deliberately manufactured to contain no significant amounts of THC and is therefore, not a psychoactive drug.
[0045] Hemp oil is not known to have any aphrodisiac effects on humans.
[0046] Damiana ( Turnera diffuse , syn. Turnera aphrodisiaca ) is a shrub native to Central and South America. It belongs to the family Turneraceae.
[0047] Blooming with small yellow flowers, the shrub has an odor somewhat like chamomile, which is due to an oil present in the plant. The leaves have traditionally been made into a tea, which was used by native people of Central and South America for its reputed aphrodisiac effects.
[0048] Damiana is also a European name. In the country of Bulgaria it is simply a female version of Damian. In Greece the name Damiana refers to a person who is tame and subdued. Additionally, the name Damiana is somewhat common in Latino/Spanish locations.
[0049] In herbal medicine, Damiana is used to treat conditions ranging from coughs, to constipation, to depression. The herbal supplement is reputed to help with energy, emphysema, low estrogen, frigidity, hot flashes, impotency, infertility, menopause, Parkinson's disease, PMS, inflammation of prostate, Lou Gehrig's disease, and more dealing with reproductive organs in both males and females.
[0050] Damiana is obtained from the shrub Turnera diffusa , which is native to the U.S. Southwest and northern Mexico. The inhabitants of this region have used Damiana for many years as a remedy for nervous disorders, and as a tonic and aphrodisiac. Damiana seems to have a positive toning effect on both the nervous system and sexual organs.
[0051] Chocolate—The word “chocolate” comes from the Aztecs of Mexico, and is derived from the Nahuatl word xocolatl (http://www.yourdictionary.com/wotd/wotd), which is a combination of the words, xocolli, meaning “bitter”, and atl, which is “water”. The Aztecs associated chocolate with Xochiquetzal , the Goddess of Fertility. Chocolate is also associated with the Mayan god of fertility. Mexican philologist Ignacio Davila Garibi, proposed that “Spaniards had coined the word by taking the Mayan word chocol and then replacing the Mayan term for water, haa, with the Aztec one, atl.” (http://www.theclevermouse.com/belovedbeans_public/coffeehistory.html). However, it is more likely that the Aztecs themselves coined the term (http://www.sacofoods.com/foodofthegods.html), having long adopted into Nahuatl the Mayan word for the “cacao” bean; the Spanish had little contact with the Mayans before Cortés' early reports to the Spanish King of the beverage known as xocolatl (http://www.news.cornell.edu/releases/Oct98/chocolate.cacao.hrs.html). However, Micheal D. Coe, professor Emeritus of Anthropology and Curator Emeritus in the Peabody Museum of Natural History at Yale University, and coauthor of the book The True History of Chocolate , argues that the word xocolatl appears in “no truly early source in the Nahuatl language or in Aztec culture.”
[0052] Chocolate has been used solely as a drink for nearly all of its history. The earliest record of using chocolate pre-dates the Mayans. Chocolate residue has been found in pottery dating to 1100 BC from Honduras (http://www.nhm.ac.uk/research-curation/projects/sloane-herbarium/hanssloane.htm) and 600-400 BC from Belize. The chocolate residue found in an early classic ancient Mayan pot in Rio Azul, northern Guatemala, suggests that Mayans were drinking chocolate around 400 A.D. In the New World, chocolate was consumed in a bitter, spicy drink called xocoatl, and was often flavored with vanilla, chile pepper, and achiote, (which is known today as annatto). Xocoatl was believed to fight fatigue, a belief that is probably attributable to the theobromine content. Other chocolate drinks combined it with such edibles as maize starch paste (which acts as an emulsifier and thickener), various fruits, and honey. In 1689 noted physician and collector Hans Sloane, developed a milk chocolate drink in Jamaica which was initially used by apothecaries, but later sold by the Cadbury brothers (Athena Review Vol. 2, no. 2 A Brief History of Chocolate, Food of the Gods).
[0053] Chocolate was also an important luxury good throughout pre-Columbian Mesoamerica, and cacao beans were often used as currency (http://www.sustainabletimes.ca/articles/chocolate.htm). For example, the Aztecs used a system in which one turkey cost one hundred cacao beans and one avocado was worth three beans.
[0054] Romantic lore commonly identifies chocolate as an aphrodisiac. The reputed aphrodisiac qualities of chocolate are most often associated with the simple sensual pleasure of its consumption. More recently, suggestion has been made that serotonin and other chemicals found in chocolate, most notably phenethylamine, can act as mild sexual stimulants. While there is no firm proof that chocolate is indeed an aphrodisiac, giving a gift of chocolate to one's sweetheart is a familiar courtship ritual.
[0055] Tang-kuei (danggui) is a long root that is known as a blood-nourishing agent. It is highly used among women because tang-kuei will help regulate uterine blood flow and contraction, but when it is in complex formulas it can be used by both men and women to nourish the blood, moisten the intestines, improve the circulation, calm tension and relieve pain. Tang-kuei can be made as tea or cooked with chicken to make soup and the taste is quite strong”.
[0056] Of the above substances the ones that are purported or rumored to have mild aphrodisiac effects on males are Maca and Yohimbine. Saw Palmetto has been reported to have the side effect of causing erectile dysfunction.
[0057] Of the above substances the ones that are purported or rumored to have mild aphrodisiac effects on females are Damiana and Maca.
[0058] Numerous approaches have been taken in attempts to treat impotence. These approaches include the use of external or internally implanted penile prosthesis. (See, e.g., U.S. Pat. No. 5,065,744, to Zumanowsky). A variety of drugs and methods for administering drugs have also been used in attempts to treat impotence. For example, U.S. Pat. No. 3,943,246 to Sturmer addresses treatment of impotence in men by buccal and peroral administration of daily doses of 300-1500 international units (I.U.) of oxytocin or daily divided doses of 150-250 I.U. of desamino-oxytocin. The patent discloses the buccal administration of 100 I.U. three times a day for 14 days, resulting in improvement of impotentia erectionis in 12 of the 16 patients treated.
[0059] U.S. Pat. No. 4,530,920 to Nestor et al. discloses that the administration of nonapeptide and decapeptide analogs of luteinizing hormone releasing hormone agonists may be useful in the induction or enhancement of sexual behavior or therapy for impotence or frigidity. Nestor et al. suggest numerous routes of administration of the analogs including buccal, sublingual, oral, parenteral (including subcutaneous, intramuscular, and intravenous administration), rectal, vaginal, and others.
[0060] U.S. Pat. No. 4,139,617 to Grunwell et al. suggests buccal and other routes of administration of 19-oxygenated-androst-5-enes for the endocrine mediated enhancement of the libido in humans.
[0061] U.S. Pat. No. 4,863,911 to Anderson et al. discloses methods for treating sexual dysfunction in mammals using a biooxidizable, blood-brain barrier penetrating estrogen derivative. One of the purported objects of the Anderson et al. invention is the treatment of “psychological impotence” in males. Test results showed that the drugs used in the study stimulated mounting behavior, intromission, and mount latency in castrated rats.
[0062] A number of publications have proposed the use of various vasodilators for the treatment of impotence in males. Attempts to utilize vasodilators for the treatment of impotence were prompted by the fact that a significant percentage of cases of impotence were noted to be vasculogenic, i.e. resulting from vascular insufficiency.
[0063] Voss et al., U.S. Pat. No. 4,801,587, issued Jan. 31, 1989, discloses the use of an ointment containing a vasodilator and a carrier agent for topical application to the penis of impotent men. The Voss et al. patent also describes application of such an ointment into the urethra of the penis using a catheter as well as a multi-step regimen for applying a vasodilator to the skin of the penis. In addition, Voss et al. proposes the surgical removal of a portion of the fibrous sheath surrounding the corpora cavernosum, thereby facilitating the penetration of a vasodilator-containing ointment into the corpora cavernosum. Vasodilators disclosed for use by Voss et al. include papaverine, hydralazine, sodium nitroprusside, phenoxybenzamine, and phentolamine. The Voss et al. patent, however, provides no information regarding the actual efficacy of the treatments proposed or the nature of the response to such treatments.
[0064] U.S. Pat. No. 4,127,118 to Latorre describes treating male impotence by direct injection of the vasodilating drugs into the corpus cavernosum and the corpus spongiosum of the penis using a syringe and one or more hypodermic needles. More particularly, the Latorre patent proposes the intracavernosal and intraspongiosal injection of sympathomimetic amines such as nylidrin hydrochloride, adrenergic blocking agents such as tolazoline hydrochloride, and direct acting vasodilators such as isoxsuprine hydrochloride and nicotinyl alcohol.
[0065] Brindley, G. S. (Br. J. Pharmac. 87:495-500, 1986) disclosed that, when injected directly into the corpus cavernosum using a hypodermic needle, certain smooth muscle relaxing drugs including phenoxybenzamine, phentolamine, thymoxamine, imipramine, verapamil, papaverine, and naftidrofuryl caused erection. This study noted that injection of an “appropriate dose of phenoxybenzamine or papaverine is followed by an unrelenting erection lasting for hours.” Injection of the other drugs studied, induced erections lasting from about 11 minutes to about 6.5 hours.
[0066] Zorgniotti et al., J. Urol. 133:39-41 (1985) demonstrated that the intracavernosal injection of a combination of papaverine and phentolamine could result in an erection in otherwise impotent men. Similarly, Althof et al. (J. Sex Marital Ther. 17(2): 101-112 (1991) reported that intracavernosal injection of papaverine hydrochloride and phentolamine mesylate resulted in improved erectile ability in about 84% of patients injected. However, in that study the dropout rate was 57%, fibrotic nodules developed in 26% of the patients, 30% of the patients developed abnormal liver function values, and bruising occurred in 19% of the patients.
[0067] Other studies describing intracavernosal injection of drugs using hypodermic needles for the treatment of impotence include: Brindley, J. Physiol. 342:24 P (1983); Brindley, Br. J. Psychiatr. 143:312-337 (1983); Virag, Lancet ii:978 (1982); and Virag, et al., Angiology 35:79-87 (1984).
[0068] While intracavernosal injection may be useful for inducing erections in impotent men, the technique has numerous drawbacks. Obvious drawbacks include pain, risk of infection, inconvenience and interference with the spontaneity of the sex act. Priapism (prolonged and other painful erection) also appears to be a potential problem when using injection methods. See, e.g. Brindley, (1986). Another problem arising in some cases of intracavernosal injection involves the formation of fibrotic lesions in the penis. See, e.g., Corriere, et al., J. Urol. 140:615-617 (1988) and Larsen, et al., (J. Urol. 137:292-293 (1987).
[0069] Phentolamine, which has been shown to have the potential to induce erection when injected intracavernosally, has also been the subject of oral administration to test its effects in men having non-specific erectile insufficiency (Gwinup, Ann. Int. Med. Jul. 15, 1988, pp. 162-163.) In that study, 16 patients ingested either a placebo or a 50 mg orally administered dose of phentolamine. Eleven of the 16 patients (including three placebo-treated patients) became tumescent, became more responsive to sexual stimulation, and were able to achieve an erection sufficient for vaginal penetration after waiting 1.5 hours to attempt intercourse.
[0070] Sonda et al. (J. Sex & Marital Ther. 16(1): 15-21 (year), reported that Yohimbine ingestion resulted in subjective improvement in erectile ability in 38% of impotent men treated, but only 5% of the treated patients reported complete satisfaction.
[0071] Zorgniotti et al, PCT/US94/09048, describes the transmucosal administration of a variety of vasodilators including phentolamine mesylate for modulating the human sexual response.
[0072] U.S. Pat. No. 4,885,173, to Stanley et al., discloses methods of administering drugs having cardiovascular or renal vascular activity through use of a lollipop assertedly facilitating drug absorption through the mucosal tissues of the mouth, pharynx, and esophagus. The Stanley et al. patent discloses that a large number of lollipop-administered drugs may improve cardiovascular function including drugs exhibiting direct vasodilating effects, including calcium channel blockers, beta-adrenergic blocking agents, serotonin receptor blocking agents, angina blocking agents, other anti-hypertensive agents, cardiac stimulating agents, and agents, which improve renal vascular function.
[0073] U.S. Pat. No. 5,059,603 to Rubin describes the topical administration to the penis of isoxsuprine and caffeine, and nitroglycerine and caffeine along with suitable carrier compounds for the treatment of impotence.
[0074] U.S. Pat. No. 5,902,593 to Kent, et al., discloses a topically applied aphrodisiac dispersed in a manually applied vehicle, which substantially increases tissue sensation. The principal ingredient is benzalkonium chloride in a water-soluble gel, which includes sorbitol, glycerin, hydroxethylcellulose and propylene glycol.
[0075] U.S. Pat. No. 5,281,423 to Reilly discloses a method of heightening sexual desire of an adult human female comprising administering to an adult human female in need of said treatment, an effective amount of hydriodic acid syrup, comprising hydriodic acid, water and dextrose.
[0076] U.S. Pat. No. 3,943,246 to Sturmer discloses a method of treating impotency in a human male in need of said treatment, which comprises administering oxytocin at a dosage of 300 to 1500 I.U. daily.
[0077] The above issued patents comprise means, which are either considered the ingestion of a drug orally or by other means. The drugs are not a good solution since it is highly probable that prolonged use will result in side effects that are unwanted.
[0078] Natural remedies for which patents have been issued include:
[0079] U.S. Pat. No. 6,803,060 to Reyes discloses a composition for boosting libido of an individual, said composition consisting essentially of an effective amount 667 mg Tribulus, 427 mg Muria Puama, 352 mg, Catuba Bark, 127 mg L-Arginine, 60 mg Avena Sativa, and 37 IU Vitamin E.
[0080] Reyes further discloses a spray composition for boosting libido of an individual, said composition consisting essentially of 35 mg Tribulus terrestris, 30 mg Epimedium sagattatium, 10 mg Muria Puama, 10 mg Serenoa reopens, 10 mg Chrysin, and 4 mg 5-Androstenediol.
[0081] U.S. Pat. No. 6,093,421 to DeLuca et al. discloses a process of increasing testosterone levels in a man comprising oral administering to a man in need of such a treatment, an effective amount of a composition containing Maca and antler.
Aphrodisiac Drugs
Testosterone
[0082] Libido is clearly linked to levels of sex hormones, particularly testosterone. (R. Shabsigh (1997). “The effects of testosterone on the cavernous tissue and erectile function”. World J. Urol ). When reduced sex drive occurs in individuals with relatively low levels of testosterone (e.g., post-menopausal women or men over age 60), testosterone supplements will often increase libido. Approaches using a number of precursors intended to raise testosterone levels have been effective in older males (Brown, G. A.; Vukovich M D, Martini E R, Kohut M L, Franke W D, Jackson D A, King D S. (2001). “Effects of androstenedione-herbal supplementation on serum sex hormone concentrations in 30- to 59-year-old men”. Int J Vitam Nutr Res .), but have not fared well when tested on other groups (Brown, G. A.; Vukovich M D, Reifenrath T A, Uhl N L, Parsons K A, Sharp R L, King D S. (2000). “Effects of anabolic precursors on serum testosterone concentrations and adaptations to resistance training in young men.”. Int J Sport Nutr Exerc Metab .).
Yohimbine
[0083] Yohimbine is the main alkaloid of Yohimbe . As a weak MAO inhibitor and alpha-adrenergic antagonist, Yohimbine may increase genital blood-flow and sexual sensitivity for some people (Adeniyi, A. A.; Brindley G S, Pryor J P, Ralph D J. (2007). “Yohimbine in the treatment of orgasmic dysfunction”. Asian J Androl . and Kovalev, V. A.; Koroleva S V, Kamalov A A. (2000). “Pharmacotherapy of erectile dysfunction.”. Urologiia )
Bremelanotide
[0084] Bremelanotide, formerly known as PT-141, is currently undergoing clinical trials for the treatment of sexual arousal disorder and erectile dysfunction. It is intended for both men and women. Preliminary results are encouraging (King, S. H.; Mayorov A V, Balse-Srinivasan P, Hruby V J, Vanderah T W, Wessells H. (2007). “Melanocortin receptors, melanotropic peptides and penile erection.”. Curr Top Med Chem.)
PEA
[0085] There is some debate in lay circles as to whether a chemical called phenylethylamine present in chocolate is an aphrodisiac. This compound, however, is quickly degraded by the enzyme MAO such that significant concentrations do not reach the brain.
Other Drugs
[0086] Stimulants affecting the dopamine system such as cocaine and amphetamines (e.g. Methamphetamine, aka Crystal meth) are frequently associated with hyperarousal and hypersexuality, though both may impair sexual functioning, particularly in the long term.
Drugs Not Considered Aphrodisiacs
[0087] Psychoactive substances like alcohol, cannabis (Cannabis Puts Females in the Mood for Love. Mark Henderson, The Times (29 Jan. 2001)) and MDMA are not aphrodisiacs in the strict sense of the definition, but they can be used to increase sexual pleasure and to reduce sexual inhibition.
[0088] Anti-erectile dysfunction drugs, such as Viagra and Levitra, are not considered aphrodisiacs because they do not have any mood effect.
Aphrodisiac Foods and Herbs
[0089] Some natural items purported to be aphrodisiacs when ingested (not at all exhaustive): Arugula (Rocket), Balut, Chocolate, Damiana, Eggs, Eurycoma longifolia (Ang, H. H.; M. K. Sim (1997). “ Eurycoma longifolia Jack enhances libido in sexually experienced male rats”. Exp Anim and Ang, H. H.; Lee K L, Kiyoshi M. (2004). “Sexual arousal in sexually sluggish old male rats after oral administration of Eurycoma longifolia Jack.”. J Basic Clin Physiol Pharmacol .), Ginkgo biloba (McKay, D. (2004). “Nutrients and botanicals for erectile dysfunction: examining the evidence”. Altern Med Rev and Cohen, A. J.; Bartlik B. (1998). “ Ginkgo biloba for antidepressant-induced sexual dysfunction.”. J Sex Marital Ther .), Ginseng (Sandroni, P. (October 2001). “Aphrodisiacs past and present: a historical review.”. Clin Auton Res. 11 (5): 303-7. and Murphy, L. L.; Lee T J. (2002). “Ginseng, sex behavior, and nitric oxide.”. Ann N Y Acad Sci .), Honey, Kelp, Maca (Gonzales, G. F.; Córdova A, Vega K, Chung A, Villena A, Góñez C. (2003). “Effect of Lepidium meyenii (Maca), a root with aphrodisiac and fertility-enhancing properties, on serum reproductive hormone levels in adult healthy men.”. J Endocrinol and Gonzales, G. F.; Córdova A, Vega K, Chung A, Villena A, Góñez C, Castillo S. (2002). “Effect of Lepidium meyenii (MACA) on sexual desire and its absent relationship with serum testosterone levels in adult healthy men.”. Andrologia ), Oat, Oysters, Shilajit, Socratea exorrhiza, Spanish Fly (cantharidin) (Karras, D. J.; Farrell S E, Harrigan R A, Henretig F M, Gealt L. (1996). “Poisoning from “Spanish fly” (cantharidin).”. Am J Emerg Med ), Tribulas terrestrias (Gauthaman, K.; A. P. Ganesan, R. N. Prasad. (2003). “Sexual effects of puncturevine ( Tribulus terrestris ) extract (protodioscin): an evaluation using a rat model.”. J Altern Complement Med and Gauthaman, K.; P. G. Adaikan, R. N. Prasad. (2002). “Aphrodisiac properties of Tribulus Terrestris extract (Protodioscin) in normal and castrated rats.”. Life Sci . and Neychev, V. K.; V. I. Mitev (2005). “The aphrodisiac herb Tribulus terrestris does not influence androgen production in young men.”. J Ethnopharmacol .), and Walnut Oil.
[0090] Some newly introduced exotic fruits or vegetables often acquire such a reputation, at least until they become more familiar; for example:
Artichokes, Asparagus, Strawberries, Tomatoes, Truffles, Turtle Eggs, Mangoes, and Mamey Sapote.
[0091] The problem with the herbal treatments is that they simply are not as powerful as the drugs. This problem is addressed by the proposed invention.
DETAILED DESCRIPTION OF THE INVENTION
[0092] The proposed invention is not a vasodilator. It is a combination of herbs with an additive catalyst substance, which promotes the herbs to stimulate the glands in the brain generating a psychotropic effect causing the body to generate its own unique chemistry specific to the augmentation and enhancement of sexual function. In the absence of the catalyst substance the herbs simply will not have the effects reported, thus the invention would be inoperative. The catalyst substance by itself has no aphrodisiac properties. It is therefore unobvious to combine it with said herbs. The unexpected result can be measured in the following way: If an herbal aphrodisiac is used by an individual the aphrodisiac effects, if measured on a scale of one to one hundred qualitatively by the user, are reported to have a score around thirteen to eighteen. The user will often make comments like, “I think it might be doing something”. If on the other hand the herbal aphrodisiac is mixed with an effective amount of the catalyst substance, the user reports the score of the effectiveness to be from eighty to one hundred on a scale of one to one hundred. The catalyst substance has to be intimately mixed with the herbs and is the critical key to the function of the invention. The catalyst substance is omega oil. In particular hemp seed oil. The hemp seed oil having all of the THC removed.
[0093] The herbs are combined with the omega oils in the form of extracts.
[0094] Examples of how the essence of herbs are extracted from the plant with hot water are organized in the following discussion. These are essentially herbal teas. Typically, one ounce by weight (about a cup by volume) of dried herb is placed in a quart jar, which is then filled to the top with boiling water, tightly lidded and allowed to steep for 4-10 hours. After straining, a cup or more is consumed, and the remainder chilled to slow spoilage. Drinking 2-4 cups a day is usual. Since the minerals and other phytochemicals in nourishing herbs are made more accessible by drying, dried herbs are considered best for infusions.
[0095] Herbal tinctures are concentrates made by dipping the plant into alcohols, the resulting fluid containing the desired ingredients of the herb. Steeping a medicinal plant in alcohol extracts the alcohol-soluble principles into a liquid form that can be stored for long periods. Different concentrations of alcohol are used to extract different constituents of the plants. For example; resins require high alcohol content and sugars usually require low alcohol content for optimal extraction.
[0096] There are many schools of thought about tincture making. In the traditional view an herb is either steeped once (single maceration) or more than once. In a double maceration the mark (or used plant material) is removed and replaced by a new batch (using the same alcohol) thus increasing the strength of the tincture. Sometimes the mark is then ashed (burnt until ash) and added back in which increase the amount of some minerals in the tincture.
[0097] In the scientific model tincture strengths are measured by a ratio of herb to alcohol (1:5 and 1:2 are the most common where the 1:2 is the stronger tincture). Many tinctures use a combination of vegetable glycerine and alcohol to extract, which changes the compounds that are extracted.
[0098] Fluid extracts are stronger than herbal tinctures, and can be preserved with alcohol or glycerin. They are just highly concentrated tinctures, made by distilling off some of the alcohol used in the tincture process. The final result is a liquid plant compound that can be 40 times more potent than a tincture.
[0099] Glycerates are herbal extracts that use glycerin as the sole extractant. They are very different and often have completely different medicinal properties than alcohol extracts. Tinctures or fluid extracts that are alcohol free should have the alcohol removed after the extraction process and replaced with glycerin which then acts just as the preservative.
[0100] In general, for the purpose of clarifying the optimum conditions of the proposed invention we will provide effective amounts of herbs by way of extracts. The extracts will be quantified by their volume, and the process by which the extract was created will be classified by the weight of herbal plant material to the volume of extractant used to capture the valuable essences from the plant. For example, a volume V of a 1 wght:2 vol process alcohol liquid extract of Maca would mean the following (numbers are used to add clarity); 1000 grams of Maca plant was placed in 2000 milliliters of alcohol and allowed to sit for a period of time, at least equal to the extract maturation time, during which time the alcohol extracts essence from the plant in the form of alkaloids. The maturation time of the steeping is the time wherein the maximum amount of alkaloids have been extracted from the plant material and dissolved into the fluid, at which point the fluid has reached saturation. Saturation meaning that the fluid cannot receive any more plant material alkaloids and if more alkaloids are extracted from the plant they cannot dissolve into the fluid, but rather they precipitate out as solids onto the floor of the container. The remaining plant material and any remaining solid precipitants are discarded and the resulting fluid is the liquid extract of value. This would constitute a 1 wght:2 vol process alcohol extract, with alcohol as a carrier, and a volume that will be slightly greater than the 1000 ml of pure alcohol that started the process. Other words that are equivalent to describe the extract would be, a volume V of mature, fully saturated herbal extract which originated from a 1 wght:2 vol alcohol extraction process wherein the alcohol remained as the carrier and the preservative.
[0101] An alcohol herbal extract can be made alcohol free by removing the alcohol and adding an effective amount of glycerin as a carrier and a preservative. We shall refer to such an extract as an alcohol herbal extract made alcohol free and further including glycerin as a carrier and preservative. More exact words might be, a volume V of mature, fully saturated herbal extract which originated from a 1 wght:2 vol alcohol extraction process wherein said alcohol was discarded and replaced with an effective amount of glycerin.
[0102] An extract that originated from a glycerin extraction process would be described as a mature, fully saturated herbal extract which originated from a 1 wght:2 vol glycerin extraction process wherein the glycerin remained as the carrier and the preservative. This is just a way of filling space.
[0103] In one embodiment of the proposed invention a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on males.
[0104] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on males. Said herbs being selected from the group consisting of Maca, Saw Palmetto, and Yohimbine.
[0105] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, some of which are known to have aphrodisiac effects on females.
[0106] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, some of which are known to have aphrodisiac effects on females. Said herbs being selected from the group consisting of Maca, Damiana, and Tang Kuei.
[0107] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on males. Said herbs being selected from the group consisting of Maca and Yohimbine.
[0108] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on males. Said herbs being selected from the group consisting of Maca and Yohimbine. Yet, further included is an effective amount Saw Palmetto, the amount of Saw Palmetto, being at least as much as the greatest amount of either Yohimbine or Maca. This mixture is unusual in that the large amount of Saw Palmetto is in danger of causing erectile dysfunction in males. Yet, in the combination of omega oils in the proposed invention the Saw Palmetto in large amounts has the effect of greater enhancement of the aphrodisiac effects of the other herbs.
[0109] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on females. Said herbs being selected from the group consisting of Damiana, Maca, and Tang-Kuei.
[0110] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on males. Yet, further included is an effective amount of chocolate.
[0111] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, some of which are known to have aphrodisiac effects on females. Yet, further included is an effective amount of chocolate.
[0112] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on males. Said herbs being selected from the group consisting of Maca and Yohimbine. Yet, further included is an effective amount of chocolate.
[0113] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on males. Said herbs being selected from the group consisting of Maca and Yohimbine. Yet, further included is an effective amount Saw Palmetto, the amount of Saw Palmetto being at least as much as the greatest amount of either Yohimbine or Maca. This mixture is unusual in that the large amount of Saw Palmetto is in danger of causing erectile dysfunction in males due to its reported side effects. Yet, in the combination of omega oils in the proposed invention the Saw Palmetto in large amounts has the effect of greater enhancement of the aphrodisiac effects of the other herbs. Yet, further included is an effective amount of chocolate.
[0114] In one embodiment of the proposed invention, a liquid plant compound is combined with an effective amount of omega oils for the enhancement of libido. The plant compound is derived from herbs, which are known to have aphrodisiac effects on females. Said herbs being selected from the group consisting of Damiana and Tang-Kuei, yet further included is an effective amount of Maca and chocolate.
[0115] In the above embodiments the effectual amounts of ingredients are present in a fluid, the total volume of the fluid aphrodisiac being V a , the total volume of the herbal extract being V h , and the volume of omega oils being V o , such that V a =V h +V o .
[0116] In the embodiments wherein the liquid herbal extract is composed of Maca and Yohimbine the total volume of the fluid aphrodisiac is V a , the total volume of the herbal extract is V h , and the volume of omega oils is V o , such that V a =V h +V o . The volume of the Maca extract is between 60% and 75% of V h and the volume of the Yohimbine extract is between 25% and 40% of V h .
[0117] In the embodiments wherein the liquid herbal extract is composed of Maca, Yohimbine, and Saw Palmetto the total volume of the fluid aphrodisiac is V a , the total volume of the herbal extract is V h and the volume of omega oils is V o , such that V a =V h +V o . The volume of the Maca extract is between 35% and 50% of V h . The volume of the Yohimbine extract is between 25% and 30% of V h . The volume of the Saw Palmetto extract is between 25% and 35% of V h .
[0118] In the embodiments wherein the liquid herbal extract is composed of Maca, Damiana, and Tang-Kuei, the total volume of the fluid aphrodisiac is V a , the total volume of the herbal extract is V h , and the volume of omega oils is V o , such that V a =V h +V o . The volume of the Maca extract is between 35% and 50% of V h . The volume of the Damiana extract is between 25% and 30% of V h . The volume of the Tang-Kuei extract is between 25% and 35% of V h .
[0119] In the above embodiments the liquid extracts are combined with effective amounts of omega oils. Again the total volume of the fluid aphrodisiac is V a , the total volume of the herbal extract is V h , and the volume of omega oils is V o , such that V a =V h +V o . The mixture is such that V h is between 75% and 85% of V a , and V o is between 15% and 25% of V a .
[0120] In the above embodiments wherein the liquid plant extract is combined with omega oils and chocolate, the chocolate can be a syrup. The volume of the chocolate syrup aphrodisiac mix is Vs. The volume of the fluid aphrodisiac is V a . The volume of the chocolate syrup is V c . The total volume of the chocolate syrup aphrodisiac mix is V s , such that V s =V a +V c . The mixture is such that V a is between 20% and 25% of V s and V c is between 75% and 80% of V s .
[0121] Thus the reader can see that there are many embodiments of the proposed invention. While the above description contains many specificities, these should not be construed as limitations on the scope of the invention, but rather as an exemplification of several preferred embodiments thereof.
[0122] One can see that the effectiveness of herbal aphrodisiacs is unexpectedly greatly enhanced by the combining of such herbs with effective amounts of omega oils, thus creating a new combination of substances, which can outperform the libido enhancing drugs that have been developed.
[0123] Accordingly the scope of the invention should be determined not by the embodiments illustrated, but by the appended claims and their legal equivalents.
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A method of enhancing the libido in an adult human comprising the administering of a composition, comprising an effective amount of an herbal aphrodisiac selected from the group consisting of those herbs, which are purported to enhance the libido in humans, and an effective amount of omega oils.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a National Phase application claiming the benefit of International Application No. PCT/EP2007/009658, filed Nov. 7, 2007, which claims priority to German Patent Application Nos. DE 10 2006 058 562.3 and DE 10 2007 029 195.9, filed Dec. 12, 2006 and Jun. 25, 2007, respectively, and the complete disclosures of each are hereby incorporated by reference in their entireties.
FIELD
The present disclosure relates to a coating apparatus for serially coating workpieces with different colours as well as metering devices and containers usable for the same.
BACKGROUND
This includes, for example, serial coating of vehicle bodies and parts thereof with electrostatic or other atomisers including rotary atomisers, air atomisers etc., which apply the coating material using an automatically controlled metering device. Here, the term metering device generally includes volumetric metering devices, for example geared pumps or plunger-type metering mechanisms, which can be driven by a controllable motor such that the material quantity applied by the atomiser (instantaneous flow rate) can be adjusted during application as requested depending for example on the respective workpiece regions and other parameters, as elucidated for example in EP 1 314 483 A2 or DE 691 03 218 T2. The volumetric metering is typically performed by controlling the rotational speed of a geared pump or the piston speed of a plunger-type metering mechanism.
In many cases, gear metering pumps are advantageous for reason of compactness, continuous paint supply and cost benefits.
In contrast, plunger-type metering mechanisms have the benefit of higher metering precision by avoiding slippage between the gear pair and the socket housing of gear metering pumps, and in electrostatic painting devices, in which high-voltage insulation is required between the atomisers and their earthed supply system, the required electrical potential isolation can be attained by the intermittent paint delivering operation of a plunger-type metering mechanism. Further benefits will be explained.
As described in EP 1 772 194 A2, it may further make sense to connect a container serving as an interim paint storage repository of an electrostatic painting device upstream the plunger-type metering mechanism, which is already filled with the new colour in order to reduce the colour exchange time required during colour changes, while painting continues with the previous colour from the plunger-type metering mechanism. This storage vessel can also be defmied as a component of a metering device in terms of the exemplary illustrations. To drain the storage vessel, it can also include a plunger in the cylinder.
In place of volumetric metering, a paint pressure controller, e.g. in accordance with EP 1 287 900 A2, or in accordance with EP 1 34 6 775 A1, the main needle valve of the atomiser can serve as the final control element of a regulator circuit to control the paint quantity or flow rate and thus serve as a metering device.
EP 1 502 658 A1, DE 101 15 463 A1, DE 101 36 720 A1 and DE 695 10 130 T2 generally disclose metering devices incorporated into the atomiser.
For the case that an atomiser shall apply coating material with a large number of colours, which however may for example be limited by a paint circulation system, and a colour change shall be performed in the shortest possible time, colour-changer valve arrangements referred to as colour changers, are usually inserted in block assembly (i.e. as a mechanical unit), which connect the numerous colour inlets with the colour outlet leading to the atomising member via a central channel. Based on its usual modular assembly they can be adjusted to a differing number of selectable colours. Typical modular colour changers for wet paint, for example, are generally disclosed by DE 198 36 604 A1 and DE 198 46 073 A1, while a colour changer for powder paint similar in principle is described in DE 601 03 281 T2. For instance, DE 199 51 956 A1 relates to the flushing of colour changers. Such colour changers are typically connected upstream of gear or plunger metering devices or, where applicable, the mentioned paint storage vessel.
If only few colours are required, it is also possible to mount a colour changer into the atomiser, where applicable with a metering device downstream thereof (EP 1 502 658 A1), to shorten the distance to flush from the colour changer to the application member, such as the bell cup of a rotary atomiser, during a colour change. For this purpose, effort has been made to construct particularly compact colour changers (EP 1 502 659 B1), which is particularly important, if colour changers are required in a double assembly, which, as is well known, share paint supply lines and are connected with the application member via separate colour sections. The installation of a colour-changer valve arrangement in practice also referred to as ICC technology (Integrated Colour Changer) into the atomiser has the advantage of significantly reducing the paint and flushing agent losses during colour change. In case of painting car bodies, for example, the losses during colour changes from approx. 45 ml paint per atomiser and colour change with conventional colour change technology are reduced to only approx. 4 ml. A similar reduction is obtained for flushing agent losses. Moreover, the duration of colour change in typical cases can be reduced by half, from around 12 to 6 seconds, leading to a capacity increase of the coating facility of around 5-10% or for example 30-60 vehicles daily.
Due to the space required for the colour changer and the paint supply lines into the atomiser, the reduced number of selectable colours is disadvantageous in known systems with colour changers mounted into the atomiser. In place of supplying paint via one of the conventional colour changers, i.e, a modular colour change block with an outlet channel shared by the paints, the paints can also be supplied e. g. directly from circulation lines to the application member through respective paint lines each leading into the atomiser via colour valves located in the atomiser, for each of the paints being provided a separate metering device, which consequently is not to be flushed during a colour change and a greater number of less frequently required paints (so-called Low-Runners) being possible to connect via an external colour changer, as described in the German patent application 10 2006 022 570.8 of 15 May 2006 and in the patent application PCT/EP2007/003874 of 2 May 2007, the complete content of which is hereby included in the current description. The number of selectable frequently required paints (High-Runner), however, is also limited here by the available space in the atomiser, the lead through of paint lines via the wrist of the painting robot and by the space required for their assembly on the robot in upstream connection of metering devices.
Special colour supply systems offer the advantage of an unlimited number of applicable colours, in which the colours are not coming out of circulation lines, but produced in a paint mixing shop and lead to the atomiser via a colour changer. These systems, however, are relatively expensive and have considerable colour change losses in comparison to circulation line systems.
As was previously mentioned, in general, colour changers in paint shops are common, since, as is well known they allow swift changing from one paint to another during painting operation. However, they have the main disadvantage of unavoidable paint losses during flushing of the larger or smaller central channel with each colour change. After optimising the paint losses in pigged lines, metering devices etc., colour changers often represent the element of the coating facility with the most individual losses. The colour change loss is larger, the larger the diameter of the central channels is selected, to enable a larger quantity of paint to be channelled in a shorter time through the colour changer, which may be desirable for various reasons (special colour supplies, tank technology, higher paint quantities, shorter cycle times for consecutive workpieces, higher viscosities etc.). In addition, the colour change losses increase with the number of connected paints and the resultant length of the central channel, meaning that the number of colours must often be undesirably limited.
To avoid colour change losses in conventional colour changers, colour change systems operating based on the docking principle were developed, in which the paint lines provided for the various colours are connectable by mechanically movable valve elements to a line leading to the atomiser (EP 1 245 295 A2, DE 100 64 065 A1 or DE 601 11 607 T2). With these paint interfaces, paint savings (of typically 10 ml for each colour change) can be attained in comparison to conventional colour changers, however, they have various practical disadvantages such as complex motion control for starting up the connection positions, high maintenance requirement, flushing of the interface, paint drying out at the interface, leakages etc.
One proposed solution to the problem of reducing paint losses during a colour change is provided by the colour changer described in EP 1 502 657 A2, the central channel of which is sub-divided into flushable sections, the High-Runner paints often required, i.e. those with a high usage volume, being connected in the front section at the colour outlet, while at the rear, the less frequently required (Low-Runner) paints are connected in the section opposite to the colour outlet. While the often required front section can be continually flushed independently of the rear section, the less frequently required section can be flushed together with the other section. Since, as with conventional colour changers, during a colour change no longer the entire central channel is flushed, losses of paint and flushing agent are reduced. However, the persistent colour change losses are particularly undesirable for colours that are often required.
After the outlet from the colour changers, a paint pressure controller is usually located, which provides initial pressure control of a metering pump or, as was explained previously, which can act as the final control element for adjusting the paint quantity. The clearance volume of this paint pressure controller must be flushed with each colour change.
Based on the above-described state of technology, such as EP 1 502 658 A1 for example, one object of the present disclosure is to provide a coating apparatus or devices that can be used for the coating of workpieces particularly with different frequently required colours, which allow a colour change with minimal or low losses of paint, flushing agent and time.
DESCRIPTION OF THE DRAWINGS
Exemplary illustrations are explained with reference to the drawings. The figures show each in schematic and simplified form:
FIG. 1 a simplified conceptual drawing of a coating apparatus in accordance with an exemplary illustration;
FIG. 2 a plunger-type metering mechanism in accordance with an exemplary illustration;
FIG. 3 (a), (b), (c) to three different colour changers, which can be used in a coating apparatus in accordance with an exemplary illustration;
FIG. 4 a modified exemplary illustration with respect to FIG. 2 ;
FIG. 5 an exemplary illustration with a gear metering pump;
FIG. 6 a practical constructional implementation of the metering device in accordance with FIG. 2 ;
FIG. 7 a radial cut through the end wall of the device in accordance with FIG. 6 ;
FIG. 8 a practical constructional implementation of the metering device in accordance with FIG. 4 ;
FIG. 9 the arrangement of a metering device for example with a container in accordance with FIG. 6 in the front arm of a painting robot;
FIG. 10 a practical constructional implementation of the metering device and its valves in accordance with FIG. 5 ;
FIG. 11 the installation of paint valves within the area of the optionally available housing of a coating apparatus;
FIG. 12 a modification to the exemplary illustration in accordance with FIG. 11 ;
FIG. 13 a schematic sectional view of the exemplary illustration in accordance with FIG. 12 ; and
FIG. 14 a further modification of the exemplary illustrations in accordance with FIGS. 11 and 12 .
DETAILED DESCRIPTION
In the automobile industry, approximately 70 or 80% of the production volume associated with a particular coating plant is generally limited to 7 colours or less. With the direct connection of these frequently required paints to the automatically controlled metering device, according to the exemplary illustrations herein, the colour change losses in terms of paint and flushing agent are reduced to a minimum due to the respectively frequent change of said High-Runner colours and likewise the required colour change times even beyond the previously described advantages of the ICC technology, without the overall number of selectable colours, including many rarely required or Low-Runner colours, for which colour change losses are less significant due to the less frequent colour changes, having to be limited. If a typical colour changer, with a shared central channel requiring flushing with each colour change, is not used for High-Runner colours, i.e. for the most frequently required colours or, equivalent, for the colours with the largest production volumes, the typical colour change losses resulting from the latter in terms of material and time are avoided. In addition, the colour change losses of a typical colour changer for less frequently required colours are also reduced, as its length is correspondingly shortened due to the omission of the most frequently required colours, unless in place thereof a respectively larger number of selectable colours is to be connected.
The colour change losses of the High-Runner colours are lowest, if both the metering device and the paint lines required for these paints are housed in the atomiser.
With direct connection of all paint lines to the metering device at each inlet, during a colour change, only the short path shared by the colours from the metering device to the application member, e.g., the bell cup of a rotary atomiser, need be flushed. Here, the associated paint valves controlled by external colour selection signals may advantageously be fitted to the metering device or mounted thereinto, however, the paint valves could also form, as shown in EP 1502658 A1, a colour changer situated upstream of the metering device with a central outlet channel shared by the paints.
It is also possible to arrange only the metering device into the atomiser itself, and, in contrast, to install the paint valves for the High-Runner colours only in the vicinity of the atomiser, for example between the atomiser and the wrist joint of the paint robot or another program-controlled automatic motion machine moving the atomiser. In this case, only one of the outlet lines from the paint valves for the colours runs into the metering device in the atomiser, and the paint valves can also form the typical colour changer. In addition, the scope of the exemplary illustrations also includes the possibility to mount both the metering device and the paint valves outside the atomiser, for example between the wrist joint and the atomiser, since also in this case, the colour change losses are still relatively low.
In other cases, conversely, it may be more convenient to arrange the metering device and/or the paint valves, where applicable in a conventional colour changer, also in the vicinity of the atomiser, but situated further away thereof, for example in or on an arm of a coating robot moving the atomiser or other program-controlled automatic motion machine. In particular, it may be convenient, in accordance with the mentioned EP 1 772 194 A2, to house a metering device comprising a plunger-type metering mechanism with an upstream paint storage vessel in the front arm of a painting robot.
In contrast, the colour changer provided for, where applicable, many but rarely required colours, is generally always arranged separate and further away from the atomiser, for example in or on an arm of the coating robot or similar. The losses when changing a colour are lower, the shorter the distance is between the colour changer and the atomiser, hence with a larger number of colours, due to the space requirement and for dynamic and other practical reasons, it can generally not be arranged in or on to the atomiser before the wrist joint of the painting robot or similar, as is often possible for the High-Runner paint valves, but at best in or on the front robot arm carrying the wrist joint, if not too many colours are connected. Within the scope of the exemplary illustrations, this colour changer could, however, be situated even further away from the atomiser, e.g., in the second robot arm, or to travel along with (on the so-called axle 7 ) or even outside the painting robot. Paint losses during a colour change as for example in this case, but also during the High-Runner colour supply described, may be avoided by additional measures such as pigging technology in connection with driving back of the paint remaining in the line up to the supply system (“Reflow”) and/or almost complete use of the colours respectively remaining in the pipe for application (“Pushout”).
The outlet of the separate colour changer for rarely required colours is connected, for example, parallel to the paint lines of the most frequently required High-Runner colours; to a separate additional inlet of the metering device or, where applicable, its storage vessel. In place of this arrangement, however, the outlet of this colour changer may also be connected directly to the atomiser, usually to its main needle valve, via a line running in parallel to the metering device for High-Runner colours and a separate metering device, which is either positioned within the atomiser or in largely optional distance outside of the atomiser.
In one example, situated in parallel to the separate colour changer for less frequently required colours, a further colour changer corresponding thereto is provided, which is connected to the paint lines for the same colours. This allows undesirable loss of time during colour changes to be avoided, since during the flushing of a colour changer and its outlet line and during the preparation for the next colour, (where applicable including Reflow) the atomiser can be supplied from the other respective colour changer. This alternating colour supply is usually referred to as A/B operation (c.f. e.g. EP 1314483 A). Both conforming supply branches (A and B) are connected in parallel to the atomiser, i.e. to two inlets of the metering device (where applicable, their storage vessel) or otherwise via a separate metering device to the main needle valve of the atomiser according to exemplary illustrations described herein. However, A/B operation is also possible for the High-Runner colour supply in accordance with the exemplary illustrations, with a further arrangement of a metering device and controlled paint valves corresponding to the arrangement of the metering device and the controlled paint valves for the frequently required colours being provided in parallel, with the paint valves of both units being connected to paint lines for the same colours, here as well. Instead, it is also possible to use a single plunger-type metering mechanism, but designed for alternating operation mainly in accordance with EP 1666158 A2, namely a motor-driven plunger-type metering mechanism with a cylinder, each of the areas of which separated by the plunger, has a plurality of controlled inlets for the various selectable colours and a controlled outlet connected with the main needle or other outlet valve of the atomiser.
For A/B operation, where each colour changer for paints generally requires less than, e.g., the 7 or fewer High-Runner colours, at least two line sections may conveniently be included, in each of which several controlled paint valves for coating materials with selectively changeable colours discharge, and from which at least one line section is flushable independent from at least one other line section, the line sections being connected to each other by a controlled lockable valve and/or with one outlet line of the colour changer. Such colour changers are generally provided by EP 1502657 A2, and for the purposes of reducing colour change losses, they allow a useful further differentiation between colours required differently frequently, the rarely required colours being connected to the line section of the colour changer further away from the colour outlet and the other colours to its other line section positioned at the paint outlet.
If two separated and parallel metering devices are included in the atomiser or in its vicinity, these metering devices can also be operated at the same time, to supply to the application member two components coming out of separate supply lines with a coating material such as 2K-lacquer.
In accordance with one particular aspect of the exemplary illustrations, which in some cases may be useful and advantageous even without the previously described feature of a colour changer for rarely required colours arranged distantly from the atomiser, the metering device mounted, for example, in the atomiser or in its vicinity has a plunger-type metering mechanism with an automatically controllable drive for the metering unit to adjust the piston speed during the application, for the construction of which a prior art can be used. The plunger-type metering mechanism in accordance with the exemplary illustrations or, where applicable, the storage vessel situated upstream of the same, however, unlike the known construction, does not have just one or if need be (as in the case of the mentioned EP 1666158) two inlets, but at least one separate inlet for each selectable and frequently required colour and at least one outlet shared by the supplyable colour materials. Besides the low material and time loss during colour changes, a plunger-type metering mechanism has specific advantages in comparison to gear metering pumps and other metering systems for example, such as improved flushablity with low flushing requirements as well as the possibility to push back the paint (Reflow) into the supply system e.g. such as circulation line directly via the paint valves, without the colour changers and the connecting section between the metering device and the colour changer having to be filled. A further significant advantage of the plunger-type metering mechanism is furthermore the fact that no paint pressure controller is required, somewhat in contrast to the presently available gear metering pumps, for which, mainly for reasons of metering precision, a separate paint pressure controller generally would have to be connected upstream for each connected colour line. The plunger-type metering mechanism avoids the disadvantages of pressure controllers such as costs, paint losses during colour change, space demand and weight-loading of the robot axles.
Among other things, to reduce colour change losses as well as for space and construction reasons, it is particularly convenient to mount the paint valves of the High-Runner paint lines controlled by colour selection signals to the metering device or to integrate them into the construction thereof. In the case of a plunger-type metering mechanism or a piston cylinder upstream thereof (which means a container with an optional, even non-circular profile ), at least the space available on one side of the piston cylinder can have multiple inlets for the paint lines for coating materials of different colours with the inlets having valves advantageously mounted into the cylinder or attached to the cylinder, which are controllable by signals for the selection of the coating materials supplied to the plunger-type metering mechanism. Such a plunger-type metering mechanism either with or without an upstream storage vessel, can also be useful and advantageous in itself and independently of the coating apparatus described here, also in any other paint supply systems, including systems in which the plunger-type metering mechanism is not situated in the atomiser or its vicinity. The same applies for the previously specified double-action plunger-type metering mechanism in accordance with EP 1666158 A2, where the inlets of one area of the cylinder provided for the various selectable colours can be situated in at or in the front end of the cylinder and the inlets of the other area can be situated at or in the opposing front end of the cylinder.
In accordance with another aspect of the exemplary illustrations, which can also be useful and advantageous in itself and regardless of the feature relating to the arrangement of the colour changer within or more or less far away from the atomiser, the colour selection valves can be mounted into a gear metering pump of conventional type or attached to the metering pump.
In accordance with a further aspect of the examples provided herein, which can also be useful and advantageous in itself and regardless of other of the described features, instead of the previously described examples, the paint valves can also be attached to or mounted into a container of a coating device, for example a coating robot, which is not used for metering, but in a normally known manner for other purposes, for example as intermediate or storage container.
The number of paint valves on or in a metering device or attached to or mounted into the housing of a coating apparatus for correspondingly many colour inlets depends on respective individual cases, but is generally more than two and may advantageously be more than four.
Turning now to FIG. 1 , an exemplary coating apparatus includes a metering device 10 , to the outlet 11 of which, the conventional main needle valve or similar of a (not shown) atomiser for colour material is connected, for example an electrostatic rotary atomiser or air atomiser. The outlet 11 is shared by a plurality, in the example shown, six colour inlets of the metering device 11 , each of which having a colour valve FV 1 , FV 2 etc. to FV 6 automatically controlled by an superordinate control program. The metering device 10 per se can be of any kind, e.g., correspond to a metering system for coating facilities per se, including plunger-type metering mechanisms and gear metering pumps or systems operating with paint pressure and paint quantity adjustment. Volumetric metering devices and particularly those with a plunger-type metering mechanism, however, may be advantageous.
In the illustrated example, the paint lines 13 most frequently required for coating operations or “High-Runner” paints (marked 2 to 6 ) are connected to the paint valves FV 2 to FV 6 of the metering device 10 , which is fed, for example, as a stub line from the conventional paint circulation lines in the coating facility or which also can be set up themselves as circulation lines. In contrast, one of the paint valves, here FV 1 , is connected via a paint line 15 to the outlet of an external colour changer 12 and used to separate the High-Runner colour change area from the Low-Runner colour changers 12 . The colour changers 12 may have the conventional modular block format with a central channel as initially explained, to which, via the paint valves of the colour changer, the paint lines 14 for less frequently required or “Low-Runner” paints are connected. The exemplary illustrations of the colour changer 12 are described below with reference to FIG. 3 .
As was previously explained, the metering device 10 and/or the paint valves FV 1 to FV 6 can primarily be positioned in the atomiser or movable with the same in its vicinity, particularly between the atomiser and the wrist joint of a painting robot or in the front arm thereof. As was also previously mentioned, the paint valves may be advantageously attached to the metering device 10 (plunger-type metering mechanism, storage vessel, metering pump or, where applicable, attached to the measuring cell or the paint pressure controller of metering systems normally known, etc.) or mounted within the same. The external colour changer 12 , in contrast, can be situated in a place which, due to the colour change losses, should presumably be as close as possible to the atomiser, but apart from that is largely optional. For reasons of dynamic and space, a location on or in the rear robot arm may be practical, if an arrangement further to the front is not realisable.
When the metering device is constructed with a plunger-type metering mechanism or a volumetrically operating metering pump e.g. with an electrical drive motor, the metering drive may be situated outside the metering pump (for example as in EP 1000667 B). In particular, the metering drive may also be incorporated into the plunger-type metering mechanism or the metering pump.
The paint supply in accordance with the exemplary illustrations is suited for any atomisers, particularly also for electrostatic atomisers, which charge the coating material, as is well known, to a high voltage potential, for example in the range of 100 kV. In this case, sensors and actuators in the atomiser, including the metering device and its electrical metering drive, may be operating on the high voltage potential of the atomiser, as well as, where applicable, an electrical drive motor for the bell cup provided in place of the otherwise conventional air turbine, if a rotary atomiser is used. As is described in detail in the patent applications DE 10 2006 045 631.9 and PCT/EP2007/008382, the metering drive on high voltage and, where applicable, the electrical bell cup motor also on this voltage potential may be fed using an isolating transformer equipped with at least his secondary coil arrangement located in the atomiser. The isolating transformer forms a high voltage isolation section between its primary and secondary circuits and separates the items in the atomiser for which it supplies power, including both motors, galvanically from the electrical power supply leading into the atomiser.
As has already been described in the cited patent applications DE 10 2006 045 631.9 and PCT/EP2007/008382, the control and sensor signals of the actuators and sensors of the atomiser can be transmitted galvanically separated in and/or out of the atomiser, for example optically or via radio. In this case, particularly the external signals used to control the metering drive can be transmitted together with other signals via a common cable or radio link.
In accordance with a specific feature, which is also of benefit and feasible regardless of the High-Runner colour supply described herein, the operation of the conventional main needle valves or other outlet or main valves of the atomiser can be controlled via pressure generated by the metering device upstream of the main valve at the outlet ( 11 ). The main valve is opened by the pressure of the metering device, as soon and as long as a relevant pressure is there, and closes automatically in the absence of pressure. The functional principle corresponds to that of a conventional paint pressure controller in a coating facility, as known e.g. from the DÜRR/BEHR Technisches Handbuch, Einführung in die Technik der PKW-Lackierung, April/1999-28 Apr. 1999, chapter. 5.3.1 Farbdruckregler, or which is known from EP 1 376 289 B1, the complete content of which is incorporated herein by reference in its entirety. Such a paint pressure controller (which need not necessarily refer to a “controller” in the sense of a closed loop regulator circuit) may, in accordance with the exemplary illustrations, mainly replace the piston drive of the normal main needle valve and the external control of the same, whereby the valve is not opened by control air, but the paint pressure itself. Accordingly, the main valve of the atomiser or another application device consisting of a needle valve or of a ball or other valve for the coating material, which is kept in the closed position by spring pressure and opened by way of the pressure of the coating material acting against the spring pressure, e.g., via a membrane, as soon as this pressure reaches a defined value, which can be fixedly or also variably adjusted. In the present example, the control inlet of the main valve is connected to the outlet of the described metering device. This (indirect) automation of the main needle control by the metering device, advantageously eliminates the very complex adjustment of the main needle switch circuit of conventional atomisers, the main needle valve of which may only be opened and closed by external signals of the program control of the coating facility (c.f. e.g. EP 1245291 B1).
In FIG. 2 , a plunger-type metering mechanism 20 is illustrated schematically, which generally includes a cylinder 21 , a piston 23 slidable in the cylinder by the piston rod 22 as well as a metering drive (not shown). The components of the plunger-type metering mechanism 20 may, due to the high voltages involved, consist of insulating material and of a ceramic material to improve the metering precision. The metering drive may usually incorporate an electrical motor used to move the piston rod, which is controlled such that by altering the piston speed during the coating process, the current quantity of coating material applied can be altered as required. Plunger-type metering mechanisms operating on the same principle are provided, for example, in EP 1384885 B and WO 93/23173.
In accordance with the exemplary illustrations, however, the plunger-type metering mechanism 20 has multiple inlets: five colour inlets in the illustrated example E 1 to E 5 , each of which has a paint valve FV 1 ′ to FV 5 ′, each of which is connected to one of the five paint lines 13 ′ for different High-Runner colours. An additional inlet E 6 , also equipped with a valve VV, is intended for discharging a thinner V used as flushing agent and also pulse air PL intended for cleaning of cylinder 21 . In addition, cylinder 21 has an outlet A with an outlet valve VA, to which an outlet line of the plunger-type metering mechanism leading to the main needle or outlet valve of the atomiser is connected.
The paint valves FV may be attached to the cylinder body 24 of the plunger-type metering mechanism or incorporated in the same, as indicated by the dotted line 24 ′. The flushing valve VV and/or the outlet valve FA can be attached or mounted, correspondingly.
If the plunger-type metering mechanism 20 of the example described in FIG. 2 as metering device 10 on the basis of the device described of FIG. 1 is used, one of the colour inlets, such as E 1 to E 5 , of the plunger-type metering mechanisms may also (instead of to a High-Runner paint line) be connected to a paint line coming from an external colour changer, e.g. the paint line coming from the colour changer 12 in FIG. 1 for rarely required colours. Instead, however, here as well, the outlet line of an external colour changer can be routed to the outlet valve of the atomiser by bypassing the plunger-type metering mechanisms 20 .
In the scope of the exemplary illustrations, the element 20 in FIG. 2 , also may be a paint storage container located upstream of the actual plunger-type metering mechanism, for example, in accordance with EP 1 772 194 A2, the piston of which, however, is usually not driven by an electrical motor, but by the coating material in the filling direction and a pressure medium such as compressed air, in the discharging direction.
A further development of the plunger-type metering mechanism 20 for alternating operation of the cylinder areas separated by the piston 23 in accordance with EP 1666158 A2, could provide an arrangement corresponding to the inlets E 1 to E 6 and the outlet A with the associated valves, for example, in the cylinder body of the plunger-type metering mechanism opposite to the cylinder body 24 .
The external colour changers 12 ( FIG. 1 ) provided for the exemplary illustrations for rarely required colours could have the structure which is schematically illustrated in FIG. 3( a ), such as, for example, generally provided by DE 19836604 A1, DE 19846073 A1 or DE 19951956 A1. It therefore consists mainly of paint valves for the twenty-four different colours used for the described example, flushing valves for pulse air PL and thinner V and a return valve RF, which are connected to the central channel 30 a of the colour changer.
Since the colours connected to the external colour changer are those which differ per se in the frequency of use, it may indeed be more practical to divide the external colour changer in the known example of EP 1502657 A2 into separated flushable channel sections. The schematically illustrated colour changer 12 b in FIG. 3( b ) corresponds substantially to the exemplary illustration in accordance with FIG. 2 of the cited EP 1502657 A2, the complete content of which is hereby incorporated by reference in its entirety. Both channel sections are designated 30 b 1 and 30 b 2 respectively and connected by the controlled lockable valve 16 b in series with each other. The more frequently required colours are connected with the paint valves designated 1 to 6 of section 30 b 1 , while in contrast, the rarely required colours are connected to the normal paint valves of section 30 b 2 . This leads, in practice, to reduced colour change losses compared to standard colour changers in accordance with FIG. 3( a ).
The colour changer 12 c illustrated in FIG. 3( c ), which may largely correspond to the example in accordance with FIG. 3 or FIG. 4 of EP 1502657 A2, consists of both parallel channel sections 30 c 1 and 30 c 2 , which are alongside the respective paint, rinse and return valves and respectively connected via a controlled lockable valve 16 c 1 or 16 c 2 to the output line of the colour changer. This colour changer, in addition to reduced colour change losses, has other benefits such as the relatively low space requirement and low weight or a large number of connectable paints at a given size.
If the same colours are connected to both channel sections 30 c 1 and 30 c 2 , the colour changers are also suited for A/B operation. Thus, an always shortened colour change period for all selectable colours is reached.
In the exemplary illustration in accordance with FIG. 2 , the paint valves for the High-Runner colours can be positioned almost flush, i.e. free of colour losses, with the inner wall of the cylinder of the plunger-type metering mechanism or, where applicable, its interim storage container (c.f. FIG. 7 ). FIG. 4 , in contrast, shows a schematic and somewhat modified exemplary illustration, in which the paint valves FV 43 connected to the High-Runner lines 43 discharge into a shared channel 41 , which, in turn, leads into the cylinder of the plunger-type metering mechanism or, where applicable, its interim storage container 40 . The paint line 45 from the outlet of the external colour changer 42 for the Low-Runner paints is connected to the shared channel 41 via an isolating valve V 45 separating the two colour supply systems for High-Runner or Low-Runner paints. Structurally, the paint line 45 can be an integral component of the conventional central channel of the colour changer 42 and turn into channel 41 or form it (c.f. FIG. 8 ). The colour changer 42 can, for example, include the arrangement to be extracted from the drawings of the paint valves F 1 to Fn for the n different available Low-Runner colours, the return valve RF 2 , the flushing valves V 1 and PL 1 for thinner or pulse air as well as, in accordance with the illustration, the isolating valve SPVFW between the paint and return valves on one side and the purge valves on the other. The Low-Runner colour changer may also correspond to one of the arrangements in accordance with FIG. 3 . pFW is a paint pressure sensor measuring the pressure of the coating material in the central channel of the colour charger shared by the different Low-Runner colours and thus in the paint line 45 to improve process security. The paint lossy central channel of the colour changer 42 simply need be filled with this colour during painting with Low-Runner paint. When painting with a High-Runner colour, the colour changer 42 is separated with isolating valve V 45 .
In FIG. 5 , another example is schematically illustrated, in which the metering device is formed by a gear metering pump 50 , which differs from conventional metering pumps due to its multiple inlets, to which paint lines 53 for the High-Runner colours via paint valve FV 53 and in parallel, paint line 55 from the outlet of the other colour changer 52 for the Low-Runner paints are connected. The paint valves FV 53 , with which the inlets for the High-Runner colours are provided, can advantageously be positioned also directly almost without colour losses at the metering gear wheels of the metering pump 50 . Here, as with the other exemplary illustrations, the paint valves can be configured as needle valves in the conventional manner. The isolating valve V 55 for the Low-Runner paints can be mounted into the inlet of the metering pump 50 or upstream thereof. The colour changer 52 can correspond to that in accordance with FIG. 4 or also to one of the colour changers in accordance with FIG. 3 . The Low-Runner colour changers in accordance with FIG. 4 and FIG. 5 can also be used for the exemplary illustrations in accordance with FIG. 1 and FIG. 2 .
In FIG. 6 , an elongate paint container 60 is illustrated, which can be, for example, the storage container for the metering devices mentioned several times and known or can instead also be a plunger-type metering mechanism in accordance with FIG. 2 . The, for example, four or five High-Runner valves FV 63 shown in accordance with the illustration, are arranged parallel to the container axis next to each other in the end wall 69 of the container 60 , possible in addition to a further valve VF 65 for the Low-Runner colours. The associated paint lines controlled by these valves can be conveniently connected by radial paint connections distributed along the circumference of the container (not shown). The isolating valve for the Low-Runner line (not shown) (V 45 in FIG. 4 ) can also be configured differently than the valve FV 63 and arranged elsewhere. The container 60 may be at least partially circular cylindrical or with another diameter and housing a movable piston.
As shown in FIG. 7 , the needles 73 of the High-Runner paint valves FV 63 , which can be the signal-controlled needle valve units of the illustrated conventional model per se, are inserted in the end wall 76 ( 69 in FIG. 6 ), such that when the valve closes, the needle ends 78 are at least near the level of the inner side 71 of the end wall 76 , i.e. aligned with this level. In 75 , the conical valve seat of paint valve FV 63 is visible. In opening 77 , for example, one of the paint connections leading radially from the circumference into the end wall 76 can be used for the High-Runner-paint lines ( 13 in FIG. 1 ) opened or closed by the paint valves FW 63 .
In place of the illustrated valve arrangement in FIG. 6 and FIG. 7 a radial installation or attachment of the paint valves FV 63 (valve FV in FIG. 1 or FIG. 2 ) is possible, for example similar to one of the examples in accordance with FIG. 8 to 14 .
As a rule, the High-Runner paint valves for the exemplary illustrations described generally should be as small as possible, so that as many valves as possible can be accommodated within the limited available space. The same applies for an installed or attached valve for the connection of Low-Runner paints (e.g. valve FV 1 in FIG. 1 ). The paint valves of the distant or separate Low-Runner colour changer, in contrast, can be constructed larger. The larger installation size has the advantage that at a given paint pressure, the flow openings can be larger and the paint flow speed correspondingly smaller, thus lowering the risk of damage to the paint materials.
The valve arrangement illustrated in FIG. 8 suits an exemplary illustration in accordance with FIG. 4 , in which the illustrated five High-Runner paint valves FV 83 are distributed radially around the central channel 85 of the Low-Runner colour changer ( 42 in FIG. 4 ) and reach the circumference of the central channel 85 with the ends 88 of their valve needles. The paint valves FV 83 can here be screwed into the circumference of a wall element 89 in a radial level shared by their needle axes which can form the end wall of the container mentioned or be attached to the actual end wall. Between the paint valves FV 83 , in accordance with the illustration, the related paint connections 84 for the High-Runner colours are distributed over the circumference of the wall element 89 . In place of the illustrated star-shaped valve arrangement, for example, other known arrangements of colour changers are also conceivable.
FIG. 9 shows a convenient arrangement of a container 90 with the accompanying end wall 69 or 76 containing the High-Runner valves and associated radial paint connections 97 , for example in accordance with FIG. 7 , and with the upstream Low-Runner colour changer 92 in the front arm 91 of a painting robot. The colour changer 92 hat as a typically modular block construction for the colour changers in the coating facility and is constructed in direct vicinity to the end wall 69 . A very similar arrangement is also possible with the examples in accordance with FIG. 8 . The arrangement of the container 90 next to a (only partially visible) plunger-type metering mechanism 99 and other details are to be seen in the drawing and can apart from that correspond to the system described in EP 1 772 194 A2, so that a more precise description is not needed.
FIG. 10 shows the possibility for the constructional configuration of the High-Runner paint valves FW 103 at paint inlet 105 of a gear-metering pump 100 corresponding to the schematic illustration in FIG. 5 . Both metering gear wheels 101 and their driveshaft 102 correspond to conventional constructions. The inlet area in accordance with the metering pump, however, is not shown completely. Similar needle valve units as installed in the other exemplary illustrations, can be installed as paint valves, for example, radially in the front plate unit of the metering pump 100 not shown, in accordance with the illustration. Also the High-Runner paint pipes controlled by the paint valves FW 103 are not shown. The paint inlet 105 can be connected to the separate Low-Runner colour changer in accordance with the exemplary illustrations via an isolating valve V 55 ( FIG. 5 ), which can be formed by valve V 105 or arranged elsewhere. The paint outlet for the metering pump 100 is referenced as 106 .
As was previously explained, the installation or attachment of paint valves described above in the context with metering devices can independent thereof more generally be useful and advantageous for any other container for coating apparatus. In FIG. 11 , such a container 110 is illustrated, which may be cylindrical or have another, for example, elongate shape in accordance with the illustration. The illustrated example 18 shows automatically signal-controlled needle valves FV 113 distributed around the circumference of the container 110 , the valve needles 114 thereof may lie crosswise with respect to the longitudinal axis of the container 110 in a shared radial level. For example, the needle valves FV 113 , in accordance with the illustration, may be inserted radially in a flange 112 surrounding the cylindrical wall 111 of the container 110 and extend through the latter with its needles 114 . In a closed position of the valves, the ends 115 of the needles contacting the valve seat can be positioned flush or almost flush against the inner surface 116 of the container wall 111 , so that similarly low colour change losses occur, such as, for example, in the examples in accordance with FIG. 7 , FIG. 8 and FIG. 10 . The paint lines controlled by the paint valves FV 113 leading into the containers 110 are not shown.
In this exemplary illustration, no separate colour changer in accordance with FIG. 1 to FIG. 5 is needed to be provided, nor any central channel of a colour changer as shown in 58 in FIG. 8 , particularly when the number of colours required does not exceed the existing number of paint valves 113 . On demand, however, the connection of a conventional colour changer for additionally selectable colours is possible, for example to one of the paint valves FV 113 or another automatically controllable inlet of the container 110 .
Coating systems are also conceivable, in which, for example, the colour inlets of the container 110 , mounted for example on a coating robot in a manner known per se can be docked with quick release valves at corresponding stationary paint connections of a paint booth.
The only substantial difference between the exemplary illustration in accordance with FIG. 12 and that in accordance with FIG. 11 is that the needles 124 of the 12 paint valves FV 123 in the illustrated example are not positioned in one radial plane, but arranged against the vertical radial level of the container axis at an angle, resulting in the angular arrangement of valve FV 123 visible in FIG. 13 . Here as well, in a closed position of the valve, the valve seat and thus the needle ends, is located in direct vicinity of the inner surface 126 of the container 120 with the advantage of correspondingly minimised paint losses in a colour change.
If two or more groups of paint valves distributed in a ringlike manner around the container circumference are offset or spaced apart along the container axis, as shown in FIG. 14 , a correspondingly large number—in the illustrated example 30 —of valve-controlled paint lines for various selectable colours can be connected to the container 140 . Both illustrated groups of paint valves FV 143 or FV 143 ′ can be positioned at an angle as shown in FIG. 12 and FIG. 13 , conveniently at an opposing tilt angle related to the radial level. One or each group of paint valves, however, can also be arranged horizontally on a common radial level to the container axis as shown in FIG. 11 . Apart from that, the exemplary illustration in accordance with FIG. 14 may correspond to those in accordance with FIG. 12 and FIG. 13 .
For the automatic control of the paint valves of the described exemplary illustrations, for example electric or pneumatic signal lines, which are not shown in the drawings, can be connected to the valves in any known manner that is convenient.
Generally, the combination of each of the various features described in the present application with one or more other described feature/s without being limited to other features is possible and advantageous depending on the manner of realisation.
Reference in the specification to “one example,” “an example,” “one embodiment,” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the example is included in at least one example. The phrase “in one example” in various places in the specification does not necessarily refer to the same example each time it appears.
With regard to the processes, systems, methods, heuristics, etc. described herein, it should be understood that, although the steps of such processes, etc. have been described as occurring according to a certain ordered sequence, such processes could be practiced with the described steps performed in an order other than the order described herein. It further should be understood that certain steps could be performed simultaneously, that other steps could be added, or that certain steps described herein could be omitted. In other words, the descriptions of processes herein are provided for the purpose of illustrating certain embodiments, and should in no way be construed so as to limit the claimed invention.
Accordingly, it is to be understood that the above description is intended to be illustrative and not restrictive. Many embodiments and applications other than the examples provided would be upon reading the above description. The scope of the invention should be determined, not with reference to the above description, but should instead be determined with reference to the appended claims, along with the full scope of equivalents to which such claims are entitled. It is anticipated and intended that future developments will occur in the arts discussed herein, and that the disclosed systems and methods will be incorporated into such future embodiments. In sum, it should be understood that the invention is capable of modification and variation and is limited only by the following claims.
All terms used in the claims are intended to be given their broadest reasonable constructions and their ordinary meanings as understood by those skilled in the art unless an explicit indication to the contrary in made herein. In particular, use of the singular articles such as “a,” “the,” “the,” etc. should be read to recite one or more of the indicated elements unless a claim recites an explicit limitation to the contrary.
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A coating apparatus for serially coating workpieces with different shades or colors is disclosed. A metering device comprises a plunger-type dosing mechanism or a metering pump that has a separate inlet with an integrated color valve for each of the most commonly used colors is located in or near the sprayer of the coating apparatus. A separate color changer can be provided for less frequently used colors. The outlet of said color changer may be connected to another inlet of the metering mechanism or to the discharge valve of the sprayer via a separate metering mechanism.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Application Ser. No. 60/849,684 filed Oct. 5, 2006, U.S. Provisional Application Ser. No. 60/866,516 filed Nov. 20, 2006, and U.S. Provisional Application Ser. No. 60/956,760 filed Aug. 20, 2007, and the complete contents of each of these applications is herein incorporated by reference.
FIELD OF THE INVENTION
[0002] The invention relates to nanoparticle compositions for solubilization and encapsulation of medicines, including medicines that are poorly water-soluble. More particularly, the invention relates to compositions having ‘smart’ properties such as mucoadhesivity, oral bioavailability, and multifunctionality for systemic targeting.
BACKGROUND OF THE INVENTION
[0003] During the last two decades numerous drug delivery systems have been developed for hydrophobic and poorly water soluble medicines. These systems are focused on overcoming the poor availability of the drug and the subsequent ineffective therapy inherent to these types of molecules.
[0004] To solve the above mentioned problem associated with the solubilization of poorly water-soluble medicines, U.S. Pat. Nos. 5,645,856 and 6,096,338 disclose methods for preparing carriers for hydrophobic drugs, and pharmaceutical compositions based thereon, in which the carrier is comprised of biocompatible oil and a pharmaceutically acceptable surfactant component for dispersing the oil in vivo upon administration of the carrier. The amphiphilic surfactant component utilized does not substantially inhibit the in vivo lipolysis of the oil. These types of formulations can be utilized as a carrier system for many hydrophobic drugs resulting sometimes in enhanced bioavailability as compared with existing formulations of such drugs. However, these formulations are not stable in vivo and there is the possibility of drug leakage from the emulsion leading to unnecessary side effects in the body. Moreover, the surfactants used may disrupt the biological membranes causing cytotoxicity. In addition, targeting of a drug using such emulsion systems is not possible.
[0005] Other drug carriers have been used such as amphiphilic block copolymers which form polymeric micelles or supramolecular assemblies wherein the hydrophobic part forms the core and the hydrophilic part the shell. The U.S. Pat. No. 5,510,103 describes block copolymers having the hydrophilic and hydrophobic segments forming micelles and entrapping the hydrophobic drugs by physical methods. The hydrophilic segment is preferably poly(ethylene oxide) and the hydrophobic segment is preferably poly(epsilon-benzyl-L-aspartate), while the preferred drug is Adriamycin.
[0006] Recently, polymeric micelles have been widely used as drug delivery carriers for parenteral administration. Micellar drug delivery carriers have several advantages including biocompatibility, solubilization of hydrophobic drugs in the core, nanometric size ranges which facilitate extravasation of the drug carrier at the site of inflammation, site-specific delivery, etc. For example, U.S. Pat. No. 5,955,509 describes the use of poly(vinyl-N-heterocycle)-b-poly(alkylene oxide) copolymers in micelles containing pharmaceutical formulations. These copolymers respond to pH changes in the environment and can be used to deliver therapeutic compounds at lower pH values. These polymeric micelles remain intact at physiological pH, while they will release their content when exposed to a lower pH environment such as in tumor tissue.
[0007] A number of amphiphilic copolymers, having non-ionic and/or charged hydrophobic and hydrophilic segments, that form micelles are reported in the literature. For example, U.S. Pat. No. 6,322,817 discloses the injectable formulation of cross-linked polymeric micelles constituted by acrylic monomers—N-isopropylacrylamide, N-vinylpyrrolidone and PEGylated monoesters of maleic acid. These polymeric nanoparticles are reported to have dissolved paclitaxel and delivered the drug to the tumor tissue through parenteral administration. However, these particles are only reported to be suitable for delivery via the intravenous route. Moreover, the reported use of alkylcyanoacrylate as one of the components in the copolymeric micelles may render the formulations toxic and unsuitable for in vivo applications.
[0008] One patent, U.S. Pat. No. 6,555,139 has disclosed a process of microfluidization or wet-micronization of hydrophobic drugs in combination with dextrins such as β-cyclodextrin. The patent indicated that the process of microfluidization facilitates the reduction of mean particle size of slightly soluble but highly permeable drugs, and creates a smooth, latex-like micro-suspension. A blend of expandable polymer and insoluble, hydrophilic excipients granulated with the micro-suspension create a matrix that after compaction erodes uniformly over a 24-hour period. However, the problems associated with these microfluidization systems are that for every molecule of drug, one molecule of β-cyclodextrin is required leading to large amounts of this compound to be administered inside the body along with drug. Moreover, drug leakage from β-cyclodextrin as well as poor bioavailability of β-cyclodextrin—drug complex has the potential to cause side effects. Finally, the particle size of up to 500 nm diameter may be responsible for limited utility for drug delivery purposes.
[0009] Another patent, U.S. Pat. No. 6,579,519 has disclosed the formulation of non-PEGylated pH sensitive and temperature sensitive cross-linked polymeric micelles constituted of N-isopropylacrylamide, acrylic acid and N-vinylpyrrolidone. These particles have extremely limited applications and can be used only for the specific purpose of topical delivery on the ocular surface. This is because of the fact that the LCST (lower critical solution temperature) of the particles is below ambient body temperature, and the particles are aggregated to a hydrophobic mass in vivo. Therefore, these particles are not suitable for systemic circulation and targeting, including oral delivery. Other similar patents are U.S. Pat. No. 6,746,635 and U.S. Pat. No. 6,824,791.
[0010] Another U.S. Pat. No. 7,094,810 describes a formulation which is composed of a hydrophilic segment made of poly(ethylene oxide) and a hydrophobic segment composed of vinyl monomers containing at least one pendant carboxyl group. More particularly, the vinyl monomers included in the polymer are acrylic acid or methacrylic acid having pendant carboxyl groups and butyl (alkyl) acrylate where the butyl segment can be a linear or branched chain. Thus, the hydrophobic segment is a mixture of non-ionizable butyl (alkyl) acrylate and ionizable (alkyl) acrylic acid which controls the hydrophobicity of the polymer. The ionizable carboxylic group of the polymer extended towards the surface of the particle is reported to be responsible for pH sensitivity.
[0011] Though the majority of these polymers can be used for injectable or topical delivery of bioactive agents, what are presently lacking are multifunctional amphiphilic polymers capable of oral delivery applications, by means of their nanoparticulate size and mucoadhesivity. The surface reactive functional groups of such “smart” nanoparticles would be capable of optional modification through PEGylation, ligand attachment, or fluorophore tagging for the purposes of systemic targeting, thus being useful for concurrent biological applications in diagnostics, therapeutics, and in imaging. Herein, we describe such an orally bioavailable smart polymeric nanoparticle system.
SUMMARY OF THE INVENTION
[0012] The invention relates to cross-linked polymeric nanoparticles, which may contain one or more bioactive agents such as poorly water-soluble medicines, and that are particularly suitable for oral delivery, but are also amenable to other applications, including injectable or topical formulations.
[0013] A further object of this invention is to provide a process for the preparation of polymeric nanoparticles that can entrap poorly water-soluble drugs, alone or in combination with other bioactive agents, to the maximum extent possible. The polymeric nanoparticles preferably entrap one or more types of medicament. Preferably the polymeric nanoparticles have an average diameter of less than or equal to 50-100 nm, and less than 5% are in excess of 200 nm in diameter.
[0014] Another object of this invention is to provide a process for the preparation of nanoparticles having inter-crosslinked polymeric chains so that the release of the entrapped medicine(s) encapsulated in these nanoparticles can be controlled.
[0015] Yet another object of this invention is to provide a process for the preparation of nanoparticles incorporating single or combinations of medicines, with the option of chemically conjugating polyethylene glycol (PEG) chains of varying chain length (50-8000 D) at the outer surface of the nanoparticles to reactive moieties on the surface of formed nanoparticles. The PEG chains help the particles to circulate in the blood for a relatively long time, following systemic administration.
[0016] Yet another object of this invention is to enable the delivery of otherwise water soluble drugs, but for which oral delivery is currently not an option, by chemically conjugating the drug, or combinations thereof, on the surface of the nanoparticles, which then act as a vehicle for absorption via the oral route so as to enhance the bioavailability of the drug.
[0017] Another objective of this invention is to use carboxylic acid, amine or aldehyde derivatives of acrylic compounds or similar vinyl derivatives alone or in combination as monomers during polymerization for rendering multifunctional characteristics of the nanoparticles so as to make ‘smart’ nanoparticles.
[0018] Still another object of this invention is to provide a process for the preparation of polymeric nanoparticles incorporating poorly soluble medicines or combinations of medicines dispersed in aqueous solution which are free from unwanted and toxic materials, such as non-reacted monomers.
[0019] Another object of this invention is to provide a process for the preparation of polymeric nanoparticles incorporating poorly water-soluble medicine or combinations of medicines which can be used for in vivo experiments for the purpose of targeting maximum amounts of medicine to a diseased site and only negligible amounts to other tissues, which obviates the disadvantages associated with the prior art. For example, the polymerized micelle complexes contemplated herein can be functionalized with a targeting moiety such as a fluorophore, a dye, a contrasting agent, an antigen, an antibody, an amino acid, or a sugar like glucosamine or related carbohydrate derivatives, through chemical conjugation with the PEG chains associated with the polymeric micelles, such that the complexes could be used, in addition to stated oral formulations, in medical therapeutics, diagnostics and imaging applications requiring targeted delivery to specific cell or tissue types.
[0020] A still further object of this invention is to mask the native taste of certain medicaments incorporated in the polymeric micelles by chemically conjugating taste modifying agents to the surface of the micelles so that the formulation is rendered more palatable during oral uptake.
[0021] A still further object of this invention is to provide a method for using polymeric nanoparticles incorporating poorly water-soluble medicine or combinations of medicines prepared according to the process of this invention for the treatment of conditions arising out of undesirable pathogenic and anatomic conditions.
[0022] According to the invention, medicinal compositions are prepared which comprise polymeric nanoparticles preferably of a size on average of less than 100 nm diameter entrapping at least one poorly water-soluble hydrophobic medicine alone or in combination with one or more additional medicines. These amphiphilic nanoparticles can be made of cross-linked polymers which are mainly composed of the following three constituents added as monomers at specific molar ratios: (1) N-isopropylacrylamide (NIPAAM), plus (2) either a water-soluble vinyl compound like vinyl acetate (VA) or vinyl pyrrolidone (VP), so as to make the particle shell more hydrophilic, or a water-insoluble vinyl derivative such as styrene (ST) or methylmethacrylate (MMA), so as to make the particle core more hydrophobic, plus (3) acrylic acid (AA), which provides surface reactive functional groups. The surface of the nanoparticles can be optionally functionalized using the reactive functional groups provided by AA, including by PEGylation for long circulation in blood, or by addition of other surface reactive groups which can be used for targeting to tissues in vivo for therapeutic, diagnostic, and imaging applications.
BRIEF DESCRIPTION OF THE FIGURES
[0023] FIG. 1 illustrates a polymeric nanoparticle with the hydrophobic core (10) composed of hydrophobic parts of the polymers entrapping the medicine (11), the hydrophilic parts forming a hydrophilic shell (12) which are present towards the aqueous medium. The nanoparticles are less than 100 nm in size, and may include one or more molecules of medicaments or other bioactive agents.
[0024] FIGS. 2 a - f illustrate three examples of poorly water soluble drugs whose solubilization has been enabled by entrapment in polymeric nanoparticles embodied in this invention. Free paclitaxel (taxol) (A), free rapamycin (C), and free rifampicin (E) are essentially insoluble in water, as evidenced by turbidity of solution and visible floating particles of each drug. In contrast, equivalent amounts of nanoparticle-encapsulated paclitaxel (B), nanoparticle-encapsulated rapamycin (D), and nanoparticle-encapsulated rifampicin (F) form transparent solutions in water.
[0025] FIG. 3 shows lower critical solution temperature (LCST) as a function of the weight percent ratio of the constituents, and in particular the molar ratio of NIPAAM in the nanoparticles. In the illustrated example, three different compositions of nanoparticles are represented, each with a different molar ratio of NIPAAM (NP), vinyl pyrrolidone (VP) and acrylic acid (AA) comprising the polymeric nanoparticles. Average size of nanoparticles (nm) is measured by dynamic light scattering and other methods. Compositions with a NIPAAM molar ratio of 90% have a LCST below that of body temperature, while compositions with a NIPAAM molar ratio of 60% has a LCST above that of body temperature.
[0026] FIG. 4 a is a Transmission Electron Microscopy (TEM) photomicrograph of NIPAAM/VP/AA polymeric nanoparticles (molar ratios of 60:20:20), which have an average diameter of 50 nm or less (100 nm scale is illustrated at bottom right).
[0027] FIG. 4 b is a TEM photomicrograph of NIPAAM/MMA/AA polymeric nanoparticles (molar ratios of 60:20:20), which have an average diameter of 50 nm or less (500 nm scale is illustrated at bottom right). Minimal polydispersity is observed.
[0028] FIG. 5 illustrates lack of demonstrable in vivo toxicity from orally delivered empty (“void”) polymeric nanoparticles. Two types of orally delivered void nanoparticles were utilized: NIPAAM/VP/AA in molar ratios of 60:20:20 (designated NVA622) and NIPAAM/MMA/AA in molar ratios of 60:20:20 (designated NMA622). Groups of four CD1 wild type mice each (two males, two females) were administered 500 mg/kg of void NVA622 or void NMA622 nanoparticles in 500 μL of water, five consecutive days a week, for two weeks. During and at the culmination of void nanoparticle administration, no weight loss, behavioral abnormalities or other abnormal features were seen. No gross (macroscopic) toxicities were observed in the mice receiving either the void NVA622 or the void NMA622 nanoparticles.
[0029] FIGS. 6 a - c illustrate in vitro cell viability (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, or MTT) assays performed with polymeric nanoparticle encapsulated paclitaxel (nanopaclitaxel), and comparison with free paclitaxel. In the illustrated example, NIPAAM/VP/AA polymeric nanoparticles in molar ratio of 60:20:20 were used for paclitaxel encapsulation. Three human pancreatic cancer cell lines (XPA-1, BxPC3 and PANC-1) were incubated with increasing concentrations (1, 10, 20, 50, and 100 nm) of either free paclitaxel (black bar) or equivalent amount of nanopaclitaxel (grey bar) for 48 hours. Also included as control in each condition were void polymeric nanoparticle equal to the amount required for encapsulating said dose of nanopaclitaxel (white bar) and solvent (dimethylsulfoxide [DMSO], blue bar) equal to the amount required for dissolving said dose of free paclitaxel. Nanopaclitaxel (grey bar) demonstrates comparable cytotoxicity in all three cell lines in vitro, compared to free paclitaxel (black bar). Thus, nano-encapsulation of the drug is not associated with loss of drug activity. In contrast, and as expected, treatment with the void polymer only does not demonstrate any significant effect of cytotoxicity compared to baseline control growth of the cells (0 nm condition). All assays were performed in triplicate and error bars represent standard deviations.
[0030] FIGS. 7 a - c illustrate in vitro cell viability (MTT) assays performed to demonstrate the synergistic effects of polymeric nanoparticle encapsulated paclitaxel (nanopaclitaxel) and polymeric nanoparticle encapsulated curcumin (nanocurcumin). Three human pancreatic cancer cell lines (XPA-1, BxPC3 and PANC-1) were incubated with increasing concentrations (1, 2, 4, 6, 8 and 10 nm) of either free paclitaxel (black bar) or equivalent amount of nanopaclitaxel (white bar) for 48 hours. In order to test therapeutic synergy with curcumin, the cells were also incubated with either free curcumin (15 μM) plus free paclitaxel (grey bar), or with equivalent amount of nanocurcumin (15 μM) plus nanopaclitaxel (blue bar). As illustrated, the combination of nanopaclitaxel and nanocurcumin demonstrates increased cytotoxicity than either free paclitaxel or nanopaclitaxel alone at any given dose of paclitaxel. Of note, and especially at the lower dosages used in two of the cell lines (XPA-1 and Panc-1), the combination of nanopaclitaxel and nanocurcumin also appears to have better efficacy than the combination of free paclitaxel and free curcumin, likely due to increased intracellular uptake of the nano-encapsulated compounds. At higher dosages, the combination therapy with either free or nano-encapsulated drugs appears to have comparable effects.
[0031] FIG. 8 illustrates the bactericidal effects of nanoparticle encapsulated rifampicin and free rifampicin against Mycobacterium tuberculosis (MTB). In this experiment, MTB was cultured for two weeks in absence of any treatment, nano-encapsulated rifampicin, free rifampicin, and void nanoparticles. There is robust MTB growth in the no treatment and in the void nanoparticle tubes, the latter consistent with lack of toxicity from the polymer per se. In contrast, MTB growth is completely inhibited in the nano-encapsulated rifampicin and free rifampicin tubes.
[0032] FIG. 9 illustrates in vitro cell viability (MTT assay) performed using the water-soluble drug gemcitabine conjugated to the acrylic acid (AA) surface reactive functional group of polymeric nanoparticle. Unlike the poorly water drugs that are encapsulated within the nanoparticle, water soluble drugs like gemcitabine can be conjugated to the nanoparticle surface, rendering this compound amenable to oral delivery. Human pancreatic cancer cell line BxPC3 is incubated with increasing dosages of either free gemcitabine (black bar), nano-gemcitabine (white bar), void polymer (grey bar), or PBS solvent (patterned bar). UT=untreated. At 96 hours, free gemcitabine and nano-gemcitabine demonstrated comparable activity. All assays were performed in triplicate and means and standard deviations are plotted.
[0033] FIG. 10 illustrates blood levels of rapamycin following oral delivery of polymeric nanoparticles. Rapamycin was encapsulated in nanoparticles comprised of increasing order of acrylic acid (AA) percentage in the co-polymeric composition. The nanoparticles were either administered as is, or after surface PEGylation. Compared are: Control A (rapamycin suspended in water); rapamycin nanoparticle comprised of NIPAAM:VP:AA in a ratio of 60:30:10 (designated as NVA631); rapamycin nanoparticle comprised of NIPAAM:VP:AA in a ratio of 60:20:20 (designated as NVA622); rapamycin nanoparticle comprised of NIPAAM:VP:AA in a ratio of 60:10:30 (designated as NVA613); and rapamycin nanoparticle comprised of NIPAAM:MMA:AA in a ratio of 60:20:20 (designated as NMA622). The corresponding PEGylated nanoparticles (PEG-NVA-631, PEG-NVA-622, PEG-NVA-613, and PEG-NMA-622) encapsulating rapamycin are designated as shaded bars. Rapamycin was administered either as free drug dispersed in water (15 mg/kg) or as equivalent dosage of nano-encapsulated rapamycin in the respective polymeric nanoparticle formulation. Six wild type C57/B6 mice were included in each arm of this study. Blood levels are measured by HPLC from samples obtained at 2 hours post oral delivery. Two types of nanoparticles, each containing 20% molar ratio of AA (NVA622 and NMA622) demonstrate highest blood levels of rapamycin following oral delivery.
[0034] FIG. 11 illustrates pharmacokinetic (PK) data of orally delivered nano-encapsulated rapamycin in mice, over a 24 hour period. Two polymeric nanoparticle formulations with highest blood levels at 2 hours ( FIG. 10 ) were selected for this study: NVA622 and NMA622, containing NIPAAM/VP/AA and NIPAAM/MMA/AA in 60:20:20 molar ratios, respectively. Six wild type C57/B6 mice were included in each arm of the study. Single dose of nano-encapsulated rapamycin (equivalent to 15 mg/kg of drug) was administered at time zero, and blood obtained from the facial vein by venupuncture, at 30 minutes, 2, 4, 8, and 24 hours post oral administration. Rapamycin levels were measured by HPLC on mouse plasma. The means and standard deviations (error bars) are plotted for each time point for each of the nanoparticle formulations. NMA622 nanoparticles have a higher area-under-the-curve (AUC) compared with NVA622 nanoparticles (Mean AUC 26,949 versus 11,684, respectively).
[0035] FIG. 12 illustrates levels of rapamycin in central and peripheral venous circulation at 2 hours post-administration of nanoparticle encapsulated rapamycin via oral route. NVA622 particles encapsulating rapamycin were administered via oral route in three mice (dose of 15 mg/kg) and rapamycin levels measured in central venous and peripheral venous (facial vein) circulation at 2 hours. The levels are identical in all three independent measurements between the two sites, consistent with equitable systemic distribution of the orally delivered nanoparticle-encapsulated rapamycin within the blood circulation.
DETAILED DESCRIPTION OF THE INVENTION
[0036] Medicinal compositions of poorly water-soluble medicines, alone or in combination with two or more medicines, entrapped into polymeric nanoparticles are described herein. Medicinal composition of water-soluble medicines such as gemcitabine conjugated to a surface of polymeric nanoparticles are also described herein. After formation, the nanoparticles are approximately spherical and preferably have a size that averages 50-100 nm or less in diameter. The nanoparticles may be described as nanometer sized particles of micellar aggregates of amphiphilic and cross-linked polymers.
[0037] In the present invention, nanoparticles of polymeric micelles are prepared by:
(i) dissolving NIPAAM and AA in water to form micelles, (ii) adding at least one compound of vinyl derivative, which may be either water-soluble or insoluble in water, but both are soluble in the said micelles and which can be polymerized through free radical polymerization, (iii) adding appropriate amount of activator and initiator, which are, for example, tetramethylethylene diamine (TMED) and ferrous ammonium sulphate. As activators and ammonium perdisulphate as activator. (iv) adding a cross-linking agent to the said micellar solution, which is preferably N,N′ methylene bis acrylamide (v) polymerizing the monomers into copolymer in presence of an inert gas such as nitrogen at 30 C to 40 C temperature for 24 hours for nearly completion of the reaction, (vi) purifying the nanoparticles of the co-polymeric micelles by dialysis for three hours to remove toxic monomers and other unreacted materials, (vii) optional surface modification of the nanoparticles by chemically conjugating PEG amine of variable chain length (50-8000 D) or other conjugated moieties to reactive functional groups on the nanoparticle surface, (viii) addition of one or more bioactive agents for entrapment within the formed polymeric nanoparticles in aqueous solution, or lyophilizing the empty polymeric nanoparticles to dry powder for future use, (ix) reconstituting the dry powder of empty polymeric nanoparticles in an aqueous solution, and addition of one or more bioactive agents for entrapment within the said polymeric nanoparticles, (x) lyophilizing the drug-loaded polymeric nanoparticles to dry powder, and (xi) reconstituting the drug loaded polymeric nanoparticles in aqueous solution for oral, injectable, or topical delivery.
[0049] Besides NIPAAM and AA, the vinyl monomers are selected from water soluble vinyl compounds such as vinyl acetate, 4-vinyl benzoic acid, N-vinylpyrrolidone (VP), and N-vinyl piperidone, while water insoluble amphiphilic vinyl compounds include methylmethacrylate (MMA), vinylmethacrylate, N-vinyl caprolactum, N-vinyl carbazole, and styrene.
[0050] In one embodiment, the nanoparticles are formed by polymerization of the monomers in the reaction mixture. The compositions are in the following molar ratios: NIPAAM, about 50% to about 90%, and preferably 60% for specific delivery routes such as oral or parenteral; a vinyl monomer like the water-soluble VP or water-insoluble MMA, about 10% to about 30%; and AA, about 10% to about 30%. The monomers are dissolved in water and ammonium perdisulphate TEMED and ferrous ammonium sulphate are added to it. N,N′ methylene bis acrylamide is also added to cross-linked the polymer. The mixture is permitted to polymerize, preferably in the presence of an inert gas (e.g., nitrogen, argon, etc.), at a temperature preferably ranging from 20° C. to 80° C., or more preferably from 30° C. to 40° C., until polymerization is complete. Completion of polymerization may be determined by depletion of monomers from the reaction mixture by HPLC or 1 H NMR of vinyl protons. The solution may be purified by dialysis, for example for 2-4 hours, to remove any toxic monomers or other unreacted species. In Example 1, NIPAAM, VP, and AA were used to prepare copolymers with the molar ratios of 60:30:10, 60:20:20, and 60:10:30, in order to potentially modulate the mucoadhesivity of orally delivered nanoparticles in the GI tract by varying the proportion of AA in the polymer. In Example 2, similar co-polymeric nanoparticles were prepared in which VP has been replaced by MMA, and in the specific example the molar ratios used was 60:20:20 for NIPAAM, MMA and AA, respectively. As will be discussed below, the proportion of monomers utilized also affects stability of the nanoparticles at body temperature.
[0051] One embodiment of the invention is illustrated in FIG. 1 , which shows that the nanoparticles have a hydrophobic core (labeled 10) composed of hydrophobic parts of the polymers entrapping the medicine (labeled 11), whereas the hydrophilic parts forming a hydrophilic shell (labeled 12) are present towards the aqueous medium. As also shown in FIG. 1 , the polymeric nanoparticles are preferably less than 100 nm in size, and may include one or more molecules of medicaments or other bioactive agents.
[0052] Due to the presence of NIPAAM in the copolymeric formulation, the nanoparticle shell is converted from a hydrophilic to a hydrophobic entity at the lower critical solution temperature (LCST), which can be modulated by changing the amount of NIPAAM in the proportion of monomers used, as seen in FIG. 3 . To render these nanoparticles suitable for systemic circulation, the nanoparticles should have a LCST above human body temperature (˜37° C.). In order to obtain a high LCST of the nanoparticles, i.e., in the 45-50° C. range, enabling systemic medicine delivery and stability of the nanoparticles at body temperature, it is required that the NIPAAM component be used in an optimum molar ratio of 50-70%, with the two remaining monomers comprising the remaining 100%. As noted above, additional monomers or functional moieties may also be included, and these do not impact the LCST.
[0053] The nanoparticles described herein can be used as is for drug delivery, or optionally, the surface of nanoparticles may be modified by functionalizing reactive surface groups (COO—) provided by AA for attachment of PEG amine chains of variable length (50-8000 D), or for the chemical conjugation of targeting moieties like ligands, antibodies, radionuclides, fluorophores, and contrast agents, or for the addition of taste masking agents like aspartame. The addition of PEG amine chains does not impede the observed oral bioavailability of the drug encapsulated nanoparticles, as seen in FIG. 10 . Herein, four independent nanoparticle formulations encapsulating rapamycin (NVA631, NVA622, NVA613, and NMA622) were administered to mice via oral route, and the drug levels at two hours in the systemic circulation compared with that of rapamycin encapsulated in corresponding PEGylated nanoparticles (PEG-NVA613, PEG-NVA622, PEG-NVA613, and PEG-NMA622). As seen, the blood levels of rapamycin following oral delivery of non-PEGylated and PEGylated nanoparticles are comparable. Those skilled in the art will be aware that PEGylation renders nanoparticle long circulating, by evading the innate reticuloendothelial system (RES), and the engineering of “RES evading” nanoparticles embodied in this invention does not impede their oral bioavailability.
[0054] The polymeric nanoparticles disclosed herein are preferably loaded with medicines or other bioactive agents to the maximum extent possible. The medicines or bioactive agents can be organic compounds that are poorly soluble or insoluble in water but readily soluble in organic solvents. The medicine or bioactive agent is added to the polymeric solution either in the form of dry powder or as a solution in chloroform, ethanol or ether depending on the solubility of the drug in that solvent to form an optically clear solution. Examples of such medicines include, but are not limited to, antineoplastic agents such as Paclitaxel, Docetaxel, Rapamycin, Doxorubicin, Daunorubicin, Idarubicin, Epirubicin, Capecitabine, Mitomycin C, Amsacrine, Busulfan, Tretinoin, Etoposide, Chlorambucil, Chlormethine, Melphalan, and Benzylphenylurea (BPU) compounds; phytochemicals and other natural compounds such as curcumin, curcuminoids, and other flavinoids; steroidal compounds such as natural and synthetic steroids, and steroid derivatives like cyclopamine; antiviral agents such as Aciclovir, Indinavir, Lamivudine, Stavudine, Nevirapine, Ritonavir, Ganciclovir, Saquinavir, Lopinavir, Nelfinavir; antifungal agents such as Itraconazole, Ketoconazole, Miconazole, Oxiconazole, Sertaconazole, Amphotericin B, and Griseofulvin; antibacterial agents such as quinolones including Ciprofloxacin, Ofloxacin, Moxifloxacin, Methoxyfloxacin, Pefloxacin, Norfloxacin, Sparfloxacin, Temafloxacin, Levofloxacin, Lomefloxacin, Cinoxacin; antibacterial agents such as penicillins including Cloxacillin, Benzylpenicillin, Phenylmethoxypenicillin; antibacterial agents such as aminoglycosides including Erythromycin and other macrolides; antitubercular agents such as rifampicin and rifapentin; and anti-inflammatory agents such as Ibuprofen, Indomethacin, Ketoprofen, Naproxen, Oxaprozin, Piroxicam, Sulindac. Preferably, the medicine(s) loaded in the compositions range from 1% to 20% (w/w) of the polymer; however, in some applications the loading may be considerably higher.
[0055] Generally, one or more bioactive agents, such as medicines which are poorly soluble in aqueous media but also including other agents that produce a biological effect, are dissolved in a suitable solvent, such as ethanol or chloroform, and added to a nanoparticle solution. This addition step can be performed before or after nanoparticle formation. Combining the medicines or bioactive agents with the nanoparticle solution results in the entrapment of the medicines or bioactive agents within the hydrophobic core (interior) of the nanoparticles. The nanoparticles containing the entrapped medicines or bioactive agents may, if desired, be lyophilized or otherwise rendered into powder form for subsequent reconstitution in a suitable fluid vehicle for human or mammalian administration. In the subsequently discussed Example 5, incorporating FIGS. 10, 11 , and 12 , the in vivo oral bioavailability of rapamycin encapsulated in polymeric nanoparticles is demonstrated.
[0056] In another embodiment of this invention, a medication, which is water soluble but otherwise has low bioavailability through the oral route, can be attached to the surface of the nanoparticles by covalent conjugation between the reactive carboxylic groups in the nanoparticle and complementary functional groups, such as amine or thiol groups, on the medication. Conjugation to the nanoparticles allows such medications to become orally bioavailable. Examples of such compounds include, but are not limited to, anti-neoplastic agents like gemcitabine.
[0057] The nanoparticles containing at least one medicine or a combination of medicines and bioactive agents prepared by the above described process (e.g., nanoparticles with entrapped medicines or medicines conjugated to a surface, or even combinations of both) may be used for the treatment of pathological conditions arising out of various diseases including but not limited to cancer, inflammation, infection and neurodegeneration.
[0058] The invention will now be described with reference to the following non-limiting examples:
EXAMPLES
Example 1
Synthesis of Cross-Linked Copolymeric Micelles of NIPAAM, VP (a Water-Soluble Vinyl Derivative), and AA
[0059] A co-polymer of NIPAAM with VP and AA was synthesized through free radical polymerization. Water-soluble monomers, NIPAAM, VP and AA were dissolved in water in 60:30:10 molar ratios for NVA631, 60:20:20 for NVA622, and 60:10:30 for NVA613. The polymerization was initiated using ammonium persulphate (APS) as initiator in N 2 atmosphere. Ferrous Ammonium Sulphate (FAS) was added to activate the polymerization reaction and also to ensure complete polymerization of the monomers to obtain a good yield. Using NVA631 as a prototypal example, in a typical experimental protocol, 62.8 mg of re-crystallized NIPAAM, 30.5 μl of freshly distilled VP and 6.61 μl of AA (freshly distilled) in 10 ml of water were used. To cross-link the polymer chain, 30 μl of MBA (0.049 g/ml) was added in the aqueous solution of monomers. Dissolved oxygen was removed by passing nitrogen gas for 30 minutes. 20 μl of FAS (0.5% w/v), 30 μl of APS and 20 μl of TEMED were then added to initiate the polymerization reaction. The polymerization was carried out at 30° C. for 24 hours in a nitrogen atmosphere. After the polymerization was complete, the total aqueous solution of polymer was dialyzed overnight using a spectrapore membrane dialysis bag (12 kD cut off). The dialyzed solution was then lyophilized immediately to obtain a dry powder for subsequent use, which is easily re-dispersible in aqueous buffer. The yield of the polymeric nanoparticle was more than 90%. When VP is replaced by other water-soluble vinyl derivatives like vinyl alcohol (VA), the method of preparation remains the same, and the co-polymer does not change in its properties.
Example 2
Synthesis of Cross-Linked Copolymeric Micelles of NIPAAM, MMA (Water-Insoluble Vinyl Derivative), and AA
[0060] A co-polymer of NIPAAM with MMA and AA was synthesized through free radical polymerization. Water-soluble monomers—NIPAAM and AA—were dissolved in water, and water-insoluble MMA was dissolved in the micellar solution of NIPAAM and AA, in 60:30:10 molar ratios for NMA631, 60:20:20 for NMA622, and 60:10:30 for NMA613. The polymerization was initiated using ammonium persulphate (APS) as initiator in N 2 atmosphere. Ferrous Ammonium Sulphate (FAS) was added to activate the polymerization reaction and also to ensure complete polymerization of the monomers to obtain a good yield. Using NMA622 as a prototypal example, in a typical experimental protocol for preparing NMA622, 66.6 mg of re-crystallized NIPAAM, 19.4 μl of freshly distilled MMA and 14 μl of AA (freshly distilled) in 10 ml of water were used. To cross-link the polymer chain, 30 μl of MBA (0.049 g/ml) was added in the aqueous solution of monomers. Dissolved oxygen was removed by passing nitrogen gas for 30 minutes. 20 μl of FAS (0.5% w/v), 30 μl of APS and 20 μl of TEMED were then added to initiate the polymerization reaction. The polymerization was carried out at 30° C. for 24 hours in a nitrogen atmosphere. After the polymerization was complete, the total aqueous solution of polymer was dialyzed overnight using a spectrapore membrane dialysis bag (12 kD cut off). The dialyzed solution was then lyophilized immediately to obtain a dry powder for subsequent use, which is easily re-dispersible in aqueous buffer. The yield of the polymeric nanoparticle was more than 90%. When MMA is replaced by other water insoluble vinyl derivatives like styrene (ST), the method of preparation remains the same, and the co-polymer does not change in its properties
Example 3
Surface Modification of NIPAAM VP/AA Copolymeric Micelles with 5 kD PEG Moiety
[0061] The formulations NVA631, NVA622 or NVA613 were prepared using the detailed protocol as described above. The exemplary functionalized PEG molecule used for post-copolymerization conjugation to AA was Methoxy-polyethylene glycol amine (Methoxy-PEGamine; molecular weight 5000 D). Conjugation of Methoxy-PEGamine with the carboxylic group of acrylic acid in the co-polymer was done by using EDCI as a crossslinker. Briefly, 100 mg of the lyophilized co-polymer powder was dissolved in 10 ml of phosphate buffer. To this, 5 mM of 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDCI) was added and stirred for 30 minutes. Thereafter, 5 mg of Methoxy-PEGamine was added to the copolymer solution and stirred overnight at room temperature. The next day, the solution was dialyzed for 2-4 hrs to remove any unconjugated Methoxy-PEGamine using a 12 kD dialysis membrane followed by subsequent lyophilization. The resulting nanoparticles are designated as PEG-NVA631, PEG-NVA-622, and PEG-NVA613. Identical PEGylation can be performed with the NIPAAM/MMA/AA formulations, and are designated PEG-NMA631, PEG-NMA622, and PEG-NMA613, respectively.
Example 4
Preparation of Polymeric Nanoparticles Encapsulating the Poorly Water Soluble Immunomodulatory and Anti-Cancer Drug, Rapamycin
[0062] The immunomodulatory and anti-cancer agent rapamycin is known to be poorly absorbed when administered through the oral route. To study the delivery of rapamycin using the nanoparticles of the invention, rapamycin was incorporated into NVA631, NVA622, NVA613, and NMA622 nanoparticles, or the respective PEGylated derivatives (PEG-NVA631, PEG-NVA622, PEG-NVA613 and PEG-NMA622) as follows: 100 mg of lyophilized dry powder of the respective nanoparticle was dispersed in 10 ml distilled water and was stirred well to reconstitute the micelles. The free drug rapamycin was dissolved in chloroform (10 mg/ml) and the drug solution in CHCl 3 was added to the polymeric solution slowly with constant vortexing and mild sonication. Rapamycin was directly loaded into the hydrophobic core of micelles. The drug-loaded micelles were then lyophilized to dry powder for subsequent use. Up to 3 mg of rapamycin per 100 mg of micellar powder was entrapped in each of the co-polymeric micelles (NVA631, NVA622, NVA613, and NMA622 and the respective PEGylated derivatives) to form a drug loaded nanoparticle solution, thus giving a total loading of 3% (w/w) of the polymer.
[0063] This example shows that poorly water soluble drugs can be easily and efficiently loaded into the nanoparticles of the invention.
Example 5
In Vivo Oral Administration of Polymeric Nanoparticles Encapsulating Rapamycin
[0064] Rapamycin is a poorly water soluble drug that has low oral bioavailability. The objective of these experiments was to determine whether nano-encapsulation of rapamycin in the polymeric nanoparticles embodied in this invention can enhance absorption upon oral administration, compared to free rapamycin in aqueous media. Nine independent sets of C57B6 wild type mice (N=6 mice per set) were studied. Rapamycin was administered to the mice as oral free rapamycin (15 mg/kg body weight) suspended in water, or the equivalent amount of rapamycin encapsulated in NVA631, NVA622, NVA613 and NMA622 nanoparticles, or the respective surface modified PEGylated derivatives. All dosages were given by oral lavage. At 2 hours post oral administration, the mice were bled and rapamycin concentrations in the blood were determined by high performance liquid chromatography (HPLC). The results of this study are presented in FIG. 10 . As can be seen, all nanoparticles tested successfully delivered high levels of rapamycin to the blood stream compared to free rapamycin in water, which was essentially undetectable. We ascribe these high systemic levels following oral delivery to both the nanoparticulate size (˜50 nm in diameter) of the carrier polymers, as well as their enhanced gastrointestinal mucoadhesivity due to the availability of free COO— (carboxyl) groups on the surface from the AA component in the polymer. Further, two of the nanoparticle formulations, NVA622 and NM622, had the highest two-hour blood levels, which we ascribe to an optimum molar ratio of mucoadhesive AA in the polymeric composition. This study also demonstrates that partial PEGylation of AA (as present in PEG-NVA631, PEG-NVA622, PEG-NVA613, and PEG-NMA622) does not impede the mucoadhesive tendencies of the nanoparticles, likely because a sufficient number of free COO— groups are available for mucosal adhesion even after the PEGylation. Therefore, the optional PEGylation of these nanoparticles, as sometimes required for long systemic circulation, does not impede oral bioavailability. The experiment in FIG. 11 confirms the rapid and robust oral uptake of the nanoparticle-encapsulated drug, with markedly high levels observed as early as 30 minutes after oral administration. Finally, the experiment in FIG. 12 confirms the equitable systemic distribution of the nanoparticle encapsulated drug in the circulation following their oral delivery, with near-identical levels of rapamycin observed in central and peripheral circulatory compartments. Thus, this example demonstrates the ability of polymeric nanoparticles embodied in this invention to efficiently deliver one or more encapsulated poorly water soluble drugs to the systemic circulation via the oral route.
Example 6
In Vitro Growth Assays of Nanoparticle Formulation of an Anticancer Agent, And an Example of Combination Therapy Achieved Using Nanoparticle Formulations of Two Independent Anticancer Agents
[0065] Paclitaxel is a poorly water soluble anticancer agent, and can be solubilized for dispersion in aqueous media using the polymeric nanoparticles described herein. Nanopaclitaxel encapsulated in NVA631 particles were utilized for in vitro cell viability (MTT) assays in a panel of three human pancreatic cancer cell lines (XPA-1, BxPC3, and PANC-1). The results of this study are presented in FIG. 6 . As seen, the nanopaclitaxel demonstrates comparable potency to free drug for any given dose of paclitaxel, confirming that the process of nano-encapsulation does not diminish the activity of parent compound. The results of two independent therapeutic agents (nanopaclitaxel and nanocurcumin) are presented in FIG. 7 . As seen, the combination of nanopaclitaxel and nanocurcumin demonstrates increased cytotoxicity than either free paclitaxel or nanopaclitaxel alone at any given dose of paclitaxel. Of note, and especially at the lower dosages used in two of the cell lines (XPA-1 and Panc-1), the combination of nanopaclitaxel and nanocurcumin also appears to have better efficacy than the combination of free paclitaxel and free curcumin, likely due to increased intracellular uptake of the nano-encapsulated compounds. At higher dosages, the combination therapy with either free or nano-encapsulated drugs appears to have comparable effects.
Example 7
Surface Modification of Polymeric Nanoparticle Formulation by a Taste Masking Agent Aspartame, and Encapsulation of the Antifungal Agent Griseofulvin in the Surface Modified Nanoparticles
[0066] The antifungal agent griseofulvin is poorly water soluble, has poor oral bioavailability, and has a bitter taste that can affect patient compliance. In this example, we demonstrate the utility of “smart” polymeric nanoparticles (illustrative example is the composition NMA622) in being amenable to surface modification by taste masking agents, and the incorporation of griseofulvin within such modified nanoparticles. 10 ml of NMA 622 polymer nanoparticles dispersion (containing 100 mg of polymer) was mixed with 500 μl of 5 mM EDCI by stirring for complete dissolution. To the clear dispersion, 30 mg of solid Aspartame was added. The solution was stirred over night for 15 to 20 hours. The clear solution was then dialyzed through 12 kD cut off dialysis bag for 4 hours with change of external water at every one hour. To the dialyzed solution, 2 mg of solid griseofulvin was added, and the solution was sonicated for 30 mins for complete dispersion, followed by gentle heating with stirring at 50 to 60 C to achieve a clear solution. If required, the process of sonication followed by gentle heating with stirring was repeated till the solution was clear. The clear solution of nano-griseofulvin at room temperature was lyophilized to a dry powder for further use.
[0067] The release kinetics of griseofulvin from surface aspartame-conjugated polymeric nanoparticles at room temperature was further studied. 10 mg of lyophilized powder of griseofulvin loaded, surface modified NMA622 polymeric nanoparticles (designated “nano-griseofulvin”) were dissolved in 1 ml of water by vortexing. Then, 10 μl of the clear solution of nano-griseofulvin was added to 1 ml of water and the absorbance of the mixture was taken at 292 nm. After every two hours, the original nano-griseofulvin solution was centrifuged at 2000 rpm for 10 mins, and 10 μl of the centrifugate was pipetted carefully from the surface and was added to 1 ml of water. Absorbance was taken at 292 nm. After 10 hours, the original nano-griseofulvin solution was kept over night, and the 292 nm absorbance at 24 hours was measured, as described above. The absorbance was similarly measured at 48 and 72 hours. The % of release was calculated from the equation (Do−Dt)/Do×100 where Do is the absorbance at zero hours and Dt is the absorbance at t hours. In this calculation it is assumed that practically all the griseofulvin released from the nanoparticles settles down during centrifugation and that the concentration of griseofulvin in water is practically zero.
[0068] Results:
Time OD % release 0 hr 0.093 0.0 2 hrs 0.085 8.6 4 hrs 0.076 18.3 6 hrs 0.072 23.0 10 hrs 0.061 34.4 24 hrs 0.053 43.0 48 hrs 0.048 48.4 72 hrs 0.018 80.6
This example demonstrates the encapsulation of another poorly water soluble drug, the antifungal agent griseofulvin, in the said polymeric nanoparticles, and the ability to alter the innate taste of the encapsulated medicament by taste masking agents conjugated to the nanoparticle surface. This example also demonstrates the favorable release kinetics of the nanoparticle-loaded drug over 72 hours, including absence of any “burst release” effects.
Example 8
Conjugation of Water Soluble Anticancer Drug Gemcitabine on the Surface of Polymeric Nanoparticles and the Application of Said “Nano-Gemcitabine” Preparation to In Vitro Cell Viability Assays in Human Cancer Cell Lines
[0069] Gemcitabine is a water soluble compound, and thus differs from the poorly water soluble drugs discussed above that are encapsulated within the hydrophobic core of the polymeric nanoparticles. Herein, we describe the chemical conjugation of gemcitabine, as one illustrative example of water soluble drugs, to the hydrophilic surface of the polymeric nanoparticles. Such conjugation is expected to render gemcitabine amenable to oral delivery, utilizing the oral bioavailability properties of the said polymeric nanoparticles used as a carrier. 10 mg of NMA622 polymeric nanoparticles were dispersed in 10 ml of water by vortexing. To the clear solution, 6.5 mg of EDCI was added and was stirred for 10 mins. Thereafter, 10.2 mg of gemcitabine powder was added, while stirring was continued. The solution was stirred further for 15-20 hours. The clear solution was then dialysed for 3 hours through 12 kD dialysis membrane against water. It was then lyophilized to dry powder for further use. In order to demonstrate retained anti-cancer effects of gemcitabine conjugated to polymeric nanoparticles, cell viability (MTT) assays were done as described in example 6, using the human pancreatic cancer cell line BxPC3. FIG. 9 confirms that nano-gemcitabine has comparable potency to free gemcitabine at 96 hours.
[0070] While the invention has been described in terms of its preferred embodiments, those skilled in the art will recognize that the invention can be practiced with modification within the spirit and scope of the appended claims.
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Polymeric nanoparticles with a hydrophobic core and a hydrophilic shell are formed from: 1) N-isopropyl acrylamide (NIPAAM), at a molar ratio of about 50% to about 90%, and preferably 60% for specific delivery routes such as oral or parenteral; either water-soluble vinyl derivatives like vinylpyrolidone (VP) or vinyl acetate (VA), or water insoluble vinyl derivatives like methyl methacrylate (MMA) or styrene (ST), at a molar ratio of about 10% to about 30%; and acrylic acid (AA), at a molar ratio of about 10% to about 30%. The formed nanoparticles may be optionally surface functionalized using reactive groups present in AA, including PEGylation, or conjugation of moieties such as chemotherapeutics, contrasting agents, antibodies, radionucleides, ligands, and sugars, for diagnostic, therapeutic, and imaging purposes. The polymeric nanoparticles are preferably dispersed in aqueous solutions. The polymeric nanoparticles incorporate one or more types of medicines or bioactive agents in the hydrophobic core; on occasion, the medicine or bioactive agent may be conjugated to the nanoparticle surface via reactive functional groups. The polymeric nanoparticles are capable of delivering the said medicines or bioactive agents through oral, parenteral, or topical routes. The polymeric nanoparticles allow poorly water soluble medicines or bioactive agents, or those with poor oral bioavailability, to be formulated in an aqueous solution, and enable their convenient delivery into the systemic circulation.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application is a continuation of, Claims priority to and incorporates by reference in its entirety U.S. patent application Ser. No. 10/308,545, filed 3 Dec. 2002 now U.S. Pat. No. 7,141,812, which is a continuation-in-part of, claims priority to, and incorporates by reference in its entirety each of:
U.S. patent application Ser. No. 10/282,441, filed 29 Oct. 2002, and titled “Devices, Methods, and Systems Involving Cast Computed Tomography Collimators”; U.S. patent application Ser. No. 10/282,402, filed 29 Oct. 2002, and titled “Devices, Methods, and Systems Involving Cast Collimators”; and PCT Patent Application Serial No. PCT/US02/17936, filed 5 Jun. 2002.
BRIEF DESCRIPTION OF THE DRAWINGS
The wide variety of potential embodiments of the present invention will be more readily understood through the following detailed description, with reference to the accompanying drawings in which:
FIG. 1 is a flowchart of an exemplary embodiment of a method of the present invention.
FIG. 2 is a flow diagram of exemplary items fabricated using a method of the present invention.
FIG. 3 is a perspective view of an exemplary casting of the present invention that illustrates aspect ratio.
FIG. 4 is an assembly view of an exemplary assembly of the present invention.
FIG. 5A is a top view of an exemplary stack lamination mold of the present invention.
FIGS. 5B-5E are exemplary alternative cross-sectional views of an exemplary stack lamination mold of the present invention taken at section lines 5 - 5 of FIG. 5A .
FIG. 6 is an unassembled cross-sectional view of an alternative exemplary stack lamination mold taken of the present invention at section lines 5 - 5 of FIG. 5A .
FIG. 7 is a cross-sectional view of an exemplary alternative stack lamination mold of the present invention taken at section lines 5 - 5 of FIG. 5A .
FIG. 8 is a perspective view of an exemplary laminated mold.
FIG. 9 is a cross-section of an exemplary mold of the present invention taken along lines 9 - 9 of FIG. 8 .
FIG. 10A is a top view an exemplary layer of the present invention having a redundant array of shapes.
FIG. 10B is a top view of an exemplary layer of the present invention having a non-redundant collection of shapes.
FIG. 11 is a top view of an exemplary stacked lamination mold of the present invention.
FIG. 12 is a cross-sectional view of an exemplary mold of the present invention taken at section lines 12 - 12 of FIG. 11 .
FIG. 13 is a side view of an exemplary cast part of the present invention formed using the exemplary mold of FIG. 11 .
FIG. 14 is a top view of an exemplary laminated mold of the present invention.
FIG. 15 is a cross-sectional view of an exemplary mold of the present invention taken at section lines 15 - 15 of FIG. 14 .
FIG. 16 is a perspective view of an exemplary cast part of the present invention formed using the exemplary mold of FIG. 14 .
FIG. 17 is a top view of an exemplary planar laminated mold of the present invention having an array of openings.
FIG. 18 is a top view of an exemplary flexible casting or mold insert of the present invention molded using the laminated mold of FIG. 17 .
FIG. 19 is a top view of an exemplary mold fixture of the present invention
FIG. 20 is a top view of an exemplary planar laminated mold of the present invention.
FIG. 21 is a top view of an exemplary flexible casting or mold insert of the present invention molded using the laminated mold of FIG. 20 .
FIG. 22 is a top view of an exemplary mold fixture of the present invention
FIG. 23 is a perspective view of an exemplary laminated mold of the present invention.
FIG. 24 is a close-up perspective view of an exemplary single cylindrical cavity of an exemplary mold of the present invention.
FIG. 25 is a perspective view of an exemplary cast part of the present invention.
FIG. 26 is a flowchart of an exemplary method of the present invention.
FIG. 27 is a perspective view of a plurality of exemplary layers of the present invention.
FIG. 28 is a perspective view of an exemplary laminating fixture of the present invention.
FIG. 29 is a top view of stack lamination mold of the present invention that defines an array of cavities.
FIG. 30 is a cross-section of a cavity of the present invention taken along section lines 30 - 30 of FIG. 29 .
FIG. 31 is a perspective view of an exemplary single corrugated feedhorn of the present invention.
FIG. 32 is a side view of an exemplary casting fixture of the present invention.
FIG. 33 is a side view of an exemplary section of cylindrical tubing of the present invention that demonstrates the shape of an exemplary fluidic channel of the present invention.
FIG. 34 is a top view of an exemplary micro-machined layer of the present invention.
FIG. 35 is a cross-sectional view of a laminated slit of the present invention taken along section lines 35 - 35 of FIG. 34 .
FIG. 36 is a side view of a portion of an exemplary flexible cavity insert of the present invention.
FIG. 37 is a top view of an exemplary base plate of the present invention.
FIG. 38 is a front view of a single exemplary flexible cavity insert assembly of the present invention.
FIG. 39 is a front view of flexible cavity inserts of the present invention.
FIG. 40 is a top view of a top plate of the present invention.
FIG. 41 is a flowchart of an exemplary embodiment of a method of the present invention.
FIG. 42A is a top view of an exemplary laminated stack of the present invention.
FIG. 42B is a cross-sectional view, taken at section lines 42 - 42 of FIG. 42A , of an exemplary laminated stack of the present invention.
FIG. 43 is side view of an exemplary mold and casting of the present invention.
FIG. 44 is a top view of an exemplary casting fixture of the present invention.
FIG. 45 is a front view of the exemplary casting fixture of FIG. 44 .
FIG. 46 is a top view of a portion of an exemplary grid pattern of the present invention.
FIG. 47 is an assembly view of components of an exemplary pixilated gamma camera of the present invention.
FIG. 48A is a top view of an array of generic microdevices of the present invention.
FIG. 48B is a cross-sectional view of an exemplary microdevice of the present invention, taken at section lines 48 - 48 of FIG. 48A , in the open state.
FIG. 49 is a cross-sectional view of the exemplary microdevice of FIG. 48B , taken at section lines 48 - 48 of FIG. 48A , in the closed state.
FIG. 50 is a cross-sectional view of an alternative exemplary microdevice of the present invention, taken at section lines 48 - 48 of FIG. 48A , and shown with an inlet valve open.
FIG. 51 is a cross-sectional view of the alternative exemplary microdevice of FIG. 50 , taken at section lines 48 - 48 of FIG. 48A , and shown with an outlet valve open.
FIG. 52 is a top view of an exemplary microwell array of the present invention.
FIG. 53 is a cross-sectional view taken at lines 52 - 52 of FIG. 52 of an exemplary microwell of the present invention.
FIG. 54 is a cross-sectional view taken at lines 52 - 52 of FIG. 52 of an alternative exemplary microwell of the present invention.
FIG. 55 is a top view of exemplary microwell of the present invention.
FIG. 56 is a cross-sectional view of an exemplary microwell of the present invention, taken at lines 55 - 55 of FIG. 55 .
DETAILED DESCRIPTION
Certain exemplary embodiments of the present invention can combine certain techniques of stack lamination with certain molding processes to manufacture a final product. As a result of the stack lamination techniques, precision micro-scale cavities of predetermined shapes can be engineered into the stack lamination. Rather than have the stack lamination embody the final product, however, the stack lamination can be used as an intermediate in a casting or molding process.
In certain exemplary embodiments of the present invention, the stack lamination (“laminated mold”) can be made up of layers comprising metallic, polymeric, and/or ceramic material. The mold can be a positive replication of a predetermined end product or a negative replication thereof. The mold can be filled with a first cast material and allowed to solidify. A first cast product can be demolded from the mold. The first cast material can comprise a flexible polymer such as silicone rubber.
Certain exemplary embodiments of a method of the present invention can further include surrounding the first cast product with a second casting material and allowing the second cast material to solidify. Still further, a second cast product can be demolded from the first cast product.
Some exemplary embodiments of the present invention can further include positioning an insert into the cavity prior to filling the mold with the first cast material, wherein the insert occupies only a portion of the space defined by the cavity. The second cast product can be nonplanar. The end product and/or the mold cavity can have an aspect ratio greater that 100:1. The end product can be attached to the substrate or it can be a free-standing structure.
In certain exemplary embodiments, the master mold can be fabricated using diverse micro-machining methods, which can allow hybrid integration of various disciplines. In certain exemplary embodiments, the master mold can be fabricated using high-precision lithographic techniques, which can allow production of accurate molds, castings, and features having virtually any shape.
In certain exemplary embodiments, layers for master mold fabrication can be produced by using low cost materials and low cost manufacturing methods such as photo-chemical machining. In certain exemplary embodiments, the layers used for master mold fabrication can have sub-cavities with controlled depths and shapes. These cavities can be used to produce integrated micro-features in cast objects.
In certain exemplary embodiments, the master molds can be produced over large areas. This allows the production of large batches of cast micro-devices or large macro devices with incorporated arrays of micro features. In certain exemplary embodiments, master molds and castings can be produced having extremely high-aspect ratios. Aspect ratio's greater than 400:1 can be achieved using photo-chemical machining combined with precision stack lamination.
In certain exemplary embodiments, hundreds to thousands of individual structures can be batch produced simultaneously, eliminating the need to produce 3D micro-structures one at a time. In certain exemplary embodiments, many diverse materials can be used to create advanced molds and/or cast devices. This can greatly enhance design and fabrication opportunities for low cost, application specific devices. Materials can include, but are not limited to, polymers, epoxy resins, polyesters, acrylics, ceramics, powder metals, castable metals, urethanes, silicon, and/or rubber etc. Materials can also be integrated for production of “smart” materials needed for fabricating advanced MEMS devices. Smart materials would include those having functional properties such as for example conductivity, electrostrictivity, piezoelectricity, magnetic, elastic, thermal, density, and/or chemical resistivity, etc.
In certain exemplary embodiments, the micro devices and/or structures can be produced as free form or attached structures. This can be achieved through molding and casting designs or through secondary machining techniques. In certain exemplary embodiments, micro devices can be produced outside of clean room facilities, thereby potentially lowering production overhead costs.
In certain exemplary embodiments, by using lithographic techniques for producing master molds and/or micro devices, arrays of devices or micro features can be accurately integrated and aligned with standard microelectronics. In certain exemplary embodiments, through the fabrication method used for producing the master molds, highly accurate, three dimensional engineering and production of micro scale devices can be possible. In certain exemplary embodiments, through the use of flexible molds, highly accurate, three dimensional engineering and production of non-planar, micro scale devices is possible. Non-planar shapes can include, but are not limited to, curves, arcs, diameters, spherical radii, inside and outside diameters of cylinders, etc.
FIG. 1 is a flowchart of an exemplary embodiment of a method 1000 of the present invention. At activity 1010 , a mold design is determined. At activity 1020 , the layers of the mold (“laminations”) are fabricated. At activity 1030 , the laminations are stacked and assembled into a mold (a derived mold could be produced at this point as shown in FIG. 1 ). At activity 1060 , a first casting is cast. At activity 1070 , the first casting is demolded.
FIG. 2 is a flow diagram of exemplary items fabricated during a method 2000 of the present invention. Layers 2010 can be stacked to form a mold or stacked lamination 2020 . A molding or casting material can be applied to mold 2020 to create a molding or casting 2030 , that can be demolded from mold 2020 .
FIG. 3 is a perspective view of an exemplary molding 3000 of the present invention that demonstrates a parameter referred to herein as “aspect ratio” which is described below. Molded block 3010 has numerous through-holes 3020 , each having a height H and a diameter or width W. For the purposes of this application, aspect ratio is defined as the ratio of height to width or H/W of a feature, and can apply to any “negative” structural feature, such as a space, channel, through-hole, cavity, etc., and can apply to a “positive” feature, such as a wall, projection, protrusion, etc., with the height of the feature measured along the Z-axis. Note that all features can be “bordered” by at least one “wall”. For a positive feature, the wall is part of the feature. For a negative feature, the wall at least partially defines the feature.
FIG. 3 also demonstrates the X-, Y-, and Z-directions or axes. For the purposes of this application, the dimensions measured in the X- and Y-directions define a top surface of a structure (such as a layer, a stack lamination mold, or negative and/or positive replications thereof) when viewed from the top of the structure. The Z-direction is the third dimension perpendicular to the X-Y plane, and corresponds to the line of sight when viewing a point on a top surface of a structure from directly above that point.
Certain embodiments of a method of the present invention can control aspect ratios for some or all features in a laminated mold, derived mold, and/or cast item (casting). The ability to attain relatively high aspect ratios can be affected by a feature's geometric shape, size, material, and/or proximity to another feature. This ability can be enhanced using certain embodiments of the present invention. For example, through-features of a mold, derived mold, and/or final part, having a width or diameter of approximately 5 microns, can have a dimension along the Z axis (height) of approximately 100 microns, or approximately 500 microns, or any value in the range there between (implying an aspect ratio of approximately 20:1, 100:1, or any value in the range therebetween, including, for example:
20:1 to 30:1, 20:1 to 40:1, 20:1 to 50:1, 20:1 to 60:1, 20:1 to 70:1, 20:1 to 80:1, 20:1 to 90:1, 20:1 to 100:1, 30:1 to 40:1, 30:1 to 50:1, 30:1 to 60:1, 30:1 to 70:1, 30:1 to 80:1, 30:1 to 90:1, 30:1 to 100:1, 40:1 to 50:1, 40:1 to 60:1, 40:1 to 70:1, 40:1 to 80:1, 40:1 to 90:1, 40:1 to 100:1,
50:1 to 60:1, 50:1 to 70:1, 50:1 to 80:1, 50:1 to 90:1, 50:1 to 100:1,
60:1 to 70:1, 60:1 to 80:1, 60:1 to 90:1, 60:1 to 100:1,
70:1 to 80:1, 70:1 to 90:1, 70:1 to 100:1,
80:1 to 90:1, 80:1 to 100:1, etc).
As another example, a through slit having a width of approximately 20 microns can have a height of approximately 800 microns, or approximately 1600 microns, or any value in the range therebetween (implying an aspect ratio of approximately 40:1, 80:1, or any value in the range therebetween, including, for example:
40:1 to 50:1, 40:1 to 60:1, 40:1 to 70:1, 40:1 to 80:1,
50:1 to 60:1, 50:1 to 70:1, 50:1 to 80:1,
60:1 to 70:1, 60:1 to 80:1,
70:1 to 80:1, etc).
As yet another example, the same approximately 20 micron slit can be separated by an approximately 15 micron wide wall in an array, where the wall can have a dimension along the Z axis (height) of approximately 800 microns, or approximately 1600 microns, or any value in the range therebetween (implying an aspect ratio of approximately 53:1, 114:1, or any value in the range therebetween, including, for example:
53:1 to 60:1, 53:1 to 70:1, 53:1 to 80:1, 53:1 to 90:1, 53:1 to 100:1, 53:1 to 110:1, 53:1 to 114:1,
60:1 to 70:1, 60:1 to 80:1, 60:1 to 90:1, 60:1 to 100:1, 60:1 to 110:1, 60:1 to 114:1,
70:1 to 80:1, 70:1 to 90:1, 70:1 to 100:1, 70:1 to 110:1, 70:1 to 114:1,
80:1 to 90:1, 80:1 to 100:1, 90:1 to 110:1, 90:1 to 114:1,
90:1 to 100:1, 90:1 to 110:1, 90:1 to 114:1,
100:1 to 110:1, 100:1 to 114:1, etc.).
Still another example is an array of square-shaped openings having sides that are approximately 0.850 millimeters wide, each opening separated by approximately 0.150 millimeter walls, with a dimension along the Z axis of approximately 30 centimeters. In this example the approximately 0.850 square openings have an aspect ratio of approximately 353:1, and the approximately 0.150 walls have an aspect ratio of approximately 2000:1, with lesser aspect ratios possible. Thus, the aspect ratio of the openings can be approximately 10:1, or approximately 350:1, or any value in the range therebetween, including for example:
10:1 to 20:1, 10:1 to 30:1, 10:1 to 40:1, 10:1 to 50:1, 10:1 to 60:1, 10:1 to 70:1, 10:1 to 80:1, 10:1 to 90:1, 10:1 to 100:1, 10:1 to 150:1, 10:1 to 200:1, 10:1 to 250:1, 10:1 to 300:1, 10:1 to 350:1,
20:1 to 30:1, 20:1 to 40:1, 20:1 to 50:1, 20:1 to 60:1, 20:1 to 70:1, 20:1 to 80:1, 20:1 to 90:1, 20:1 to 100:1, 20:1 to 150:1, 20:1 to 200:1, 20:1 to 250:1, 20:1 to 300:1, 20:1 to 350:1,
30:1 to 40:1, 30:1 to 50:1, 30:1 to 60:1, 30:1 to 70:1, 30:1 to 80:1, 30:1 to 90:1, 30:1 to 100:1, 30:1 to 150:1, 30:1 to 200:1, 30:1 to 250:1, 30:1 to 300:1, 30:1 to 350:1,
40:1 to 50:1, 40:1 to 60:1, 40:1 to 70:1, 40:1 to 80:1, 40:1 to 90:1, 40:1 to 100:1, 40:1 to 150:1, 40:1 to 200:1, 40:1 to 250:1, 40:1 to 300:1, 40:1 to 350:1,
50:1 to 60:1, 50:1 to 70:1, 50:1 to 80:1, 50:1 to 90:1, 50:1 to 100:1, 50:1 to 150:1, 50:1 to 200:1, 50:1 to 250:1, 50:1 to 300:1, 50:1 to 350:1,
75:1 to 80:1, 75:1 to 90:1, 75:1 to 100:1, 75:1 to 150:1, 75:1 to 200:1, 75:1 to 250:1, 75:1 to 300:1, 75:1 to 350:1,
100:1 to 150:1, 100:1 to 200:1, 100:1 to 250:1, 100:1 to 300:1, 100:1 to 350:1,
150:1 to 200:1, 150:1 to 250:1, 150:1 to 300:1, 150:1 to 350:1,
200:1 to 250:1, 200:1 to 300:1, 200:1 to 350:1,
250:1 to 300:1, 250:1 to 350:1,
300:1 to 350:1, etc.
Moreover, the aspect ratio of the walls can be approximately 10:1, or approximately 2000:1, or any value in the range therebetween, including for example:
10:1 to 20:1, 10:1 to 30:1, 10:1 to 40:1, 10:1 to 50:1, 10:1 to 100:1, 10:1 to 200:1, 10:1 to 500:1, 10:1 to 1000:1, 10:1 to 2000:1,
20:1 to 30:1, 20:1 to 40:1, 20:1 to 50:1, 20:1 to 100:1, 20:1 to 200:1, 20:1 to 500:1, 20:1 to 1000:1, 20:1 to 2000:1,
30:1 to 40:1, 30:1 to 50:1, 30:1 to 100:1, 30:1 to 200:1, 30:1 to 500:1, 30:1 to 1000:1, 30:1 to 2000:1,
40:1 to 50:1, 40:1 to 100:1, 40:1 to 200:1, 40:1 to 500:1, 40:1 to 1000:1, 40:1 to 2000:1,
50:1 to 100:1, 50:1 to 200:1, 50:1 to 500:1, 50:1 to 1000:1, 50:1 to 2000:1,
100:1 to 200:1, 100:1 to 500:1, 100:1 to 1000:1, 100:1 to 2000:1,
200:1 to 500:1, 200:1 to 1000:1, 200:1 to 2000:1,
500:1 to 1000:1, 500:1 to 2000:1,
1000:1 to 2000:1, etc.
Another example of aspect ratio is the space between solid (positive) features of a mold, derived mold, and/or casting. For example, as viewed from the top, a casting can have two or more solid rectangles measuring approximately 50 microns wide by approximately 100 microns deep with an approximately 5 micron space therebetween (either width-wise or depth-wise). The rectangles can have a height of 100 microns, or 500 microns, or any value in the range therebetween (implying an aspect ratio of 20:1, or 100:1, or any value therebetween, including, for example:
20:1 to 30:1, 20:1 to 40:1, 20:1 to 50:1, 20:1 to 60:1, 20:1 to 70:1, 20:1 to 80:1, 20:1 to 90:1, 20:1 to 100:1,
30:1 to 40:1, 30:1 to 50:1, 30:1 to 60:1, 30:1 to 70:1, 30:1 to 80:1, 30:1 to 90:1, 30:1 to 100:1,
40:1 to 50:1, 40:1 to 60:1, 40:1 to 70:1, 40:1 to 80:1, 40:1 to 90:1, 40:1 to 100:1,
50:1 to 60:1, 50:1 to 70:1, 50:1 to 80:1, 50:1 to 90:1, 50:1 to 100:1,
60:1 to 70:1, 60:1 to 80:1, 60:1 to 90:1, 60:1 to 100:1,
70:1 to 80:1, 70:1 to 90:1, 70:1 to 100:1,
80:1 to 90:1, 80:1 to 100:1, etc).
In another example the same rectangles can have a space there between of approximately 20 microns, and the rectangles can have dimensions along the Z axis of approximately 800 microns, or approximately 5000 microns, or any value therebetween (implying an aspect ratio of approximately 40:1, or 250:1, or any value therebetween, including, for example:
40:1 to 50:1, 40:1 to 75:1, 40:1 to 100:1, 40:1 to 150:1, 40:1 to 200:1, 40:1 to 250:1,
75:1 to 100:1, 75:1 to 150:1, 75:1 to 200:1, 75:1 to 250:1,
100:1 to 150:1, 100:1 to 200:1, 100:1 to 250:1,
150:1 to 200:1, 150:1 to 250:1,
200:1 to 250:1, etc).
FIG. 4 is an assembly view of an exemplary assembly 4000 of the present invention that includes mold 4010 and cast part 4020 formed from mold 4010 . Because certain exemplary embodiments of the present invention can utilize lithographically-derived micro-machining techniques (or in some cases, non-lithographically-derived micro-machining techniques, such as laser machining) combined with molding and/or casting, laminated molds can be conceived as negatives 4010 or positives 4020 of the desired end product. The terms “negative” or “positive” replications can be subjective terms assigned to different stages of reaching an end product. For certain embodiments, any intermediate or the end product can be considered a negative or positive replication depending on a subject's point of view. For the purpose of this application, a “positive” replication is an object (whether an intermediate or an end product) that geometrically resembles at least a portion of the spatial form of the end product. Conversely, a “negative” replication is a mold that geometrically defines at least a portion of the spatial form of the end product. The following parameters are described for the purpose of demonstrating some of the potential design parameters of certain embodiments of a method of the present invention.
Layer Thickness
One design parameter can be the thickness of the micro-machined layers of the stack lamination mold. According to certain exemplary embodiments of the present invention, to achieve high-aspect ratios, multiple micro-machined foils or layers can be stacked in succession and bonded together. In certain exemplary embodiments of the present invention, the layer thickness can have a dimensional role in creating the desired shape in the third dimension. FIG. 5A is a top view of an exemplary stack lamination mold 5000 . FIGS. 5B-5E are exemplary alternative cross-sectional views of exemplary stack lamination mold 5000 taken at section lines 5 - 5 of FIG. 5A . As shown in FIG. 5B and FIG. 5D , respectively, stacks 5010 and 5020 utilize relatively thick layers. As shown in FIG. 5C and FIG. 5E , respectively, stacks 5030 and 5040 utilize relatively thinner layers in succession to smooth out resolution along the z-axis. Specific layers can have multiple functions that can be achieved through their thickness or other incorporated features described herein.
Cross-Sectional Shape of Layer
One design parameter can be the cross sectional shape of a given layer in the mold. Through the use of etching and/or deposition techniques, many cross sectional shapes can be obtained. FIG. 6 is an unassembled cross-sectional view of an alternative exemplary stack lamination mold 5000 taken at section lines 5 - 5 of FIG. 5A . Each of exemplary layers 6010 , 6020 , 6030 , and 6040 of FIG. 6 define an exemplary through-feature 6012 , 6022 , 6032 , 6042 , respectively, each having a different shape, orientation, and/or configuration. These through-features 6012 , 6022 , 6032 , 6042 are bordered by one or more “sidewalls” 6014 , 6024 , 6034 , and 6044 , respectively, as they are commonly referred to in the field of lithographic micro-machining.
Etching disciplines that can be utilized for a layer of the mold can be broadly categorized as isotropic (non-linear) or anisotropic (linear), depending on the shape of the remaining sidewalls. Isotropic often refers to those techniques that produce one or more radial or hour glassed shaped sidewalls, such as those shown in layer 6010 . Anisotropic techniques produce one or more sidewalls that are more vertically straight, such as those shown in layer 6020 .
Additionally, the shape of a feature that can be etched through a foil of the mold can be controlled by the depth of etching on each surface and/or the configuration of the photo-mask. In the case of photo-chemical-machining, a term such as 90/10 etching is typically used to describe the practice of etching 90% through the foil thickness, from one side of the foil, and finishing the etching through the remaining 10% from the other side, such as shown on layer 6030 . Other etch ratios can be obtained, such as 80/20, 70/30, and/or 65/35, etc., for various foils and/or various features on a given foil.
Also, the practice of displacing the positional alignment of features from the top mask to the bottom mask can be used to alter the sidewall conditions for a layer of the mold, such as shown in layer 6040 .
By using these and/or other specific conditions as design parameters, layers can be placed to contribute to the net shape of the 3-dimensional structure, and/or provide specific function to that region of the device. For example, an hourglass sidewall could be used as a fluid channel and/or to provide structural features to the device. FIG. 7 is a cross-sectional view of an alternative exemplary stack lamination mold taken at section line 5 - 5 of FIG. 5A . FIG. 7 shows a laminated mold 5000 having layers 7010 , 7020 , 7030 , 7040 that define cavity 7060 . To achieve this, layers 7010 , 7020 are etched anisotropically to have straight sidewalls, while layer 7030 is thicker than the other layers and is etched isotropically to form the complex shaped cross-section shown.
Cross-Sectional Surface Condition of Layer
Another design parameter when creating advanced three-dimensional structures can be the cross-sectional surface condition of the layers used to create a laminated mold. As is the case with sidewall shape, surface condition can be used to provide additional function to a structure or a particular region of the structure. FIG. 8 is a perspective view of a generic laminated mold 8000 . FIG. 9 is a cross-section of mold 8000 taken at lines 9 - 9 of FIG. 8 . Any sidewall surface, top or bottom surface can be created with one or more specific finish conditions on all layers or on selected layers, such as for example, forming a relatively rough surface on at least a portion of a sidewall 9100 of certain through-features 9200 of layer 9300 . As another example, chemical and/or ion etching can be used to produce very smooth, polished surfaces through the use of selected materials and/or processing techniques. Similarly, these etching methods can also be manipulated to produce very rough surfaces.
Secondary techniques, such as electro-plating and/or passive chemical treatments can also be applied to micromachined surfaces (such as a layer of the mold) to alter the finish. Certain secondary techniques (for example, lapping or superfinishing) can also be applied to non-micromachined surfaces, such as the top or bottom surfaces of a layer. In any event, using standard profile measuring techniques, described as “roughness average” (R a ) or “arithmetic average” (AA), the following approximate ranges for surface finish (or surface conditions) are attainable using micromachining and/or one or more secondary techniques according to certain embodiments of the present invention (units in microns):
50 to any of: 25, 12.5, 6.3, 3.2, 1.6, 0.80, 0.40, 0.20, 0.10, 0.050, 0.025,
25 to any of: 12.5, 6.3, 3.2, 1.6, 0.80, 0.40, 0.20, 0.10, 0.050, 0.025,
12.5 to any of: 6.3, 3.2, 1.6, 0.80, 0.40, 0.20, 0.10, 0.050, 0.025,
6.3 to any of: 3.2, 1.6, 0.80, 0.40, 0.20, 0.10, 0.050, 0.025,
3.2 to any of: 1.6, 0.80, 0.40, 0.20, 0.10, 0.050, 0.025,
1.6 to any of: 0.80, 0.40, 0.20, 0.10, 0.050, 0.025,
0.80 to any of: 0.40, 0.20, 0.10, 0.050, 0.025,
0.40 to any of: 0.20, 0.10, 0.050, 0.025,
0.20 to any of: 0.10, 0.050, 0.025,
0.10 to any of: 0.050, 0.025, 0.050 to any of: 0.025, etc.
Additional Layer Features
Certain exemplary embodiments of the present invention can include layer features that can be created through the use of lithographic etching and/or deposition. These embodiments can include the size, shape, and/or positional orientation of features relative to the X- and/or Y-axes of a layer and/or their relationship to features on neighboring layers along the Z-axis of the assembled laminated mold. These parameters can define certain geometric aspects of the structure. For example, FIG. 10A is a top view of a layer 10010 having a pattern of repeating features (a redundant array of shapes), and FIG. 10B is a top view of a layer 10020 having a variety of differently shaped features (a non-redundant collection of shapes). Although not shown, a layer can have both redundant and non-redundant features. The terms “redundant” and/or “non-redundant” can refer to either positive or negative features.
Thus, these parameters also can define the shapes and/or spatial forms of features, the number of features in a given area, secondary structures and/or spaces incorporated on or around a feature, and/or the spaces between features. The control of spacing between features can provide additional functionality and, for instance, allow integration of devices with micro-electronics. For example, conductive micro features could be arrayed (redundantly or non-redundantly) to align accurately with application specific integrated circuits (ASIC) to control features. Also, features could be arrayed for applications where non-linear spacing between features could enhance device functionality. For example, filtration elements, could be arrayed in such a way as to match the flow and pressure profile of a fluid passing over or through a filtration media. The spacing of the filtration elements could be arrayed to compensate for the non-linear movement of the fluid.
Cavity Definition Using Lithography;
A cavity formed in accordance with certain exemplary embodiments of the present invention can assume a shape and/or spatial form that includes one or more predetermined “protruding undercuts”. Imaginably rotating the X-Y plane about its origin to any particular fixed orientation, a cavity is defined as having a “protruding undercut” when a first section of the cavity taken perpendicular to the Z-axis (i.e., parallel to the X-Y plane) has a predetermined dimension in the X- and/or Y-direction greater than the corresponding dimension in the X- and/or Y-direction of a second section of the cavity taken perpendicular to the Z-axis, the second section further along in the direction of eventual demolding of a cast part relative to the mold (assuming the demolding operation involves pulling the cast part free from the mold). That is, the X-dimension of the first section is intentionally greater than the X-dimension of the second section by a predetermined amount, or the Y-dimension of the first section is intentionally greater than the Y-dimension of the second section by a predetermined amount, or both. In still other words, for the purposes of this patent application, the term protruding undercut has a directional component to its definition.
FIG. 11 is a top view of an exemplary stacked laminated mold 11000 . FIG. 12 is a cross-sectional view of a mold 11000 taken at section lines 12 - 12 of FIG. 11 , and showing the layers 12010 - 12060 of mold 11000 that cooperatively define a cavity having protruding undercuts 12022 and 12042 . Direction A is the relative direction in which a part cast using mold 11000 will be demolded, and/or pulled away, from mold 11000 . FIG. 12 also shows that certain layers 12020 , 12040 of mold 12000 have been formed by controlled depth etching. FIG. 13 is a side view of a cast part 13000 formed using mold 11000 .
To make layers for certain embodiments of a laminated mold of the present invention, such as layers 2010 of FIG. 2 , a photo-sensitive resist material coating (not shown) can be applied to one or more of the major surfaces (i.e., either of the relatively large planar “top” or “bottom” surfaces) of a micro-machining blank. After the blank has been provided with a photo-resist material coating on its surfaces, “mask tools” or “negatives” or “negative masks”, containing a negative image of the desired pattern of openings and registration features to be etched in the blank, can be applied in alignment with each other and in intimate contact with the surfaces of the blank (photo-resist materials are also available for positive patterns). The mask tools or negatives can be made from glass, which has a relatively low thermal expansion coefficient. Materials other than glass can be used provided that such materials transmit radiation such as ultraviolet light and have a reasonably low coefficient of thermal expansion, or are utilized in a carefully thermally-controlled environment. The mask tools can be configured to provide an opening of any desired shape and further configured to provide substantially any desired pattern of openings.
The resulting sandwich of two negative masks aligned in registration and flanking both surfaces of the blank then can be exposed to radiation, typically in the form of ultraviolet light projected on both surfaces through the negative masks, to expose the photo-resist coatings to the radiation. Typically, the photo-resist that is exposed to the ultraviolet light is sensitized while the photo-resist that is not exposed is not sensitized because the light is blocked by each negative masks' features. The negative masks then can be removed and a developer solution can be applied to the surfaces of the blank to develop the exposed (sensitized) photo-resist material.
Once the photo-resist is developed, the blanks can be micro-machined using one or more of the techniques described herein. For example, when using photo-chemical-machining, an etching solution can react with and remove the layer material not covered by the photo-resist to form the precision openings in the layer. Once etching or machining is complete, the remaining unsensitized photo-resist can be removed using a chemical stripping solution.
Sub-Cavities on Layers
Cavities can include sub-cavities, which can be engineered and incorporated into the molding and casting scheme using several methods. FIG. 14 is a top view of a laminated mold 14000 . FIG. 15 is a cross-sectional view of mold 14000 taken at section lines 15 - 15 of FIG. 14 , and showing the sub-cavities 15010 within layer 15030 of mold 14000 . Note that because layer 15030 is sandwiched between layers 15020 and 15040 , sub-cavities 15010 can be considered “sandwiched”, because sub-cavities are at least partially bounded by a ceiling layer (e.g., 15020 ) and a floor layer (e.g., 15040 ). Note that, although not shown, a sub-cavity can extend to one or more outer edges of its layer, thereby forming, for example, a sandwiched channel, vent, sprew, etc. FIG. 16 is a perspective view of cast part 16000 formed using mold 14000 , and having protrusions 16010 that reflectively (invertedly) replicate sandwiched sub-cavities 15010 .
Because cast part can very accurately reflect the geometries of sub-cavities, such sub-cavities can be used to produce secondary features that can be incorporated with a desired structure. Examples of secondary features include fluid channels passing through or between features, protrusions such as fixation members (similar to Velcro-type hooks), reservoirs, and/or abrasive surfaces. Moreover, a secondary feature can have a wall which can have predetermined surface finish, as described herein.
There are a number of methods for producing sub-cavities in a laminated mold. For example, in the field of photo-chemical-machining, the practice of partially etching features to a specified depth is commonly referred to as “controlled depth etching” or CDE. CDE features can be incorporated around the periphery of an etched feature, such as a through-diameter. Because the CDE feature is partially etched on, for example, the top surface of the layer, it can become a closed cavity when an additional layer is placed on top.
Another method could be to fully etch the sub-cavity feature through the thickness of the layer. A cavity then can be created when the etched-through feature is sandwiched between layers without the features, such as is shown in FIG. 15 .
Combinations of micro-machining techniques can be used to create sub-cavities. For example, photo-chemical-machining (PCM) can be used to create the etched-through feature in the layer, while ion etching could be applied as a secondary process to produce the sub-cavities. By combined etching techniques, the sub-cavities can be etched with much finer detail than that of PCM.
Micro-Structures, Features, and Arrays on Non-Planar Surfaces
Certain exemplary embodiments of the present invention can allow the production of complex three-dimensional micro-devices on contoured surfaces through the use of a flexible cavity mold insert.
One activity of such a process can be the creation of a planar laminated mold (stack lamination), which can define the surface or 3-dimensional structures. A second mold (derived mold) can be produced from the lamination using a flexible molding material such as silicone RTV. The derived mold can be produced having a thin backing or membrane layer, which can act as a substrate for the 3-dimensional surface or features. The membrane then can be mechanically attached to the contoured surface of a mold insert, which can define the casting's final shape with the incorporated 3-dimensional features or surface.
Because a mold can be derived from a series of previous molds, any derived mold can be considered to be descended from each mold in that series. Thus, a given derived mold can have a “parent” mold, and potentially a “grandparent” mold, etc. Likewise, from a stack lamination can descend a first derived, descendant, or child mold, from which a second derived, descendent, or grandchild mold can be descended, and so forth. Thus, as used herein to describe the relationship between molds and castings, the root verbs “derive” and “descend” are considered to be synonymous.
As an example, FIG. 17 is a top view of a planar laminated mold 17010 having an array of openings 17020 . FIG. 18 is a top view of a flexible casting or mold insert 18010 molded using laminated mold 17010 . Flexible mold insert 18010 has an array of appendages 18020 corresponding to the array of openings 17020 , and a backing layer 18030 of a controlled predetermined thickness.
FIG. 19 is a top view of a mold fixture 19010 having an outer diameter 19020 and an inner diameter 19030 . Placed around a cylinder or mandrel 19040 within mold fixture 19010 is flexible mold insert 18010 , defining a pour region 19050 .
Upon filling pour region 19050 , a casting is formed that defines a cylindrical tube having a pattern of cavities accessible from its inner diameter and corresponding to and formed by the array of appendages 18020 of flexible mold insert 18010 .
As another example, FIG. 20 is a top view of a planar laminated mold 20010 having an array of openings 20020 . FIG. 21 is a top view of a flexible casting or mold insert 21010 molded using laminated mold 20010 . Flexible mold insert 21010 has an array of appendages 21020 corresponding to the array of openings 20020 , and a backing layer 21030 of a controlled predetermined thickness.
FIG. 22 is a top view of a mold fixture 22010 having an outer diameter 22020 and an inner diameter 22030 . Placed around the inside diameter 22030 within mold fixture 22010 is flexible mold insert 21010 , defining a pour region 22050 .
Upon filling pour region 22050 , a casting is formed that defines a cylindrical tube having a pattern of cavities accessible from its outer diameter and corresponding to and formed by the array of appendages 21020 of flexible mold insert 21010 .
Through these and related approaches, the 3-dimensional structure or surface can be built-up at the planar stage, and can be compensated for any distortions caused by forming the membrane to the contoured surface. The fabrication of the laminated mold can use specific or combined micro-machining techniques for producing the layers that define the aspect-ratio and 3-dimensional geometry. Micro-surfaces and/or structures can be transferred to many contours and/or shapes. For example, micro-patterns can be transferred to the inside and/or outside diameter of cylinders or tubes. Specific examples demonstrating the capabilities of this method are provided later in this document.
Cavity Inserts
The term mold insert is used herein to describe a micro-machined pattern that is used for molding and/or fabrication of a cast micro-device, part, and/or item. The laminated or derived mold described in this document also can be considered a mold insert. Cavity inserts are described here as a subset of a mold insert. Cavity inserts are objects and/or assemblies that can be placed within a cavity section of a mold but that do not take up the entire cavity space, and that provide further features to a 3-dimensional mold.
As an example, FIG. 23 is a perspective view of a laminated mold 23010 having an array of cylindrical cavities 23020 , each extending from top to bottom of mold 23010 . FIG. 24 is a close-up perspective view of a single cylindrical cavity 23020 of mold 23010 . Suspended and extending within cavity 23020 are a number of cavity inserts 23030 . FIG. 25 is a perspective view of a cast part 25010 having numerous cavities 25020 formed by cavity inserts 23030 .
A cavity insert can also be produced using certain embodiments of the present invention. This is further explained later in the section on non-planar molds. An insert can be a portion of a mold in the sense that the insert will be removed from the cast product to leave a space having a predetermined shape within the product. An insert alternatively can become part of a final molded product. For instance, if it is desirable to have a composite end product, then a process can be engineered to leave an insert in place in the final molded product.
As an example of a cavity insert, a 3-dimensional mold insert can be produced using one or more embodiments of the present invention, the insert having an array of cavities that are through-diameters. The cast part derived from this mold can reverse the cavities of the mold as solid diameters having the shape, size and height defined by the mold. To further enhance functionality, cavity inserts can be added to the mold before the final casting is produced. In this case, the cavity insert can be a wire formed in the shape of a spring. The spring can have the physical dimensions required to fit within a cavity opening of the mold, and can be held in position with a secondary fixture scheme. The spring-shaped cavity insert can be removed from the cast part after the final casting process is completed. Thus, the cavity section of the mold can define the solid shape of the casting while the cavity insert can form a channel through the solid body in the shape and width of the insert (the spring). The cavity can serve as, for example, a reservoir and/or a fluid flow restrictor.
The examples given above demonstrate the basic principle of a cavity insert. Additional design and fabrication advances can be realized by using this method to create cavity inserts. For example, photo-chemical-machining can be used to create a mold that has larger cavity openings, while reactive-ion-etching can be used to create finer features on a cavity insert.
Fabricating the Laminated Mold
Certain exemplary embodiments of the present invention can involve the fabrication of a laminated mold which is used directly and/or as an intermediate mold in one or more subsequent casting and/or molding processes.
FIG. 26 is a block diagram illustrating various devices formed during an exemplary method 26000 for fabricating a laminated mold having micro-machined layers that can be patterned and/or etched, and stacked to create a 3-dimensional mold. The laminated mold can be produced as a negative or positive replication of the desired finished casting. For the purpose of creating a laminated mold, any of three elements can be implemented:
1) creating a lithographic mask 26010 defining the features of each unique layer, 2) using lithographic micro-machining techniques and/or micro-machining techniques to produce patterned layers 26020 , and/or 3) aligning, stacking, and/or laminating the patterned layers into a stack 26030 in order to achieve the desired 3-dimensional cavity shape, aspect ratios, and/or mold parameters desired for a laminated mold 26040 .
Lithographic Techniques
Using lithography as a basis for layer fabrication, parts and/or features can be designed as diameters, squares, rectangles, hexagons, and/or any other shape and/or combination of shapes. The combinations of any number of shapes can result in non-redundant design arrays (i.e. patterns in which not all shapes, sizes, and/or spacings are identical, as shown in FIG. 10 ). Lithographic features can represent solid or through aspects of the final part. Such feature designs can be useful for fabricating micro-structures, surfaces, and/or any other structure that can employ a redundant and/or non-redundant design for certain micro-structural aspects. Large area, dense arrays can be produced through the lithographic process, thereby enabling creation of devices with sub-features and/or the repeatable production of multiple devices in a batch format. Note that such repeatable batch production can occur without substantial degradation of the mold.
Lithography can also allow the creation of very accurate feature tolerances since those features can be derived from a potentially high-resolution photographic mask. The tolerance accuracy can include line-width resolution and/or positional accuracy of the plotted features over the desired area. In certain embodiments, such tolerance accuracy can enable micro-scale fabrication and/or accurate integration of created micro-mechanical devices with microelectronics.
Photographic masks can assist with achieving high accuracy when chemical or ion-etched, or deposition-processed layers are being used to form a laminated mold through stack lamination. Because dimensional changes can occur during the final casting process in a mold, compensation factors can be engineered at the photo-mask stage, which can be transferred into the mold design and fabrication. These compensation factors can help achieve needed accuracy and predictability throughout the molding and casting process.
Photographic masks can have a wide range of potential feature sizes and positional accuracies. For example, when using an IGI Maskwrite 800 photoplotter, an active plotting area of 22.8×31.5 inches, minimum feature size of 5 microns, and positional accuracy of +−1 micron within a 15×15 inch area is possible. Using higher resolution lithographic systems for mask generation, such as those employed for electron beam lithography, feature sizes as small as 0.25 microns are achievable, with positional tolerances similar to the Maskwrite plotter, within an area of 6×6 inches.
Layer Machining and Material Options
Another aspect to fabricating the laminated mold can be the particular technique or techniques used to machine or mill-out the features or patterns from the layer material. In certain embodiments, combining lithographic imaging and micro-machining techniques can improve the design and fabrication of high-aspect-ratio, 3-dimensional structures. Some of the micro machining techniques that can be used to fabricate layers for a laminated mold include photo-etching, laser machining, reactive ion etching, electroplating, vapor deposition, bulk micro-machining, surface micro-machining, and/or conventional machining.
In certain exemplary embodiments, a laminated mold need only embody the mechanical features (e.g., size, shape, thickness, etc.) of the final casting. That is, it does not have to embody the specific functional properties (i.e. density, conductivity) that are desired to fulfill the application of the final casting. This means that any suitable techniques or materials can be used to produce the layers of the mold.
Thus, there can be a wide variety of material and fabrication options, which can allow for a wide variety of engineered features of a layer, laminated mold, and/or derived mold. For instance, although photo-chemical machining can be limited to metallic foils, by using laser machining or reactive ion etching, the choice of materials can become greatly expanded. With regard to laser machining, Resonetics, Inc. of Nashua, N.H. commercially provides laser machining services and systems. For laser machining, a very wide range of materials can be processed using UV and infra-red laser sources. These materials include ceramics, metals, plastics, polymers, and/or inorganics. Laser micro-machining processes also can extend the limits of chemical machining with regards to feature size and/or accuracy. With little or no restriction on feature geometry, sizes on the order of 2 microns can be achievable using laser machining.
When a wide variety of materials are available for making the laminated mold, process-compatibility issues can be resolved when choosing the material from which to create the mold. An example of this would be to match the thermal properties of casting materials with those of the laminated mold, in instances where elevated temperatures are needed in the casting or molding process. Also the de-molding properties of the mold and/or casting material can be relevant to the survival of the mold. This, for example, might lead one to laser-machine the layers from a material such as Teflon, instead of a metal. The laser machining process could be compatible with the Teflon and the Teflon could have greater de-molding capabilities than a metallic stack lamination.
In certain exemplary embodiments of the present invention, only a single laminated stack is needed to produce molds or castings. Also, in certain exemplary embodiments of the present invention, molds and/or castings can be produced without the need for a clean-room processing environment.
For certain exemplary embodiments of the present invention, the ability to create a single laminated mold and then cast the final parts can allow for using much thinner foils or advanced etching methods for producing the individual layers. Since feature size can be limited by the thickness of each foil, using thinner foils can allow finer features to be etched.
Certain exemplary embodiments of the present invention can combine various micro-machining techniques to create layers that have very specific functional features that can be placed in predetermined locations along the Z-axis of the mold assembly. For example, photo-chemical-machining can be used to provide larger features and high resolution ion-etching for finer features.
Various methods, as described above, can be used to produce layers for a laminated mold. The following examples are given to demonstrate dimensional feature resolution, positional accuracy, and/or feature accuracy of the layers.
Ion etching: when using a Commonwealth Scientific Millitron 8000 etching system, for example, a uniform etch area of 18 inches by 18 inches is achievable. Feature widths from 0.5 microns and above are attainable, depending on the lithographic masks and imaging techniques used. A feature, for example a 5 micron wide slot, etched to a depth of 10 microns can be etched to a tolerance of +−1.25 microns in width, and +−0.1 microns in depth. The positional tolerance of features would be the same as those produced on the lithographic masks.
Photo-chemical-machining: when using an Attotech XL 547 etching system, for example, a uniform etch area of 20 inches by 25 inches is achievable. Etched through-feature widths from 20 microns and above are attainable, with solid features widths of 15 microns and above also being attainable. A feature, for example a 30 micron diameter etched through 25 microns of copper, can be etched to a tolerance of +−2.5 microns or 10% of the foil thickness. The positional tolerance of such features would be the same as those produced on the lithographic masks.
Laser micromachining: when using a PIVOTAL laser micromachining system, for example, a uniform machining area of 3 inches by 3 inches is achievable. Machined through-feature sizes from 5 microns and above are attainable. A feature, for example a 5 micron wide slit machined through 25 microns of stainless steel, can be machined to a tolerance of +−1 micron. Positional tolerance of +−3 microns is achievable over the 3 inch by 3 inch area.
Electro-forming: depending on the size limitations of the photographic masks used for this process, electro-forming over areas as large as 60 inches by 60 inches is attainable. Electro-formed layers having thickness of 2 microns to 100 microns is achievable. A feature, for example a 5 micron wide slit, 15 microns deep, can be formed to a tolerance of +−1 micron. Positional tolerance of features would be the same as those produced on the lithographic masks.
Layer Assembly and Lamination
As described above, in certain exemplary embodiments of the present invention, layers can be designed and produced so that feature shape and placement from layer to layer define the desired geometry along the X-, Y-, and/or Z-axes of a mold. The total number (and thickness) of layers in the assembly can define the overall height and aspect ratio of the feature. A feature can be either the solid shape or the space between given structural components.
What follows are several exemplary methods of bonding the layers together to form the laminated mold. One exemplary method used to bond layers together is a metal-to-metal brazing technique. This technique can provide a durable mold that can survive high volume production casting and/or can provide efficient release properties from the castings. Prior to assembly, the layers can have 0.00003 inches of a eutectic braze alloy deposited on the top and bottom surfaces of the layers, using standard electro-plating techniques. An example of a braze material is CuSil™, which is comprised of copper and silver, with the percentage of each being variable for specific applications. CuSil™ can be designed specifically to lower the temperatures needed to flow the alloy during the brazing process.
One of the potential concerns during the laminating process is to maintain accurate registration of the assembly layers, and/or control the movement of the layers and the bonding fixture when brought to the elevated temperatures needed to flow the braze material. Several methods can be used to achieve this registration and/or control. The first can involve the practice of having two or more alignment features on the layers. FIG. 27 is a perspective view of a plurality of exemplary layers 27000 . As illustrated in FIG. 27 , one such alignment feature can be a diameter 27010 , and the other alignment feature can be an elongated slot 27020 . The slot and the diameter can be positioned on each layer one hundred eighty degrees opposed, for example, and can be parallel in orientation with the grain and/or perpendicular to the plane of the layer material.
FIG. 28 is a perspective view of an exemplary laminating fixture 28000 , which can be fabricated from graphite, for example, and can have two graphite diameter pins 28010 that can be fixed to the lamination fixture at the same distance apart as the diameter 27010 and slot 27020 on the etched layers 27000 . The layers can be placed over the pins 28010 so that each layer is orientated accurately to the layer below, using the slot and diameter to align each layer. Alternatively, two or more diameters can be provided on the layers 27000 , each of which corresponds to a pin of laminating fixture 28000 .
During the brazing process, the layered assembly can be heated in a hydrogen atmosphere to a temperature of 825 degrees Celsius, which can cause the CuSil™ braze to flow. As the temperatures elevate, the layers and the fixture material can expand. The slotted alignment feature 27020 can allow the fixture 28000 material to expand or move at a dissimilar rate than the layers, by the presence of the elongated slot on the layer 27000 . The slot 27020 can be greater in length than the diameter of pin 28010 in the fixture. The additional length of the slot can be determined by the different coefficient for expansion between the graphite and the assembly layers.
Other methods for maintaining the layer alignment during a heated bonding process can include fabricating the bonding fixture from the same material as the assembly layers, which can thus limit the dissimilar movement of the layers and fixture. The alignment and bonding fixture can also be made so that the alignment pins fit nearly perfectly to alignment features on the layers, but the pins in the fixture are allowed to float while being held perpendicular to the face of the alignment fixture.
In order to minimize positional errors when bonding layers (stacking errors), tolerances on certain features can be controlled. Referring to FIG. 27 , the positional accuracy of features 27010 and 27020 can be controlled by the photographic masks used to produce the layers (exemplary tolerances for masks are provided in the section titled “Lithographic Techniques”, above). The geometric size and tolerance of features 27010 and 27020 can be governed by the layer thickness and/or micromachining method used to produce them (exemplary tolerances for various micromachining techniques are provided in the section titled “Layer Machining and Material Options”, above).
When producing a laminated mold, numerous factors can be an influence on the overall tolerances of the features of the mold and/or the casting. For example, when using a stacking fixture, any of the laminating fixture's surface flatness, the laminating fixture's perpendicularity, and the laminating fixture's parallelism can be an influence. Also, the dimensional tolerance of the alignment feature(s) of a layer and/or the positional tolerance of that feature(s) can be an influence. For example, if an alignment pin, protrusion, or other “male” feature will engage a corresponding hole, indentation, or “female” feature to assist in aligning two or more layers, the dimensional tolerance and/or vocational tolerance of male and/or female feature can be an influence on the overall tolerances.
For example, referring to FIG. 28 , bonding fixture 28000 can include alignment pins 28010 fitted into the top surface of fixture 28000 . In a particular experiment, through the use of a surface grinding process, followed by a planetary lapping and polishing process, the sides and top surface of bonding fixture 28000 were parallel and perpendicular to a tolerance of +−2 microns, with the top surface finish being optically flat to +−one half the wavelength of visible light (400 to 700 nanometers), or about 200 to 350 nanometers. The positional accuracy of the alignment pins and the machined diameters through fixture 28000 was +−5 microns, and the pins were perpendicular to the surface of the fixture to +−2 microns, measured at a pin height of 2 to 5 millimeters. The surface of the described fixture measured 6×6 inches, and was produced using an SIP 5000 . Swiss jig boring milling center. Hardened steel alignment pins, having a diameter of 0.092 inches, were precisely ground to a tolerance of +−1.25 microns using a standard grinding operation.
The process of laminating the layers can include placing the processed layers over the alignment pins until the desired number of layers have been assembled. The assembled layers and fixture then can be placed in a brazing furnace with uniform weight applied to the top of the fixture. The furnace temperature can be raised to a temperature of 825 degrees Celsius, in a hydrogen atmosphere (a vacuum atmosphere has also been shown to work) for 45 minutes. This temperature can be sufficient to allow the braze material to uniformly flow and connect the layers together at all contact points. The fixture then can be cooled in the hydrogen atmosphere for 2 hours and removed for disassembly. The graphite pins can be removed, freeing the bonded structure from the lamination fixture.
The brazed lamination now can be ready for the final process step, which can be to coat the entire assembly with a hard nickel surface. The nickel coating can be applied to the laminated assembly using electro-plating techniques, which can deposits 0.0001 inches of nickel. The nickel-plated surface can act as an interface material that can enhance the release and durability properties of the assembled mold.
Another exemplary method that can be used to bond layers can make use of a thermo-cured epoxy rather than metal-to-metal brazing. Prior to assembly, the layers can be coated with an epoxy, MAGNA-TAC® model E645, diluted 22:1 with acetone. The thinned epoxy can be applied to the top and bottom surfaces of the layers using a standard atomizing spray gun. The layers can be spray coated in such a way that the coverage of the epoxy will bond the layers without filling the micro-machined features. A dot coverage of 50% has shown to work. The parameters for dilution and coverage can be provided by the epoxy manufacture, such as the Beacon Chemical Company.
The layers then can be assembled to a bonding fixture using, for example, the same technique described in the braze process. The assembled fixture then can be placed in a heated platen press, such as a Carver model # 4122 . The assembled layers and fixture can be compressed to 40 pounds per square inch and held at a temperature of 350 degrees F. for 3 hours, and allowed to cool to room temperature under constant pressure. The assembly then can be removed from the fixture using, for example, the same technique used for the brazed assembly.
In certain embodiments, the technique described in the second example can be considerably less expensive and time consuming than that used for the first. Using the epoxy process, savings can be realized due to the cost of the plating and the additional requirement imposed by the hydrogen braze process compared to epoxy stack laminating. The master derived from the first example can provide more efficient de-molding properties and also can survive a greater number of castings than the epoxy bonded mold. The epoxy-bonded mold can demonstrate a cost effective alternative to brazing and can be used for prototyping or when smaller production quantities are required.
Casting and Molding Process
Exemplary embodiments of the present invention can involve the creation of a high-resolution casting mold, having high-aspect-ratio, as well as 3-dimensional features and shapes. A precision stack lamination, comprised of micro-machined layers, can be used as a laminated mold. The laminated mold can be used to produce advanced micro-devices and structures (a.k.a., “micro-electro-mechanical structures” and “MEMS”) and/or can be used to create second (or greater) generation derived molds.
The following paragraphs describe the casting process in terms of the materials, fixtures, and/or methods that can be used to produce second-generation molds and final castings.
Mold Duplication and Replication
For certain exemplary embodiments of the present invention, the process options for producing molds and cast parts can be numerable. For example, molds can be made as negative 4010 or positive 4020 replications of the desired cast part as shown in FIG. 4 . If the mold is made as a positive, a second-generation mold can be created. If the mold is made as a negative, the final part can be cast directly from the mold.
For certain exemplary embodiments of the present invention, the process used to create the layers for the laminated mold can be a determining factor. For example, some production situations can require a second-(or even third) generation derived version of the laminated mold.
In certain situations, process parameters can be greatly enhanced by combining molding and casting materials having certain predetermined values for physical properties such as durometer, elasticity, etc. For example, if the cast part is extremely rigid, with poor release properties, a second-generation consumable mold can be used to create the final casting. Further specific examples of this practice, and how they relate to 3-dimensional micro-fabrication are described later in this document.
Feature size and positional accuracy for molds and produced parts can be compensated for at the layer production stage of the process. For example, known material properties such as thermal expansion or shrinkage can be accurately accounted for due to, for example, the accuracy levels of the photographic masks and/or laser machining used to produce mold layers. Feature resolution, using various mold making and casting materials, can be accurately replicated for features having a size of 1 micron and greater. Surface finishes have also been reproduced and accurately replicated. For example, layers have been used to form a laminated mold which was used to produce a derived silicone RTV mold. The surface finish of a 0.0015 inch thick stainless steel layer (specified finish as 8-10 micro inches RA max) and a 0.002 inch thick copper layer (specified finish as 8-20 micro inches RA max) were easily identified on the molded surfaces of the derived RTV mold. The surfaces were observed at 400× magnification using a Nikon MM11 measuring scope. The same surface finishes were also easily identified when cast parts were produced from the derived mold using a casting alloy CERROBASE™. Very smooth surface finishes, such as those found on glass, have also been reproduced in molds and castings.
Materials for Molds and Castings
For certain exemplary embodiments of the present invention, there can be hundreds, if not thousands of material options for mold making and casting. Described below are some potential considerations regarding the selection of mold and casting materials that can meet the requirements of, for instance, 3-dimensional MEMS.
To insure the accuracy and repeatability of certain cast micro-devices, the casting material can have the capability to resolve the fine 3-dimensional feature geometries of the laminated mold. Typical dimensions of MEMS can range from microns to millimeters. Other structures having micro features can have much larger dimensions.
For certain embodiments, the mold's cavity geometry can influence the release properties between the mold and the casting, thereby potentially implicating the flexibility (and/or measured durometer) of the materials used. Other material compatibility issues also can be considered when using a casting process.
Certain exemplary embodiments of a process of the present invention have been developed in order to enable the production of 3-dimensional micro-structures from a wide range of materials, tailored to specific applications. The ability to use various materials for molds and castings can greatly expand the product possibilities using this technique.
One material that has been successfully used for creating castings from a laminated mold is an elastomeric product, referred to generally as RTV silicone rubber, although other materials could also be successful depending on process or product requirements. A wide range of silicone-based materials designed for various casting applications are commercially available through the Dow Corning Corporation of Midland, Mich. For example, the Silastic® brand products have proven successful, possibly because of their resolution capability, release characteristics, flexibility, durability, and/or the fact that they work in a wide range of process temperatures.
Although other types of silicone rubber products could be used, each of the Dow Corning Silastic® brand products that have been used consists of two components; a liquid silicone rubber and a catalyst or curing agent. Of the Dow Corning Silastic® brand products, there are two basic curing types: condensation, and addition cure. The two types can allow for a range of variations in material viscosities and cure times. The three primary products used in the earliest tests are Silastic® J RTV Silicone Rubber, Silastic® M RTV Silicone Rubber, and Silastic® S RTV Silicone Rubber. Product specifications are provided in several of the examples at the end of this document.
The Dow Corning Silastic® products used thus far have similar specifications regarding shrinkage, which increases from nil up to 0.3 percent if the silicone casting is vulcanized. Vulcanization can be accomplished by heating the silicone to a specific elevated temperature (above the casting temperature) for a period of 2 hours. Vulcanizing can be particularly useful when the casting is to be used as a regenerated mold, and will be subjected to multiple castings.
In addition to RTV silicone rubber, urethanes and other materials also have properties that can be desirable for laminated molds, derived molds, and/or castings, depending on the specific requirement. For example, when producing certain 3-dimensional micro-structures with extreme aspect ratios, very fine features, or extreme under-cuts, de-molding can be difficult. In certain situations, the rigidity of the mold also can be relevant, especially in certain cases where mold features have high-aspect ratios. For example, the practice of sacrificing or dissolving laminated second or third generation molds can be used when castings require very rigid molds, and/or where the de-molding of castings becomes impossible.
There are several families of materials that can be used for producing laminated molds, derived molds, and/or final cast devices including, for example:
Acrylics: such as, for example, PMMA acrylic powder, resins, and/or composites, as well as methacrylates such as butyl, lauryl, stearyl, isobutyl, hydroxethyl, hydroxpropyl, glycidyl and/or ethyl, etc. Plastic polymerics: such as, for example, ABS, acetyl, acrylic, alkyd, flourothermoplastic, liquid crystal polymer, styrene acrylonitrile, polybutylene terephthalate, thermoplastic elastomer, polyketone, polypropylene, polyethylene, polystyrene, PVC, polyester, polyurethane, thermoplastic rubber, and/or polyamide, etc. Thermo-set plastics: such as, for example, phenolic, vinyl ester, urea, and/or amelamine, etc. Rubber: such as, for example, elastomer, natural rubber, nitrile rubber, silicone rubber, acrylic rubber, neoprene, butyl rubber, flurosilicone, TFE, SBR, and/or styrene butadiene, etc. Ceramics: such as, for example, silicon carbide, alumina, silicon carbide, zirconium oxide, and/or fused silica, calcium sulfate, luminescent optical ceramics, bio-ceramics, and/or plaster, etc. Alloys: such as, for example, aluminum, copper, bronze, brass, cadmium, chromium, gold, iron, lead, palladium, silver, sterling, stainless, zinc platinum, titanium, magnesium, anatomy, bismuth, nickel, and/or tin, etc. Wax: such as, for example, injection wax, and/or plastic injection wax, etc.
There can be many material options within these groups that can be utilized when employing certain embodiments of the present invention. For example, in certain embodiments, metals and metal alloys can be primarily used as structural materials of final devices, but also can add to function. Exemplary functional properties of metals and/or alloys can include conductivity, magnetism, and/or shape memory.
Polymers also can be used as structural and/or functional materials for micro-devices. Exemplary functional properties can include elasticity, optical, bio-compatibility, and/or chemical resistivity, to name a few. Materials having dual (or more) functionality, often referred to as engineered “smart” materials, could be incorporated into a final molded product or a mold. Additional functionality could utilize electrostatic, mechanical, thermal, fluidic, acoustic, magnetic, dynamic, and/or piezo-electric properties. Ceramics materials also can be used for applications where specialty requirements may be needed, such as certain high-temperature environments. Depending on the material that is chosen, there can be many alternative methods to solidify the casting material. The term “solidify” includes, but is not limited to, methods such as curing, vulcanizing, heat-treating, and/or chemically treating, etc.
Mold Fixtures, Planar and Contoured
For certain exemplary embodiments of the present invention, there can be a wide range of engineering options available when designing a casting mold. The casting process and geometry of the final product can determine certain details and features of the mold. Options can be available for filling and/or venting a mold, and/or for releasing the casting from the mold.
Two basic approaches have been used for demonstrating the certain exemplary methods for mold design and fabrication. These approaches can be categorized as using a single-piece open-face mold or a two-part closed mold.
In certain exemplary embodiments of the present invention, each of the mold types can include inserting, aligning, and assembling the laminated mold (or duplicate copy) in a fixture. The fixture can serve several purposes, including bounding and/or defining the area in which to pour the casting material, capturing the casting material during the curing process, allowing the escape of air and/or off-gases while the casting material is degassed, and/or enabling mechanical integration with the casting apparatus.
The fixture can be configured in such a way that all sides surrounding the mold insert are equal and common, in order to, for example, equalize and limit the effects of thermal or mechanical stresses put on the mold during the casting process. The mold fixture also can accommodate the de-molding of the casting.
Certain exemplary embodiments of this method can provide the ability to mold 3-dimensional structures and surfaces on contoured surfaces. The basic technique is described earlier in this document in the design parameter section. One element of the technique can be a flexible mold insert that can be fixed to a contoured surface as shown in FIGS. 19 and 22 . The mold insert can be made with a membrane or backing thickness that can allow for integration with various fixture schemes that can define the contoured shape.
For non-planar molds, the contour of the mold fixture can be produced by standard machining methods such as milling, grinding, and/or CNC machining, etc. The flexible mold insert can be attached to the surface of the mold using any of several methods. One such method is to epoxy bond the flexible insert to the fixture using an epoxy that can be applied with a uniform thickness, which can be thin enough to accommodate the mold design. Other parameters that can be considered when choosing the material to fix a membrane to a fixture include durability, material compatibility, and/or temperature compatibility, etc. A detailed description of a non-planar mold is given as an example further on.
Casting and Molding Processes
Various techniques can be used for injecting or filling cavity molds with casting materials, including injection molding, centrifugal casting, and/or vibration filling. An objective in any of these techniques can be to fill the cavity with the casting material in such a way that all of the air is forced out of the mold before the cast material has solidified. The method used for filling the cavity mold can depend on the geometry of the casting, the casting material, and/or the release properties of the mold and/or the cast part.
As has been described earlier, an open face mold, using flexible RTV rubber has been found to work effectively. In certain embodiments, an open face mold can eliminate the need for having carefully designed entrance sprue and venting ports. The open face mold can be configured to create an intermediate structure that can have a controlled backing thickness which can serve any of several purposes: 1) it can be an open cavity section in the casting mold which can serve as an entrance point in which to fill the mold; 2) it can serve as a degassing port for the air evacuation during the vacuum casting process; 3) it can create a backing to which the cast part or parts can be attached and/or which can be grasped to assist in de-molding the casting from the flexible mold.
In casting processes in which the casting material is heated, the mold temperature and the cooling of the casting can be carefully controlled. For example, when casting a lead casting alloy such as CERROBASE, the alloy can be held at a temperature of 285 degrees F., while the mold material can be preheated 25-30 degrees higher (310-315 degrees F.). The molten alloy can be poured and held at or above the melting point until it is placed in the vacuum environment. The mold then can be placed in a vacuum bell jar, and held in an atmosphere of 28 inches of mercury for 3-4 minutes. This can remove any air pockets from the molten metal before the alloy begins to solidify. As soon as the air has been evacuated, the mold can be immediately quenched or submersed in cold water to rapidly cool the molten metal. This can help minimize shrinkage of the cast metal.
In certain exemplary embodiments of the present invention, no vent holes or slots are provided in the mold, and instead, air can be evacuated from the mold prior to injection. In certain exemplary embodiments of the present invention, temperature variation and its effect on the micro-structure can be addressed via enhanced heating and cooling controls in or around the mold. In certain exemplary embodiments of the present invention, heat can be eliminated from the curing process by replacing the molding materials with photo-curing materials.
Some of the methods that can be used for micro-molding and casting include micro-injection molding, powder injection molding, metal injection molding, photo molding, hot embossing, micro-transfer molding, jet molding, pressure casting, vacuum casting, and/or spin casting, etc. Any of these methods can make use of a laminated or derived mold produced using this method.
De-Molding and Finish Machining
A controlled backing thickness can be incorporated into the casting to create an intermediate structure. One purpose of the intermediate can be to create a rigid substrate or backing, that allows the casting to be grasped for removal from the mold without distorting the casting. The thickness of the backing can be inversely related to the geometry of the pattern or features being cast. For example, fine grid patterns can require a thicker backing while coarse patterns can have a thinner backing. The backing can be designed to have a shape and thickness that can be used to efficiently grasp and/or pull the cast part from the mold.
Following de-molding, the intermediate can be machined to remove the backing from the casting. Because the thickness of the backing can be closely controlled, the backing can be removed from the cast structure by using various precision machining processes. These processes can include wire and electrode EDM (electrode discharge machining), surface grinding, lapping, and/or fly cutting etc.
In instances where extremely fine, fragile patterns have been cast, a dissolvable filler or potting material can be poured and cured in the cast structure prior to the removal of the backing from the grid. The filler can be used to stabilize the casting features and eliminate possible damage caused by the machining process. The filler can be removed after machining-off the backing. A machinable wax has been found to be effective for filling, machining, and dissolving from the casting.
In some part designs, de-molding the casting from the mold might not be possible, due to extreme draft angles or extremely fine features. In these cases, the mold can remain intact with the cast part or can be sacrificed by dissolving the mold from casting.
EXAMPLES
A wide range of three-dimensional micro-devices can be fabricated through the use of one or more embodiments of various fabrication processes of the present invention, as demonstrated in some of the following examples.
Example 1
Sub-Millimeter Feedhorn Array
This example demonstrates fabrication of an array of complex 3-dimensional cavity features having high aspect ratio. This example makes use of a second-generation derived mold for producing the final part, which is an array of sub-millimeter feedhorns. A feedhorn is a type of antenna that can be used to transmit or receive electromagnetic signals in the microwave and millimeter-wave portion of the spectrum. At higher frequencies (shorter wavelengths) the dimensions can become very small (millimeters and sub-millimeter) and fabrication can become difficult.
Using certain exemplary embodiments of the present invention, a single horn, an array of hundreds or thousands of identical horns, and/or an array of hundreds or thousands of different horns can be fabricated.
FIG. 29 is a top view of stack lamination mold 29000 that defines an array of cavities 29010 for fabricating feedhorns. FIG. 30 is a cross-section of a cavity 29010 taken along section lines 30 - 30 of FIG. 29 . As shown, cavity 29010 is corrugated, having alternating cavity slots 30010 separated by mold ridges 30020 of decreasing dimensions, that can be held to close tolerances.
In an exemplary embodiment, an array of feedhorns contains one thousand twenty identical corrugated feedhorns, each designed to operate at 500 GHz, and the overall dimensions of the feed horn array are 98 millimeters wide by 91 millimeters high by 7.6 millimeters deep. The fabrication of this exemplary array can begin with the creation of a laminated mold, comprised of micro-machined layers, and assembled into a precision stack lamination.
Step 1: Creating the laminated mold: The laminated mold in this example was made of 100 layers of 0.003″ thick beryllium copper (BeCu) sheets that were chemically etched and then laminated together using an epoxy bonding process. Infinite Graphics, Inc. of Minneapolis, Minn. was contracted to produce the photo-masks needed for etching the layers. The masks were configured with one thousand twenty diameters having a center-to-center spacing of 2.5 millimeters. An IGI Lazerwrite photo plotter was used to create the masks, which were plotted on silver halite emulsion film. The plotter resolution accuracy was certified to 0.5 micrometers and pattern positional accuracy of plus or minus 0.40 micrometers per lineal inch. The layers were designed so that horn diameters were different from layer to layer, so that when the layers were assembled, the layers achieved the desired cross-section taper, slot, and ridge features shown in simplified form in FIG. 30 . A total of 100 layers were used to create a stacked assembly 7.6 millimeters thick. The layers were processed by Tech Etch, Inc. of Plymouth, Mass., using standard photo-etching techniques and were etched in such a way that the cross-sectional shape of the etched walls for each layer are perpendicular to the top and bottom surfaces of the layer (commonly referred to as straight sidewalls).
In this example, the method chosen to bond the etched layers together used a thermo-cured epoxy (MAGNA-TAC model E645), using the process and fixturing described earlier in the section on layer assembly and lamination. The assembled fixture was then placed in a 12 inch×12 inch heated platen press, Carver model No. 4122. The fixture was compressed to 40 pounds per square inch and held at a temperature of 350 degrees F. for 3 hours, then allowed to cool to room temperature under constant pressure. The assembly was then removed from the fixture and the alignment pins removed, leaving the bonded stack lamination. The laminated mold (stack lamination) was then used to produce the final casting mold.
Step 2: Creating the casting mold: The second step of the process was the assembly of the final casting mold, which used the precision stack lamination made during step 1 as a laminated mold. The casting mold created was a negative version of the lamination, as shown in perspective view for a single feed horn 31000 in FIG. 31 . Also shown is a feedhorn ridge 31010 that can correspond to a cavity slot 30010 , and a feedhorn base 31020 .
For this example, Silastic® J RTV Silicone Rubber was used to make the final casting mold. This product was chosen because it is flexible enough to allow easy release from the laminated mold without damaging the undercut slots and rings inside the feedhorns, and because of its high-resolution capability. Described below are the product specifications.
Silastic ® J:
Durometer Hardness:
56 Shore A points
Tensile Strength, psi:
900
Linear Coefficient of Thermal Expansion:
6.2 × 10 −4
Cure Time at 25 C.:
24 hours
The Silastic® J Silicone RTV was prepared in accordance with the manufacturer's recommendations. This included mixing the silicone and the curing agent and evacuating air (degassing) from the material prior to filling the mold-making fixture. At the time the example was prepared, the most effective way of degassing the Silicone prior to filling the mold fixture was to mix the two parts of the Silicone and place them in a bell jar and evacuate the air using a dual stage vacuum pump. The material was pumped down to an atmosphere of 28 inches of mercury and held for 5 minutes beyond the break point of the material. The Silicone was then ready to pour into the mold fixture.
As shown in the side view of FIG. 32 , an open-face fixture 32000 was prepared, the fixture having a precision-machined aluminum ring 32010 , precision ground glass plate 32030 , rubber gaskets 32040 , 32050 and the laminated mold 32060 . The base 32020 of the fixture was thick Plexiglas. On top of the Plexiglas base was a glass substrate 32030 . Rubber gasket 32040 separated the glass base and the glass substrate. An additional rubber gasket 32050 was placed on the top surface of the glass substrate 32030 and the laminated mold 32060 was placed on the top gasket. The rubber gaskets were used to prevent unwanted flashing of material during casting. A precision-machined aluminum ring 32010 was placed over the laminated mold subassembly and interfaced with the lower rubber gasket 32040 .
Generally, the height of the ring and dimensions of the above pieces can depend upon the dimensions of the specific structure to be cast. The ring portion 32010 of the fixture assembly served several purposes, including bounding and defining the area in which to pour mold material, capturing the material during the curing process, and providing an air escape while the mold material was degassed using vacuum. The fixture was configured in a way that all sides surrounding the laminated mold 32060 were equal and common, in order to equalize and limit the effects of thermal or mechanical stresses put on the lamination from, the mold material.
An open-face mold was used for this example. The mold insert and molding fixture were assembled and filled with the silicone RTV, then the air was evacuated again using a bell jar and vacuum pump in an atmosphere of 28 inches of mercury. After allowing sufficient time for the air to be removed from the silicone, the mold was then heat-cured by placing it in a furnace heated to and held at a constant temperature of 70 degrees F. for 16 hours prior to separating the laminated mold from the derived RTV mold. The molding fixture was then prepared for disassembly, taking care to remove the laminated mold from the RTV mold without damaging the lamination, since the lamination can be used multiple times to create additional RTV molds.
The resulting RTV mold was a negative version of the entire feedhorn array consisting of an array of one thousand twenty negative feedhorns, similar to the simplified single horn 31010 shown in perspective view in FIG. 31 .
Step 3: Casting the feedhorn array: In this example, the cast feedhorn arrays were made of a silver loaded epoxy, which is electrically conductive. In certain exemplary embodiments of the present invention, binders and/or metallic (or other) powders can be combined and/or engineered to satisfy specific application and/or process specifications. The conductive epoxy chosen for this example provided the electrical conductivity needed to integrate the feedhorn array with an electronic infrared detector array.
The conductive epoxy was purchased from the company BONDLINE™ of San Jose, Calif., which designs and manufactures engineered epoxies using powdered metals. Certain of its composite metal epoxies can be cured at room temperature, have high shear strength, low coefficient of thermal expansion, and viscosities suited for high-resolution casting.
Exemplary embodiments of the present invention can utilize various techniques for injecting or filling cavity molds with casting materials. In this example, a pressure casting method was used.
The BONDLINE™ epoxy was supplied fully mixed and loaded with the silver metallic powder, in a semi-frozen state. The loaded epoxy was first normalized to room temperature and then pre-heated per the manufacturer's specification. In the pre-heated state the epoxy was uncured and ready to be cast. The uncured epoxy was then poured into the open-face mold to fill the entire mold cavity. The mold was then placed in a pressurized vessel with an applied pressure of 50 psi using dry nitrogen, and held for one hour, which provided sufficient time for the epoxy to cure. The mold was then removed from the pressure vessel and placed in an oven for 6 hours at 225 degrees F., which fully cured the conductive epoxy.
Step 4. Demolding and finish machining: After the cast epoxy had been cured, it was ready for disassembly and demolding from the casting fixture and mold. The mold material (RTV silicone) was chosen to be flexible enough to allow the cast feedhorn array to be removed from the casting mold without damaging the undercuts formed by the slots and ridges. When done carefully, the mold could be reused several times to make additional feedhorn arrays.
The backing thickness 31020 of the RTV mold shown in FIG. 31 came into play during the de-molding process. The backing was cast thick enough to allow easy grasping to assist with separating the casting mold from the cast piece. In this example, the RTV casting mold was flexible and allowed easy separation without damaging the undercut slots and rings inside the cast feedhorns.
Depending on the piece being cast, machining, coating, and/or other finish work can be desirable after de-molding. In this example, a final grinding operation was used on the top surface (pour side of the mold) of the feedhorn array because an open face mold was used. This final grinding operation could have been eliminated by using a closed, two-part mold.
Example 2
Individual Feedhorns Produced in a Batch Process
This example makes use of certain exemplary embodiments of the present invention to demonstrate the production of sub-millimeter feedhorns in a batch process. The example uses the same part design and fabrication process described in example 1, with several modifications detailed below.
Process Modifications: The process detailed in example 1 was used to produce an array of one thousand twenty feedhorns. The first modification to the process was the casting material used to produce the array. The casting material for this example was a two-part casting polymer sold through the Synair Corporation of Chattanooga, Tenn. Product model “Mark 15. Por-A-Kast” was used to cast the feedhorn array and was mixed and prepared per the manufacturer's specifications. The polymer was also cast using the pressure filling method described in example 1.
The next modification was a surface treatment applied to the cast polymer array. A conductive gold surface was deposited onto the polymer array in order to integrate the feedhorns with the detector electronics. The gold surface was applied in two stages. The first stage was the application of 0.5 microns of conduction gold, which was sputter-coated using standard vacuum deposition techniques. The first gold surface was used for a conductive surface to allow a second stage electro-deposition or plating of gold to be applied. The second gold plating was applied with a thickness of 2 microns using pure conductive gold.
The final modification was to dice or cut the feedhorns from the cast and plated array into individual feedhorns, that were then suitable for detector integration. A standard dicing saw, used for wafer cutting, was used to cut the feedhorns from the cast array.
Example 3
Array of 3-Dimensional Micro-Structures
Process steps 1 and 2 described in example 1 were used to produce a large area array of micro-structures, which are described as negatives of the feedhorn cavities, shown as a single feedhorn in FIG. 31 . The laminated mold and molding fixture was used to cast the micro-structures using Dow Corning's Silastic® M RTV Silicone Rubber. This product was chosen because it is flexible enough to release from the mold insert, without damaging the circular steps in the structure, but has the hardness needed to maintain the microstructures in a standing position after being released from the mold. Described below are the product specifications.
Silastic ® M
Durometer Hardness:
59 Shore A points
Tensile Strength, psi:
650
Linear Coefficient of Thermal Expansion:
6.2 × 10 −4
Cure Time at 25 C.:
16 hours
The Silicone RTV was prepared in accordance with the manufacturer's recommendations, using the process described earlier in example 1, step 2. The laminated mold and molding fixture were assembled and filled with the silicone RTV, using the process described earlier in example 1, step 2. The molding fixture was then prepared for disassembly, taking care to separate the mold insert from the cast silicone array. The resulting casting was an array consisting of one thousand twenty 3-dimensional micro-structures. The shape and dimension of a single structure is shown in simplified form in FIG. 31 .
Example # 4
Cylindrical Tubing with Micro-fluidic Channels on the Inside
Diameter
Certain exemplary embodiments of the present invention have been used to produce a 2.5 centimeter length of clear urethane tubing, having 3-dimensional micro-fluid channels on the inside diameter of the tubing. The fluidic tubing was produced using a flexible cavity insert with a controlled backing thickness. The following example demonstrates how the cavity insert can enable the production of three-dimensional features on the inside and outside diameters of cylindrical tubing.
Step 1: Creating the mold insert: The first step in the process was to fabricate the micro-machined layers used to produce the cavity insert. The cast tubing was 2.5 centimeters long, having a 3.0 millimeter outside diameter and a 2.0 millimeter inside diameter, with 50 three-dimensional micro-fluidic channels, equally spaced around the interior diameter of the tube. FIG. 33 shows a side view of the tubing 33000 , the wall of which defines numerous fluidic channels 33010 . Although each fluidic channel could have different dimensions, in this example each channel was 0.075 mm in diameter at the entrance of the channel from the tube, and each channel extended 0.075 mm deep. Each channel tapered to a diameter of 0.050 mm, the taper beginning 0.025 mm from the bottom of each channel.
Photo-chemical machining was used to fabricate the layers for the laminated mold. FIG. 34 is a top view of a such a laminated mold 34000 , which was created using several photo masks, one of which with a similar top view. Mold 34000 includes an array of fluidic channels 34010 In this particular experiment, the length of channels 34010 was approximately 25 millimeters, and the width of each collection of channels was approximately 6.6 millimeters.
FIG. 35 is a cross-section of mold 34000 taken at section lines 35 - 35 of FIG. 34 . To the cross-sectional shape of channel 34010 , a first copper foil 35010 having a thickness of 0.025 mm, and a second copper foil 35020 having a thickness of 0.050 mm, were chemically etched and then laminated together using a metal-to-metal brazing process. Each of the layers used in the laminated mold assembly used a separate photo-mask. The masks used for layer 35020 were configured with a 9.50×0.075 mm rectangular open slot, arrayed redundantly in 50 places, a portion of which are illustrated in FIG. 34 . To achieve the desired taper, two masks were used for layer 35010 . The bottom mask was configured with a 9.50×0.075 mm rectangular open slot and the top mask was configured with a 9.50×0.050 rectangular open slot, each of the slots were also redundantly arrayed in 50 places. The photo-masks were produced to the same specifications, by the same vendor as those described in example 1, step 1.
The layers were designed so that the slot placement was identical from layer to layer, which when assembled, produced the cross-sectional shape for the channels as shown in FIG. 35 . The final thickness of the lamination was specified at 0.083 millimeters, which required one 0.025 layer of copper foil, and one 0.050 thick layer of copper foil, leaving a total thickness amount of 0.002 millimeters for braze material on each side of each etched layer. The layers were photo-etched by the same vendor, and same sidewall condition as those described in example 1, step 1. The method chosen to bond the grid layers together was a metal-to-metal brazing technique described earlier, in detail as one of two exemplary methods of bonding layers together (eutectic braze alloy)
Step 2: Creating the flexible cavity insert: The next step of the process was to create a flexible cavity insert from the brazed layered assembly. FIG. 36 is a side view of cavity insert 36000 , which was produced from the brazed assembly with a backing 36010 having a thickness of 0.050 millimeters. The cavity insert 36000 was produced using Silastic® S RTV Silicone Rubber as the base material. The RTV Silicone Rubber was used because of its resolution capability, release properties, dimensional repeatability, and its flexibility to form the insert to a round pin that would be assembled to the final molding fixture. The material properties of Silastic® S are shown below.
Silastic ® S
Durometer Hardness:
26 Shore A points
Tensile Strength, psi:
1000
Linear Coefficient of Thermal Expansion:
6.2 × 10 −4
Cure Time at 25 C.:
24 hours
The casting fixture used to create the RTV cavity insert was similar to that shown in FIG. 32 and is described in detail in the prior examples. A modification was made to the fixture assembly, which was a top that was placed over the pour area of the mold fixture. This top was placed and located to close the mold after air evacuation and reduce the backing thickness 36010 of the RTV insert to a thickness of 0.050 millimeters, shown in FIG. 36 . The Silastic® S RTV Silicone Rubber used for the cavity insert fabrication was prepared in accordance with the manufacturers recommendations, using the process described earlier in example 1, step 2.
Step 3: Assembling the molding fixture: The final molding fixture was then ready to be assembled. The molding fixture included a base plate ( FIG. 37 ), the cavity inserts ( FIG. 38 ), and a top plate ( FIG. 40 ). FIG. 37 is a top view of the base plate 37000 , which was made from a 0.25 inch aluminum plate that was ground flat and machined using standard CNC machining techniques. The base had six machined diameters 37010 through the plate. These six diameters would accept the cavity insert pins described later. The plate also had machined diameters through the plate, which would accept dowel pins 37020 that were used to align and assemble the top plate and the base plate, as well as 4 bolt diameters 37030 to hold the top and bottom plates together.
FIG. 38 is a side view of an insert fixture 38000 , that includes the flexible cavity insert 36000 attached to a 3 centimeter long, 1.900 millimeter diameter steel pin 38010 . The pin 38010 was ground to the desired dimensions using standard machine grinding techniques. The RTV cavity insert 36000 was cut to the proper size before being attached to the pin. The RTV insert 36000 was attached to outside diameter of the pin 38010 using a controlled layer of two-part epoxy.
FIG. 39 is a side view of several insert fixtures 39000 that have been attached to a base plate 37000 . Each insert 36000 was attached its corresponding pin 38010 so that the end of pin 38010 could be assembled to a corresponding machined diameter 37010 of base plate 37000 without interference from insert 36000 . Once each insert 36000 was attached around the diameter of its corresponding pin 38010 and the pin placed in the corresponding through-diameter of base plate 37010 , the pin was held perpendicular to base plate 37000 and in alignment with a top plate of the fixture.
FIG. 40 is a top view of a top plate 40000 of the fixture, which was also fabricated of aluminum and machined using CNC techniques. There were six 3.0 millimeter diameters 40010 milled through the thickness of plate 40000 , which was 3.0 centimeters thick. Diameters 40010 defined the cavity areas of the mold that would be filled during the final casting process, and aligned to the pins assembled to the base plate. Also incorporated into the top plate were bolt features 40020 and dowel features 40030 needed to align and assemble the top plate 40000 to the base plate 37000 . The thickness of top plate 40000 was specified to slightly exceed the desired length of the final cast tubing, which was cut to its final length after casting. The casting fixture was then assembled, first by assembling the cavity insert 38000 to the base plate 37000 , followed by assembling the top plate 40000 to the base using bolts and dowels. The top view of a representative cavity section for an assembled fixture is shown in FIG. 19 .
Step 4: Casting the fluidic tubes: Several fluidic tubes were produced using the assembled casting fixture. A clear urethane was used for the final casting because of its high-resolution, low shrink factor, and transparent properties, which allowed for final inspection of the interior diameter features through the clear wall of the tube. The casting material was purchased from the Alumilite Corporation of Kalamazoo, Mich., under the product name Water Clear urethane casting system. The manufacturer described the cured properties as follows:
Hardness, Shore D:
82
Density (gm/cc)
1.04
Shrinkage (in/in/) maximum
0.005
Cure Time (150 degrees F.)
16
hr
The urethane was prepared in accordance with the manufacturer's recommendations. This included the mixing and evacuation of air (degassing) from the material prior to filling the mold. The most effective way found for degassing the urethane prior to filling the mold fixture was to mix parts A and B, place them in a bell jar, and evacuate the air using a dual stage vacuum pump. The mixture was pumped down to an atmosphere of 28 inches of mercury and held for 15 minutes beyond the break point of the material The urethane was then ready to pour into the mold fixture.
The assembled mold fixture was heated to 125 degrees F. prior to filling the cavities with the urethane. The pre-heating of the mold helped the urethane to flow and fill the cavities of the mold, and aided in the degassing process. The cavity sections of the mold were then filled with the urethane, and the air was evacuated again using a bell jar and vacuum pump in an atmosphere of 28 inches of mercury. After allowing sufficient time for the air to be removed from the urethane, the mold was then removed from the vacuum bell jar and placed in an oven. The mold was heated and held at a constant temperature of 150-180 degrees F. for 16 hours prior to separating the cast tubes from the mold. The molding fixture was then disassembled and the cast tubes were separated from the cavity inserts. The inserts were first removed from the base plate of the fixture. The tubes were easily separated from the cavity insert assembly due to the flexibility and release properties of the silicone RTV, combined with the hardness of the urethane tubes.
Example # 5
Tubing with Micro-fluidic Channels on the Outside Diameter
Example # 4 described the method used for producing cast urethane tubing with micro-fluidic features on the inside diameter of the tube. The current example demonstrates how that process can be altered to produce tubing with the micro-fluidic channels on the outside diameter of the tubing. This example uses a similar part design and the fabrication process described in example 4, with several modifications detailed below.
One process modification involved step 3, assembling the molding fixture. For this step, a modification was made to the fixture design that enabled the molded features to be similar to that shown in FIGS. 20-22 . The first modification was in the size of the machined diameters in the base plate and the top plate of the fixture described in example 4. The flexible RTV cavity insert that was attached to a pin in example 4 was instead attached to the inside diameters of the top fixture plate, similar to that shown in FIG. 22 . In order to accommodate the existing RTV cavity insert, the cavity diameters of the top plate were milled to a size of 1.900 millimeters. The RTV cavity insert was then attached to the milled diameter of the top plate using the same epoxy technique described in example 4. The base plate of the fixture was also modified to accept a 1.0 millimeter diameter pin, and was assembled similar to the that shown in FIG. 22 . The same casting process was used as described in example 4. After following the final casting process, with the altered molding fixture, the urethane tubes were produced having the same fluidic channels located on the outside diameter of the cast tube.
Additional Embodiments
X-Ray and Gamma-Ray Collimators, Grids, and Detector Arrays
Certain exemplary embodiments of the present invention can provide methods for fabricating grid structures having high-resolution and high-aspect ratio, which can be used for radiation collimators, scatter reduction grids, and/or detector array grids. Such devices can be used in the field of radiography to, for example, enhance image contrast and quality by filtering out and absorbing scattered radiation (sometimes referred to as “off-axis” radiation and/or “secondary” radiation).
Certain embodiments of such devices can be used in nearly every type of imaging, including astronomy, land imaging, medical imaging, magnetic resonance imaging, tomography, fluoroscopy, non-destructive inspection, non-destructive testing, optical scanning (e.g., scanning, digital copying, optical printing, optical plate-making, faxing, and so forth), photography, ultra-violet imaging, etc. Thus, certain embodiments of such devices can be comprised in telescopes, satellites, imaging machines, inspection machines, testing machines, scanners, copiers, printers, facsimile machines, cameras, etc. Moreover, these machines can process images using analog and/or digital techniques.
For the purposes of this description, the term “collimator” is used generally to describe what may also be referred to as a radiation collimator, x-ray grid, scatter reduction grid, detector array grid, or any other grid used in an imaging apparatus and/or process.
Certain collimators fabricated according to one or more exemplary embodiments of the present invention can be placed between the object and the image receptor to absorb and reduce the effects of scattered x-rays. Moreover, in certain exemplary embodiments, such collimators can be used in a stationary fashion, like those used in SPECT (Single Photon Emission Computed Tomography) imaging, or can be moved in a reciprocating or oscillating motion during the exposure cycle to obscure the grid lines from the image, as is usually done in x-ray imaging systems. Grids that are moved are known as Potter-Bucky grids.
X-ray grid configurations can be specified by grid ratio, which can be defined as the ratio of the height of the grid to the distance between the septa. The density, grid ratio, cell configuration, and/or thickness of the structure can have a direct impact on the grid's ability to absorb off-axis radiation and/or on the energy level of the x-rays that the grid can block.
Certain exemplary embodiments of the present invention can allow for the use of various materials, including high-density grid materials. Also, certain exemplary can make use of a production mold, which can be derived from a laminated mold.
Numerous additional aspects can be fabricated according to certain exemplary embodiments of the present invention. For example, the laminated mold can be produced from a stack lamination or other method, as discussed above. Moreover, X-ray absorbent material, such as lead, lead alloys, dense metallic composites, and/or epoxies loaded with dense metallic powders can be cast into a mold to produce x-ray absorbing grids. High-temperature ceramic materials also can be cast using a production mold.
In addition, the open cells of the ceramic grid structure can be filled with detector materials that can be accurately registered to a collimator. The molds and grids can be fabricated having high-resolution grid geometries that can be made in parallel or focused configurations. The mold can remain assembled to the cast grid to provide structural integrity for grids with very fine septal walls, or can be removed using several methods, and produce an air-cell grid structure.
FIG. 41 is a block diagram illustrating an exemplary embodiment of a method 41000 of the present invention Method 41000 can include the following activities:
1) creating a lithographic mask 41010 defining the features of each unique layer, 2) using lithographic micro-machining techniques and/or micro-machining techniques to produce patterned layers 41020 , and 3) aligning, stacking, and/or laminating the patterned layers 41030 in order to achieve the desired 3-dimensional cavity shape, high-aspect ratios, and/or other device features desired for the laminated mold 41040 , 4) fabricating a casting mold 41050 derived from the laminated mold, and/or 5) casting x-ray grids (or other parts) 41060 using the derived casting mold.
The following discussion describes in detail exemplary activities involved in fabricating certain exemplary embodiments of a laminated mold, fabricating a derived mold from the laminated mold, and finally casting a collimator from the derived mold. Certain variations in the overall process, its activities, and the resulting collimator are noted throughout.
In certain exemplary embodiments, the final collimator can be customized as a result of the casting process. For instance, conventional collimators have two separated flat major sides that are parallel to each other, thereby forming a flat, generally planar grid structure. Although certain exemplary embodiments of the present invention includes methods for forming these collimators, exemplary embodiments of the invention also can be used to form non-planar collimators.
An exemplary embodiment of a method of the present invention can begin with the acquisition, purchase, and/or fabrication of a first collimator. This first collimator can serve as the master collimator from which one or more molds can be formed. The master collimator can be made by any means, including stack lamination, but there is no limitation with respect to how the first or master collimator can be made. Also, as will be explained in more detail, because the master collimator is not necessarily going to be a collimator used in radiography, it is possible to customize this master collimator to facilitate mold formation.
The mold itself can be fabricated of many materials. When formed of a flexible material, for example, it is possible to use the mold to make a non-planar collimator. The material of the mold can be customized according to cost and performance requirements. In some embodiments, it is possible to make a mold of material that is substantially transparent to radiation transmission. The mold could be left embedded in the final cast collimator. This particular variation can be applicable when the final collimator has very narrow septal walls and the mold is needed to provide support and definition for the collimator. The mold generally also can be reused to form multiple final (or second) collimators to achieve economies of manufacturing scale.
Radiation Opaque Casting Materials for Collimators and Grids
A broad selection of base materials can be used for the fabrication of parts, such as x-ray collimators and scatter reduction grids. One potential characteristic of a grid material is sufficient absorption capacity so that it can block selective x-rays or gamma photons from reaching an image detector. In certain embodiments of the present invention, this characteristic can require high density and/or high atomic number (high z) materials. Certain exemplary embodiments of the present invention can utilize lead, tungsten, and/or various lead alloys for grid fabrication, but also can include the practice of loading various binders or alloys with dense powder metals, such as tungsten. The binders can be epoxies, polymers, and/or dense alloys which are described in detail below.
For certain exemplary embodiments of the present invention, lead can be used for casting purposes because of its high density and low melting point, which can allow the molten lead to be poured or injected into a mold. In certain situations, however, pure lead can shrink and/or pull away from molds when it solidifies, which can inhibit the casting of fine features. This can be overcome by using lead alloys, made from high-density materials, which can allow the metal alloy to flow at lower temperatures than pure lead while reducing shrink factors.
A typical chief component in a lead alloy is bismuth, a heavy, coarse crystalline metal that can expand by 3.3% of its volume when it solidifies. The presence of bismuth can expand and/or push the alloy into the fine features of the mold, thus enabling the duplication of fine features. The chart below shows the physical properties of pure lead and two lead alloys that were used to produce collimators. The alloys were obtained from Cerro Metal Products Co. of Bellefonte, Pa. Many other alloys exist that can be used to address specific casting and application requirements.
MELT
DENSITY
BASE MATERIAL
COMPOSITION
POINT
(g/cc)
Pure Lead
Pb
621.7
11.35
degrees F.
CERROBASE ™
55.5% BI, 44.5% Pb
255
10.44
degrees F.
CERROLOW-117 ™
44.7% BI, 22.6% Pb,
117
9.16
19.1% In, 8.3% Sn,
degrees F.
5.3% Cd,
The physical properties of lead alloys can be more process-compatible when compared to pure lead, primarily because of the much lower melting point. For example, the low melt point of CERROBASET™ can allow the use of rubber-based molds, which can be helpful when casting fine-featured pieces. This can be offset in part by a slightly lower density (about 8%). The somewhat lower density, can be compensated for, however, by designing the grid structure with an increased thickness and/or slightly wider septal walls.
Also, the alloy can be loaded with dense powder metals, such as tungsten, gold, and/or tantalum, etc., to increase density. Similarly, epoxy binders can be loaded with a metallic powder such as, for example, powdered tungsten, which has a density of 19.35 grams per cubic centimeter. In this approach, tungsten particles ranging in size from 1-150 microns, can be mixed and distributed into a binder material. The binder material can be loaded with the tungsten powder at sufficient amounts needed to achieve densities ranging between 8 and 14 grams per cubic centimeter. The tungsten powder is commercially available through the Kulite Tungsten Corporation of East Rutherford N.J., in various particle sizes, at a current cost of approximately $20-$25 dollars per pound.
The binders and metallic powders can be combined and engineered to satisfy specific application and process issues. For example, tungsten powder can be added to various epoxies and used for casting.
The company BONDLINE™ of San Jose, Calif., designs and manufactures engineered adhesives, such as epoxies, using powdered metals. Such composite metal epoxies can be cured at room temperature, can have high shear strength, low coefficient of thermal expansion, and viscosities that can be suited for high-resolution casting. Powdered materials combined with epoxy can be stronger than lead or lead alloys, but can be somewhat lower in density, having net density ranging from 7-8 grams per cubic centimeter. This density range can be acceptable for some collimator applications. In applications where material density is critical the practice of loading a lead alloy can be used. For example, tungsten powder can be combined with CERROBASE™ to raise the net density of the casting material from 10.44 up to 14.0 grams per cubic centimeter.
Certain exemplary embodiments of the present invention also include the casting of grid structures from ceramic materials, such as alumina, silicon carbide, zirconium oxide, and/or fused silica. Such ceramic grid structures can be used to segment radiation imaging detector elements, such as scintillators. The Cotronics Corporation of Brooklyn, N.Y., manufactures and commercially distributes Rescor™ Cer-Cast ceramics that can be cast at room temperature, can have working times of 30-45 minutes, can have cure times of 16 hours, and can withstand temperatures ranging from 2300 to 4000 degrees F.
Additional Embodiments
Anti-Scatter Grids for Mammography and General Radiography
One or more exemplary embodiments of the present invention can provide cellular air cross grids for blocking scattered X-ray radiation in mammography applications. Such cross grids can be interposed between the breast and the film-screen or digital detector. In some situations, such cross grids can tend to pass only the primary, information-containing radiation to the film-screen while absorbing secondary and/or scattered radiation which typically contains no useful information about the breast being irradiated.
Certain exemplary embodiments of the present invention can provide focused grids. Grids can be made to focus to a line or a point. That is, each wall defining the grid can be placed at a unique angle, so that if an imaginary plane were extended from each seemingly parallel wall, all such planes would converge on a line or a point at a specific distance above the grid center—the distance of that point from the grid known as the grid focal distance. A focused grid can allow the primary radiation from the x-ray source to pass through the grid, producing the desired image, while the off-axis scattered rays are absorbed by the walls of the grid (known as septal walls).
In certain embodiments, the septal walls can be thick enough to absorb the scattered x-rays, but also can be as thin as possible to optimize the transmission ratio (i.e., the percentage of open cell area to the total grid area including septal walls) and minimize grid artifacts (the shadow pattern of grid lines on the x-ray image) in the radiograph.
The relation of the height of the septal walls to the distance between the walls can be known as the grid ratio. Higher grid ratios can yield a higher scatter reduction capability, and thus a higher Contrast Improvement Factor (CIF), which can be defined as the ratio of the image contrast with and without a grid. A higher grid ratio can require, however, a longer exposure time to obtain the same contrast, thus potentially exposing the patient to more radiation. This dose penalty, known as the Bucky factor (BF), is given by BF=CIF/Tp, where Tp is the fraction of primary radiation transmitted. Certain exemplary embodiments of the present invention can provide a grid design that arrives at an optimal and/or near-optimal combination of these measures.
One or more exemplary embodiments of the present invention can include fine-celled, focused, and/or large area molded cross-grids, which can be sturdily formed from a laminated mold formed of laminated layers of metal selectively etched by chemical milling or photo-etching techniques to provide open focused passages through the laminated stack of etched metal layers. In certain applications, such molded and/or cast cross grids can maximize contrast and accuracy of the resulting mammograms when produced with a standard radiation dosage.
In certain exemplary embodiments, the laminated mold for the molded cross grids can be fabricated using adhesive or diffusion bonding to join abutting edges of thin partition portions of the laminated abutting layers with minimum intrusion of bonding material into the open focused passages.
Exemplary embodiments of the present invention can utilize any of a wide number of different materials to fabricate such molded and/or cast cross grids. A specific application can result in any of the following materials being most appropriate, depending on, for example, the net density and the cell and septa size requirements:
Lead or lead alloy alone can offer a density of 9-11 grams per cc; Lead alloy can be loaded with a dense composite (e.g., tungsten, tantalum, and/or gold, etc.) powder to form a composite having a density of 12-15 grams per cc; Polymer can be loaded with a dense composite (e.g., lead, tungsten, tantalum, and/or gold, etc.) powder to form a composite having a density of 8-9 grams per cc; The cast grid made of lead alloy or any of the above combinations can be encapsulated in a low density polymer such that the transmission is minimally affected but scatter is significantly reduced.
In addition, certain embodiments of the present invention can be employed to fabricate grids and/or collimators for which the mold can be pre-loaded with dense powder, followed by alloy or polymer. Alternatively, polymer or alloy can be pre-loaded with dense powder then injected into the mold. In certain embodiments, the casting can be removed from a flexible mold. In other embodiments, the mold can be dissolved or consumed to de-mold the casting. In certain embodiments, a master can be removed layer-by-layer from rigid mold. Alternatively, the lost wax approach can be used in which the model is dissolvable wax, dissolvable PMMA, dissolvable polyurethane, dissolvable high-resolution ceramic, and/or some other dissolvable material.
Additional Embodiments
Computed Tomography Collimator and Detector Array
Certain exemplary embodiments of the present invention can provide a system that includes an x-ray source, a scatter collimator, and a radiation detector array having a plurality of reflective scintillators. Such a system can be used for computer-assisted tomography (“CT”). Computed tomography is often performed using a CT scanner, which can also be known as a CAT scanner. In certain embodiments, the CT scanner can look like a large doughnut, having a square outer perimeter and a round hole. The patient can be positioned in a prone position on a table that can be adjusted up and down, and can be slid into and out of the hole of the CT scanner. Within the chassis of the CT scanner is an x-ray tube on a rotating gantry which can rotate around the patient's body to produce the images. On the opposite side of the gantry from the x-ray tube can be mounted an array of x-ray detectors.
In certain exemplary embodiments of the present invention, the x-ray source can project a fan-shaped beam, which can be collimated to lie within an X-Y plane of a Cartesian coordinate system, referred to as the “imaging plane”. The x-ray beam can pass through the object being imaged, such as a patient. The beam, after being attenuated by the object, can impinge upon the array of radiation detectors. The intensity of the attenuated beam radiation received at the detector array can be dependent upon the attenuation of the x-ray beam by the object. Each detector element of the array can produce a separate electrical signal that can provide a measurement of the beam attenuation at the detector location. The attenuation measurements from all the detectors can be acquired separately to produce an x-ray transmission profile of the object.
For certain exemplary embodiments of the present invention, the detector array can include a plurality of detector elements, and can be configured to attach to the housing. The detector elements can include scintillation elements, or scintillators, which can be coated with a light-retaining material. Moreover, in certain exemplary embodiments, the scintillators can be coated with a dielectric coating to contain within the scintillators any light events generated in the scintillators. Such coated scintillators can reduce detector element output gain loss, and thereby can extend the operational life of a detector element and/or array, without significantly increasing the costs of detector elements or detector arrays.
In certain exemplary embodiments of the present invention, the x-ray source and the detector array can be rotated with a gantry within the imaging plane and around the object to be imaged so that the angle at which the x-ray beam intersects the object can constantly change. A group of x-ray attenuation measurements, i.e., projection data, from the detector array at one gantry angle can be referred to as a “view”, and a “scan” of the object can comprise a set of views made at different gantry angles during one revolution of the x-ray source and detector. In an axial scan, the projection data can be processed to construct an image that corresponds to a two-dimensional slice taken through the object.
In certain exemplary embodiments of the present invention, images can be reconstructed from a set of projection data according to the “filtered back projection technique”. This process can convert the attenuation measurements from a scan into integers called “CT numbers” or “Hounsfield units”, which can be used to control the brightness of a corresponding pixel on a cathode ray tube display.
In certain exemplary embodiments of the present invention, detector elements can be configured to perform optimally when impinged by x-rays traveling a straight path from the x-ray source to the detector elements. Particularly, exemplary detector elements can include scintillation crystals that can generate light events when impinged by an x-ray beam. These light events can be output from each detector element and can be directed to photoelectrically responsive materials in order to produce an electrical signal representative of the attenuated beam radiation received at the detector element. The light events can be output to photomultipliers or photodiodes that can produce individual analog outputs. Exemplary detector elements can output a strong signal in response to impact by a straight path x-ray beam.
Without a collimator, X-rays can scatter when passing through the object being imaged. Particularly, the object can cause some, but not all, x-rays to deviate from the straight path between the x-ray source and the detector. Therefore, detector elements can be impinged by x-ray beams at varying angles. System performance can be degraded when detector elements are impinged by these scattered x-rays. When a detector element is subjected to multiple x-rays at varying angles, the scintillation crystal can generate multiple light events. The light events corresponding to the scattered x-rays can generate noise in the scintillation crystal output, and thus can cause artifacts in the resulting image of the object.
To, for example, reduce the effects of scattered x-rays, scatter collimators can be disposed between the object of interest and the detector array. Such collimators can be constructed of x-ray absorbent material and can be positioned so that scattered x-rays are substantially absorbed before impinging upon the detector array. Such scatter collimators can be properly aligned with both the x-ray source and the detector elements so that substantially only straight path x-rays impinge on the detector elements. Also, such scatter collimators can shield from x-ray radiation damage certain detector elements that can be sensitive at certain locations, such as the detector element edges.
Certain exemplary embodiments of a scatter collimator of the present invention can include a plurality of substantially parallel attenuating blades and a plurality of substantially parallel attenuating wires located within a housing. In certain exemplary embodiments, the attenuating blades, and thus the openings between adjacent attenuating blades, can be oriented substantially on a radial line emanating from the x-ray source. That is, each blade and opening can be focally aligned. The blades also can be radially aligned with the x-ray source. That is, each blade can be equidistant from the x-ray source. Scattered x-rays, that is, x-rays diverted from radial lines, can be attenuated by the blades. The attenuating wires can be oriented substantially perpendicular to the blades. The wires and blades thus can form a two-dimensional shielding grid for attenuating scattered x-rays and shielding the detector array.
At least one embodiment of the invention can include a feature that provides any of at least 5 functions: 1) separation of the collimator by a predetermined distance from an array of radiation detection elements; 2) alignment of the collimator to the array of radiation detection elements (or vice versa); 3) attachment of the collimator to the array of radiation detection elements; 4) attach the collimator, to a gantry or other detector sub-assembly; and/or 5 ) align the collimator to a gantry or other detector sub-assembly.
As an illustrative example, one embodiment of such a feature could resemble “stilts” that can be formed independently or integrally to a collimator and that can separate the collimator by a predetermined distance from an array of radiation detection elements. In another embodiment, one or more of the stilts could serve as an alignment pin to align the collimator with the array of radiation detection elements. In another embodiment, one or more of the stilts could include and/or interface with an attachment mechanism to attach the collimator to the array of radiation detection elements. For example, an end of a stilt could slide into, via an interference fit, a socket of the array of radiation detection elements. As example, a stilt could include a hemispherical protrusion that snaps into a corresponding hemispherical indentation in a socket of the array of radiation detection elements.
As another illustrative example, one embodiment of such a feature could invert the description of the previous paragraph by providing “holes” in the collimator that interface with “stilts” attached to or integral with the radiation detection elements.
As yet another illustrative example, an embodiment of the feature could be manifested in a collimator having an array of through-holes, each having a square cross-section. At one end of all or certain through-holes could be the feature, such as a groove that extends around a perimeter of the square through-hole. A radiation detection element could have a square outer perimeter that includes a lip having corresponding dimensions to the groove that allows the radiation detection element to snap into the through-hole of the collimator via an interference fit, thereby fixing the position of the radiation detection element with respect to the collimator, aligning the radiation detection element with the collimator, and attaching the radiation detection element to the collimator.
Moreover, a modular collection of radiation detection elements, potentially cast according to an embodiment of the present invention, could attach to a collimator via one or more attachment features, any of which could be formed independently of, or integrally with, either the radiation detection module and/or the collimator.
Depending on the embodiment, the scatter collimator can include blades and wires, open air cells, and/or encapsulated cells. Certain exemplary embodiments can be fabricated as a true cross grid having septa in both radial and axial directions. The cross-grid structure can be aligned in the radial and axial directions or it can be rotated. Thus, the cross grid can be aligned in two orthogonal directions.
Depending on the grid design, it might not be practical and/or possible to remove the mold from the cast grid because of its shape or size, e.g., if very thin septa or severe undercuts are involved. In such cases, a material with a low x-ray absorptivity can be used for the mold and the final grid can be left encapsulated within the mold. Materials used for encapsulation can include, but are not limited to, polyurethanes, acrylics, foam, plastics etc.
Because certain exemplary embodiments of the present invention can utilize photolithography in creating the laminated mold, great flexibility can be possible in designing the shape of the open cells. Thus, round, square, hexagonal, and/or other shapes can be incorporated. Furthermore, the cells do not all need to be identical (a “redundant pattern”). Instead, they can vary in size, shape, and/or location (“non-redundant” pattern) as desired by the designer. In addition, because of the precision stack lamination of individual layers that can be employed in fabricating the master, the cell shapes can vary in the third dimension, potentially resulting in focused, tapered, and/or other shaped sidewalls going through the cell.
Because the cell shape can vary in the third dimension (i.e. going through the cell), the septa wall shape can also vary. For example, the septa can have straight, tapered, focused, bulging, and/or other possible shapes. Furthermore, the septa do not all need to be identical (a “redundant pattern”). Instead, they can vary in cross-sectional shape (“non-redundant” pattern) as desired by the designer.
Certain exemplary embodiments of the present invention can provide a collimator or section of a collimator as a single cast piece, which can be inherently stronger than either a laminated structure or an assembly of precisely machined individual pieces. Such a cast collimator can be designed to withstand any mechanical damage from the significant g-forces involved in the gantry structure that can rotate as fast as 4 revolutions per second. Furthermore, such a cast structure can be substantially physically stable with respect to the alignment between collimator cells and detector elements.
Some exemplary embodiments of the present invention can provide a collimator or section of a collimator as a single cast collimator in which cells and/or cell walls can be focused in the radial direction, and/or in which cells and/or cells walls can be accurately aligned in the axial direction.
Conversely, certain exemplary embodiments of the present invention can provide a collimator or section of a collimator as a single cast collimator in which cells and/or cell walls can be focused (by stacking layers having slightly offset openings) in the axial direction, and/or in which cells and/or cells walls can be curved (and focused) in the radial direction.
Exemplary embodiments of the present invention can utilize any of a wide number of different materials to fabricate the scatter collimator. A specific application can result in any of the following materials being most appropriate, depending on, for example, the net density and the cell and septa size requirements. Lead or lead alloy alone can offer a density of 9-11 grams per cc;
Lead alloy can be loaded with a dense composite (e.g., tungsten, tantalum, and/or gold, etc.) powder to form a composite having a density of 12-15 grams per cc; Polymer can be loaded with a dense composite (e.g., lead, tungsten, tantalum, and/or gold, etc.) powder to form a composite having a density of 8-9 grams per cc; The cast grid made of lead alloy or any of the above combinations can be encapsulated in a low density polymer such that the transmission is minimally affected but scatter is significantly reduced.
In addition, certain embodiments of the present invention can be employed to fabricate grids and/or collimators for which the mold can be pre-loaded with dense powder, followed by alloy or polymer. Alternatively, polymer or alloy can be pre-loaded with dense powder then injected into the mold. In certain embodiments, the casting can be removed from a flexible mold. In other embodiments, the mold can be dissolved or consumed to de-mold the casting. In certain embodiments, a master can be removed layer-by-layer from rigid mold. Alternatively, the lost wax approach can be used in which the model is dissolvable wax, dissolvable PMMA, dissolvable polyurethane, dissolvable high-resolution ceramic, and/or some other dissolvable material.
The above description and examples have covered a number of aspects of certain exemplary embodiments of the invention including, for example, cell size and shape, different materials and densities, planar and non-planar orientations, and focused and unfocused collimators.
Additional Embodiments
Nuclear Medicine (SPECT) Collimator and Detector Array
In conventional X-ray or CT examinations, the radiation is emitted by a machine and then passes through the patient's body. In nuclear medicine exams, however, a radioactive material is introduced into the patient's body (by injection, inhalation or swallowing), and is then detected by a machine, such as a gamma camera or a scintillation camera.
The camera can have a detector and means to compute the detected image. The detector can have at least one a scintillator crystal, which typically is planar. The scintillator can absorb the gamma radioactive radiation, and emit a luminous scintillation in response, which can be detected by an array of photomultiplier tubes of the detector. The computation means can determine the coordinates of a locus of interaction of the gamma rays in the scintillator, which can reveal the projected image of the body.
Because the radiation source in the patient can emit radiation omnidirectionally, a collimator can be located between the body and the scintillator. This collimator can prevent the transmission of those radioactive rays that are not propagating in a chosen direction.
Certain embodiments of the present invention can be used to fabricate structures useful for nuclear medicine. For example, collimators used in nuclear medicine, including pinhole, parallel-hole, diverging, and converging collimators, can be fabricated according to one or more exemplary methods of the present invention.
As another example, exemplary methods of the present invention can be used to fabricate high precision, high attenuation collimators with design flexibility for hole-format, which can improve the performance of pixelated gamma detectors.
Certain exemplary embodiments of certain casting techniques of the present invention can be applied to the fabrication of other components in detector systems.
FIG. 47 is an assembly view of components of a typical pixelated gamma camera. Embodiments of certain casting techniques of the present invention can be used to produce collimator 47010 , scintillator crystals segmentation structure 47020 , and optical interface 47030 between scintillator array (not visible) and photo-multiplier tubes 47040 .
In an exemplary embodiment, collimator 47010 can be fabricated from lead, scintillator crystals segmentation structure 47020 can be fabricated from a ceramic, and optical interface 47030 can be fabricated from acrylic.
In certain exemplary embodiments, through the use of a common fabrication process, two or more of these components can be made to the same precision and/or positional accuracy. Moreover, two or more of these components can be designed to optimize and/or manage seams and/or dead spaces between elements, thereby potentially improving detector efficiency for a given choice of spatial resolution. For example, in a pixelated camera with non-matched detector and collimator, if the detector's open area fraction (the fraction of the detector surface that is made up of converter rather than inter-converter gap) is 0.75, and the collimator's open area fraction (the fraction of the collimator surface that is hole rather than septum) is 0.75, the overall open area fraction is approximately (0.75)=0.56. For a similar camera in which the collimator holes are directly aligned with the pixel converters, the open area fraction is 0.75, giving a 33% increase in detection efficiency without reduction in spatial resolution.
Certain embodiments of the present invention can provide parallel hole collimators and/or collimators having non-parallel holes, such as fan beam, cone beam, and/or slant hole collimators. Because certain embodiments of the present invention use photolithography in creating the master, flexibility is possible in designing the shape, spacing, and/or location of the open cells. For example, round, square, hexagonal, or other shapes can be incorporated. In addition, because certain embodiments of the present invention use precision stack lamination of individual layers to fabricate a laminated mold, the cell shapes can vary in the third dimension, resulting in focused, tapered, and/or other shaped sidewalls going through the cell. Furthermore, the cells do not all need to be identical (“redundant”). Instead, they can vary in size, shape or location (“non-redundant”) as desired by the designer, which in some circumstances can compensate for edge effects. Also, because a flexible mold can be used with certain embodiments of the present invention, collimators having non-planar surfaces can be fabricated. In some cases, both surfaces are non-planar. However, certain embodiments of the present invention also allow one or more surfaces to be planar and others non-planar if desired.
Certain embodiments of the present invention can fabricate a collimator, or section of a collimator, as a single cast piece, which can make the collimator less susceptible to mechanical damage, more structurally stable, and/or allow more accurate alignment of the collimator with the detector. Certain embodiments of the present invention can utilize any of a number of different materials to fabricate a collimator or other component of an imaging system. A specific application could result in any of the following materials being chosen, depending, in the case of a collimator, on the net density and the cell and septa size requirements:
Lead or lead alloy alone can offer a density of 9-11 grams per cc Polymer can be loaded with tungsten powder to form a composite having a density comparable to lead or lead alloys Polymer can also be combined with other dense powder composites such as tantalum or gold to yield a density comparable to lead or lead alloys Polymer can be combined with two or more dense powders to form a composite having a density comparable to lead or lead alloys Lead alloy can be loaded with tungsten powder to form a composite having a density of 12-15 grams per cc Lead alloy can be loaded with another dense composites (tantalum, gold, other) to form a composite having a density of 12-15 grams per cc Lead alloy can be combined with two or more dense powders to form composites having a density of 12-15 grams per cc (atomic number and attenuation) The cast grid made of lead alloy or any of the above combinations can be encapsulated in a low-density material such that the transmission is minimally affected but scatter is reduced.
Thus, depending on the specific application, certain embodiments of the present invention can create any of a wide range of densities for the cast parts. For example, by adding tungsten (or other very dense powders) to lead alloys, net densities greater than that of lead can be achieved. In certain situations, the use of dense particles can provide high “z” properties (a measure of radiation absorption). For certain embodiments of the present invention, as radiation absorption improves, finer septa walls can be made, which can increase imaging resolution and/or efficiency.
In addition, certain embodiments of the present invention can be employed to fabricate grids and/or collimators for which the mold can be pre-loaded with dense powder, followed by alloy or polymer. Alternatively, polymer or alloy can be pre-loaded with dense powder then injected into the mold. In certain embodiments, the casting can be removed from a flexible mold. In other embodiments, the mold can be dissolved or consumed to de-mold the casting. In certain embodiments, a master can be removed layer-by-layer from rigid mold. Alternatively, the lost wax approach can be used in which the model is dissolvable wax, dissolvable PMMA, dissolvable polyurethane, dissolvable high-resolution ceramic, and/or some other dissolvable material.
With certain embodiments of the present invention, the stack-laminated master does not need to embody the net density of the final grid. Instead, it can have approximately the same mechanical shape and size. Similarly, the final grid can be cast from relatively low cost materials such as lead alloys or polymers. Furthermore, these final grids can be loaded with tungsten or other dense powders. As discussed previously, using certain embodiments of the invention, multiple molds can be made from a single master and multiple grids can be cast at a time, if desired. Such an approach can lead to consistency of dimensions and/or geometries of the molds and/or grids.
Because of the inherent precision of the lithographic process, certain embodiments of the present invention can prevent and/or minimize assembly build up error, including error buildup across the surface of the grid and/or assembly build up error as can occur in collimators in which each grid is individually assembled from photo-etched layers. In addition, process errors can be compensated for in designing the laminated mold.
Example 6
Lead Collimator for Gamma Camera (Nuclear Medicine Application)
Step 1: Creating the laminated mold: In this exemplary process, 0.05 mm thick copper foils were chemically etched and then laminated together using a metal-to-metal brazing process, for producing a laminated mold. Photo-masks were configured with a 2.0×2.0 millimeter square open cell, with a 0.170 mm septal wall separating the cells. The cells were arrayed having 10 rows and 10 columns, with a 2 mm border around the cell array. Photo-masks were produced to the same specifications, by the same vendor as those described in example 1, step 1.
The layers were designed so that the cell placement was identical from layer to layer, which when assembled, produced a parallel cross-sectional shape. FIG. 42A is a top view of an x-ray grid 42000 having an array of cells 42002 separated by septal walls 42004 . FIG. 42B is a cross-sectional view of x-ray grid 42000 taken along section lines 42 - 42 of FIG. 42B showing that the placement of cells 42002 can also be dissimilar from layer to layer 42010 - 42050 , so that when assembled, cells 42002 are focused specifically to a point source 42060 at a known distance from x-ray grid 42000 .
The total number of layers in the stack lamination defined the thickness of the casting mold and final cast grid. The final thickness of the lamination was specified at 0.118 inches, which required 57 layers of copper foil, leaving a total thickness amount of 0.00007 inches between each layer for a braze material. The layers were processed by Tech Etch of Plymouth Mass., using standard photo-etching techniques and were etched in such a way that the cross-sectional shape of the etched walls were perpendicular to the top and bottom surfaces of the foil (commonly referred to as straight sidewalls).
The method chosen to bond the grid layers together was a metal-to-metal brazing technique described earlier in detail as one of two exemplary methods of bonding layers together (eutectic braze alloy). The brazed lamination was then electro-plated with a coating of hard nickel, also described earlier.
Step 2: Creating a derived mold: An RTV mold was made from the stack laminated mold from step 1. Silastic® M RTV Silicone Rubber was chosen as the base material for the derived mold. This particular material was used to demonstrate the resolution capability, release properties, multiple castings, and dimensional repeatability of the derived mold from the laminated mold. Silastic® M has the hardest durometer of the Silastic® family of mold making materials. The derived mold was configured as an open face mold.
The fixture used to create the derived casting mold is shown in FIG. 32 and was comprised of a precision machined aluminum ring 32010 , precision ground glass plates 32020 and 32030 , rubber gaskets 32040 and 32050 , and the laminated mold 32060 . The base of the fixture 32020 was a 5 inch square of 1 inch thick Plexiglas. On the top surface of the Plexiglas base was a 1″ thick, 3 inch diameter glass substrate 32030 . The base and the glass substrate were separated by a 1/16 inch thick, 4.5 inch diameter rubber gasket 32040 . An additional 3.0 inch rubber gasket 32050 was placed on the top surface of the glass substrate 32030 . The rubber gaskets helped prevent unwanted flashing of molten material when casting. The laminated mold 32060 was placed on the top gasket.
The shape and thickness of the glass created the entrance area where the casting material was poured into the mold. The material formed in this cavity was referred to as a controlled backing. It served as a release aid for the final casting, and could later be removed from the casting in a final machining process. A precision machined aluminum ring 32010 having a 4.5 inch outside diameter and a 4 inch inside diameter was placed over the master subassembly and interfaced with the lower 4.5 inch diameter rubber gasket.
As illustrated in FIG. 32 , the height of the ring was configured so that the distance from the top surface of the master to the top of the ring was twice the distance from the base of the fixture to the top of the laminated mold. The additional height allowed the RTV material to rise up during the degassing process. The ring portion of the fixture assembly was used to locate the pouring of the mold material into the assembly, captivate the material during the curing process, and provide an air escape while the mold material was degassed using vacuum. The fixture was configured in such a way that all sides surrounding the laminated mold were equal and common, in order to limit the effects or stresses put on the lamination from the mold material.
The Silastic® M RTV Silicone Rubber used for the mold fabrication was prepared in accordance with the manufacturer's recommendations, using the process described earlier in example 1, step 2.
The laminated mold was characterized, before and after the mold-making process, by measuring the average pitch distance of the cells, the septal wall widths, overall distance of the open grid area, and the finished thickness of the part. These dimensions were also measured on the derived casting mold and compared with the laminated mold before and after the mold-making process. The following chart lists the dimensions of the lamination before and after the mold-making and the same dimensions of the derived RTV mold. All dimensions were taken using a Nikon MM-11 measuring scope at 200× magnification. These dimensions demonstrated the survivability of the master and the dimensional repeatability of the mold.
Master Lamina-
Master Lamina-
tion (before
RTV Mold
tion (after
Grid Feature
mold-making)
Silastic ® M
mold-making)
Septal Wall
0.170
0.161
0.170
Width (mm)
Cell Width
2.000 × 2.000
2.010 × 2.010
2.000 × 2.000
(mm)
Cell Pitch
2.170 × 2.170
2.171 × 2.171
2.170 × 2.170
(mm)
Pattern area
21.530 × 21.530
21.549 × 21.549
21.530 × 21.530
(mm)
Thickness
2.862
2.833
2.862
(mm)
Step 3: Casting the final collimator: A fine-featured lead collimator was produced from the derived RTV silicone mold described in step 2. FIG. 43 is a side view of an assembly 43000 that includes an open face mold 43010 that was used to produce a casting 43020 from CERROBASE™ alloy. Casting 43020 was dimensionally measured and compared to the laminated mold 43010 . The backing 43030 of casting 43020 was 6 millimeters in thickness and was removed using a machining process.
Grid Features
Master Lamination
Cast Collimator
Septal Wall Width (mm)
0.170
0.165
Cell Width (mm)
2.000 × 2.000
2.005 × 2.005
Cell Pitch (mm)
2.170 × 2.170
2.170 × 2.170
The first step of the casting process was to pre-heat the derived RTV mold to a temperature of 275 degrees F., which was 20 degrees above the melting point of the CERROBASE™ alloy. The mold was placed on a heated aluminum substrate, which maintained the mold at approximately 275 degrees F. when it was placed in the vacuum bell jar.
In certain casting procedures, the material can be forced into the mold in a rapid fashion, and cooled and removed quickly. In this case, the casting process was somewhat slowed in order to fully fill and evacuate the air from the complex cavity geometry of the mold. The CERROBASE™ was then heated in an electric melting pot to a temperature of 400 degrees F., which melted the alloy sufficiently above its melt point to remain molten during the casting process.
The next step was to pour the molten alloy into the mold, in such a way as to aid in the displacement of any air in the cavity. This was accomplished by tilting the mold at a slight angle and beginning the pour at the lowest point in the cavity section of the mold. It was found that if the mold was placed in a flat orientation while pouring the molten alloy, significant amounts of air were trapped, creating problems in the degassing phase of the process. Instead, once the mold was sufficiently filled with the molten alloy, the mold was slightly vibrated or tapped in order to expel the largest pockets of air. The mold, on the heated aluminum substrate, was then placed in the vacuum bell jar, pumped down to atmosphere of 25-28 inches of mercury for 2 minutes, which was sufficient time to evacuate any remaining air pockets. The mold was then removed from the vacuum bell jar and submersed in a quenching tank filled with water cooled to a temperature of 50 degrees F. The rapid quench produced a fine crystalline grain structure when the casting material solidified. The casting was then removed from the flexible mold by grasping the backing 43030 , by mechanical means or by hand, and breaking the casting free of the mold using an even rotational force, releasing the casting gradually from the mold.
The final process step was removing the backing 43030 from the attached surface of the grid casting 43020 to the line shown in FIG. 43 . Prior to removing the backing, the grid structure of the final casting 43020 was filled or potted with a machinable wax, which provided the structural integrity needed to machine the backing without distorting the fine walls of the grid casting. The wax was sold under the product name MASTERT™ Water Soluble Wax by the Kindt-Collins Corporation, of Cleveland, Ohio. The wax was melted at a temperature of 160-180 degrees F., and poured into the open cells of the cast grid. Using the same technique described above, the wax potted casting was placed in vacuum bell jar and air evacuated before being cooled. The wax was cooled to room temperature and was then ready for the machining of the backing.
A conventional surface grinder was used to first rough cut the backing from the lead alloy casting. The remaining casting was then placed on a lapping machine and lapped on the non-backing side of the casting using a fine abrasive compound and lapping wheel. The non-backing side of the casting was lapped first so that the surface was flat and parallel to within 0.010-0.015 millimeters to the adjacent cast grid cells. The rough-cut backing surface was then lapped using the same abrasive wheel and compound so that it was flat and parallel to within 0.100-0.015 millimeters of the non-backing side of the casting. A thickness of 2.750 millimeters was targeted as the final casting thickness. Upon completion of the lapping process, the casting was placed in an acid solution, comprised of 5% dilute HCl and water, with mild agitation until the wax was fully dissolved from the cells of the casting.
In an alternative embodiment, individual castings could also be stacked, aligned, and/or bonded to achieve thicker, higher aspect ratio collimators. Such collimators, potentially having a thicknesses measured in centimeters, can be used in nuclear medicine.
Example 7
Non-Planar Collimator
A non-planar collimator can have several applications, such as, for example, in a CT environment. To create such an example of such a collimator, the following process was followed:
Step 1: Creating a laminated mold: For this example, a laminated mold was designed and fabricated using the same process and vendors described in Example 1, step 1. The laminated mold was designed to serve as the basis for a derived non-planar casting mold. The laminated mold was designed and fabricated with outside dimensions of 73.66 mm×46.66 mm, a 5 mm border around a grid area having 52×18 open cell array. The cells were 1 mm×1.980 mm separated by 0.203 septal walls.
The layers for the laminated mold were bonded using the same process described in Example 1, step 1 (thermo-cured epoxy). The dimensions of the laminated mold were specified to represent a typical collimator for CT x-ray scanning. Silastic® J RTV Silicone Rubber was chosen as a base material to create a derived non-planar casting mold because of its durometer which allowed it to more easily be formed into a non-planar configuration. The laminated mold and fixture was configured as an open face mold.
Step 2: Creating a derived non-planar mold: Silastic® J RTV Silicone Rubber was used for the derived mold fabrication and was prepared in accordance with the manufacturers recommendations, using the process described earlier in example 1, step 2. FIG. 44 is a top view of casting assembly 44000 . FIG. 45 is a side view of casting assembly 44000 .
The derived RTV mold 44010 was then formed into a non-planar configuration as shown in FIG. 45 . The surface 44020 of casting fixture base 44030 defined a 1-meter radius arc to which mold 44010 was attached. A 1-meter radius was chosen because it is a common distance from the x-ray tube to the collimator in a CT scanner. Mold 44010 was fastened to the convex surface 44020 of casting base 44030 with a high temperature epoxy adhesive. A pour frame 44040 was placed around casting fixture base 44030 . Pour frame 44040 had an open top to allow pouring the casting material to a desired fill level and to allow evacuating the air from the casting material.
The laminated mold was characterized, before and after producing the derived non-planar mold, by measuring the average pitch distance of the cells, the septal wall widths, overall distance of the open grid area, and the finished thickness of the part. These dimensions were also measured on the derived non-planar mold and compared with the master before and after the mold-making process. The following chart lists the dimensions of the master lamination before and after the mold-making and the same dimensions of the RTV mold in the planar state and curved state. All dimensions are in millimeters and were taken using a Nikon MM-11 measuring scope at 200× magnification.
Master Lamination
RTV Mold
RTV Mold
Grid
(before mold-
(planar)
(curved)
Features
making)
Silastic ® J
Silastic ® J
Septal Wall
0.203
0.183
0.193*
Cell Width
1.980 × 1.000
2.000 × 1.020
2.000 × 1.020
Cell Pitch
2.183 × 1.203
2.183 × 1.203
2.183 × 1.213
Pattern area
39.091 × 62.353
39.111 × 62.373
39.111 × 62.883
Thickness
7.620
7.544
7.544
*measured in the direction of curvature.
Step 3: Casting a non-planar collimator: The derived non-planar RTV mold described in step 2, was used to create castings. Using the derived non-planar mold, the castings were produced from CERROBASE™ alloy and were dimensionally measured and compared to the laminated mold.
Grid Features
Master Lamination
Cast Collimator
Septal Wall Width (mm)
0.203
0.197*
Cell Width (mm)
1.000 × 1.980
1.006 × 1.986
Cell Pitch (mm)
1.203 × 2.183
1.203 × 2.183
*measured in the direction of curvature.
The process used to fill the derived non-planar mold with the casting alloy and the de-molding of the casting was the same process described in Example 6.
The final process step included the removal of the backing from the grid casting. A wire EDM (electrode discharge machining) process was found to be the most effective way to remove the backing from the casting, primarily due to the curved configuration of the casting. The wire EDM process used an electrically charged wire to burn or cut through the casting material, while putting no physical forces on the parts. In this case, a fine 0.003 inch molybdenum wire was used to cut the part, at a cutting speed of 1 linear inch per minute. This EDM configuration was chosen to limit the amount of recast material left behind on the cut surface of the part, leaving the finished septal walls with a smooth surface finish. The casting was fixtured and orientated so that the radial cutting of the backing was held parallel to the curved surface of the casting, which was a 1 meter radius.
Example 8
Mammography Scatter Reduction Grid
Another exemplary application of embodiments of the present invention is the fabrication of a mammography scatter reduction grid. In this example, a derived clear urethane mold for a fine-featured focused grid was made using a photo-etched stack lamination for the master model. For making this mold, the master was designed and fabricated using the lamination process detailed in Example 7. A clear urethane casting material was chosen as an example of a cast grid in which the mold was left intact with the casting as an integral part of the grid structure. This provided added strength and eliminated the need for a fragile or angled casting to be removed from the mold.
Step 1: Creating a laminated mold: The laminated mold was fabricated from photo-etched layers of copper. The mold was designed to have a 63 mm outside diameter, a 5 mm border around the outside of the part, and a focused 53 mm grid area. FIG. 46 is a top view of a grid area 46000 , which was comprised of hexagonal cells 46010 that were 0.445 mm wide, separated by 0.038 mm septal walls 46020 . The cells were focused from the center of the grid pattern to a focal point of 60 centimeters, similar to that shown in FIG. 42B . The grid was made from 35 layers of 0.050 mm thick stainless steel, which when assembled created a 4:1 grid ratio. Each grid layer utilized a separate photo-mask in which the cells are arrayed out from the center of the grid pattern at a slightly larger distance from layer to layer. This created the focused geometry as shown in FIG. 42B . With this cell configuration, the final casting produced a hexagonal focused grid with a transmission of about 82%. The photo-masks and etched layers were produced using the same vendors and processes described in example 1, step1.
Step 2: Creating a derived urethane mold: Urethane mold material was chosen for its high-resolution, low shrink factor, and low density. Because of its low density, the urethane is somewhat transparent to the transmission of x-rays. The mold material, properties, and process parameters were as described earlier in example 4, step 4.
The fixture used to create the derived urethane casting mold was the same as that described in Example 6, step 2.
Before assembling the mold fixture, the laminated mold was sprayed with a mold release, Stoner E236. The fixture was assembled as shown in FIG. 32 and heated to 125 degrees F. Then it was filled with the Water Clear urethane and processed using the same parameters described in example 4, step 4. The laminated mold was characterized, before and after making the derived mold, by measuring the average pitch distance of the cells, the septal wall widths, overall distance of the open grid area, and the finished thickness of the lamination. These dimensions were also measured on the derived urethane casting mold and compared with the lamination before and after the mold-making process. The following chart lists the dimensions of the lamination before and after the mold-making and the same dimensions of the urethane mold. All dimensions were in millimeters and were taken using a Nikon MM-11 measuring scope at 200× magnification.
Master Lamina-
Urethane Casting
Master Lamina-
tion (before
System
tion (after
Grid Features
mold-making)
Water Clear
mold-making)
Septal Wall
0.038
0.037
0.038
Width
Cell Width
0.445
0.446
0.445
(hexagonal)
(hexagonal)
(hexagonal)
Cell Pitch
0.483
0.483
0.483
Pattern area
53.000
52.735
53.000
(mm2)
Thickness
1.750
1.729
1.750
Step 3: Casting the anti-scatter grid: A focused scatter reduction grid was produced by casting a lead alloy, CERROLOW-117™ alloy into the derived urethane mold described in step 2. The backing thickness of the casting was 2 millimeters and was removed using a surface grinding process.
The first step of the process was to pre-heat the derived urethane mold to a temperature of 137 degrees F., which was 20 degrees above the 117 degree melting point of the CERROLOW™ alloy. The mold was placed on a heated aluminum substrate, which maintained the mold to approximately 117 degrees F. when it was placed in the vacuum bell jar. The CERROLOW™ was then heated in an electric melting pot to a temperature of 120 degrees F., which melted the alloy sufficiently above the melt point of the material, keeping the material molten during the casting process. The process steps for filling the mold were the same as those described in Example 6, step 3.
The CERROLOW™ alloy was chosen for casting because of its high resolution capability, low melting point, and relatively high density. The urethane mold was left remaining to provide structural integrity for the fine lead alloy features. The urethane is also somewhat transparent to x-rays because of its low density (1 g/cm3) compared to the casting alloy.
Example 9
Collimator with Tungsten Loaded Alloy (Variation of Example 6)
Additional collimator samples have been produced using the same process described in Example 6 above, with the exception of the casting alloy and that it was loaded with tungsten powder prior to the casting process. The tungsten powder (Kmp 115) was purchased through the kulite tungsten corporation of east rutherford, N.J. CERROLOW™ alloy was loaded to raise the net density of the alloy from a density of 9.16 grams per cubic centimeter to 13 grams per cubic centimeter.
In certain radiological applications, elimination of secondary scattered radiation, also known as Compton scatter, and shielding can be an objective. The base density of the CERROLOWT™ alloy can be sufficient on its own to absorb the scattered radiation, but the presence of the tungsten particles in the septal walls can increase the density and improve the scatter reduction performance of the part. The casting was dimensionally measured and compared to the laminated mold used to create the derived RTV mold.
Grid Features
Master Lamination
Cast Collimator
Material
Copper
CERROLOW-117 Plus
Tungsten Powder
Density (g/cc)
8.96
12.50
Septal Wall Width
0.038
0.036
Cell Width
0.445
0.447
(hexagonal)
(hexagonal)
Cell Pitch
0.483
0.483
*all dimensions are in millimeters.
Prior to casting, the tungsten powder was loaded or mixed into the CERROLOWT™ alloy. The first step was to super-heat the alloy to 2-3 times its melting point temperature (between 234-351 degrees F.), and to maintain this temperature. The tungsten powder, having particle sizes ranging from 1-15 microns in size, was measured by weight to 50% of the base alloy weight in a furnace crucible. A resin-based, lead-compatible soldering flux was added to the tungsten powder to serve as a wetting agent when combining the powder and the alloy. The resin flux was obtained from the Indium Corporation of America of Utica N.Y., under the name Indalloy Flux # 5RMA.
The flux and the powder were heated to a temperature of 200 degrees F. and mixed together after the flux became liquid. The heated CERROLOW™ alloy and the fluxed powder then were combined and mixed using a high-shear mixer at a constant temperature of 220 degrees F. The net density of the alloy loaded with the powder was measured at 12.5 grams per cubic centimeter. The loaded alloy was molded into the derived RTV mold, and finished machined using the same process described in Example 6.
Example 10
Collimator Structure Cast from a Ceramic (Variation of Example 7)
This example demonstrates a structure that could be co-aligned with a cast collimator. The structure could be filled with detector materials, such as a scintillator, for pixilation purposes. Ceramic was chosen for high temperature processing of the scintillator materials, which are normally crystals.
Additional cast samples have been produced using a castable silica ceramic material using the same mold described in Example 7 above. The ceramic material, Rescor™-750, was obtained from the Cotronics Corporation of Brooklyn, N.Y. The ceramic material was prepared prior to casting per the manufacturer's instructions. This included mixing the ceramic powder with the supplied activator. Per the manufacturer's instructions, an additional 2% of activator was used to reduce the viscosity of the mixed casting ceramic, in order to aid in filling the fine cavity features of the mold.
The mold was filled and degassed using a similar process and the same mold and non-planar fixture as Example 7 above, covered with a thin sheet of plastic, and allowed to cure for 16 hours at room temperature. The ceramic casting then was removed from the RTV mold and post cured to a temperature of 1750 degrees F., heated at a rate of 200 degrees F. per hour. Post-curing increased the strength of the cast grid structure. The ceramic casting then was ready for the final grinding and lapping process for the removal of the backing.
Additional Fields of Use
Additional exemplary fields of use, illustrative functionalities and/or technology areas, and representative cast devices are contemplated for various embodiments of the invention, as partially listed below. Note that any such device, and many others not specifically listed, can utilize any aspect of any embodiment of the invention as disclosed herein to provide any of the functionalities in any of the fields of use. For example, in the automotive industry, inertial measurement can be provided by an accelerometer, at least a component of which that has been fabricated according to a method of the present invention. Likewise, in the telecommunications field, one or more components of an optical switch, and possibly an entire optical switch, can be fabricated according to a method of the present invention.
Embodiments of such devices can provide any of a number of functionalities, including, for example, material, mechanical, thermal, fluidic, electrical, magnetic, optical, informational, physical, chemical, biological, and/or biochemical, etc. functionalities. Embodiments of such devices can at least in part rely on any of a number of phenomena, effects, and/or properties, including, for example, electrical, capacitance, inductance, resistance, piezoresistance, piezoelectric, electrostatic, electrokinetic, electrochemistry, electromagnetic, magnetic, hysteresis, signal propagation, chemical, hydrophilic, hydrophobic, Marangoni, phase change, heat transfer, fluidic, fluid mechanical, multiphase flow, free surface flow, surface tension, optical, optoelectronic, electro-optical, photonic, wave optic, diffusion, scattering, interference, diffraction, reflection, refraction, absorption, adsorption, mass transport, momentum transport, energy transport, species transport, mechanical, structural dynamic, dynamic, kinematic, vibration, damping, tribology, material, bimetallic, shape memory, biological, biochemical, cell transport, electrophoretic, physical, Newtonian, non-Newtonian, linear, non-linear, and/or quantum, etc. phenomena, effects, and/or properties.
Moreover, note that unless stated otherwise, any device, discrete device component, and/or integrated device component fabricated according to any method disclosed herein can have any dimension, dimensional ratio, geometric shape, configuration, feature, attribute, material of construction, functionality, and/or property disclosed herein.
Among the many contemplated industries and/or fields of use are:
Aerospace Automotive Avionics Biotechnology Chemical Computer Consumer Products Defense Electronics Manufacturing Medical devices Medicine Military Optics Pharmaceuticals Process Security Telecommunications Transportation
Among the many contemplated technology areas are:
Acoustics Active structures and surfaces Adaptive optics Analytical instrumentation Angiography Arming and/or fusing Bio-computing Bio-filtration Biomedical imaging Biomedical sensors Biomedical technologies Cardiac and vascular technologies Catheter based technologies Chemical analysis Chemical processing Chemical testing Communications Computed tomography Computer hardware Control systems Data storage Display technologies Distributed control Distributed sensing DNA assays Electrical hardware Electronics Fastener mechanisms Fluid dynamics Fluidics Fluoroscopy Genomics Imaging Inertial measurement Information technologies Instrumentation Interventional radiography Ion source technologies Lab-on-a-chip Measurements Mechanical technologies Medical technologies Microbiology Micro-fluidics Micro-scale power generation Non-invasive surgical devices Optics Orthopedics Power generation Pressure measurement Printing Propulsion Proteomics Radiography RF (radio frequency) technologies Safety systems Satellite technologies Security technologies Signal analysis Signal detection Signal processing Surgery Telecommunications Testing Tissue engineering Turbomachinery Weapon safeing
Among the many contemplated cast devices and/or cast device components are at least one:
accelerometer actuator airway amplifier antenna aperture application specific microinstrument atomizer balloon catheter balloon cuff beam beam splitter bearing bioelectronic component bio-filter biosensor bistable microfluidic amplifier blade passage blower bubble capacitive sensor capacitor cell sorting membrane chain channel chromatograph clip clutch coextrusion coil collimator comb comb drive combustor compression bar compressor conductor cooler corrosion sensor current regulator density sensor detector array diaphragm diffractive grating diffractive lens diffractive phase plate diffractor diffuser disc display disposable sensor distillation column drainage tube dynamic value ear plug electric generator electrode array electronic component socket electrosurgical hand piece electrosurgical tubing exciter fan fastener feeding device filter filtration membrane flow passage flow regulator fluid coextrusion fluidic amplifier fluidic oscillator fluidic rectifier fluidic switch foil fuel cell fuel processor fuse gear grating grating light valve gyroscope hearing aid heat exchanger heater high reflection coating housing humidity sensor impeller inducer inductor infra-red radiation sensor infusion sleeve infusion test chamber interferometer introducer sheath introducer tip ion beam grid ion deposition device ion etching device jet joint lens lens array lenslet link lock lumen manifold mass exchanger mass sensor membrane microbubble microchannel plate microcombustor microlens micromirror micromirror display microprism microrelay microsatellite component microshutter microthruster microtiterplate microturbine microwell mirror mirror display mixer multiplexer nozzle optical attenuator optical collimator optical switch ordinance control device ordinance guidance device orifice phase shifter photonic switch pin array plunger polarizer port power regulator pressure regulator pressure sensor printer head printer head component prism processor processor socket propeller pump radiopaque marker radiopaque target rate sensor reaction chamber reaction well reactor receiver reflector refractor regulator relay resistor resonator RF switch rim safe-arm device satellite component scatter grid seal septum shroud shunt shutter spectrometer stent stopper supercharger switch tank temperature regulator temperature sensor thruster tissue scaffolding titerplate transmission component transmitter tunable laser turbine turbocharger ultra-sound transducer valve vane vessel vibration sensor viscosity sensor voltage regulator waveplate well wheel wire coextrusion
Additional detailed examples of some of the many possible embodiments of devices and/or device components that can be fabricated according to a method of the present invention are now provided. Additional potential embodiments of these and/or other contemplated devices and/or device components are described in U.S. patent and/or Patent Application Nos. US2001/0031531, US2001/0034114, U.S. Pat. Nos. 408,677, 460,377, 1,164,987, 3,379,812, 3,829,536, 4,288,697, 4,356,400, 4,465,540, 4,748,328, 4,801,379, 4,812,236, 4,825,646, 4,856,043, 4,951,305, 5,002,889, 5,043,043, 5,147,761, 5,150,183, 5,190,637, 5,206,983, 5,252,881, 5,378,583, 5,447,068, 5,450,751, 5,459,320, 5,483,387, 5,551,904, 5,576,147, 5,606,589, 5,620,854, 5,638,212, 5,644,177, 5,681,661, 5,692,507, 5,702,384, 5,718,618, 5,721,687, 5,729,585, 5,763,318, 5,773,116, 5,778,468, 5,786,597, 5,795,748, 5,814,235, 5,814,807, 5,836,150, 5,849,229, 5,851,897, 5,924,277, 5,929,446, 5,932,940, 5,949,850, 5,955,801, 5,955,818, 5,962,949, 5,963,788, 5,985,204, 5,994,801, 5,994,816, 5,998,260, 6,004,500, 6,011,265, 6,014,419, 6,018,422, 6,018,680, 6,055,899, 6,068,684, 6,075,840, 6,084,626, 6,088,102, 6,124,663, 6,133,670, 6,134,294, 6,149,160, 6,152,181, 6,155,634, 6,175,615, 6,185,278, 6,188,743, 6,197,180, 6,210,644, 6,219,015, 6,226,120, 6,226,120, 6,242,163, 6,245,487, 6,245,849, 6,250,070, 6,252,938, 6,261,066, 6,276,313, 6,280,090, 6,299,300, 6,307,815, 6,310,419, 6,314,887, 6,318,069, 6,318,849, 6,324,748, 6,328,903, 6,333,584, 6,333,584, 6,336,318, 6,338,199, 6,338,249, 6,340,222, 6,344,392, 6,346,030, 6,350,983, 6,360,424, 6,363,712, 6,363,843, 6,367,911, 6,373,158, 6,375,871, 6,381,846, 6,382,588, 6,386,015, 6,387,713, 6,392,187, 6,392,313, 6,392,524, 6,393,685, 6,396,677, 6,397,677, 6,397,793, 6,398,490, 6,404,942, 6,408,884, 6,409,072, 6,410,213, 6,415,860, 6,416,168, 6,433,657, 6,440,284, 6,445,840, 6,447,727, 6,450,047, 6,453,083, 6,454,945, 6,458,263, 6,462,858, 6,467,138, 6,468,039, 6,471,471, and/or 6,480,320, each of which are incorporated by reference herein in their entirety.
MicrovalvesMicrovalves can be enabling components of many microfluidic systems that can be used in many industry segments. Microvalves are generally classified as passive or active valves, but can share similar flow characteristics through varied orifice geometries. Diaphragm microvalves can be useful in many fluidic applications. FIG. 48A is a top view of an array 48010 of generic microdevices 48000 .
FIG. 48B is a cross section of a particular microdevice 48000 in this instance a diaphragm microvalve, taken along section lines 48 - 48 of FIG. 48A , the microvalve including diaphragm 48010 and valve seat 48020 , as shown in the open position. FIG. 49 is a cross section of the diaphragm microvalve 48000 , again taken along section lines 48 - 48 of FIG. 48A , the microvalve in the closed position.
The flow rate through diaphragm microvalve 48000 can be controlled via the geometric design of the valve seat, which is often referred to as gap resistance. The physical characteristics of the valve seat, in combination with the diaphragm, can affect flow characteristics such as fluid pressure drop, inlet and outlet pressure, flow rate, and/or valve leakage. For example, the length, width, and/or height of the valve seat can be proportional to the pressure drop across the microvalve's diaphragm. Additionally, physical characteristics of the diaphragm can influence performance parameters such as fluid flow rate, which can increase significantly with a decrease in the Young's modulus of the diaphragm material. Valve leakage also can become optimized with a decrease in the Young's modulus of the diaphragm, which can enable higher deflection forces, further optimizing the valve's overall performance and/or lifetime.
Typical microvalve features and specifications can include a valve seat: The valve seat, which is sometimes referred to as the valve chamber, can be defined by its' size and the material from which it is made. Using an exemplary embodiment of a method of the present invention, the dimensions of the chamber can be as small as about 10 microns by about 10 microns if square, about 10 microns in diameter if round, etc., with a depth in the range of about 5 microns to millimeters or greater. Thus, aspect ratios of 50, 100, or 200:1 can be achieved. The inner walls of the chamber can have additional micro features and/or surfaces which can influence various parameters, such as flow resistance, Reynolds number, mixing capability, heat exchange fouling factor, thermal and/or electrical conductivity, etc.
The chamber material can be selected for application specific uses. As examples, a ceramic material can be used for high temperature gas flow, or a chemical resistant polymer can be used for chemical uses, and/or a bio-compatible polymer can be used for biological uses, to name a few. Valve chambers can be arrayed over an area to create multi-valve configurations. Each valve chamber can have complex inlet and outlet channels and/or ports to further optimize functionality and/or provide additional functionality.
Typical microvalve features and specifications can also include a diaphragm: The diaphragm can be defined by its size, shape, thickness, durometer (Young's modulus), and/or the material from which it is made. Using an exemplary embodiment of a method of the present invention, the dimensions of the diaphragm can be as small as about 25 microns by about 25 microns if square, about 25 microns in diameter if round, etc., with thickness of about 1 micron or greater. The surface of one side or both sides of the diaphragm could have micro features and/or surfaces to influence specific parameters, such as diaphragm deflection and/or flow characteristics. The diaphragm can be fabricated as a free form device that is attached to the valve in a secondary operation, and/or attached to a substrate. Diaphragms can be arrayed to accurately align to a matching array of valve chambers. Potential performance parameters can include valve seat and diaphragm material, diaphragm deflection distance, inlet pressure, flow, and/or lifetime.
Micropumps
FIGS. 50 and 51 are cross-sectional views of a particular micro-device 48000 , in this case a typical simplified micropump, taken along section lines 48 - 48 of FIG. 3048A . Micropumps can be an enabling component of many microfluidic systems that can be used in many industry segments. Reciprocating diaphragm pumps are a common pump type used in micro-fluidic systems. Micropump 50000 includes two microvalves 50010 and 50020 , a pump cavity 50030 , valve diaphragms 50040 and 50050 , and actuator diaphragm 50060 .
At the initial state of pump 50000 , the actuation is off, both inlet and outlet valves 50010 and 50020 are closed, and there is no fluid flow through pump 50000 . Once actuator diaphragm 50060 is moved upwards, the cavity volume will be expanded causing the inside pressure to decrease, which opens inlet valve 50010 and allows the fluid to flow into and fill pump cavity 50030 , as seen in FIG. 50 . Then actuator diaphragm 50060 moves downward, shrinking pump cavity 50030 , which increases the pressure inside cavity 50030 . This pressure opens outlet valve 50020 and the fluid flows out of the pump cavity 50030 as seen in FIG. 51 . By repeating the above steps, continuous fluid flow can be achieved. The actuator diaphragm can be driven using any of various drives, including pneumatic, hydraulic, mechanical, magnetic, electrical, and/or piezoelectrical, etc. drives.
Typical microvalve features and specifications can include any of the following, each of which are similar to those features and specifications described herein under Microvalves:
Valve seats Valve actuators (diaphragm) Cavity chamber Actuator diaphragm
Potential performance parameters can include valve seat, chamber material, actuator diaphragm material, valve diaphragm material, deflection distance for actuator, deflection distance for valve diaphragms, inlet pressure, outlet pressure, chamber capacity, flow rate, actuator drive characteristics (pulse width, frequency, and/or power consumption, etc.), and/or lifetime.
Microwells and Microwell Arrays
Microwells can be an enabling component in many devices used for micro-electronics, micro-mechanics, micro-optics, and/or micro-fluidic systems. Precise arrays of micro-wells, potentially having hundreds to thousands of wells, can further advance functionality and process capabilities. Microwell technology can be applied to DNA micro-arrays, protein micro-arrays, drug delivery chips, microwell detectors, gas proportional counters, and/or arterial stents, etc. Fields of use can include drug discovery, genetics, proteomics, medical devices, x-ray crystallography, medical imaging, and/or bio-detection, to name a few.
For example, using exemplary embodiments of the present invention, microwells can be engineered in the third (Z) dimension to produce complex undercuts, pockets, and/or sub-cavities. Wells can also be arrayed over various size areas as redundant or non-redundant arrays. These features can include the dimensional accuracies and/or tolerances described earlier. Also, a range of surface treatments within the well structure are possible that can enhance the functionality of the well.
Examples of Microwell Applications
DNA Microarrays: Scientists can rely on DNA microarrays for several purposes, including 1) to determine gene identification, presence, and/or sequence in genotype applications by comparing the DNA on a chip; 2) to assess expression and/or activity level of genes; and/or 3) to measure levels of proteins in protein based arrays, which can be similar to DNA arrays.
DNA microarrays can track tens of thousands of reactions in parallel on a single chip or array. Such tracking is possible because each probe (a gene or shorter sequence of code) can be deposited in an assigned position within the cell array. A DNA solution, representing a DNA sample that has been chopped into constituent sequences of code, can be poured over the entire array (DNA or RNA). If any sequence of the sample matches a sequence of any probe, the two will bind, and non-binding sequences can be washed away. Because each sequence in the sample or each probe can be tagged or labeled with a fluorescent, any bound sequences will remain in the cell array and can be detected by a scanner. Once an array has been scanned, a computer program can convert the raw data into a color-coded readout.
Protein Microarrays: The design of a protein array is similar to that of a DNA chip. Hundreds to thousand of fluorescently labeled proteins can be placed in specific wells on a chip. The proteins can be deposited on the array via a pin or array of pins that are designed to draw fluidic material from a well and deposit it on the inside of the well of the array. The position and configuration of the cells on the array, the pins, and the wells are located with the accuracy needed to use high-speed pick-and-place robotics to move and align the chip over the fluidic wells. A blood sample is applied to the loaded array and scanned for bio-fluorescent reactions using a scanner.
Certain embodiments of the invention enable DNA or Protein microarrays having a potentially large number of complex 3-dimensional wells to be fabricated using any of a range of materials. For example, structures can be fabricated that combine two or more types of material in a microwell or array. Additional functionality and enhancements can be designed into a chip having an array of microwells. Wells can be produced having cavities capable of capturing accurate amounts of fluids and/or high surface-to-volume ratios. Entrance and/or exit configurations can enhance fluid deposition and/or provide visual enhancements to scanners when detecting fluorescence reactions. Very precise well locations can enable the use of pick and place robotics when translating chips over arrays of fluidic wells. Certain embodiments of the invention can include highly engineered pins and/or pin arrays that can be accurately co-aligned to well arrays on chips and/or can have features capable of efficiently capturing and/or depositing fluids in the wells.
Arterial Stents: Stents are small slotted cylindrical metal tubes that can be implanted by surgeons to prevent arterial walls from collapsing after surgery. Typical stents have diameters in the 2 to 4 millimeter range so as to fit inside an artery. After insertion of a stent, a large number of patients experience restenosis—a narrowing of the artery—because of the build-up of excess cells around the stent as part of the healing process. To minimize restenosis, techniques are emerging involving the use of radioactive elements or controlled-release chemicals that can be contained within the inner or outer walls of the stent.
Certain embodiments of the invention can provide complex 3-dimensional features that can be designed and fabricated into the inside, outside, and/or through surfaces of tubing or other generally cylindrical and/or contoured surfaces. Examples 4 and 5 teach such a fabrication technique for a 3 mm tube. Certain embodiments of the invention can allow the manufacture of complex 2-dimensional and/or 3-dimensional features through the wall of a stent. Micro surfaces and features can also be incorporated into the stent design. For example, microwells could be used to contain pharmaceutical materials. The wells could be arrayed in redundant configurations or otherwise. The stent features do not have to be machined into the stent surface one at a time, but can be applied essentially simultaneously. From a quality control perspective, features formed individually typically must be 100% inspected, whereas features produced in a batch typically do not. Furthermore, a variety of application specific materials (e.g., radio-opaque, biocompatible, biosorbable, biodissolvable, shape-memory) can be employed.
Microwell Detectors: Microwells and microwell arrays can be used in gas proportional counters of various kinds, such as for example, in x-ray crystallography, in certain astrophysical applications, and/or in medical imaging. One form of microwell detector consists of a cylindrical hole formed in a dielectric material and having a cathode surrounding the top opening and anode at the bottom of the well. Other forms can employ a point or pin anode centered in the well. The microwell detector can be filled with a gas such as Xenon and a voltage can be applied between the cathode and anode to create a relatively strong electric field. Because of the electric field, each x-ray striking an atom of the gas can initiate a chain reaction resulting in an “avalanche” of hundreds or thousands of electrons, thereby producing a signal that can be detected. This is known as a gas electron multiplier. Individual microwell detectors may be used to detect the presence and energy level of x-rays, and if arrays of microwell detectors are employed, an image of the x-ray source can be formed. Such arrays can be configured as 2-dimensional and/or 3-dimensional arrays.
Certain embodiments of the invention can enable arrays of complex 3-dimensional wells to be fabricated and bonded or coupled to other structures such as a cathode material and anode material. It is also possible to alter the surface condition of the vertical walls of the wells, which can enhance the laminar flow of electrons in the well. A number of possible materials can be used to best meet the needs of a particular application, enhancing parameters such as conductivity, die-electrical constant, and/or density. Certain embodiments of the invention can further enable the hybridizing of micro-electronics to a well array, in particular because of accurate co-alignment between the micro-electronic feature(s), and/or the structural elements of the well.
Typical Microwell Features, Specifications and Potential Performance Parameters:
FIG. 52 is a top view of an exemplary microwell array 52000 , showing microwells 52010 , and the X- and Y-axes. Array 52000 is shown as rectangle, but could be produced as a square, circle, or any other shape. Either of the array's dimensions as measured along the X- or Y-axes can range from 20 microns to 90 centimeters. Microwells 52010 are shown having circular perimeters, but could also be squares, rectangles, or any other shape. Array 52000 is shown having a redundant array of wells 52010 , but could be produced to have non-redundant wells. The positional accuracy of wells 52010 can be accurate to the specifications described herein for producing lithographic masks. Wells can range in size from 0.5 microns to millimeters, with cross-sectional configurations as described herein.
Using certain embodiments of a method of the present invention, certain materials can be used to produce microwell arrays for specific uses. For example, a ceramic material can be used for high-temperature gas flow, a chemical resistant polymer can be used for chemical uses, and/or a bio-compatible polymer can be used for biological uses, to name a few. Specialty composite materials can enhance application specific functionality by being conductive, magnetic, flexible, hydrophilic, hydrophobic, piezoelectric, to name a few.
Using an embodiment of a method of the present invention, microwells with certain 3-dimensional cross-sectional shapes can be produced. FIG. 52 is a top view of an exemplary array 52000 of microwells 52010 .
FIG. 53 is a cross-sectional view, taken at section lines 52 - 52 of FIG. 52 , of an exemplary microwell 53000 having an entrance 53010 . Entrance 53010 is shown having a tapered angle, which could be angled from 0 degrees to nearly 180 degrees. Entrance 53010 is also shown having a different surface than well area 53020 . Well area 53020 can be square, round, rectangular, or any other shape. Well area 53020 can range in size from 0.5 microns to millimeters in width and can be dimensionally controlled in the Z-axis to have aspect ratios of from about 50:1 to about 100:1.
FIG. 54 is a cross-sectional view, taken at section lines 52 - 52 of FIG. 52 , of an alternative exemplary microwell 54000 that defines an entrance 54010 , a well 54020 , and an exit 54030 . Microwell 54000 can be used in applications that require fluids that are conveyed from below or above the entrance 54010 and/or exit 54030 , and deposited in well 54020 . Using an embodiment of a method of the present invention, microwell 54000 can be produced so that well 54020 is hydrophilic and entrance 54010 and exit 54030 are hydrophobic to, for example, enable the deposition of fluid into well 54020 , and discourage the fluid deposition, retention, and/or accumulation on entrance 54010 , on exit 54030 , and/or on the chip's surface. For uses where microelectronic controls or chips are employed, the material surrounding and/or defining entrance 54010 and/or 54030 can be conductive or non-conductive, as required. Well 54020 can be dimensioned to accurately contain a pre-determined amount of fluid.
The shape and size of corner feature 54040 can be defined to encourage the discharge of a fluid material from a fluidic channel on a pin, when a pin is produced using any of certain embodiments of the invention. For example, pins can be produced having fluidic channels or undercuts that are positioned radially at the end of the pin. The undercuts can serve as reservoirs that increase surface area-to-volume ratios and/or hold accurate amounts of fluids. If the undercuts are designed to be relatively flexible and larger than the opening dimension at feature 54040 , fluid can be squeezed from the reservoir as the fluid passes by corner feature 54040 . Entrance 54010 can have an angle that promotes the visibility of a material, such as a fluid, in well 54020 . The material surrounding and/or defining well 54020 can be fabricated to have micro-surface features to increase the well's surface area-to-volume ratio.
FIG. 55 is a top view of an exemplary microwell 55000 showing a well area 55010 and sub-cavities 55020 . FIG. 56 is a cross-sectional view, taken at section lines 56 - 56 of FIG. 55 , of microwell 55000 showing well 55010 and sub-cavities 55020 . Well 55010 can extend through the material that defines it, as shown in FIG. 56 , or can be a closed well having a solid floor. Sub-cavities 55020 can be incorporated within a well to, for example, increase an area of the surface(s) bordering the well, a volume, and/or surface area-to-volume ratio of the well. Sub-cavities 55020 can be continuous rings as shown in FIG. 55 . Alternatively, sub-cavities 55020 can be discrete pockets forming sub-wells within well 55010 . Sub-cavities 55020 can be positioned on a horizontal floor or subfloor of well 55010 as shown in FIG. 55 , on the vertical walls of well 55010 , and/or on another surface. Sub-cavities 55020 can have circular, square, rectangular, and/or any of a variety of other cross-sectional shapes. Sub-cavities 55020 can also be positioned to provide an enhanced visual perspective of a deposited material from which could be angled from 0 degrees to nearly 0.180 degrees, such as an approximately perpendicular angle, so as to enhance scanning performance or resolution.
Filtration
Filtration can be an important element in many industries including medical products, food and beverage, pharmaceutical and biological, dairy, waste water treatment, chemical processing, textile, and/or water treatment, to name a few. Filters are generally classified in terms of the particle size that they can separate. Micro-filtration generally refers to separation of particles in the range of approximately 0.01 microns through 20 microns. Separation of larger particles than approximately 10-20 microns is typically referred to as particle separation. There are two common forms of filtration, cross-flow and dead-end. In cross-flow separation, a fluid stream runs parallel to a membrane of a filter while in dead-end separation, the filter is perpendicular to the fluid flow. There are a very large number of different shapes, sizes, and materials used for filtration depending on the particular application.
Certain embodiments of the invention can be filters suitable for micro-filtration and/or particle filtration applications. Certain embodiments of the invention allow fabrication of complex 2-dimensional and/or 3-dimensional filters offering redundant or non-redundant pore size, shape, and/or configuration. For example, a circular filter can have an array of redundant generally circular through-features, each through-feature having a diameter slightly smaller than a target particle size. Moreover, the through-feature can have a tapered, countersunk, and/or undercut entrance, thereby better trapping any target particle that encounters the through-feature. Further, the cylindrical walls defined by the through-feature can have channels defined therein that are designed to allow a continued and/or predetermined amount of fluid flow around a particle once the particle encounters the through-feature. The fluid flow around the particle can create eddys vortices, and/or other flow patterns that better trap the particle against the filter.
Certain embodiments of the filter can have features that allow the capture of particles of various sizes at various levels of the filter. For example, an outer layer of the filter can capture larger particles, a middle layer can capture mid-sized particles, and a final layer can capture smaller particles. There are numerous techniques for accomplishing such particle segregation, including providing through-features having tapered, stepped, and/or diminishing cross-sectional areas.
In certain embodiments, the filter can include means for detecting a pressure drop across the filter, and/or across any particular area, layer, and/or level of the filter. For example, in a filter designed to filter a gas such as air, micro pitot tubes can be fabricated into each layer of the filter (or into selected layers of the filter). Such pressure measurement devices can be used to determine the pressure drop across each layer, to detect the level of “clogging” of that layer, and/or to determine what size and/or concentration of particles are entrapped in the filter.
Further, certain embodiments of the invention allow for fabrication of filters in a wide range of materials including metals, polymers, plastics, ceramics, and/or composites thereof. In biomedical applications, for instance, a biocompatible material can be used that will allow filtration of blood or other body fluids. Using certain embodiments of the invention, filtration schemes can be engineered as planar or non-planar configurations.
Sorting
Sorting can be considered a special type of filtration in which particles, solids, and/or solids are separated by size. In biomedical applications for example, it may be desirable to sort blood or other types of cells by size and deliver different sizes to different locations. Certain embodiments of the invention can enable the fabrication of complex 3-dimensional structures that allow cells to be sorted by size (potentially in a manner similar to that discussed herein for filters) and/or for cells of different sizes to be delivered through different size micro-channels or between complex 3-dimensional structures. Structures can be material specific and on planar or non-planar surfaces.
Membranes
Membranes can offer filtration via pore sizes ranging from nanometers to a few microns in size. Membrane filtration can be used for particles in the ionic and molecular range, such as for reverse osmosis processes to desalinate water. Membranes are generally fabricated of polymers, metals, or ceramics. Micro-filtration membranes can be divided into two broad types based on their pore structure. Membranes having capillary-type pores are called screen membranes, and those having so-called tortuous-type pores are called depth membranes.
Screen membranes can have nearly perfectly round pores that can be dispersed randomly over the outer surface of the membrane. Screen membranes are generally fabricated using a nuclear track and etch process. Depth membranes offer a relatively rough surface where there appear to be openings larger than the rated size pore, however, the fluid must follow a random tortuous path deeper into the membrane to achieve their pore-size rating. Depth membranes can be fabricated of silver, various cellulosic compounds, nylon, and/or polymeric compounds.
Certain embodiments of the invention enable fabrication of membranes having complex 3-dimensional shapes, sizes, and/or configurations made of polymers, plastics, metals, and/or ceramics, etc. Furthermore, such membranes can embody redundant or non-redundant pores, and can be fabricated to be flexible, rigid, and/or non-planar depending upon the material and/or application requirements.
Heaters
Certain exemplary embodiments of the present invention can provide heaters and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment of the present invention can provide a resistive heater having numerous wire, strip, and/or coil, etc. elements having substantially large length and/or width dimensions with respect to their thickness dimensions. Certain exemplary embodiments of the present invention can provide heaters that utilize a Seebeck effect for heating.
Heat Exchangers
Certain exemplary embodiments of the present invention can provide heat exchangers and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment of the present invention can provide a heat exchanger having numerous “fins” or other surfaces having substantially large length and/or width dimensions with respect to their thickness dimensions, thereby providing relatively large surface area to volume ratios to facilitate heat transfer. Such heat exchangers can be used for heating and/or cooling of a target fluid and/or material. Also, exemplary embodiments of the present invention can provide thin-walled tubular heat exchangers, having tubes that potentially incorporate “fins” and/or other heat transfer surfaces. Exemplary embodiments of fins and the like can have secondary features that can be useful for further increasing surface area, manipulating and/or optimizing flow, controlling fouling, etc. Certain exemplary embodiments of the present invention can provide heat exchangers that utilize a Peltier, Seebeck, and/or Joule effect for cooling and/or heating.
Mass Exchangers
Certain exemplary embodiments of the present invention can provide mass exchangers and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment of the present invention can provide a mass exchanger having numerous “fins” or other surfaces capable of releasing an impregnated and/or bound material, and/or having receptors for receiving a target material. Each such fin can have substantially large length and/or width dimensions with respect to their thickness dimensions, thereby providing relatively large surface area to volume ratios to facilitate mass transfer. Another exemplary embodiment can provide a mass exchanger, such as pieces of packing, each having numerous surfaces and having a large surface area to volume ratio. Another exemplary embodiment can provide a mass exchanger, such as a static mixer having numerous fluid dividing/mixing surfaces. Exemplary embodiments of fins and the like can have secondary features that can be useful for further increasing surface area, manipulating and/or optimizing mass transfer, etc.
Surface Reactors
Certain exemplary embodiments of the present invention can provide surface reactors and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment of the present invention can provide a surface reactor having numerous “fins” or other surfaces comprising and/or bound to a material capable of reacting with a target material, and/or catalyzing such a reaction. Each such fin can have substantially large length and/or width dimensions with respect to their thickness dimensions, thereby providing relatively large surface area to volume ratios to facilitate higher reaction rates. Exemplary embodiments of fins and the like can have secondary features that can be useful for further increasing surface area, manipulating and/or optimizing reaction rates, controlling heating, cooling, mixing, and/or flow, etc.
Fuel Cells
Certain exemplary embodiments of the present invention can provide a fuel cell having one or more discrete and/or integrated components such as a channel, manifold, separator, pump, valve, filter, heater, cooler, heat exchanger, mass exchanger, and/or surface reactor, etc., of any size and/or configuration. Such a fuel cell can be useful as a power cell, battery, charger, etc. For example, an embodiment of the invention can provide a fuel cell having a solid electrolyte disposed between an oxygen electrode and a fuel electrode, and one or more separators can contact the surface of one of the electrodes opposite of the electrolyte. At least one electrode of the cell can define a micro-channel pattern, wherein the micro-channel cross-section can be varied, such that reactant gas flowing through the micro channels can achieve tailored local flow, pressure, and/or velocity distributions. An exemplary embodiment of the invention can provide a proton exchange diffusion membrane fuel cell having a membrane and/or channels. An exemplary embodiment of the invention can provide a fluid fuel cell, such as a hydrogen fuel cell, proton exchange member, and/or a direct methanol fuel cell, utilizing one or more fluid mixers, mixing chambers, pumps, and/or recirculators.
Turbomachinery and Machinery
Certain exemplary embodiments of the present invention can provide turbomachinery devices and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment can provide a microturbine having an impeller, rotor, blades, stages, seals, and/or nozzles, etc., any of which can high a high aspect ratio be formed from a material having a high strength, and/or be formed from a material having desired thermal performance capabilities, such as a ceramic. The microturbine can that can be coupled to a microgenerator for generating electrical power and/or can be used for generating thrust. Another exemplary embodiment can provide a microcombustion engine having free pistons magnetically coupled to electromagnets for control and power transfer.
Ion Beam Technologies
Certain exemplary embodiments of the present invention can provide ion beam devices and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, space propulsion, surface cleaning, ion implantation, and high energy accelerators use two or three closely spaced multiple-aperture electrodes to extractions from a source and eject them in a collimated beam. The electrodes are called “grids” because they are perforated with a large number of small holes in a regular array. A series of grids constitute an “ion optics” electrostatic ion accelerator and focusing system.
Ion Thrusters
On-board propulsion systems can be used to realize a variety of spacecraft maneuvers. In satellites, for example, these maneuvers include the processes of orbit raising (e.g., raising from a low Earth orbit to a geostationary orbit), stationkeeping (e.g., correcting the inclination, drift and eccentricity of a satellite's orbit) and attitude control (e.g., correcting attitude errors about a satellite's roll, pitch and yaw axes).
Certain exemplary embodiments of the present invention can provide propulsion and/or micropropulsion devices and/or components potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment can provide an ion thruster, microthruster, Kaufman-type ion engine, and/or electric rocket engine that can be useful for maintaining the orbit and/or relative position of a geosynchronous satellite. Such a device can utilize an orifice, orifice array, and/or grid. In certain embodiments, an ion thruster grid can have a spherically-formed and/or domed screen pattern with, for example, a high resolution and/or high aspect ratio.
Ion beam sources designed for spacecraft propulsion, that is, ion thrusters, typically are preferred to have long lifetimes (10,000 hours or more), be efficient, and be lightweight. Ion thrusters have been successfully tested in space, and show promise for significant savings in propellant because of their high specific impulse (an order of magnitude higher than that of chemical rocket engines). They have yet to achieve any significant space use, however, because of lifetime limitations resulting from grid erosion and performance constraints resulting from thermal-mechanical design considerations, particularly the spacing of metallic grids, including molybdenum.
In an ion thruster, a plasma is created and confined within the body of the thruster. Ions from the plasma are electrostatically accelerated rearwardly by an ion-optics system. The reaction with the spacecraft drives it forwardly, in the opposite direction. The force produced by the ion thruster is relatively small. The ion thruster is therefore operated for a relatively long period of time to impart the required momentum to the heavy spacecraft. For some missions the ion thruster must be operable and reliable for thousands of hours of operation, and with multiple starts and stops.
The ion-optics system can include grids to which appropriate voltages are applied in order to accelerate the ions rearwardly. In a typical electron bombardment ion thruster, a cathode produces electrons that strike neutral gas atoms introduced through a propellant feed line. The electrons ionize the gas propellant and produce a diffuse plasma. In a radio frequency ion thruster, the propellant is ionized electromagnetically by an external coil, and there is no cathode. In both cases, an anode associated with the plasma raises its positive potential. To maintain the positive potential of the anode, a power supply pumps to ground potential some of the electrons that the anode collects from the plasma. These electrons are ejected into space by a neutralizer to neutralize the ion beam. Magnets act to inhibit electrons and ions from leaving the plasma. Ions drift toward the ion optics, and enter the holes in a screen grid. A voltage difference between the screen grid and an accelerator grid accelerates the ions, thereby creating thrust. The screen grid is at the plasma potential, and the accelerator grid is held at a negative potential to prevent downstream electrons from entering the thruster. Optionally, the optics can include a decelerator grid located slightly downstream of the accelerator grid and held at ground potential or at a lesser negative potential than the accelerator grid to improve beam focusing and reduce ion impingement on the negative accelerator grid.
The grids can be in a facing orientation to each other, spaced apart by relatively small clearances such as about 0.035 inches at room temperature. The grids can include aligned apertures therethrough. Some of the ions accelerated by the applied voltages can pass through the apertures, providing the propulsion. Others of the ions can impact the grids, heating them and etching away material from the grids by physical sputtering. The heating and electrostatic forces on the grids can combine to cause substantial mechanical forces at elevated temperature on the grids, which can distort the grids unevenly. The uneven distortion of the grids can cause adjacent grids to physically approach each other, rendering them less efficient and prone to shorting against each other. These effects can be taken into account in the design of the grids and the operation of the ion thruster, so that the thruster can remain functional for the required extended lifetimes. However, limitations may be placed on the operation of the ion thruster because of grid distortion, such as a relatively slow ramp-up in power during startup and operation, so that the adjacent grids do not expand so differently that they come into contact.
A factor that can affect the efficiency and/or the weight of ion thrusters is how closely and precisely the grids can be positioned while maintaining relative uniformity in the grid-to-grid spacing at high operating temperatures or in conditions where the spatial temperature is nonuniform and thermal distortion can occur because of temperature gradients.
Grids are frequently made of molybdenum formed into a domed shape. The molybdenum can resist material removal by physical sputtering. The domed shape can establish the direction of change due to thermal expansion and/or can aid in preventing a too-close approach of the adjacent grids as a result of differences in temperatures of the adjacent grids.
Exemplary embodiments of ion thruster grids of the present invention, such as those formed according to an exemplary embodiment of a method of the present invention, can be precisely formed into matching shapes, which can account for deformation that can occur due to thermal expansion when a thruster heats in operation. Changes in the actual spacing and the uniformity of spacing over the grid surfaces between the grids can potentially be predicted and/or controlled. Exemplary embodiments of ion thruster grids of the present invention, such as those formed according to an exemplary embodiment of a method of the present invention, can be formed of any moldable material, include tungsten, molybdenum, ceramics, graphite, etc.
Exemplary embodiments of ion thruster grids of the present invention, such as those formed according to an exemplary embodiment of a method of the present invention, can have relatively long lifetimes, allow for precise alignment and/or spacing between grids, and/or allow for precise alignment and/or spacing of grid openings.
Ion Beam Grids
Ion beams can be used in the production of components in the micro-electronics industry and magnetic thin film devices in the storage media industry. Typically, an ion beam, such as an argon ion beam, has a large area, a high current and an energy of between 100 eV and 2 keV. The beam can be used in a number of ways to modify the surface of a substrate, for example by sputter deposition, sputter etching, milling, or implantation.
In a typical ion beam source (or ion gun) a plasma is produced by admitting a gas or vapor to a low pressure discharge chamber containing a heated cathode and an anode which serves to remove electrons from the plasma and to give a surplus of positively charged ions which pass through a screen grid or grids into a target chamber which is pumped to a lower pressure than the discharge chamber. Ions are formed in the discharge chamber by electron impact ionization and move within the body of the ion gun by random thermal motion. The plasma will thus exhibit positive plasma potential which is higher than the potential of any surface with which it comes into contact. Various arrangements of grids can be used, the potentials of which are individually controlled. In a multigrid system, the first grid encountered by the ions is usually positively biased whilst the second grid is negatively biased. A further grid may be used to decelerate the ions emerging from the ion source so as to provide a collimated beam of ions having more or less uniform energy. For ion sputtering a target is placed in the target chamber where this can be struck by the beam of ions, usually at an oblique angle, and the substrate on to which material is to be sputtered is placed in a position where sputtered material can impinge on it. When sputter etching, milling or implantation is to be practiced the substrate is placed in the path of the ion beam.
Hence, in a typical ion gun an ion arriving at a multiaperture extraction grid assembly first meets a positively biased grid. Associated with the grid is a plasma sheath. Across this sheath is dropped the potential difference between the plasma and the grid. This accelerating potential will attract ions in the sheath region to the first grid. Any ion moving through an aperture in this first grid, and entering the space between the first, positively biased grid, and the second, negatively biased, grid is strongly accelerated in an intense electrical field. As the ion passes through the aperture in the second grid and is in flight to the grounded target it is moving through a decelerating field. The ion then arrives at an grounded target with an energy equal to the potential of the first, positive, grid plus the sheath potential.
Exemplary embodiments of ion beam grids of the present invention, such as those formed according to an exemplary embodiment of a method of the present invention, can have relatively long lifetimes, allow for precise alignment and/or spacing between grids, and/or allow for precise alignment and/or spacing of grid openings. Such grids can be planar and/or non-planar, can have redundant and/or non-redundant grid openings, can have anisotropic and/or isotropic grid openings, and/or can be constructed of nearly any moldable material, including composite materials.
Microfluidics
Certain exemplary embodiments of the present invention can provide fluidic and/or microfluidic devices and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment can provide a pressure regulator and/or controller that utilizes a valve, orifice, and/or nozzle having a high aspect ratio and formed using an embodiment of the present invention.
Actuators
Certain exemplary embodiments of the present invention can provide actuators and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment can provide a valve actuator having an electromagnetic, magnetic, piezoelectric, electrostatic, bimetallic, and/or shape memory component formed using an embodiment of the present invention and having a high aspect ratio.
Attenuators
Certain exemplary embodiments of the present invention can provide attenuators and/or components thereof, potentially having high resolution and/or high aspect ratios. For example, an exemplary embodiment can provide an acoustical attenuator having numerous microbaffles for absorbing undesired sound waves, such as sound waves of a particular frequency range. Such baffles can be textured, dimensioned, and/or shaped to enhance their performance capabilities. Likewise, attenuators can be provided for attenuating flow, electromagnetic radiation (e.g., light, electrical current, x-rays, etc.), etc.
Motion Devices
Certain exemplary embodiments of the present invention can provide gyroscopes, accelerometers, tilt detectors, etc., and/or components thereof, potentially having high resolution and/or high aspect ratios. Such devices can be useful for navigation, stabilitization, airbag crash systems, vibration detection, earthquake detection, anti-theft and/or security systems, active suspensions, automated braking systems, vehicle rollover prevention systems, headlight leveling systems, seatbelt tensioners, motor controllers, pedometers, stereo speakers, computer peripherials, flight simulators, sports training, robots, machine health monitors, etc. For example, an exemplary embodiment can provide an accelerometer having a cantilevered inertial mass coupled to at least one electrical element, such as a capacitive sensor that is adapted to generate a signal upon sufficient change in acceleration (movement) of the cantilevered inertial mass. In certain embodiments, the mass and electrical element can be substantially co-planar. In certain embodiments, the mass can have a substantial aspect ratio, and electrical elements can be provided in orthogonal and/or multiple planes, so that changes in orientation, displacement, and/or motion (e.g., linear, curvilinear, and/or rotational velocity, acceleration, jerk, pulse, etc.) in any direction can be sensed, measured, and/or analyzed.
Mirrors
Certain exemplary embodiments of the present invention can provide a mirror and/or components thereof, potentially having high resolution and/or high aspect ratios. Such a mirror can be a component of an optical device and/or an opto-mechanical device, such as an opto-mechanical switching cell and/or a laser scanner, such as is used in a bar-code scanner or a holographic data storage system. Exemplary arrays of mirrors can be redundant and/or non-redundant. Exemplary mirrors can be planar and/or non-planar. Exemplary mirrors can have a reflectivity that varies in any fashion (e.g., linearly, non-linearly, polarly, radially, controllably, periodically, thermally, etc.) across a surface of the mirror.
Grating Light Valves
Grating light valves can resemble small reflectors/diffractors, each comprising several structures that resemble ribbon-like beams supported on each end, which can electrostatically actuated upwards or downwards (typically a fraction of the wavelength of visible light). The ribbon-like structures can be arranged to form an element that variably reflects or diffracts light, in either a continuous or discrete (on-off) manner. Grating light valves can have utility in optical attenuators, switches, relays, direct-to-plate printers, HDTV monitors, electronic cinema projectors, and/or commercial flight simulator displays.
Exemplary embodiments of grating light valves of the present invention, such as those formed according to an exemplary embodiment of a method of the present invention, can include redundant and/or non-redundant arrays of reflector and/or diffractor elements. Each such element can be planar and/or non-planar, and can include an actuator, such as those used in optical switching arrays.
Fuses
Certain exemplary embodiments of the present invention can provide methods for fabricating a fuse and/or components thereof, potentially having a high-resolution and/or high-aspect ratio, which can be used for triggering and/or disconnecting the flow of fluid and/or current. For example, fluid fuse comprising a low melting (fusible) alloy can be useful for triggering and/or actuating a sprinkler head in a fire protection system. As another example, an electrical fuse comprising an electrically fusible alloy can be useful for disconnecting a current flow to an electronic and/or electrical device.
Signal Detecting Collimators and Devices
Certain exemplary embodiments of the present invention can provide methods for fabricating a grid structure and/or components thereof, potentially having a high-resolution and/or high-aspect ratio, which can be used for signal detection collimators. Such devices can be used in the field of acoustics to, for example, enhance acoustical signal detection and/or analysis, by for example, reflecting, dispersing, filtering, and/or absorbing sound waves. Such devices can be used in the field of imaging to, for example, enhance image contrast and quality by refracting, diffracting, reflecting, dispersing, filtering, and/or absorbing scattered radiation (sometimes referred to as “off-axis” radiation and/or “secondary” radiation). In this context, “radiation” means electromagnetic radiation, and can include radio, television, microwave, infrared, visible light, ultraviolet, alpha-rays, beta-rays, gamma rays, and/or x-rays, etc., and can even include high energy particles, ion beams, etc. Moreover, much of the following discussion regarding radiation is analogous to acoustical energy, vibration, and/or other forms of energy that have a varying and/or frequency component (e.g., a time-varying component, a spatially-varying component, a dimensionally-varying component, etc.).
As an example, certain exemplary embodiments of the present invention can provide a collimator having optical properties, such as cell walls capable of absorbing certain wavelengths, that can be used as a notch filter. Other such collimators can have certain cells filled with a material that has certain refractive properties, thereby providing a lens effect with those cells. Other such collimators can have reflective and/or curved cell walls thereby serving as a reflector and/or wave guide.
Certain exemplary embodiments of the present invention can provide a collimator having at least one curved face, and possibly having both faces curved, such that each cell is “pointed” in a different direction. In various embodiments, the curve can be circular, elliptical, curvilinear, cylindrical, and/or spherical, etc., and can be concave and/or convex.
Such collimators can be useful for detecting a direction of a radiation source with respect to the collimator and/or the imaging machine comprising the collimator, particularly when the machine also comprises a pixilated detector array and an image processing capability.
Thus, in certain embodiments, such as those in which the “outer” face of the collimator is convex, such collimators can function as a form of “wide-angle lens” for whatever type of radiation the collimator is designed to pass. Moreover, by analyzing the time variance of the detected radiation, such machines can determine changes in direction or intensity of the emitted and/or incoming radiation. Further, by analyzing the frequency components of the detected radiation, such machines can determine, perhaps with a high degree of precision, the nature of the radiation source.
As an example, an imaging machine comprising such a curved collimator could be deployed at a location having a relatively wide view of a stadium parking lot. The collimator can direct light originating from any particular location in the view to a corresponding detector element. By virtue of its power, time, and/or frequency analysis capability, such an imaging machine could detect the source of a bright and rapid flash of infrared and visible light and/or other forms of radiation, such as occurs when a handgun is fired. The imaging machine could then alert authorities to the location of the fired handgun, and could trigger a video camera to turn to and zoom in on the location to capture a visible image of the scene, potentially capturing images of the faces of witnesses and/or perpetrators, license plate numbers, etc.
As another example, an imaging machine comprising such a curved collimator could be deployed at a location having a relatively wide view of a port, shipping channel, runway, rail yard, border crossing, roadway, warehouse, parking lot, etc. Once deployed, the imaging machine can detect, for example, gamma radiation, such as emitted from a radioactive source, such as a radioactive medical waste, nuclear fuel, and/or a radiation bomb. Upon detection, the imaging machine could alert authorities to the approach, movement, and/or specific location of the radioactive source.
As yet another example, an imaging machine comprising a concave collimator could be deployed at a conveyor and opposite a radiation source, such as is used for scanning passenger bags in commercial airports, train stations, bus depots, etc. In an environment with many such conveyors each having a radiation source, such a collimator can isolate radiation to that coming from its corresponding radiation source.
Although the invention has been described with reference to specific embodiments thereof, it will be understood that numerous variations, modifications and additional embodiments are possible, and accordingly, all such variations, modifications, and embodiments are to be regarded as being within the spirit and scope of the invention. Also, references specifically identified and discussed herein are incorporated by reference as if fully set forth herein.
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Certain exemplary embodiments of the present invention comprise a device comprising a cast collimator derived from a metallic foil stack lamination mold, said collimator defining a feature adapted to contain a plurality of radiation detection elements. In certain embodiments, the collimator can define a feature adapted to contain a plurality of radiation detection elements, such as scintillators. Certain exemplary embodiments of the present invention comprise a device comprising a cast component derived from a metallic foil stack lamination mold. In various exemplary embodiments, the cast components can be a mechanical, electrical, electronic, optical, fluidic, biomedical, and/or biotechnological component. It is emphasized that this abstract is provided to comply with the rules requiring an abstract that will allow a searcher or other reader to quickly ascertain the subject matter of the technical disclosure. This abstract is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims.
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CROSS REFERENCE TO RELATED APPLICATION
This application claims priority to German patent application number 10 2007 052 875.4, filed Nov. 7, 2007.
FIELD OF THE INVENTION
The invention relates to an inflatable restraint type safety device for the protection of vehicle occupants.
BACKGROUND OF THE INVENTION
So-called curtain airbags are known in vehicle engineering and are widely used. Such a curtain airbag forms an upper and lower edge, and the upper edge is connected to the internal vehicle structure along the side of the interior in the area of the roof rail. When in an undepolyed state, the curtain airbag is folded or rolled around its lower edge. If an accident occurs, namely if there is a side collision or the vehicle rolls over, the curtain airbag is filled with gas and unfolds in front of at least one side window of the vehicle. Following the accident, the curtain airbag has to be removed in a repair facility and has to be replaced by a new one. This naturally gives rise to considerable cost. These devices are irreversibly deployed and are not reused once activated.
A further disadvantage of curtain airbags of the type known is as follows: vehicle safety systems are known which do not only activate safety equipment such as airbags, belt tensioners and similar when the vehicle strikes an obstacle, but may be deployed beforehand, with proximity sensors being provided for this purpose. In particular in the case of side collisions, such systems offer advantages, as in contrast to frontal crashes, there is practically no crumple zone to absorb impact. Because of the above, however, curtain airbags may only be triggered as a result of such proximity sensors if the associated electronic system interprets the incoming signals so as to establish that a side impact will certainly occur.
However, with regard to ideal protection of the vehicle occupants, it would be desirable if curtain airbags could also be activated in a preventative sense, in other words at a relatively early stage of a possible accident, even if there is still the chance that no actual side impact or rollover will occur.
The present invention therefore sets itself the task of creating a safety device which can already be activated at an early point in time, even if it is not yet certain that an accident will occur.
SUMMARY OF THE INVENTION
The safety device in accordance with the invention for the protection of the vehicle occupants can work reversibly. This is achieved in that the curtain airbag is rolled up into a roll around its upper edge when in quiescent or uninflated state, and that at least the ends of the upper edge are held to fixing elements in rotatable fashion. Therefore, when in the quiescent state, the curtain airbag is rolled up like a roller blind and can easily be rolled back up or retracted into this state after use. Return elements, for example in the form of constant force springs, are preferably present for this purpose.
It is also advantageous if the curtain airbag when in quiescent state is rolled up onto a shaft, which is fastened to the vehicle structure in a rotatable fashion. This means that the curtain airbag can be rolled up again particularly easily after unfolding. This in turn means that the trigger threshold for the curtain airbag can be lowered, so that the airbag may also be triggered unnecessarily, i.e. in cases where an accident does not subsequently occur. In such a case, following the re-rolling of the curtain airbag, the deployment process can be repeated without the need to visit a garage or workshop. Thus the curtain airbag in accordance with this invention is deployable in a reversible manner.
In the case of curtain airbags as they have been known up to now, the gas generator which fills the curtain airbag or a gas lance which is connected with the gas generator is located in the area of the upper edge of the curtain airbag and the unfolding and expansion of the curtain airbag is achieved by means of the developing gas pressure when gas streams into the curtain airbag in this upper area. In the case of the safety device according to the present invention, further measures are taken for deployment. Therefore preferably means are present which interact with the lower area of the curtain airbag in case of an accident, in order to unroll the curtain airbag. Alternatively or in addition to this, it is possible to fill the curtain airbag from below, for which purpose a lower section of the curtain airbag is connected with a pressure source by means of a hose or gas duct.
Because of the reversibility, it is possible to unfold the curtain airbag in accordance with this invention at an early point in time when a possible impact is detected, the unfolding needs not necessarily occur as rapidly as has been the case with previous curtain airbags. It is therefore also possible not to make use of a pyrotechnical type of gas generator, but, for example, to make use of a compressed air system, which is particularly possible in the case of trucks and lorries which have such a system for other purposes.
BRIEF DESCRIPTION OF THE DRAWINGS
Further preferred embodiments result from the subclaims and also from the embodiments which will now be described in more detail with reference to the drawings. The drawings show:
FIG. 1 is a schematic representation of a safety device in quiescent state in accordance with a first embodiment of the present invention,
FIG. 1 a is an enlarged cut-away section of section D 1 from FIG. 1 ,
FIG. 2 is a cross-section along line A-A from FIG. 1 ,
FIG. 3 shows the system in FIG. 1 following activation of the safety device,
FIG. 4 is a cross-section along Line B-B from FIG. 3 ,
FIG. 5 shows a control scheme for the safety device of the first embodiment,
FIG. 6 is a schematic perspective view of a second embodiment of the invention in activated state,
FIG. 7 is a cross-section along Line C-C from FIG. 6 ,
FIG. 8 is a plan view of the items shown in FIG. 6 from Direction R, whereby a filling hose is shown in two positions,
FIG. 9 is a cross-section through the curtain airbag from FIG. 6 in rolled-up state, and
FIG. 10 shows the curtain airbag from FIG. 9 at an early stage of expansion.
DETAILED DESCRIPTION OF THE INVENTION
FIGS. 1 and 2 show a first embodiment of a safety device in accordance with this invention in a quiescent or undeployed state, whereby FIG. 2 is a cross-section along Line A-A from FIG. 1 . The safety device is in the form of a curtain airbag 10 , which is wound round a hollow shaft 20 . Curtain airbag 10 is basically rectangular with an upper edge 10 a , which extends from a first end to a second end. Hollow shaft 20 is fixed in rotatable fashion to the inner structure of a motor vehicle by means of bearings 22 , namely in the area of the roof rail. This means that also the upper edge 10 a is held in rotatable fashion in relation to bearings 22 serving as fixing elements. At least one constant force spring is present (not shown) which acts on hollow shaft 20 in such a way that in the absence of further forces, it urges the airbag 10 to move to or remain in the rolled-up state shown in FIGS. 1 and 2 .
As can be seen, for example, in FIG. 2 , hollow shaft 20 extends along the upper edge 10 a of curtain airbag 10 and is also connected with curtain airbag 10 in this area. At one end of the hollow shaft 20 , as can be seen in FIG. 1 a , the outflow area 26 a of a gas generator 26 projects into the interior of hollow shaft 20 . This gas generator 26 is mounted in a holder 28 so as to be non-rotatable, and holder 28 is sealed against hollow shaft 20 by means of a seal, whereby hollow shaft 20 can be rotated around holder 28 . As an alternative to gas generator 26 , an outlet valve connected with a compressed air system could also be provided. If gas generator 26 is ignited, gas streams away from it through hollow shaft 20 and through openings 20 a in the walls of the hollow shaft into the interior of curtain airbag 10 . Because curtain airbag 10 is wound onto hollow shaft 20 around its upper edge 10 a , however, the fact that the gas streams in does not lead to unfolding, i.e. to unrolling of curtain airbag 10 , without further measures.
In view of the foregoing, means are provided which actively unroll curtain airbag 10 in case of actuation. These means, in the first embodiment shown here, includes two pistons 32 , which are held in cylinders 34 . These pistons 32 are each connected with the lower edge 10 b of curtain airbag 10 by means of a pull cable 36 being guided by two reversing rollers 38 . Compressed gas connections 40 are present, through which gas can stream into the respective working chamber 34 of cylinder 34 and therefore can drive the respective piston, which means that lower edge 10 b of curtain airbag 10 is pulled downwards by means of pull cables 36 , therefore unrolling the curtain airbag 10 . Preferably curtain airbag 10 is first completely unrolled before curtain airbag 10 is filled with gas, as is shown in the control scheme in FIG. 5 .
The signals of a proximity sensor are led to an evaluation unit. This evaluation unit processes incoming signals—possibly together with further signals—and evaluates if an accident is probable. If the probability lies above a certain threshold value, first the piston-cylinder-units are activated and then, with a certain time delay, which is sufficient to unroll the curtain airbag, the gas generator 26 is ignited, so that the curtain airbag 10 is filled with gas and therefore deploys to develop its full protective effect.
FIGS. 6 to 10 show a second embodiment of the invention. Here too, the curtain airbag 10 is rolled round its upper edge 10 a on a shaft 40 ; however, in this case shaft 40 is not hollow. As also in the first embodiment, upper edge 10 a of curtain airbag 10 is connected with this shaft 40 so as to be incapable of rotation, and shaft 40 is held in rotatable fashion on the inner structure of the vehicle by means of bearings (not shown).
In contrast to the first embodiment, the curtain airbag of the second embodiment is not filled with gas from above, but from below. For this purpose, curtain airbag 10 forms a horizontally-running chamber 14 and several vertically-running chambers 12 extending upwards from the horizontally-running chamber 14 . Horizontally-running chamber 14 extends up to a side edge 10 c of curtain airbag 10 , where it opens into a filling hose 16 (only shown in FIG. 8 ). Filling hose 16 runs completely outside curtain airbag 10 and is connected with a pressure source, as indicated in FIG. 8 in schematic form. The position of filling hose 16 in the rolled-up curtain airbag 10 (broken line) and in the fully-unrolled curtain airbag (solid line) are also shown in FIG. 8 .
FIG. 9 shows a cross-section through rolled-up curtain airbag 10 . FIG. 10 shows the items of FIG. 9 at an early unrolled and expansion stage of curtain airbag 10 . In contrast to the first embodiment, the unrolling and the filling occur simultaneously, whereby depending on the concrete form of the safety device, the pressure building up in vertically-running chambers 12 may be sufficient in order to unroll the airbag. However, additional means may also be present which support the unrolling such as that described in connection with the first embodiment.
FIG. 7 shows the curtain airbag 10 in fully-unrolled and filled condition in a view corresponding to FIG. 9 .
In the second embodiment it would also be possible not to provide a continuous shaft 40 , but only to fix both ends of the upper edge 10 to the inner vehicle structure so as to be capable of rotation. However, it can be expected that a more even rolling up behaviour is possible in the presence of a continuous shaft.
The invention was basically described above in relation to passenger vehicles. However, a further possible application of the safety device according to the invention would be drivers' cabins of trucks. Here, a corresponding safety device can in particular serve to protect the driver or the passenger if the driver's cab should tip over, by unrolling and inflating the curtain airbag 10 in front of the corresponding side window. In this case, the trigger signal is generated from an inclination or tilt sensor, not by a proximity or impact sensor. As the driver's cabin of a truck tips over relatively slowly, the problem that unrolling and inflation takes longer in the case of the safety device in accordance with the invention than with a traditional curtain airbag is without significance. Because of the reversibility of the safety device, it is in particular also possible to unroll and fill the curtain airbag on quite slight tilting of the driver's cabin, even if there is still a chance that the cabin will not tip over completely.
While the above description constitutes the preferred embodiment of the present invention, it will be appreciated that the invention is susceptible to modification, variation, and change without departing from the proper scope and fair meaning of the accompanying claims.
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A safety device for protection of vehicle occupants is described. The safety device exhibits a curtain airbag ( 10 ) located in the area of the roof frame, with an upper edge ( 10 a ), which is rolled up in quiescent state and unrolled in the case of an accident. The curtain airbag can be filled with gas. In order to enable the safety device to be used reversibly, the curtain airbag ( 10 ) is rolled up to roll around its upper edge ( 10 a ) when in quiescent state, and the upper edge is held by fixing elements in a manner which the airbag is rotatable.
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BACKGROUND OF THE INVENTION OF THE INVENTION
1. Field of the Invention
This invention relates to improvements in free flow conveyors, and more specifically to a free flow conveyor in which roller chains are incorporated to define an upper coveying path in common with another one therebelow so as to simplify the system thereof and to reduce the driving energy required.
2. Description of the Pior Art
In order to convey pallets freely loaded on a pair of roller chains which respectively travel freely on both sides of the conveying path, a free flow conveyor typical of the prior art has been favorably employed in a production line for electrical components. In such a free flow conveyor typical of the prior art, the conventionally basic mechanism, as shown in FIG. 1, comprises an upper conveying feed path 10 for the pallets, a conveying return path 12 for the pallets therebelow, sprocket members 14a, 16a, 14b, and 16b mounted within each conveying path with endless roller chain members 18, 20 respectively wound thereon, and separately equipped motor members 22, 24 for independently driving the roller chain members 18, 20. Referring to FIG. 1 in particular, shown therein and designated by reference numeral 26 are the pallets which are freely loaded on the roller chain members 18, 20, and designated by the numerals 28, 30, respectively, are elevator members for transferring the pallets at both terminal ends of the conveying feed path 10 and the conveying return path 12. The elevator members 28, 30 have their own endless roller chain members 32, 34, respectively, for supporting the pallets. For example, initially, after the endless roller chain 32 of elevator mechanism 28 has received the pallets which have been conveyed on the conveying feed path 10, the elevator 28 is lowered to the level of the conveying return path 12, and secondly, the roller chain 32 is fed in the counterclockwise direction so as to transfer the pallets 26 to the conveying return path 12. The pallets 26 conveyed onto the conveying return path 12 are then transferred to the other endless roller chain 34 of elevator mechanism 30, after which the elevator 30 is elevated up to the level of the conveying feed path 10, and subsequently, the pallets are transferred to the conveying feed path 10 by clockwise movement of the endless roller chains 34.
Such being the foregoing case with the conventional free flow conveyor, however, the mechanism of moving the endless roller chains independently for each conveying path, and of providing separately equipped driving motors may lead to considerable disadvantages which include not only the need for an intricate mechanism and an increasing number of component members, but large operating costs due to the large amount of driving energy required.
OBJECTS OF THE INVENTION
Accordingly, one of the objects of the present invention is to the above disadvantages associated with the previously known mechanism used in free flow conveyors.
Another object is to provide a simple mechanism and a reduction in operating costs.
SUMMARY OF THE INVENTION
In accordance with a more specific aspect of the present invention and in order to attain the above objects, the free flow conveyor which conveys, in order, a plurality of pallets freely loaded on roller chains to a required destination characteristically comprises a conveying feed path for the pallets installed at a first horizontal elevation, a conveying return path for the pallets disposed therebelow, and roller chains mounted on both sides of the conveying paths so as to be endlessly wound on both conveying paths installed respectively thereabove and therebelow so that the roller chains can be commonly driven by connecting each roller chain with a common driving source.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other objects and advantages of the free flow conveyor of the present invention will become more apparent from the following description of the preferred embodiments with reference to the accompanying drawings, wherein:
FIG. 1 is a schematic view in perspective of the free flow conveyor of the prior art; FIG. 2 is a schematic view in perspective of the free flow conveyor of the present invention; and
FIG. 3 is a side view of the free flow conveyor illustrated FIG. 2.
DETAILED DESCRIPTION OF THE INVENTION
Referring first to FIG. 2, a driving shaft 38 and a driven shaft 40 are rotatably supported so as to leave a required spacing above a conveyor frame designated by the reference numeral 36 and sprocket members 42, 44, as illustrated in the drawing, are securely mounted on both ends thereof. Driven shaft members 46, 48 are rotatably supported in positions corresponding to the above driving and driven members 38 and 40, respectively, and other sprocket members 50, 52 are securely mounted on both ends thereof. The sprocket group 42, 50, 52, 44 located on one side of the driving shaft 38 and each driven shaft member 40, 46, 48 have wound thereon in common an endless roller chain 54, and the sprocket members group 42, 50, 52, 44 located on the other side have wound thereon in common another endless roller chain 56 from which an independent free flow conveyor is formed. In both conveying paths consisting of the roller chains 54, 56, a conveyor line located at the upper level will be employed as a conveying feed path 58 for the pallets, and another conveyor line located therebelow will be employed as a conveying return path 60 for the pallets.
A sprocket 62 is secured on one end of the driving shaft 38, and an endless chain 68 is wound between a sprocket 66 secured to an output shaft of a motor 64 to be used for a common driving source for the two conveying paths and sprocket 62, whereby the power of the motor 64 is transmitted. As shown in FIGURE 2 and FIG. 3, a tension sprocket 70 is adjustably mounted in the horizontal direction in cooperation with the chain 68 for power transmission, and thereby gives an adequate tension thereto. The pair of endless chain members 54, 56 are respectively equipped with other tension sprocket members 72, 74 which also give tension thereto to the same degree.
At both the starting and terminal points of the conveying feed path 58 for the pallets, as shown in FIG. 2, there is schematically shown endless roller chain members 76, 78 for feeding a pallet 26 at right angles with respect to the conveying direction of the path 58, which are respectively mounted in a manner of free elevation by means of short-stroke pneumatic cylinder members 80, 82. Since the endless roller chain members 76, 78 are normally located at an elevation slightly lower than the level of the conveying feed path 58 for the pallets, the members 76 and 78 never interfere with the travel of the pallets. In a similar manner, at the starting and terminal points of the conveying return path 60 for the pallets, endless roller chain members 84, 86 are mounted in a similar manner as are the members 76 and 78 in the foregoing path 58. Similarly, since the endless roller chain members 84, 86 are normally located at an elevation slightly lower than the level ofthe conveying return path 60 for the pallets, the members 84 and 86 do not interfere with the travel of the pallets.
As shown in FIG. 2, other endless roller chain members 88, 90 for pallet transfer are correspondingly mounted outside both the starting and terminal points of each conveying path and are supported by linear actuator members 92, 94 which freely elevate and lower members 88 and 90 between the levels of conveying feed path 58 for the pallets and the conveying return path 60 for the pallets, respectively. In an exemplary embodiment illustrated in FIG. 2, a pneumatic cylinder having a long-travel stroke length sufficient for the piston rod is illustrated, however, it will be of course apparent that various other types of elevating mechanisms may be selectably adopted according to the practical conditions applicable for a particular field.
The free flow conveyor of the present invention is basically comprised as described in the foregoing. With the motor 64 driven, the roller chains 54, 56 mounted on both sides of the upper and lower conveying paths travel simultaneously in a required direction whereby such can attain not merely a simplification of the drive mechanism but also a reduction in costs involved in the production of the system as a result of not having independently mounted motors respectively for both the upper and lower conveying paths as is the case with the free flow conveyor of the prior art described with reference to FIG. 1. With the result of necessitating only a single motor sufficient for the driving operation, the present invention can contribute greatly to advantageous effects, such as, for example, a minimization of electric power consumption, curtailment of operating costs, or the like.
Now for reference, the movements of pallets on the free flow conveyor of the present invention will be described with the passage of time as follows. For example, the pallet 26 conveyed in the horizontal direction on the conveying feed path 58 for the pallets is stopped with the aid of a stopper, not shown, at the required position both in the vicinity of the terminal end thereof and above the roller chains 78. Consequently, when the pneumatic cylinder 82 is energized, the roller chains 78 are elevated to a level higher than the level of conveying path 58 so as to support the pallet 26. Then, the roller chains 78 are driven in the clockwise direction, and the pallet 26 is fed out to the side of the upper conveying path 58. At this time, the other roller chains 90 are disposed at the fed-out position, and receive the pallet 26, after which the roller chains 90 are lowered to the level of conveying return path 60 for the pallets by means of the linear actuator 94 which is reversely energized. The roller chains 90 are driven in the counterclockwise direction so as to transfer the pallet 26 onto roller chains 86, the conveyor unit of which has been elevated above the level of return path 60 by means of its pneumatic cylinder 83. The pneumatic cylinder 83 is subsequently lowered so as to place the pallet 26 upon conveyor return path 60 whereby the pallet 26 is able to be transferred to the opposite terminal end of the conveyor system at which time the pallet 26 is then stopped by means of a stopper, not shown. Next, the roller chain 84 is elevated by means of its pneumatic cylinder 81 so as to support the pallet 26 before chain 84 is driven in the clockwise direction so as to feed the pallet 26 out to the side of the conveying path 60, whereby the pallet 26 is transferred to another roller chain 88 which waits for the pallet 26 at the same level. The roller chain 88 is then elevated up to the level of the upper conveying path 58 by means of the linear actuator 92, and chains 88 are then driven in the counterclockwise direction so as to transfer the pallet 26 onto the roller chain 76 which has been elevated by means of its pneumatic cylinder 80. Thereafter, with the pneumatic cylinder 80 reversely energized, the roller chain 76 is lowered, and the pallet 26 supported thereon is freely loaded onto both roller chains 54, 56 of the upper conveying path 58 and is again fed through the path 58 in the required direction. Afterwards, the cycle, as described above, is repeated.
While the invention has been particularly shown and described with reference to preferred embodiments thereof, it will be understood by those skilled in the art that modifications in form and details can be made thereto without departing from the spirit and scope of the invention.
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A free flow conveyor which conveys in order a plurality of pallets freely loaded on roller chains in a required direction comprises a conveying feed path for the pallets to be defined at a first horizontal elevational level, another conveying return path for the pallets to be defined therebelow, and roller chains, to be mounted on both sides of the conveying paths, being endlessly wound in common with both feed and return paths so that the roller chains can be commonly driven. This invention will therefore provide a simple mechanism and a reduction in operating costs so as to eliminate the disadvantages of a free flow conveyor to which the prior art pertains.
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This is a continuation of application Ser. No. 616,965, filed June 4, 1984, abandoned.
BACKGROUND OF THE DISCLOSURE
This application relates to blending or mixing apparatus. More specifically, this application relates to apparatus for blending or mixing a substance such as candy cookies, nuts or fruit witht he material of a cold flowable substance e.g. ice-cream.
A development in the refreshment field has been made with respect to the marketing or products generally falling within the general category of ice-cream products. This development contempaltes that ice-cream be blended with or otherwise mixed with products such as candy e.g., individual candies such as M & M candy and the like, cookies, nuts, fruit or any of many desired materials which may be considered to enhance the taste and desirability of ice cream.
To provide such a product, apparatus have been developed to achieve the desired mixing or blending. For the most part these apparatus have included a container having a mixing means disposed therein. The container is designed to receive the ingredients being mixed. to contain the mixing operation and thereafter to permit discharge of the mixed materials.
Mixing devices of a known type, however, have not proven satisfactory. One problem experienced with respect to such devices has been their inability to achieve satisfactory and relatively uniformed blending. A second problem experienced with such apparatus has been their inability to maintain the products being mixed in a proper refrigerated state. In this regard, failure to maintain the products n the proper refrigerated state during blending and during dispensing results in a greatly reduced viscosity, i.e. a soupy product, clogging of the apparatus, and unacceptable down time to clean the machine between uses to prevent bacteria build up.
An additional and very serious problem with known apparatus has been the development of high pressures in the mixing container, particularly adjacent the discharge orifice, during operation of the apparatus. Such high pressure causes poor blending, adverse structural problems with the equipment potentially causing shortened equipment life, and overall poor operation.
SUMMARY OF THE INVENTION
It is an object of the present invention, therefore, to provide a blending machine which is uniquely suitable for use in blending flowable materials.
It is another object of the present invention to provide a blending machine wherein materials such as ice-cream and additive materials may be mixed or blended to achieve relatively uniform blending in a short period of time.
Yet an additional object of the present invention is to provide a novel blending machine wherein the blending chamber is uniformly refrigerated to maintain the ingredients at a desired and proper consistency during the blending operation and during subsequent dispensing of the product.
Yet a further object of the present invention is to provide a novel blending machine wherein unacceptable back-pressures resulting from the blending operation are not experienced.
These objects and others not enumerated are achieved by the blending apparatus according to the invention, one embodiment of which may include a blending container, means displaceable into and out of said blending container for mixing ingredients contained in said blending container and means for uniformly lowering the temperature of the inner surface of the blending container.
BRIEF DESCRIPTION OF THE DRAWING
A more complete understanding of the present invention may be had from the following detailed description, particularly from read in light of the accompanying drawings, wherein:
FIG. 1 is a front elevational view, having portions cut away, of a mixing apparatus according to the present invention;
FIG. 2 is a side elevational view, also having portions cut away, of a mixing apparatus according to the present invention;
FIG. 2A is a partial view, increased in scale, of the portion of FIG. 2 designated in the circular set off;
FIG. 3 is an elevational cross-sectional view of the auger and cutter structure utilized in the embodiment of mixing apparatus of FIG. 1; and
FIG. 4 is a top view of the apparatus of FIG. 1.
DETAILED DESCRIPTION
Referring therefore to FIG. 1, an ice cream blending machine structured in accordance with the present invention is shown and designated generally by reference numeral 10.
Machine 10 includes a base plate 12 which may be secured such as by bolts or other suitable means (not shown) to a support platform such as a sturdy counter top or the like. Rigidly secured to the upper surface of base plate 12 are positioning plates 14. The positioning plates 14 are displaced to either side of center, as best may be seen in FIG. 1, and define both positioning means and securing means for first and second, vertically disposed U-shaped channels 16 and 17. Channels 16 and 17 are oriented such that their open aspects are facing outwardly with respect to the central vertical axis of the machine. Further, channels 16 and 17 are disposed by positioning plates 14 such that their respective flanges are co-planar and the plans of their webs are parallel.
Channels 16 and 17 are secured to positioning plate 14 by a plurality of machine screws 18 which pass through suitable bores in the webs of the channels and which are threadedly received within tapped bores formed in positioning plates 14. Similarly, positioning plates 14 are secured to base plate 12 by machine screws 19 received through bores in plates 14 and threadedly engaged in tapped bores formed in baseplate 12.
The upper ends of channels 16 and 17 are rigidly secured together in the desired spaced position by a thrust plate 20 which extends between the webs of channels 16 and 17. Thrust plate 20 is secured to channels 16 and 17 by a plurality of machine screws 21 which are slidably received through suitable bores formed in the webs of channels 16 and 17 and which are threadedly received within tapped bores formed in thrust plate 20.
Also secured to mounting plate 12, forward of channels 16 and 17 (as best seen in FIG. 2), is a drain assembly including a drain pan 24 having a drain pipe stub 25 depending therefrom. Stub 25 extends downwardly from pan 24 into and through a through bore 26 formed in base plate 12. Further, the lower end of stub 25 is suitable for connection to a drain line or other suitable means for disposing of waste materials from pan 24.
Disposed upwardly of mounting plate 12 and secured between channels 16 and 18 is a gear motor support plate 28. Support plate 28 is substantially identical in perimetric configuration to thrust plate 20 such as to extend between and be secured to channels 16 and 17. Gear motor support plate 28 is adjustably secured to channels 16 and 17 by a plurality of machine screws 30 which extend through vertically extending slots 31 (FIG. 2) formed in the webs of channels 16 and 17 and which are threadedly received within tapped bores formed in support plate 28. As will be recognized by those skilled in these arts, adjustment of the vertical position of support plate 28 is achieved by loosening screws 30, sliding the support plate 28 vertically within the limits of slots 31 to the desired position, and tightening screws 30. It should also be noted that support plate 28 may be rigidly mounted with respect to channels 16 and 17, in which case thrust plate 20 would be adjustably vertically mounted by providing vertically oriented slots in channels 16 and 17 for slidably and adjustably receiving machine screws 21 therethrough.
Extending vertically between thrust plate 20 and support plate 28 are first and second guide rails 33 and 34 respectively. (See FIGS. 1 and 4). First guide rail 33 is secured to the interior face of the web of channel 16 by suitable means such as machine screws (not shown), at a position generally centrally of the flanges of channel 16. Similarly, second guide rail 34 is secured to the interior face of the web of channel 17 at a position generally centrally of the flanges of the web of channel 17.
The interior surface of first guide rail 33 is relieved to define a vertically extending channel 35 for receiving a cam follower as is discussed below in detail. Similarly, the interior surface of second guide rail 34 is relieved to define a vertically extending channel 36, also for receiving a cam follower.
Rigidly secured to the underside of support plate 28 is a worm drive motor 38. The motor is secured by bolts 39 which extend through bores formed in support plate 28 and which are recieved within suitable bores in motor 38. The output shaft of motor 38 is operatively connected such as by keying or the like, to a vertically extending threaded shaft 42. The upper end of shaft 42 is provided with a shallow, axially extending bore 43 in which is recieved a ball bearing 44 which cooperates with a recess 45 in thrust plate 20 such as to act as a thrust bearing for shaft 42. This structure best may be seen in FIG. 2A.
Threaded shaft 42 is provided with ball screw threads which cooperate with a ball nut follower 46. Ball nut follower 46 is threadedly engaged with shaft 42 such that rotation of shaft 42 in response to operation of motor 38 causes upward or downward displacement of follower 46 depending upon the direction of rotation of shaft 42.
Resting on the upper surface of ball nut follower 46 is an auger spindle mounting plate 48. Auger spingle mounting plate 48 exxtends into the area which is central of channels 16 and 17., The forward portion of plate 48 defines a support means for the auger system described below and its drive spindles. That section of auger spindle mounting plate 48 which is disposed centrally of channels 16 and 17 is provided with a throughbore to accommodate the passage therethrough of shaft 42.
Similarly, resting on th inner upper surface of mounting plate 48 and secured thereto by bolts as to discussed below is auger motor mounting plate 49.
Rigidly secured to the lower surface of mounting plate 48 are a first cam follower support plate 50 and a second cam follower support plate 51. First cam follower support plate 50 is a generally rectangular plate which depends from the lower surface of mounting plate 48 and which defines a mounting means for a cam follower 53 (FIG. 4) which is operatively received within the channel 35 of first guide rail 33. Similarly, second cam follower support plate 51 is a generally rectangular plate which depends from the lower surface of mounting plate 48 and which defines a mounting means for a cam follower 54 which is operatively received within the channel 36 of second guide rail 34. In this regard the followers 53 and 54 may be rollers or other suitable cam follower means from among those which are well known to those having skill in these arts. Further, there may be more than one cam follower attached to the respective plates 50 and 51 if it is so desired.
Transverse positioning of support plates 50 and 51 is achieved by the provision of parallel spacer bars 55 and 56 which extend generally horizontally between and which are secured to plates 50 and 51. Forward spacer bar 55 is positioned in front of threaded shaft 42 and rearward space bar 56 is positioned behind threaded shaft 42 as best may be seen in FIG. 4. In this regard, if so desired only a single spacer bar may be utilized. As support plate 48 is displaced upwardly or downwardly by the operation of motore 38 and therewith the rotation of threaded shaft 42, the cooperation of cam followers 53 and 54 within channels 35 and 36 respectively, retains support plate 48 in proper angular alignment with respect to shaft 42 and thus, in proper operating position.
Disposed on the forward end of mounting plate 48 is a throughbore 58. Coaxial with throughbore 58 and supported by the upper surface of mounting plate 48 are a bearing flange 59, a journal bearing 60, an auger drive pulley 61 and a cutter drive pulley 62. Cutter drive pulley 62 is rigidly secured to a cutter shaft 63 which extends vertically coaxially within throughbore 58. Disposed on the lower end of cutter shaft 63 is a cutter device 64, the structure and operation of which are discussed below in detail.
Mounted between journal bearing 60 and cutter drive pulley 62 is auger drive pulley 61. Auger drive pulley 61 is rigidly secured to a cylindrical auger shaft 65 which is rotatably received through and coaxial with throughbore 58. Secured to the lower end of auger shaft 65 is auger 66. The cylindrical structure of shaft 65 permits cutter shaft 63 to extend coaxially therethrough. Thus, auger shaft 65 is disposed concentrically of cutter shaft 63 and adapted for relative rotational movement therebetween.
As best may be seen in FIGS. 1 and 2, the fluting of auger 66 is such as to cause downward displacement of material in response to clockwise rotation of the auger. The tendency toward such downward displacement tends to generate increased pressure in the material being displaced as it approaches the lower end ofthe auger. In order to preclude the generation of unacceptable pressures in apparatus 10, the lower portions of the periphery of the fluting of auger 66 are provided with a plurality of spaced notches 68. These notches permit backflow of material in amount sufficient to relieve downstream pressure. In this regard the size of the notches for any particular application may be determined empirically. However for the application of the preferred embodiment, i.e. for blending ice cream with other additives, a notch formed by a 5/8 inch diameter end mill disposed at an angle of 45 degress to the longitudinal asix of the auger has been found to operate satisfactorily. An additional beneficial effect of notches 68 is improved mixing and blending of the recirculation of the materials being blended.
As is discussed below in detail, pulleys 61 and 62 are operatively connected through suitable V-belts 70 and 72 to a drive means. By reason of the different effective diameters of pulleys 61 and 62 it is apparent that they are designed to rotate at different angular velocities. In this regard, as is discussed below in detail. V-belts 70 and 72 are driven by drive pulleys which are equal in diameter. Thus, in the ordinary operation of machine 10, the auger 66 and cutter 64 rotate at different angular velocities.
As best may be seen in FIG. 3, auger 66 is provided with an axially extending throughbore 74 and a coutnerbore 75 coaxial therewith. The intersection of bore 74 and counterbore 75 defines a radially extending shoulder 76. Shoulder 76 defines a reaction surface for a spring 78 which cooperates with cutter shaft 63 to maintain cutter shaft 63 properly positioned within auger 66 including when the auger is removed from the machine for cleaning or the like.
Considering the structure of cutter shaft 63 in detail, the shaft includes an upper shaft section 80, a lower shaft section 81 and a coupling 82. Upper shaft section 80 and lower shaft section 81 are threadedly received within coaxial threaded bores provided in coupling 82. It will be recognized, however, that other coupling structures, e.g. bayonet type couplings, may also be utilized to connect the respective shaft sections. The lower radial surface of coupling 82 defines an upper reaction surface for spring 78. The force exerted by spring 78 against coupling 82 tends to displace cutter shaft 63 upwardly thus establishng and maintaining a surface-to-surface engagement between the upper surface of cutter device 64 and the lower surface of auger 66. The upper shaft section 80 is opeatively secured, such as by keying or the like, to cutter drive pulley 62 for rotation therewith.
Rigidly secured to the lower surface of mounting plate 48 and coaxial with cutter shaft 63 is a bearing box 84 through which is rotatably received cylindrical auger shaft 65. Thus, the auger assembly is rotatably supported vertically by bearing 60 and for rotation by the cooperation of bearing 60 and the bearings of bearing box 84. As is discussed below in detail, the effective angle of taper of auger 66 corresponds to the vertical angle of blending receiver 86.
Rigidly secured to the under surface of the rearward portion of mounting plate 49 is a drive motor 87. Rigidly secured to the output shaft od drive motor 87 is a two-stage pulley 88 having a first sheave 89 acting as an auger drive pulley and a second sheave 90 acting as a cutter drive pulley. Auger drive pulley sheave 89 is connected to auger pulley 61 through V-belt 72. Thus, operation of drive motor 87 causes the rotation of sheaves 89 and 90 and through V-belts 70 and 72, also the rotation of pulleys 61 and 62. As noted above, the fact that the diameters of sheaves 89 and 90 are equal, coupled with the difference in diameters between pulleys 61 and 62, causes the auger 66 and cutter 64 to rotate at different angular velocities thus enhancing the operation of the blending machine.
Referring to FIG. 4, it can be seen that mounting plate 49 is provided with a center slot 68, the longitudinal axis of which is along a line connecting the centers of rotation of cutter shaft 63 and second sheave 90. Slot 68 permits the passage therethrough of shaft 42. Spaced from and on either side of slot 68 as a pair of slots 69 the longitudinal axis of which are parallel to the axis of slot 68. Slots 69 accommodate the passage therethrough of bolts 71 which also pass through suitable bores in plate 48. Thus, by loosening bolts 71 and diisplacing plate 49 with respect to plate 48, the tension on V-belt, 70 and 72 may be suitably adjusted.
Considering now blending receiver 86, the receiver structure is mounted within a support box 92 rigidly secured such as by bolts or the like to the front surfaces of the flanges of U-shaped channels 16 and 17. Mounted within support box 92 is blding receiver 86. Blending receiver 86 includes a container having an upper cylindrical section 94, a lower cylindrical section 95 having a diameter smaller than upper cylindrical section 94, and a central conical section 96 the upper diameter of which equal to the diameter of section 94 and the lower diameter of which is equal to the diameter of section 95. In this regard, the angle of taper of conical section 96 corresponds to the angle of taper of auger 66 which, during the operation of aapparatus 10, is received within blending receiver 86 such that the perimetric surface of auger 66 is within a short distance, e.g. 0.005 inches, of the surface of receiver 86.
Disposed in the bottom of lower cylinder section 95 is discharge orifice having an orifice plate (not shown) mounted therein. The orifice plate is provided with an opening which controls the rate of discharge of blended materials from blending receiver 86. The opening may also be shaped such as to cause the materials being discharged to take on a desired configuration.
Rigidly secured to the outer lower portion of conical section 96 is a cooling ring 98. Cooling ring 98 may be made of suitable conductive material such as aluminum so as to facilitate removal of heat from blending receiver 86 during operation of machine 10. Disposed on opposite sides of cooling ring 98 are a first and second refrigeration element 100, only one being shown. Each refrigeration element includes a thermo-electric cooling element and a water-cooled heat sink. Thus heat is removed from cooling ring 98 by the thermo-electric cooler of elements 100 whereafter it is transferred to water flowing through the heat sinks. In this regard, as best may be seen in FIG. 2, the refrigeration elements 100 include electrical leads 101 for connection to a standard source of power, a water supply line 103 and a water discharge line 104. The amounts of water utilized for cooling are not great. Thus local water may be used for the heat transfer. Alternatively a closed loop water system with external heat exchange or other sources of water for heat transfer can also be utilized. The cooling capability of the heat removal means should be at least equal to the heat generation expected from operation of the auger 66 during blending.
The controls for worm drive motor 38 and drive motor 88 may be selected from any of the standard type motor controls which are well known to those having ordinary skills in these arts. It has been found that push button control elements are the most convenient for operators and render the operation of the device well within the capability of an operator with very little training.
Considering therefore the operation of the device and assuming that the apparatus is assembled as shown and the power has been provided, the first and second refrigeration elements 100 are activated to bring the temperature of the blending receiver 86 in the general vacinity of cooling ring 98 to the desired low temperature most appropriate for blending a mixture of ice-cream and candy in the context of the operation of the apparatus shown. In this regard it has been found that establishing and maintaining a temperature of approximately 20° F. or below has been most beneficial in the operation of the apparatus.
With the blending receiver procooled the operator will then load ice-cream into the blending receiver in the amount desired to provide either a single or doule portion of blended product. Thereafter, worm driver motor 38 is activated to advance auger 66 into the blending receiver 86 such as to pole a pocket into the previously charged ice-cream. In the embodiment shown, auger 66 is advanced to within 2 inches of the discharge orifice. Thereafter the motor 38 is reversed and the auger withdrawn to permit deposition of the blend-in materials, e.g candy, cookies, nuts or fruit or other such materials into the ice-cream.
Thereafter, motor 38 is activated to advance auger 66 into the ice-cream material. Upon advancement of the auger into receiver 86 by a desired amount, motor 88 is activated to cause rotation of auger 66 and cutter device 64 at different angular velociites as discussed above. The effect of the auger rotation and the rotation of cutting device 64 serves both to blend the ice cream with the blend-in materials such as to effect a consistent mixture of the materials and to advance the blended product out of the dispenser through the orifice plate to provide an attractive single or double portion no matter what the relative consistency of the ingredients being blended. The rotation of the cutter cooperates with the discharge orifice to cut any large portion of blending ingredient which may pass into the area of the discharge orifice thus improving blending and also precluding blockage of the discharge orifice.
Upon completion of the mixing and discharge cycles the auger is withdrawn. Thereafter the blending receiver and auger can be rinsed in anticipation of a subsequent charge of materials. In this regard it will be recognized by those skilled in the art that a permenantly installed rinse water nozzle may be provided to facilitate cleaning the blending receiver and auger between loads. It has been found that rinsing is best achieved by advancing auger 66 into receiver 86 and therefater rinsing the auger and chamber at the same time.
As will be recognized by those having skilled in these arts the blending apparatus as disclosed above constitues a unique apparatus having particular utility with respect to the blending of ice-cream with nearly any type of materials such as candy, cookies, nuts or fruit. Maintaining the blending receiver in a refrigerated state facilitates the blending and provides for consistent product cycle after cycle.
The apparatus itself may be constructed using well known materaisl which are consistent with food handling needs where the blending is for food purposes, which materials may be chosen from any of the well knowns of those having ordinary skill in these arts.
It will also be recognized that many modifications will be made to the disclosed preferred embodiment without departing from the spirit and scope of this invention.
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A blending apparatus particularly adapted for blending or mixing candy, cookies, nuts or fruit with the material of a cold flowable substance, such as ice cream, includes a blending container, a rotatable auger having a rotatable cutter displaceable into and out of the container, and a device for causing recirculation of at least a portion of the ingredients within the container during mixing. The auger is rotatable within the container with the cutter being rotated at a different angular velocity from the auger. The cutter is effective to cut large portions of the ingredients in the container into smaller portions.
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BACKGROUND OF THE INVENTION
This invention relates to coating by vapor deposition and more particularly to a vapor deposition coating machine that is capable of coating large objects with metal.
Various processes exist for coating substances, particularly metals, with metal, usually for the purpose of enhancing the appearance of the coated substance or protecting the coated substance from its environment, or both. For example, a chromium finish is applied to steel through electroplating procedures to improve the appearance of the steel and to a lesser measure to inhibit oxidation. Similarly, steel is often coated with zinc so as to provide a protective coating as well as a sacrificial anode. Aluminum shapes and the like when subjected to anodizing treatments are provided with attractive and durable coatings.
Of all the metal coating processes, perhaps ion vapor deposition, which is a vacuum vapor plating process, provides the most secure bond between the metal substrate and the metal coating. Indeed, the bond is characterized by relatively deep diffusion between the molecules of the two metals at the interface between those metals. In short, it is similar to a diffusion bond. The effectiveness of the bond to a large measure derives from the ability to thoroughly clean the substrate as an adjunct of the ion vapor deposition process and to deposit the metal coating in a powerful ion bombardment.
Heretofore coating by ion vapor deposition procedures has been confined to relatively small objects, because the machines for practicing such procedures were incapable of accommodating large objects. This left larger objects for other, less effective coating procedures. U.S. Pat. Nos. 3,750,623 and 3,926,147 illustrate the most efficient apparatus heretofore developed for coating by ion vapor deposition. In each, the workpiece that is to be coated is an extremely small object, such as a machine screw. The apparatus does not have the capability of coating large sheet metal shapes or other large objects such as might be utilized in the airframe of a high performance aircraft.
SUMMARY OF THE INVENTION
One of the principal objects of the present invention is to provide a machine or apparatus for coating large substrates with a desired metal using vapor deposition procedures. Another object is to provide a machine of the type stated which is ideally suited for coating large flat shapes. A further object is to provide a machine of the type stated in which the object to be coated remains stationary in a vacuum chamber and the source of coating metal moves within the chamber opposite the object to be coated. An additional object is to provide a machine of the type stated which provides a generally uniform coating. These and other objects and advantages will become apparent hereinafter.
The present invention is embodied in a vacuum coating machine including a vessel that forms a vacuum chamber, means for evacuating the vessel, means for supporting a workpiece within the vacuum chamber, an evaporator unit within the chamber and including a trough-like boat and means for introducing the coating metal into the boat, means for heating the boat sufficiently to melt the coating metal introduced into it, and means for moving the evaporator unit through the chamber. The invention also consists in the parts and in the arrangements and combinations of parts hereinafter described and claimed.
DESCRIPTION OF THE DRAWINGS
In the accompanying drawings which form part of the specification and wherein like numerals and letters refer to like parts wherever they occur:
FIG. 1 is a perspective view of a vapor deposition coating machine constructed in accordance with the invention, and with the door of the vacuum vessel open and the rack partially withdrawn;
FIG. 2 is an elevational view looking into the open end of the vessel;
FIG. 3 is a fragmentary sectional view showing the channel and slide which support the rack;
FIG. 4 is a sectional view taken along line 4--4 of FIG. 3 and showing the slide and channel that support the rack;
FIG. 5 is a sectional view taken along line 5--5 of FIG. 2 and showing the evaporator assembly in plan;
FIG. 6 is a fragmentary sectional view of the evaporator unit and connecting cables taken along line 6--6 of FIG. 5;
FIG. 7 is a sectional view of one of the evaporator assemblies, showing one of the evaporator units on it in elevation;
FIG. 8 is a fragmentary sectional view taken along line 8--8 of FIG. 5 and showing one of the nuts by which the carriage of the evaporator assembly is coupled with its lead screw;
FIG. 9 is a sectional view taken along line 9--9 of FIG. 6 and showing the electrical cable that leads to the common electrode of the carriage as well as the cooling hoses for that cable;
FIG. 10 is a sectional view taken along line 10--10 of FIG. 5 and showing the right angle gear box and the shafts which power the wire feed devices of the evaporator units;
FIG. 11 is a side elevational view of the vacuum vessel forming part of the invention; and
FIG. 12 is a top plan view of the boat for an evaporator unit.
DETAILED DESCRIPTION
Referring now in detail to the drawings (FIG. 1), A designates a machine for depositing a thin metal coating on a relatively large workpiece B such as a sheet metal shape or the like. The metal of the coating may be aluminum or any of the metal which lends itself to ion vapor deposition. Similarly, the metal of the workpiece may be any metal that is capable of accepting metal deposited by ion vapor deposition. Such metals are, titanium, steel, and aluminum, to name a few. Of course, the deposited metal and the substrate metal should be compatible.
The machine A includes (FIG. 1) a vacuum vessel 2 of cylindrical configuration which typically may be 7 feet in diameter and 12 feet in length. The vessel 2 has a cylindrical wall 4 and an end wall 6 that is welded to one end of the cylindrical wall 4, thereby forming a cylindrical vacuum chamber 8 that is permanently closed at its one end. The other end, when the chamber 8 is under vacuum, is closed by a door 10 supported on a hinge 12. The door 10 is secured firmly against the end of the cylindrical wall 4 by clamps 14. The chamber 8 is connected to a vacuum pump 16 through duct 18 that opens into the chamber 8 through the cylindrical wall 4. In addition, the cylindrical wall 4 contains viewing ports 20 (FIG. 11) for observing the interior of the chamber 8 under vacuum conditions. The cylindrical chamber 8 contains two basic components (FIGS. 1 & 2), namely a rack 22 by which the workpiece B is supported and an evaporator assembly 24 which discharges the metal that is deposited on the workpiece B. The rack 22 is located slightly above the center axis of the cylindrical chamber 8, while the evaporator assembly 24 is located slightly below the center axis. This arrangement enables the workpiece B, when suspended from the rack 22, to be located at about the level of the center axis and directly above the evaporator assembly 24.
The rack 22 is supported on a pair of channels 26 (FIG. 2) which are mounted securely on the cylindrical wall 4 of the vessel 2 with the one being directly across the chamber 8 from the other. The two channels 26 open inwardly, and each contains a slide 28 (FIGS. 3 & 4) that moves longitudinally within it. Each slide 28 has a series of upper and lower wheels 30 which roll along the upper and lower flanges, respectively, of the channel 26 for that slide 28. While the upper wheels 30 need not be located directly opposite the lower wheels 30--and for the most part they are not--the peripheries of neither the upper nor the lower wheel 30 extend past the longitudinal centerline of the slide 28. Indeed, a slight gap exists along the longitudinal centerline between the upper and the lower wheels 30.
The rack 22 is actually supported on the slides 28, which in turn are supported on the channels 26. The rack 22 includes (FIGS. 1-3) a frame 32 of rectangular configuration, with the frame 32 being long enough to extend substantially the entire length of the chamber 8 and wide enough to extend from one slide 28 to the other. Along each side, the frame 36 has a flange 34 (FIG. 3), and the two flanges 34 project laterally into the spaces between the upper and lower wheels 30 of the slide 28. Thus, the rack 22 rests on the lower wheels 30, yet may be pulled completely out of the chamber 8 when the door 10 is open. As the rack 22 moves out of the chamber 8, so do the slides 28, but at only one-half the velocity, so that when the rack 22 is completely out of the chamber 8, it is supported beyond the channels 26 on the slides 28. While the lower wheels 30 continue to support the rack 22 from beneath, the upper wheels 30 prevent the rack 22 from tipping over the front ends of the slides 28. In short, the rack 22 operates much like a fully suspended drawer of the type utilized in file cabinets.
The rack frame 32 has cross members 36 (FIG. 3) which extend from one side of the frame 32 to the other, and attached to these cross members 36 are dielectric insulators 38 which in turn have an expanded metal screen 40 attached to them. The arrangement is such that the screen 40 is secured firmly to the rack frame 32, yet is electrically isolated from the frame 32 as well as the vacuum vessel 2. The screen 40 has a spring contactor 42 (FIG. 2) at its back end, and that contactor aligns with a contact 44 on the end wall 6 of the vessel 2. The contact 44, in turn, is connected to the positive terminal or anode of a direct current voltage source through a lead 46 (FIGS. 5 & 11) that passes through the end wall 6. Thus, when the rack 22 is in its rearmost position, that is the position it assumes when wholly within the chamber 8, the spring contactor 42 bears against the contact 44, and the screen 40 may be connected with the high positive potential. However when the rack 22 is pulled outwardly, the contractor 42 separates from the contact 44, insuring that the screen 40 is at a neutral voltage.
The evaporator assembly 24 rests on a supporting framework 54 (FIGS. 2 & 5) that is attached to the cylindrical wall 4 of the vessel 2 in the lower position of the vacuum chamber 8. The framework 54 has a pair of horizontal cross rails 56 which extend completely across the vacuum chamber 8, with one being located near the door 10. The evaporator assembly 24 moves over the rails 56 from one side of the vacuum chamber 8 to the other and back again.
The evaporator assembly 24 includes a carriage 58 (FIGS. 5 & 7) consisting of a pair of longitudinal beams 60 (FIGS. 6 & 7) that extend practically the entire length of the chamber 8, and these beams at their ends are connected by blocks 62 (FIGS. 2 & 5), each of which has a pair of rollers 64 on it. The rollers 64 ride on the cross rails 56. Set inwardly on the carriage 58 from each end block 62 is a nut 66 (FIG. 8) and each nut 66 has a lead screw 68 (FIG. 5) extended through it. The two lead screws 68 have their ends located in bearings 70 mounted on the cylindrical wall 4 of the vessel 2. The bearings 70 at one side of the chamber 8 are incorporated into seal or vacuum pass through units 72 through which the ends of the lead screws 68 pass. Beyond the seal units 72, the end of the two lead screws 68 are connected with a reversible gear motor 74 through a sprocket and chain drive 76 (FIG. 11).
The gear motor 74 is mounted on the exterior surface of the vessel 2. When the gear motor 74 is energized, the two lead screws 68 revolve, and since they are connected with the carriage 58 at the nuts 66, the rotary motion of the screws 68 is converted into translational motion for the carriage 58. Thus, the carriage 58 moves along the cross rails 56, and since the motor 74 is reversible, the carriage 58 may be moved from one side of the chamber 8 to the other and then back again. The carriage 58 supports a plurality of evaporator units 80 (FIGS. 5-7) which are mounted in succession at equally spaced intervals along the beams 60 of the carriage 58.
All the evaporator units 80 are serviced by several common appliances that are likewise mounted on the carriage 58. These include a common electrode 82 (FIGS. 5 & 7) of tubular configuration which extends along one side of the carriage 58 and a parallel support tube 84 that extends along the other side of the carriage 58. Actually, the electrode 82 and support tube 84 rest on cross blocks 86, which span the two beams 60 of the carriage, and are secured firmly to the blocks 86 by clips 88.
The common electrode 82 which is formed in a tubular configuration from a suitable metal such as copper, is closed at its end closest to the door 10 by an end fitting, and at its other end by an adapter 92 (FIG. 5) Extended through the interior of the hollow electrode 82 from the adapter 92 to the end fitting is a water tube 98 (FIG. 7) that is considerably smaller in diameter than the electrode 82. The opposite end of the water tube 98 is in communication with the interior of the tubular electrode 82 through a return passage in the end fitting. Coupled to the water tube 98 and the electrode 82 at the adaptor 92 are flexible water hoses 100 and 102, respectively (FIG. 5), which extend downwardly to pass through fittings in the cylindrical wall 6, beyond which the former is connected with a supply of cooling water and the latter with a drain. The cooling water from the hose 100 flows through the adaptor 92 to the water tube 98 which delivers that water to the end fitting. Here the cooling water reverses direction and is discharged into the interior of the common electrode 82 where it flows back toward the adaptor 92. The water leaves the adaptor 92 and flows out of the vacuum chamber 8 through the flexible hose 102, beyond which it is discharged to a drain. In this manner cooling water is continually circulated through the common electrode 82 to prevent it from overheating under high current loads.
At four locations along its length, the common electrode 82 is embraced by a clamp-type connector 104 (FIGS. 6 & 7) and each of these is in turn bolted to an end fitting 106 at which a flexible electrical cable 108 terminates. Each cable 108 originates at a fitting 110 (FIG. 6) in the bottom of the cylindrical wall 4, there being a separate fitting 110 for each cable 108. Also extended between each pair of fittings 106 and 110 is a small diameter inlet hose 112, and a large diameter outlet hose 114. Indeed, both the cable 108 and the inlet hose 112 are located within the outlet hose 114 (FIG. 9). At the exterior of the vessel 2, cooling water is introduced into the inlet hose 112 and that water flows upwardly to the end fitting 106 where it is reversed in direction and returned through the outlet hose 114. This flow of water maintains the cable 108 at reasonably low temperatures under heavy current loads. The fitting 110 in the cylindrical wall 4 electrically isolates the two hoses 112 and 114 as well as the cable 108 from the vessel 2.
Each evaporator unit 80 includes (FIG. 7) a clamp-type bracket 116 that fits around the common electrode 82 and another clamp-type bracket 118 that fits around the support tube 84. The brackets 118 and 116 which are located directly opposite from each other, are connected by an evaporator boat 120 which is, in effect, an upwardly opening trough (FIG. 12) formed from a substance that is a good electrical conductor and is further capable of withstanding high temperatures on the order of 1800° C., since the boat serves as a resistance type heating element between the two brackets 116 and 118. Intermetallic composites are suitable for the boat 120. The brackets 116 and 118 are formed from a metal such as copper, which is capable of conducting electricity, and in comparison to the boat 120, they are quite massive.
Inasmuch as the bracket 116 is clamped around the common electrode 82 it remains at the same electrical potential as the electrode 82, which is connected to a source of alternating current through the water cooled cables 108. Heat from the bracket 116 is transferred to the common electrode 82 by conduction.
The other bracket 118 is connected to he source of alternating current through a separate flexible cable 122 (FIGS. 6 & 7) so that the alternating current is impressed across the boat 120 to heat the same. The cable 122 extends between an end fitting 124 on the bracket 118 and a pass through fitting 126 (FIG. 6) in the bottom of the cylindrical wall 4 for the vessel 2. The fitting 124 electrically connects the cable 122 with the bracket 118, while the fitting 126 electrically isolates the cable 122 from vessel 2. Alongside the cable 122 is an inlet hose 128 for conducting cooling water and both the cable 122 and the inlet hose 128 are contained within an outlet hose 130 that likewise extends from the lifting 126 in wall 4 to the end fitting 124 on the bracket 118. Cooling water supplied through the inlet hose 128 passes upwardly to the end fitting 124 where it is reversed in direction and discharged into the outlet hose 130. As the cooling water flows outwardly through the hose 130, it cools the cable 122, preventing it from overheating under high current demands. Heat from the bracket 118 is transferred to the fitting 124 by conduction. The cable 122 and its fittings 124 and 126 and and hoses 128 and 130 are practically identical to their counterparts associated with the cable 108 (FIG. 9).
In addition to the bracket 116 and 118 and the evaporator boat 120 that extends between them, the evaporator unit 80 further has a wire feed device 132 (FIG. 7) that includes a bifurcated spool holder 133 that is attached to the beams 60 at the bottom of the carriage 58 for holding a spool 134 of wire w, the metal of the wire w being that which is desired to be imparted to the workpiece B as a coating over it. In most instances, this metal will be aluminum. Leading away from the spool 134 is an initial guide tube 136 which is mounted on and terminates at a bearing block 138 that is secured to the beam 60 over which the common electrode 82 passes. Extended through the bearing block 138 is a wire feed shaft 140, which is fitted with a drive roller 142 over which the wire w passes after emerging from the initial guide tube 136. The wire w is forced tightly against the drive roller 142 by an idler roller 144 that is carried on a spring loaded link 146 which is likewise mounted on the bearing block 138. The link 146 may be depressed to move the idler roller 144 away from drive roller 142 so that the wire w from the spool 134 may be hand fed between the two rollers 140 and 142. The block 138 also has a final guide tube 148 mounted on it, and this tube extends upwardly away from the drive roller 142 and loops over the common electrode 82 and the bracket 116 on it, with the end of the final tube 148 being directed toward the upwardly opening trough of the evaporator boat 120. Thus, as the feed shaft 140 revolves, the drive roller 142 will withdraw wire w from the spool 134 and will force it upwardly through the final guide tube 148. The wire w emerging from the final tube 148 passes into the evaporator boat 120 and if the boat 120 is hot enough, the wire w will melt to form a pool of molten metal within the boat 120.
The remaining evaporator units 80 are identical in construction, and those units are spaced evenly over the entire top of the carriage 58. Thus, the evaporator units 80 are located along the entire length of the rack 20 from which workpieces B are suspended.
The wire feed shaft 140 extends along the entire length of the carriage 58 (FIG. 6) and passes through the bearing blocks 138 of all the evaporator units 80 so that the wire feed shaft 140 is common to and powers the wire feed devices 132 of all the units 80. At the end of the carriage 58 closest to the end wall 6, the carriage 58 is fitted with a right angle gear box 160 (FIG. 10) into which the feed shaft 140 extends, and the gear box 160 has a splined drive shaft 162 (FIG. 5) extended completely through it at a right angle to the feed shaft 140. Indeed, the drive shaft 162 extends horizontally through the vacuum chamber 8 and has its ends confined in bearings 164 mounted on the cylindrical wall 4 of the vessel 2. The one bearing 164 is formed integral with a seal or pass through unit 166, which enables the shaft 162 to extend completely through the wall 4 while a vacuum is maintained in the chamber 8. Beyond the seal unit 164 the shaft 162 is coupled with a variable speed gear motor 166 that is mounted on the exterior surface of the wall 4. When the motor 168 is energized, it rotates the drive shaft 162 which, being coupled to the feed shaft 140 through the gear box 160, rotates the feed shaft 140 and the rollers 142 on the feed shaft 140. The rollers 142 in turn drive the wire w upwardly through the final guide tubes 148 of the various evaporator units 80. Moreover, the spline or the drive shaft 162 fits loosely through the gear box 160 so that as the carriage 58 moves across the vacuum chamber 8, the gear box 160 merely slides over the shaft 162, yet remains engaged with the shaft 162 from a rotary standpoint.
To prevent the evaporator units 80 from coating important components of the evaporator assembly 24, the carriage 58 is provided with a shield 170 (FIGS. 5-7) that extends generally over the top and along the side of it. The shield 170 completely obscures the wire feed device 132 and the feed shaft 140. If further covers the common electrode 82 and the support tube 84. However, along its top it has apertures through which the evaporator boats 120 are fully exposed. Also the lead screws 68 and the drive shaft 162 are encapsulated in bellows (not shown) which expand and contract as the carriage 58 moves left and right through the vacuum chamber 8.
Not only does the evaporator assembly 24 possess a shield 172, but the vessel 2 likewise contains a shield 180 (FIG. 2) that is located along one side of the chamber 8 and is capable of being moved between lowered and raised positions. In the lowered position, the shield 180 will overlie the boat 120 on the evaporator assembly 24, assuming that the evaporator assembly 24 is at the side of the chamber 8 at which the shield 180 is located, and this enables the shield 180 to prevent coating of the workpiece B. However, when the shield 180 is moved to its raised position, it no longer obscures the workpiece B and indeed the boats 120 are exposed directly to the workpiece B so that the molten metal within them will be deposited on the workpiece B. Actually, the shield 180 is hinged to a bracket 182 which in turn is secured to the side of the cylindrical wall 4 for the vessel 2.
The shield 180 is pivoted between its raised and lowered positions by a cable 184 which at both of its ends attaches to the shield and extends therefrom in two passes generally along the front cross rail 56 and thence along the opposite side of the cylindrical wall to a drum which is operated by a handle 188 (FIG. 11) located outside the vessel 2. Thus, when the handle 188 is moved, the cable 184 shifts and pivots the shield 180. The direction in which the shield 180 moves is, of course, dependent on the direction in which the handle 188 is turned.
OPERATION
To prepare the coating machine A for coating a workpiece B, the door 10 of the vacuum vessel 2 is opened and the rack 22 is withdrawn as far as possible so as to be presented entirely outside of vacuum chamber 8 (FIG. 1). Then, by means of hooks 190, the workpiece B is suspended from the screen 40 of the rack 22. Next the rack 22 is moved back into the vessel 2 so as to be housed entirely within the vacuum chamber. In this regard, the hooks 190 should be short enough to prevent the workpiece B from interferring with the evaporator units 80 on the carriage 58. When the rack 22 reaches its fully inserted position, the spring contactor 42 on the expanded metal screen 40 will bear against the contact 44 on the end wall 6 of the vessel 2. Next, the gear motor 74, is energized to move the carriage 58 to that side of the chamber 8 at which the movable shield 180 is located. Also, the shield 180 is moved to its lowered position by turning the handle 188, and in that position the shield 180 overlies all of the evaporator units 80 on the carriage 58.
Once the rack 22, the workpiece B, the carriage 58 and the movable shield 180 have assumed the foregoing positions, the door 10 is closed and the clamps 14 are tightened to secure the door 10 in place. Next, the vacuum pump 16 is energized to evacuate the vacuum chamber 8. Indeed, the pump 16 lowers the pressure in the chamber to about 10 -4 mm Hg, whereupon the chamber 8 is partially back-filled with argon or some other inert gas until the pressure reaches 1×10 -2 to 2×10 -2 mm Hg., while the low pressure inert gas is in the chamber 8 a high negative voltage on the order of 1,000 to 2,000 volts DC is applied to the workpiece B. Actually, this voltage is impressed across the metal screen 40 on the rack 22 and the vacuum vessel 2, so that the workpiece B is at an electrical potential substantially different from that of the vacuum vessel 2 and the carriage 58 within it. In this condition, a phenomenon known as glow discharge occurs and as a result of glow discharge argon ions bombard the surface of the workpiece B. This bombardment removes any foreign particles so that the surface of the workpiece B is absolutely clean. In short, glow discharge cleans the workpiece atomically. The glow discharge cleaning lasts for 15 to 30 minutes, depending on the size and configuration of the workpiece B.
Once the glow discharge cleaning has been completed, an alternating electrical current is applied to the cables 108 and 122, and this potential is impressed across the boats 120 at the clamp-type brackets 116 and 118. The boats 120, being resistance-type heating elements, experience a rise in temperature, and indeed the rise is sufficient to bring the temperature of the boats 120 above the temperature at which the metal of the coating wire w will melt. The heat which is developed is prevented from destroying the common electrode 82 by the cooling water which is circulated through that electrode. Similarly, the cables 108, which conduct current to the electrode 82, are maintained at a reasonable temperature by the water which is circulated through the inlet and the outlet hoses 112 and 114 associated with those cables 108. Likewise, the cables 122, which conduct current to the clamp-type brackets 118 of the boats 120, are prevented from over heating by cooling water circulated through their inlet and outlet hoses 128 and 130.
When the boats 120 reach the proper operating temperature, the gear motor 168 is energized, and this motor powers the drive shaft 162 which in turn rotates the wire feed shaft 140 that is common to all of the evaporator units 80. Each roller 142 on the feed shaft 140 bears against a different coating wire w and drives that coating wire w upwardly through the upper guide tube 148 which in turn directs the wire w downwardly into the boat 120 where the wire w melts and into a molten pool (FIG. 7). Due to the extremely low pressure in the vacuum chamber 8, the molten metal in effect evaporates quite rapidly from the pool and migrates through the vacuum chamber 8. The gear motor 168 is adjusted to feed the wire w at precisely the rate at which the metal evaporates from the pool so that the pool contains the same amount of molten metal for the duration of the coating operation.
Once all of the evaporator units 80 on the carriage 58 are operating consistently, the handle 188 at the exterior of the vessel 2 is turned to move the shield 180 upwardly to its raised position. This exposes the workpiece B to the evaporator boats 120, and by reason by the substantial difference in electrical potential between the workpiece B and the metal of the pool, the evaporated metal is attracted to the workpiece B which is coated thereby. To provide a uniform coating, the gear motor 74 is energized, and it rotates the lead screws 68 which in turn move the carriage 58 over the cross rails 58 to the other side of the vacuum chamber. Indeed, the carriage 58 may be moved back and forth several times merely by reversing the motor 74, and in this manner a coating of practically any desired thickness may be acquired.
The coating produced by the machine A is extremely secure and durable, for it is in effect diffusion bonded to the workpiece B. Furthermore, since the carriage moves through chamber 8 the workpiece can be almost as wide and as long as the chamber 8 itself. This is to be distinguished with ion vapor deposition machines of conventional structure which are suitable for coating only extremely small objects such as machine screws, nuts annd the like.
Whereas the machine A is well suited for ion vapor deposition coating, it may also be used for mere physical vapor deposition. In that case, the workpiece B and the boats 120 remain at the same potential. In other words, in physical vapor deposition, the screen 40 of the rack is not placed at a high negative DV voltage. The application of metal to glass so as to form mirrors is an example of physical vapor deposition.
This invention is intended to cover all changes and modifications of the example of the invention herein chosen for purposes of the disclosure which do not constitute departures from the spirit and scope of the invention.
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A machine for vapor coating a workpiece with a coating metal supplied in wire form includes a vessel enclosing a vacuum chamber and having a door for providing access to the vacuum chamber. The vessel is connected with a vacuum pump for evacuating the vacuum chamber. Mounted within the vacuum chamber is a rack having an attachment screen which is electrically isolated from the remainder of the vessel so that the screen may be placed at a DC potential significantly higher than the vessel. When the door of the vessel is open, the rack may be withdrawn from the chamber for loading the workpiece thereon. The chamber also contains a carriage that moves from one side of the chamber to the other beneath the rack, and the carriage has a plurality of evaporator units mounted along it. Each evaporator unit includes a trough-like boat and means for feeding the coating metal wire into the boat. An electrical potential is impressed across the boat, which functions as a resistance-type heater, and that potential is sufficient in magnitude to elevate the temperature of the boat enough to melt the coating metal wire fed into it. Once all of the evaporator units in the carriage are operating consistently, the carriage is moved across the chamber one or more times, and the vaporized coating metal emitted from the boat is deposited on the workpiece, providing a firmly bonded uniform coating.
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[0001] The present invention relates to a method of introducing at least one human cytocbrome P450 (“human P450”) into a non-human animal cell whose own equivalent endogenous cytocbrome P450 (“endogenous P450”) enzyme activities have been disabled so as to replace those endogenous P450 activities with the human equivalent. The resulting transgenic animal is referred to as a P450-humanised animal. The present invention also relates to transgenic non-human animals produced by the method of the invention and uses therefor, especially but not exclusively, the animal or cells or tissue derived therefrom is/are of use in assessing xenobiotic/drug metabolism, toxicity or other properties or functions of the human cytochrome P450-dependent monooxygenase system such as metabolism or biosynthesis of endogenous compounds.
BACKGROUND TO THE INVENTION
[0002] A significant proportion of therapeutic drug candidates fail to become marketable drugs because of adverse metabolism or toxicity discovered during clinical trials. These failures represent a very significant waste of development expenditure and consequently there is a need for new technologies that can more reliably, quickly and economically predict at the preclinical development stage the metabolic and toxicological characteristics of drug candidates in man. At present, most pre-clinical metabolic and toxicity testing of drug candidates relies on laboratory animals, human and/or mammalian cell lines or tissues in culture. None of these methods is completely reliable in predicting metabolism or toxicity in a human subject. Metabolic data from animals can differ significantly from that obtained from a human subject due to differences in the enzymes involved. Interpretation of data from cell culture or isolated tissue studies can be problematic since such systems are unable to reflect whole body metabolism.
[0003] It is recognised that hepatic P450s are the single most important factor in determining the mammalian metabolism and toxicity of most therapeutic drugs and P450s expressed in other tissues can be critical in determining local drug metabolism, disposition or toxicity. A major technical challenge in producing P450-humanised animals lies in the large number of endogenous P450s that need to be made inactive, for example in the mouse there are 107 known P450s. It is known in the prior art to selectively inhibit some P450s with either exogenous agents or by targeted deletion of individual P450 genes. However, as many P450s involved in foreign compound metabolism exhibit overlapping substrate specificities, these approaches are not a generally effective way of anulling endogenous P450 metabolism in order to produce a transgenic animal exhibiting humanised P450 metabolism. However, all cytochrome P450s receive electrons from a single donor, cytochrome P450 reductase (CPR) and deletion of this protein would therefore inactivate all P450-mediated metabolism. While complete deletion of CPR is lethal at the embryonic stage of development, mice where the CPR gene is flanked with loxP sequences so that CPR can be conditionally deleted in the postnatal period in a specific tissue by developmentally controlled expression of cre recombinase can survive to adulthood in good health. For instance, in a co-pending application (PCT/GB03/002967 unpublished at the time of this present application) it is known to produce and use a Hepatic Reductase Null (“ERN”) mouse in which the cytochrome P450 reductase (CPR) enzyme on which all P450s depend has been deleted in the liver. IRN™ mice thus therefore completely lack P450-mediated metabolism in the liver and provide a starting point for the development of P450-humanised animals that are predictive of drug metabolism in man.
[0004] In the present invention, we have developed new strains of P450-humanised transgenic non-human animals in which endogenous P450s are made inactive in a specific tissue and one or more functional human P450s are expressed. Since liver P450s are the single most important factor in determining the metabolism and toxicity of most therapeutic drugs, it is envisaged that non-human animals humanised for P450s in the liver will be particularly useful as predictors of the metabolism and toxicity of drug candidate compounds in man.
[0005] A particular advantage of the method of the present invention resides in the production of P450-humanised transgenic animals/cells/tissues, in that the animals/cells tissues are able to combine the benefits of normal experimental animal models with those of human cell/tissue culture in a single system. This system or humanised transgenic animal will provide the pharmaceutical industry with an improved alternative for use in all pre-clinical metabolism, toxicity and drug disposition studies.
STATEMENT OF THE INVENTION
[0006] According to a first aspect of the invention there is provided a method of introducing at least one functional human cytochrome P450 into non-human cell(s) whose own endogenous P450s have been rendered inactive, the method comprising introducing DNA encoding said at least one human P450 such that said human P450 remains functional where the cell's own endogenous P450s are inactive.
[0007] Throughout the specification and the claims which follow, unless the context requires otherwise, the word “comprise”, or variations such as “comprises” or “comprising” will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.
[0008] Preferably the method comprises rendering the non-human cell's own endogenous P450s inactive by deletion of the endogenous CPR gene and where function of the at least one introduced human cytochrome P450 is maintained either by it being in modified form such that it can function independently of any separate CPR protein or by introducing into the non-human cell DNA encoding a CPR such that said at least one introduced human P450 can function in the non-human animal cell(s). Reference herein to a functional human cytochrome P450 indicates that the human cytochrome P450 is enzymatically active.
[0009] In preferred embodiments of the present invention as described above and below, the transgenic non-human animal or mammal is a monkey, dog, cat, rabbit, hamster, rat, or mouse. More preferably, the transgenic non-human cell(s) are derived from a mouse.
[0010] To express active human P450 in CPR-null non-human cells, it is necessary not only to introduce human P450 genes, but also a corresponding CPR moiety to allow the expressed human P450 proteins to be enzymatically active. Expression of enzymatically active human P450(s) in a non-human animal cell whose endogenous P450s have been rendered inactive by deletion of the endogenous CPR may therefore be achieved by expressing the human P450 moiety either by; as part of a human P450-CPR fusion protein, wherein the introduced CPR moiety is tightly coupled to the P450 moiety or; in combination with a separate co-expressed human CPR.
[0011] In one embodiment of the invention therefore, a DNA sequence comprising contiguous coding sequences, with appropriate modifications, for a human P450, for example and without limitation CYP3A4 or CYP2D6, and a CPR, for example human CPR, are introduced into a non-human animal cell whose endogenous CPR gene has been deleted, so that said cell will express a human P450-CPR fusion protein in which the human P450 moiety is a fully functional P450 enzyme without the need for a separate CPR. Thus, such a fusion protein whose expression is driven by a suitable gene promoter, for example CMV or a tissue-specific promoter such as rat albumin or an inducible promoter such as CYP1A1, and introduced into transgenic mice, will provide an expression of the fusion element or protein in a constitutive or conditional fashion.
[0012] It will be appreciated that the method of conditional deletion of CPR can be directed to tissues other than the liver and can be made conditional on the administration of specific exogenous compounds by the use of different gene promoter sequences from which it is possible to drive expression of the cre recombinase. Accordingly, the method of the present invention allows for tissue selective conditional deletion of CPR in tissue other than and including the liver.
[0013] In a further embodiment of the invention, separate DNA sequences comprising, respectively, a coding sequence for a human P450, and a CPR are introduced into a non-human animal cell whose endogenous CPR gene has been deleted so that said cell will express enzymatically active human P450.
[0014] Where CPR is introduced into cells whose endogenous P450s have been made inactive by deletion of the endogenous CPR, it is preferable to express the introduced CPR in a manner that prevents reactivation of the endogenous P450s. Thus, in one embodiment of the method, in order to avoid electron transfer from the introduced CPR whether it is expressed as a separate polypeptide from the introduced human P450(s) or as part of a fusion protein, the expressed CPR protein is targeted to a specific cellular compartment where endogenous P450s are not expressed, for instance and without limitation the plasma membrane.
[0015] Preferably, the fusion protein or separate human cytochrome P450 and P450 reductase fusion proteins is/are targeted to a specific cellular component where non-human animal P540s are not expressed
[0016] Preferably, therefore, the DNA sequence introduced into a non-human animal c ell and comprising a CPR coding sequence, will also comprise a sequence chosen to direct the expressed polypeptide to an intracellular compartment remote from the endogenous P450s, for instance a sequence encoding the transmembrane spanning region of a seven transmembrane segment receptor protein.
[0017] Preferably, an intracellular targeting sequence is added to the fusion protein or separate human cytochrome P450 and P450 reductase fusion proteins
[0018] Preferably, a plurality of DNA sequences encoding different human cytochrome P450s are introduced into the non-human cell(s).
[0019] The choice of human P450 isoforms for introduction into P450-humanised non-human animals is predominantly driven by the known relative importance of various P450 isoforms in metabolism in the relevant tissue. Thus, for example, to date the single most significant isoform in the human liver CYP3A4, and so CYP3A4 is therefore the first human P450 isoform of choice for P450 humanisation of liver. The choice of human P450s for the multi-P450-humanised mouse of the present invention is dictated by the need of the user, in this respect it is expected that any one or more of the following human isoforms will be preferred 3A4, 2D6, 2C9, 1A2, 2Cl9, 2C8. However, it will be appreciated that the isoform(s) incorporated into the animal cell is/are dependent on the user's requirement. In this way, the humanised transgenic animal may be “designed” to investigate the role of specific isoforms in the metabolic process.
[0020] The present invention therefore advantageously provides a method of producing a multi-P450-humanised transgenic non-human animal.
[0021] In another embodiment of the invention, the method further includes introducing at least one further DNA sequence encoding a human protein other than a P450 that is involved in xenobiotic metabolism.
[0022] In this particular embodiment of the invention other human proteins of interest, for example and without limitation, a DNA sequence encoding a human drug transporter, for instance human Mdr-1, may be introduced into a non-human animal cell whose own corresponding endogenous gene has been deleted and in which functional human P450(s) are also expressed where the endogenous P450s have been made non-functional will permit the functions of the, for example, human drug transporter protein to be studied in the non-human animal in the context of human P450 metabolism.
[0023] It will be appreciated that this aspect of the invention includes any one or more of the features as hereinbefore described.
[0024] According to a yet further aspect of the invention there is provided use of human cells, especially hepatocytes, introduced into an immune-deprived reductase null animal so as to investigate contribution of human cells or hepatocytes in P450-mediated product metabolism and/or toxicity and/or drug candidate screening.
[0025] In this embodiment of the invention, human cells or hepatocytes may grow in, for example the liver or spleen of SCID (severe combined immune deficiency) mice. SCID mice are homozygous for the Prkdc scid mutation and lack both T and B cells due to a defect in V(D)J recombination. Therefore, these mice easily accept foreign tissue transplants, including human tumours, making them effective models for testing new cancer treatments and as hosts for human immune system tissues (i.e., SCID-hu).
[0026] Accordingly, in this embodiment of the invention only the human cells or hepatocytes will contribute to cell or hepatocyte-mediated P450 metabolism and thus may be advantageously used as a human metabolism model in the absence of background mouse metabolism.
[0027] According to a yet further aspect of the invention there is provided use of a transgenic animal, tissues and/or cells derived therefrom as hereinbefore described that have been modified to contain and express DNA encoding at least one human P450 and/or another protein involved in metabolism so as to investigate human P450 mediated metabolism in said a transgenic animal, tissues and/or cells derived therefrom.
[0028] The present invention advantageously provides a tool for the investigation not only of metabolism of xenobiotics but of the functions of human P450s in the metabolism and biosynthesis of endogenous compounds such as and without limitation neurosteroids, and in disease states such as and without limitation, choleastasis, artherogenesis, hormonal imbalances, neurological disorders, degenerative diseases, skin conditions, cardiovascular disease, cancer and glaucoma and any other disease in which P450s play a role.
[0029] A yet further advantage of the present invention is in the provision of, for example, a CYP3A4-humanised transgenic mouse which may be used for problem-solving studies in drug metabolism and toxicity.
[0030] The invention will now be described by way of example only with reference to the following figures wherein:
[0031] FIG. 1 illustrates the pshuttle-CMV-3A4, fall length of human CYP3A4 cDNA fusion with human P450 reductase cDNA (codons for first 57 amino acids deleted) ligated into the Kpn I/Not I site of the shuttle vector pshuttle-CMV;
[0032] FIG. 2 illustrates 1′ hydroxy-midazolam production by mouse hepatocytes during midazolam metabolism; and
[0033] FIG. 3 illustrates midazolam concentrations during midazolam metabolism by mouse hepatocytes.
[0034] FIG. 4A shows a bar chart of relative fluorescence determined by a RT-PCR assay of CYP34A-CPR fusion construct mRNA expression in Ad-3A4/red virus-infected mouse liver.
[0035] FIG. 4B shows an immunoblot analysis of CYP34A-CPR fusion protein expression in Ad-3A4/red virus-infected mouse liver.
[0036] FIG. 5 shows a graph of blood levels of midazolam (ng/ml) in HRN mice infected with Ad-3A4/red virus.
[0037] FIG. 6 shows a bar chart of relative metabolite concentration (area under peak) form control, Ad-GFP and AD-3A4/red infected cells; FIG. 6A is metabolism of midazolam and FIG. 6B is of bufuralol.
DETAILED DESCRIPTION OF THE INVENTION
Materials and Methods
The HRN™ Mouse
[0038] All P450s require reducing electrons supplied by the enzyme cytochrome P450 reductase (CPR). Deletion of CPR therefore simultaneously inactivates all P450s. While CPR deletion is lethal in the embryo, HRN™ mice use a developmentally regulated conditional CPR deletion targeted to post-natal liver cells. HRN™ ice therefore survive to adulthood and can breed while nevertheless completely lacking hepatic P450-mediated metabolism (Henderson CJ et al. J Biol Chem. 278:13480-6, 2003). They therefore provide a suitable background on which to express human P450 activities in order to achieve P450 humanisation.
Transgenic Mouse Production
[0039] An adenoviral vector may be used to introduce the human P450/CPR combination to HRN™ cells. Alternatively, germ line transgenic animals incorporating the same transgenes can be produced. This is achieved by first generating transgenic mice incorporating the selected CYP3A4/CPR humanisation transgenes and then crossbreeding these with HRN™ mice to produce CYP3A4-humanised animals. Production of CYP3A4/CPR transgenic mice is achieved by using targeted transfection of embryonic stem cells and subsequent blastocyst injection. Crossbreeding of CYP3A4/CPR transgenics with HRN™ to produce P450-humanised animals may be used for the production of multi-P450-humanised mice. Alternatively, embryonic stem cells may be produced where the CPR gene is flanked by loxP sites and where expression sequences for targeted human P450(s) and CPR or for human P450-CPR fusion protein(s) have been introduced. Animals derived from such embryonic stem cells may then be crossbred with various animal strains in which cre recombinase is expressed under the control of different promoters to produce offspring P450-humanised in different tissues or under different induction conditions, depending on the tissue specificity or inducibility of the promoter controlling cre recombinase expression.
Humanisation Strategies
[0040] In order to establish the optimal method of expressing functional human P450 activities in HRN™ cells, experimental transgenes encoding cytosolic fusion proteins, targeted fusion proteins, targeted CPR with separate cytosolic P450s are compared and evaluated. In each case, the ability of the P450 to interact with the CPR component is determined by expressing these alternatives in appropriate cell culture systems and then testing them in vivo by adenovirus transfection of HRN™ mice.
Cell Line for Evaluation of Human P450 Transgenes
[0041] We use a suitable immortalised cell line for initial in vitro evaluation of the various transgene strategies. This is based on an immortalised cell line derived from HRN™ or on an existing cell line known to be deficient in CPR and P450 expression (e.g. CHO cells), which is then transfected to over express recombinant mouse P450. The cell line will is then used to test experimental transgenes for their ability to produce human P450 activity without activation of the mouse P450.
Adenoviral Delivery of Transgenes In Vivo
[0042] The invention requires transgene expression in the liver and adenovirus transgene delivery to liver cells of mature mice is a feasible method of introducing human P450 transgenes for appropriate expression in HRN™. Previous published work has shown that adenoviral vectors can deliver transgenes to virtually all hepatocytes in mouse liver. We used this method to initially evaluate the suitability of the various human P450 expression strategies outlined above in vivo. This approach permits the generation of prototype humanised animals for evaluation relatively quickly and more cost effectively. Once generated, adenovirus-transfected animals are dosed with appropriate test compounds to evaluate metabolism as having the correct characteristics for metabolism by the introduced human P 450 without evidence of endogenous P450 reactivation.
In Vivo Validation of Transgenic Mice
[0043] Information relating to drug bioavailability, toxicology and active transport data is collected. Such data shows humanised mice acting as effective predictors of the properties of a given compound in man where wild-type mice do not. Data is obtained from humanised HRN™ mice and control HRN™ mice. Test compounds with known P450 metabolic profiles in mouse and man are selected and administered orally to humanised and control mice. Mass spectroscopic assays for each drug has been developed and used to determine circulating concentrations of administered drug and known metabolites. Where appropriate, pathological investigations may be conducted to establish compound toxicity.
Isolation of Mouse Hepatocytes
[0044] Wild-type and hepatic CPR-null mice were anaesthetised by intraperitoneal injection of pentobarbitone (100 mg/kg body weight) and the livers immediately perfused with Calcium-free Krebs-Ringer phosphate buffer, pH 7.4 (KRPB) via the hepatic portal vein at a flow rate of 12 ml/min for 10 minutes followed by Calcium-free Krebs-Ringer hydrogen carbonate buffer, pH 7.4 (KRHB) at 12 ml/min for 5 minutes and then 0.2 mg/ml collagenase in KRHB containing 0.3 mM calcium chloride at 12 ml/min for 10 minutes. Cell suspensions were then produced by mechanically disrupting removed liver tissue, filtration through bolting cloth and washing in KRHB.
[0045] Mouse hepatocytes were grown at 37° C. in complete Leibowitz L15 (CL-15) medium supplemented with 8.3% fetal calf serum (FCS), penicillin (41 IU/ml), streptomycin (41 μg/ml), tryptose phosphate broth (8.3%, v/v), hydrocortisone 21-hemisuccinate (10 μM), insulin (1 μM), hemin (5 μg/ml) and glutamine (240 μg/ml). Hepatocytes were seeded at a density of 8×10 5 cells per well on 6-well plates and incubated at 37° C. for one day before infection with human cytochrome P450 3A4-human cytochrome P450 reductase fusion gene by adenoviral vector.
Ad-3A4/Red Plasmid Construction and Virus Preparation
[0046] The human P450 3A4 (CYP3A4)-P450 reductase (CPR) fusion cDNA comprised contiguous modified CYP3A4 and CPR coding sequences. The CYP3A4 sequence was modified at the N-ternminus by insertion of a Kpn I restriction site following the Kozak sequence and just before ATG start codon and by deletion of the TGA stop codon. The CPR sequence was modified by deletion of coding sequence for the first 57 amino acids (ER anchor) and flanked at the C-terminus by a NotI restriction site. The CYP3A4-CPR fusion cDNA was inserted into the shuttle vector pshuttle-CMV (Stratagene) [ FIG. 1 ] and Ad-3A4/red virus prepared using the AdEasy XL Adenoviral vector system (Stratagene).
Virus Infection and Determination of Catalytic Activity in Cultured Cells
[0047] Hepatocytes from HRN™ mice were infected with Ad-3A4/red adenovirus according to methods of the AdEasy XL Adenoviral vector system (Stratagene). After 4-days of infection with virus, the cell medium was replaced with 2 ml of fresh CL-15 plus bufaralol (10 μM) or midazolam (10 EM). After 0.5, 1, 2 and 4 hours of incubation, 200 gi aliquots of medium were transferred to Eppendorf tubes with 200 μl ice-cold acetonitrile containing 5 μM dextrorphan as internal standard for mass spectrometric analysis.
Mass Spectrometric Analysis for Bufuralol, Midazolam and Specific Metabolites
[0048] Analysis for the loss of bufuralol and midazolam was carried out using reverse-phase HPLC with tandem mass spectrometric detection (LC-MS/MS). An aliquot of each standard and sample (20 μL) was injected onto the liquid chromatography system and eluted under isocratic conditions of 50% H 2 O with 0.1% (v/v) Formic acid and 50% Acetonitrile at a flow rate of 0.5 mL/min through a Phenomenex MercuryMS Luna 3 μM C18(2), 20×2 mm HPLC column.
[0049] Positive ions for parent compounds and specific fragment products were monitored in Multiple Reaction Monitoring (MRM) mode using a Micromass Quaffro Micro Mass Spectrometer with Micromass MassLynx software version 3.5, monitoring for the positive bufuralol parent ion at 262.41 m/z with the specific product ion at 188.12 m/z; for the positive midazolam parent ion at 326.35 m/z with the specific product ion at 291.22 m/z and for internal standard dextrorphan parent ion at 258.47 m/z with the specific product ion at 157.21 m/z.
[0050] Analysis for the appearance of the specific metabolites 1′-hydroxybufuralol and 1′-hydroxymidazolam was carried out as above, but using gradient elution from the HPLC column and MRM of the positive 1′-hydroxybufuralol parent ion at 278.4 m/z with the specific product ion at 186.2 m/z and of the positive 1′-hydroxymidazolam parent ion at 342.3 m/z with the specific product ion at 203.2 m/z.
[0000] Real-Time Quarztitative Polymerase Chain Reaction (RT-PCR) Assay of Ad-3A4/Red mRNA
[0051] Messenger RNA was prepared from liver tissue and assayed for the presence of CYP3A4-coding sequences by real-time quantitative PCR. RNA was diluted to 0.1 μg/μl and DNase-treated (Promega UK) at 37° C. for 10 mins. cDNA was synthesized using 100 units of Superscript II reverse transcriptase (Invitrogen) and 0.15 g of random primers (Promega UK) in a solution of 50 mM Tris/HCL, pH 8.3, 75 mM KCL and 3Mm MgCl 2 containing 10 mM dithiothreitol and 1 mM dNTPs. The reaction was equilibrated at 25° C. for 10 mins before synthesis proceeded at 42° C. for 50 min. The reaction was terminated by incubation at 70° C. for 10 min, and cDNA was diluted to 200 μl and stored at −20° C. until use. Matching oligonucleotide primers and probes for real-time PCR were designed using Primer Express™ (PerkinElmer Applied Biosystems) software. Each PCR mix (12.5 μl) contained 2.5 μl cDNA, 299 nM forward primer (5′-CACCAAGAAGCTTTTAAGATTTGATTT-3′) (SEQ ID NO:1) and reverse primer (5′-TTGGGATGAGGAATGGAAAGA-3′) (SEQ ID NO:2) and 1001 nM probe (5′-TGGATCCATTCTTTCTCTCAATAACA-3′) (SEQ ID NO:3) in 1× (final concentration) TaqMan® Master Mix (PerkinElmer). Amplification of cDNA was performed over 41 cycles in the Prism Model 7700 Sequence Detector instrument. The first cycle was performed using 50° C. for 2 min, followed by 95° C. for 10 min. Cycles 2-41 were performed at 95° C. for 15s, followed by 60° C. for 1 min. Reactions were monitored by measuring fluorescence at 518 nm with excitation at 494 nm. Each assay was performed in triplicate, and specificity of PCR reactions from various primers were examined routinely by agarose-gel electrophoresis. GAPDH was used as an internal standard and results were analysed using 7700 system software.
Immunoblot Analysis of Ad-3A4/Red Expression
[0052] Hepatic microsome proteins, prepared from snap-frozen tissues, were loaded at 5 mg protein per lane onto 9% polyacrylamide gels and separated by electrophoresis in buffer containing 10% sodium dodecyl sulphate (SDS). Separated proteins were transferred to nitrocellulose membranes and immunostained with a polyclonal antiserum to human cytochrome P450 reductase.
EXAMPLE 1
Generalised Scheme for P450 Humanisation in a Tissue-Specific or Inducible Manner
[0053] A transgenic mouse is generated carrying the following transgenes: (1) a human P450-CPR fusion gene with intracellular targeting sequences is preceded by an interfering gene fragment flanked by loxP sequences preceded by a ubiquitous promoter, for instance the ROSA26 promoter where the interfering fragment is designed so that no transcription of the fusion gene occurs; (2) the endogenous CPR gene replaced by a CPR gene flanked by loxP sequences; (3) a cre recombinase gene under the control of a tissue-specific or inducible promoter. Under conditions where ere recombinase is expressed, either as the result of cellular differentiation or of administration of inducing agents, recombination at the loxP sites results in deletion of the endogenous CPR and consequent deactivation of endogenous P450s together with activation of expression of the human P450-CPR fusion gene by virtue of deletion of the interfering fragment. In this way, both deactivation of endogenous P450s and expression of the functioning human P450(s) are restricted to a specific tissue type or to specific conditions of induction.
EXAMPLE 2
Expression of Human Cytochrome P450 3A4 Activity in Isolated Hepatocytes from Hepatic CPR-null Mice
[0054] In this study, isolated hepatocytes from hepatic CPR-null mice were infected with adenovirus carrying a human cytochrome P450 3A4-cytochrome P450 reductase fusion gene under control of the CMV promoter. This resulted in expression of human P450 3A4 activity in the infected hepatocytes showing that cells from the CPR-null animals can be used as the basis of ‘humanised’ metabolic systems.
[0055] In order to determine the effect of human recombinant CYP3A4/reductase on hepatic CPR-null hepatocytes P450 monooxygenase activities, the catalytic activity of the CYP3A4 was measured using midazolam, monitoring disappearance of the added drug and accumulation of the metabolites 1′hydroxy-midazolam in hepatocytes from wild-type mice and hepatocytes from hepatic CPR-null mice with or without infection with the Ad-3A4/red fusion vector.
[0056] After 4 hours incubation, 1′hydroxy-midazolam concentrations in hepatocyte cultures from hepatic CPR-null mice incubated with midazolam were only approximately 25% of those produced in cultures from wild-type mice. However, cultures from CPR-null mice that had been infected with Ad-3A4/red produced approximately 3 times as much 1′hydroxy-midazolam as those from wild-type animals as can be seen in the graph represented by FIG. 2 , which shows 1′hydroxy-midazolam production during midazolam metabolism by mouse hepatocytes over a 4 hr incubation period.
[0057] Corresponding effects were seen on the disappearance of midazolam as is apparent from FIG. 3 (midazolam concentration during midazolam metabolism by mouse hepatocytes over a 4 hr incubation period).
EXAMPLE 3
Expression of the CYP3A4-CPR Fusion Protein in HRN Mice
[0058] Eight HRN mice received Ad-3A4/red virus (100 μl at 10 9 pfu/ml intravenously). The animals were killed four days later and liver tissue collected and snap-frozen in liquid nitrogen.
[0059] RT-PCR analysis revealed expression of CYP3A4-CPR mRNA in livers of four of the eight infected mice, as indicated by the presence of CYP3A4 coding sequence. FIG. 4A shows CYP3A4-CPR fusion construct mRNA expression in Ad-3A4/red virus-infected mouse liver determined by RT-PCR assay of CYP3A4 coding sequence.
[0060] With regard to FIG. 4B , we have shown CYP3A4-CPR fusion protein expression in Ad-3A4/red virus-infected mouse livers determined by immunoblot analysis of hepatic microsome proteins with an anti-CPR antiserum. Arrows indicate bands due to the CYP3A4-CPR fusion protein (3A4-CPR) in adenovirus-infected HRN mice and of native cytochrome P450 reductase (CPR) in wild-type mice. Lanes are identified as follows: 1-8=Ad-3A4/red virus-infected HRN mice 1-8 respectively; 9,10=Blank; 11=uninfected HRN mouse liver microsomes (no adenovirus); 12=Wild-type mouse liver microsomes. Thus, expression of the fusion protein was confirmed by immunoblotting of hepatic microsomal proteins with the anti-CPR antiserum which revealed reactive bands in microsomes from the same four mice that had yielded positive results for the mRNA. These bands ran more slowly than that produced by the native CPR protein, consistent with the higher molecular mass of the fusion protein ( FIG. 4B ).
[0061] These results demonstrate that adenoviral delivery of the Ad-3A4/red plasmid in vivo results in expression of the CYP3A4-CPR fusion protein in liver.
EXAMPLE 4
Human CYP3A4 Metabolism in Ad-3A4/red Virus-Infected HRN Mouse Liver
[0062] Four adult female HRN mice received 100 μl of 10 9 pfu/ml Ad-3A4/red virus intravenously. Seventy-two hours later the animals received oral doses of 2.5 mg/kg midazolam. Blood samples were collected from each animal at 15, 30, 45, 60, 90, 120, 180 and 240 minutes after midazolam dosing. Midazolam concentrations were assayed by mass spectroscopy.
[0063] FIG. 5 shows blood midazolam concentrations following oral administration of 2.5 mg/kg midazolam. Values are mean±standard error of the mean in HRN animals infected with the Ad-3A4/red virus compared to concentrations in non-infected HRN animals and with wild-type animals. As expected, midazolam was rapidly metabolized by the wild-type animals. Circulating midazolam concentrations reached a peak value of 128 ng/ml and had become undetectable again within 3 hours. In comparison, HRN animals exhibited severely impaired midazolam metabolism with circulating midazolam concentrations reaching a peak value of 260 ng/ml and remaining detectable beyond 6 hours. In HRN animals infected with the Ad-3A4/red virus, however, there was clear evidence of restored ability to metabolize midazolam with peak midazolam concentration achieved being only 109 ng/ml.
[0064] These results demonstrate that adenoviral delivery of the Ad-3A4/red plasmid and expression of the CYP3A4-CPR fusion protein in HRN mice restores the animal's ability to metabolize midazolam, a substrate of CYP3A4.
EXAMPLE 5
Lack of Electron Transfer Between the CYP3A4-CPR Fusion Protein and Cytochrome P450s
[0065] Expression of a cytochrome P450-CPR fusion protein in HRN mouse cells introduces the possibility of electron transfer from the introduced CPR moiety reactivating endogenous cellular cytochrome P450s. It is preferable from the point of view of producing a humanised cell if such ‘crosstalk’ between the fusion protein CPR moiety and cellular cytochrome P450s is kept to a minimum. To establish whether such crosstalk takes place, expression of the CYP3A4-CPR fusion protein was induced in two cell lines by infection with the Ad-3A4/red adenoviral vector.
[0066] With regard to FIG. 6 , Chinese Hamster Ovary (CHO) cell line transfected with human cytochrome P450 2D6 (CYP2D6) grown in culture were infected with Ad-3A4/red. Four days later, fresh medium containing either midazolam or bufaralol at 10 μM was added to the cultures and four hours later medium was collected for analysis by mass spectroscopy for the presence of 1′-hydroxymidazolam or 1′-hydroxybufuralol respectively. A bar chart was made of relative metabolite concentration values shown are relative ‘area under the peak’ values. Each value is mean±standard error for four culture wells. ‘Control’ indicates uninfected CHO/2D6 cells; ‘Ad-GFP’ indicates c ells infected with a control adenovirus containing green fluorescent protein cDNA; ‘Ad-3A4/red’ indicates cells infected with the Ad-3A4/red CYP3A4-CPR fusion protein adenovirus.
[0067] In CHO cells expressing CYP2D6, whether uninfected or infected with a control adenovirus vector introducing a green fluorescent protein (Ad-GFP) mRNA, midazolam metabolism was extremely slow. Infection with Ad-3A4/red increased midazolam metabolism by more than 10-fold ( FIG. 6A ). In contrast, metabolism of the CYP2D6 substrate bufuralol was substantial in control CHO/2D6 cells and hardly altered at all after infection with Ad-3A4/red ( FIG. 6B ).
[0068] These results demonstrate that while expression of the CYP3A4-CPR fusion protein results in markedly increased metabolism of midazolam which is predominantly a CYP3A4 substrate, metabolism of bufuralol which is predominantly a CYP2D6 substrate is unaffected. These results indicate that while the CPR moiety of the CYP3A4-CPR fusion protein is efficient at transferring electrons to the CYP3A4 moiety of the fusion protein, it does not significantly interact with the separate CYP2D6 protein. The fusion protein CPR is not therefore likely to cause significant reactivation of and cellular cytochrome P450s in cells from the HRN mouse or other CPR-null cells.
[0069] We have been able to demonstrate the principle of the humanisation using P450-CPR fusion genes: cultured hepatocytes from HRN™ mice have been infected with an adenovirus carrying an inserted artificial gene encoding a human CYP3A4-CPR fusion protein. The fusion protein comprising a human CYP3A4 enzymatic profile but is able to be independent of any separate cellular CPR since its own CPR moiety supplies the reducing electrons required by the P450 moiety. CPR-null hepatocytes infected with the fusion protein gene have been compared with uninfected CPR-null hepatocytes and hepatocytes from normal mice in their ability to metabolise test compounds and are known to have differing susceptibility to metabolism by human CYP3A4. Hepatocytes from CPR-null mice had very much reduced ability to metabolise the test compounds compared to normal hepatocytes. Infection with the human CYP3A4-CPR fusion gene restored metabolism, more strongly for the compound known to be a good substrate for human 3A4 than for compound known to be a poor substrate. These results demonstrate that human CYP3A4 activity could be expressed over the mouse P450-null background and illustrates the basic concept of 450 humanisation.
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A method of introducing at least one human cytochrome P450 into a non-human animal c ell in which corresponding endogenous P450 enzyme activities have been disabled, thus the method provides a way of using a non-human animal cell to make predictions regarding P450-mediated metabolism in a human. The present invention also provides transgenic non-human animals produced by the method of the invention and uses therefor, especially in assessing xenobiotic/drug metabolism and toxicity.
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BACKGROUND
Field of the Invention
[0001] The present invention generally relates to automation systems maintenance and specifically, to the monitoring and diagnostics of robot characteristics predictive of failures and methods to mitigate and prevent catastrophic line failures.
[0002] Assembly line stoppages in wafer-handling system IC processing significantly inhibit overall tool performance and reliability in manufacturing plants because failures in wafer-handling systems have significant mean time to repair (MTTR).
[0003] Based on some chipmaker data, more than 90% of failures were caused by improper placement of the wafer in the robot's end effectors, resulting in broken product wafers during transfer and handling. The problems were usually addressed by the replacement of wafer-handling components or manually recalibrating the handler. Overall, less than 10% of the root causes for failures are clearly identified. The problems are often incorrectly identified as failed system components, including motors, cabling, or the robot itself.
[0004] Studies indicate that a number of operands in the reliability equation can be increased with deployment of in situ diagnostic tools in wafer-handling systems, resulting in higher MTBF (mean productivity time between failures) and higher MCBF (mean cycles between failures), based on Semi E10-0701 guidelines.
[0005] Predictable Failure
[0006] Current robotic wafer-handling systems exhibit a binary behavior, functioning or down. Moreover, these same systems can successfully perform operations even while calibration and functionality of their critical wafer-handling devices are degrading, which leads to expensive consequences if nothing is done during this period to remedy the failing mechanism before catastrophic failure occurs to close the line. Since some relevant parameters are not monitored adequately, and the robotic systems approach critical failures, predictable failures occur, failures which can be mitigated or eliminated with appropriate timely action. What is needed are those monitoring parameters and timely mitigating actions.
[0007] Once a failure occurs, proper diagnosis and analysis frequently require the robot to be removed from the wafer-processing line and delivered to specially designed test fixtures located at the supplier's laboratory. A great deal of cost can be incurred moving the robot between the wafer fab and the supplier's lab. In situ analysis methods are needed, which monitor the performance on line and give warnings when components are degrading or failing. Thus monitoring and prediction are key to reducing costs. What is needed are ways to monitor degradation phenomena, and take measures to eliminate the natural course of consequences with machine vigilance and mitigation actions.
[0008] Automatic calibration methods have new found support in controller programmed servos in using references to position. High-resolution encoders provide feedback to the controller, indicating the position of each motor. Controller software continuously compares the actual motor feedback position to the software-commanded motor position to generate appropriate drive signals. The controller's integrated drives provide the necessary motor drive current. Through this tight integration, the controller has real-time knowledge of the velocity and torque of each motor. However, the position feedback can be improved, as there are still catastrophic system failures which are not caught by the current encoder feedback methods. Therefore physical position feedback is needed.
[0009] In the “touch calibration” mode, the controller commands a robot axis to slowly move the end effecter into the predefined nominal location for handoff of wafers in process tools. When the end effecter makes light contact, the axis slows down and the motor torque changes, indicating physical contact. The controller captures the encoder position as the calibration point. Since the controller is aware of the precise torque requirements of each motor, touch calibration is achieved with very low contact forces. Sophisticated torque-data processing algorithms are used to eliminate false triggers and ensure calibration consistency despite dynamic mechanical characteristics of the robot.
[0010] In situ automatic calibration also provides the foundation for additional reliability tools to monitor and diagnose the health of robotic systems while they are being used in manufacturing equipment. These new capabilities can be generally described as wafer-map tuning, calibration tracking, and mechanical-systems monitoring, precise tuned mapping and mechanical system integrity.
[0011] Calibration Approaches
[0012] In a series of steps, technicians can calibrate robot end effectors by using leveling tools, turning screws, and nudging robots into desired positions for wafer handling. One major semiconductor equipment OEM has estimated that highly skilled system technicians are only able to calibrate handlers to within 0.5 mm repeatability using manual methods.
[0013] A number of “auto-teach” methods have been deployed in recent years to improve upon manual teach methods, but many of these approaches cannot support full in situ diagnostics of handlers. One common auto-teach method uses a combination of specially designed fixtures and sensors placed in the wafer-handling station. In some systems, fixtures detect position using mapping lasers. Others use proximity sensors to detect the location of the end effector. While reducing the time it takes to teach wafer handlers, these approaches also require special fixtures for the end effectors and robots. Often, these special fixtures must be used when handlers are re-calibrated in the field. The use of sensors can also present additional reliability concerns as they require vigilance as well.
[0014] Touch-sensing calibration is use to evaluate mechanical integrity of handlers by monitoring the position, velocity, and torque of each motor in the system. However, handlers with mechanically damaged robots can give the false impression that systems are working properly if positions are detected and measured only by calibration sensors. Real-time access to motor torque and other system servo control data supports the ability to provide full in situ analysis of robot performance. What is needed are real-time implementations to detect proper positions to a finer scale.
[0015] Calibration Quality Tracking
[0016] While robot calibration may be successfully achieved when the robot is being set up, the quality of calibration during operation is rarely known. To be certain of continuous monitoring, the calibration sequence must be repeated. However, there is no certainty that the new calibration data is better than the original set-up data. What is needed are methods to calibrate and integrate the “drift” into the control mechanism to account drift for in situ without removal or robot removal for repair prematurely.
[0017] One solution is to compare incoming calibration data, collected by the controller, and the set-up baseline data while robots are operating. The calibration data is compared to the baseline and significant deviations are recognized as a critical change in the wafer-handling equipment. The equipment can be recalibrated with automatic routines, without special tools and with handler devices in situ. Trends in the change of calibration data are monitored as well. The abilities to monitor the repeatability of calibration and easily perform automatic calibration routines allow the system to maintain performance and wafer-handling. However, these methods only work within tolerances, and the robot will need to be repaired once the tolerances are exceeded. Methods are needed to correct for the drift and even integrate that into the controller motion program, such that drift is accounted for in a continuous fashion, not limited to pre-sets and boundaries of calibration positions.
[0018] Precisely Tuned Mapping
[0019] Robots typically utilize mapping lasers or through-beam sensors to determine the presence of wafers on each handling device and whether or not wafers are properly positioned. Untimely recognition of a wafer through-beam sensor can result in expensive failures due to the potential for damaging devices on substrates.
[0020] Establishing and maintaining proper mapping-system parameters require precision tuning. Wafers can vary in thickness and optical properties depending on the process steps being completed, as well as what type of products are being made. Generally, wafers must be mapped at two angles to ensure that they are properly detected in the correct locations and to enable detection of cross-slotted wafers.
[0021] A major factor in the incorrect mapping of wafers is an effect known as “keystoning.” This occurs when the mapping scan and fan angles are incorrectly selected for the optical properties of the wafer-mapping device. By using an automated tuning algorithm to optimize mapping parameters, the keystoning effect is significantly reduced. During operation, mapping parameters are monitored and compared to baseline performance. Significant deviations are recognized and the user is alerted that mapping parameters may need to be retuned. The user can quickly diagnose the condition and optimize mapping parameters. Even with this procedure, failures occur. For any number of reasons, tolerances become small, phase shift angles stray to the 0° and 180° poles. Therein the feedback positional controls break down and the robot cannot not be stopped in time to prevent over shooting it target. Failures are expensive. What is needed are methods to read phase shift angles near the 0 and 180 poles, to catch out of sync control commands and retain failure prevention mechanisms. What are needed are more predictive failure mechanisms for stopping the assembly line before catastrophic system failures occur.
[0022] Mechanical Integrity
[0023] Other methods in situ tool monitor mechanical-system integrity. Wear in a robot's drive mechanism can go unnoticed, resulting in eventual and predictable critical failures. Wear is a normal occurrence in any mechanical device. Changes in lubrication or wear conditions also can alter the dynamic properties of wafer-handling actuators. Any change in the mechanical dynamics causes changes in the required energy to move robots, which is directly related to the torque, acceleration and velocity output of each motor for a given movement.
[0024] In some approaches, motor torque, velocity error, and position error are analyzed for minimum, maximum, mean, and standard deviation relative to baseline performance for an optimum mechanical system. Capturing this information while the robot is in situ enables preventive maintenance prior to system failure.
[0025] Following a move sequence, the data demonstrates that motion performance alone does not sufficiently inform the user about the mechanical integrity. Using an in situ method, a user gains knowledge of trends in the motor torque profile and can recognize mechanical deterioration long before a performance failure threshold is met. What are needed are automated implementation aware of these known degradation parameters, so that corrective measures are self initiated, automated, to predict failure and take commensurate counter measured response to stave off failure.
[0026] Servomotors are used extensively in robotic manipulators. The short story is that servo operation lags behind the command pulses. Their control is another area of where quicker response or even predictive response is mandatory to avert expensive consequences. Servomotors rotate according to command pulses, but there is a lag and the servo continues to move until the command pulses are exhausted. The feedback control loop includes an encoder which returns the number of command pulses received and output by the servo. If the command pulses returned by the encoder are smaller than the number output by the controller, the driver will try to rotate the servo more until the number is equal, number of pulses sent equals the number of pulse returned, ie the driver attempts to rotate the servomotor until the “deflection counter” is zero. This is not a problem unless the robot exceeds the position target, as the time lag between when the controller sends pulses and when the encoder writes back to the deflection counter, can be in some circumstances, received too late.
[0027] Quadrature output encoders are used extensively because they allow the determination of direction of rotation as well as incremental servomotor position. The encoder disks have signal generators which operate on out of phased pulse trains to inform controllers which direction the servo is turning and allow programming mechanism to use feedback to stop and reverse direction. The servo encoder is a type of pulse generator, which outputs three types of pulse signals, A/B phase signals. A phase and B phase are encoder pulse trains with the same cycle length phase shifted approximately 90%, with Z phase (index signal) pulse, generally once per revolution. What is needed are encoder implementations which provide feedback under even the phase change periods which are not served by the current encoder pulse train phasing. Furthermore, the digital counters for the A and B phase shift pulse channels operate reasonably well when the phase signals are plus or minus 90 degrees out of phase but are not guaranteed to function near the 0° and 180° phase shifts. There can be a 10°-20° phase shift spread centered around 0° and 180° whereby there is no error coverage. The controller circuitry cannot accurately count pulses near the 0 v and 5 v range. Therefore if the error occurs near the 0° and 180° phase shift angles, the stop signal will not handle the error timely and a failure can occur. What is needed is a way to catch servo phase shift channels signals even when polar phase shift angles occur.
[0028] In many robotic control mechanisms, the servo drives one or more belt drives or pulleys which extend the mechanical arm mechanism of the servo. Thus, even where the processor deflection counter is set to zero to stop the motor, the arm continues for a number of pulses. Although this dead movement by the servo may be small, the pulley multiplication factors amplify the total extension out from the servo, effectively multiplying the error from feedback lag.
[0029] Servomotor operation can be controlled by voltage, usually the default, velocity, position or in torque operation modes. Feedback is received in voltage, position, velocity, torque or current. Parameter relationships are usually well established. However, the occurrence of failures implies that perhaps only the major parameter relationships have been established What are needed are methods and devices which can continuously monitor important parameters in real-time, identifying and distinguishing the important characteristics and warning only when normal working bands are exceeded, foretelling of component failure, so that downtime can be avoided through preventive maintenance or work-a-rounds can be developed or catastrophic failure averted. While fail safe positions are designed for, infrequently these fail, and catastrophic results occur. What is needed are methods to monitor and prevent failures which would occur in the general course of servomotor use in robot systems.
SUMMARY
[0030] The present invention discloses a system and method for monitoring and diagnosing a robot mechanism. An aspect of the invention applies intelligence of physical robot arm linkage parameters respecting component relative rotation or load transfer; storing rotation or translation relationship parameters characteristic of resonant frequencies between at least one mechanical link; receiving servo motor signals; digitizing and storing servo known baseline data time histories; performing transformation from a time domain to a frequency domain on signal to obtain normal base signal continuously monitoring servo signal for pre-set action triggers.
[0031] Monitoring continues in real-time loop, receiving and digitizing known datum servo signals, obtaining signal frequency content from a time-frequency domain transform on monitored signal, determining if any received signal frequencies exceeded out-of-band margins, matching found out-of-band frequencies to any stored physical parameter characteristic frequencies, and notifying executive of any found matches. The mechanical mechanisms having resonant frequencies based on physical characteristics in the robot components affecting current, voltage, position or torque signal are used by signal processing using the resonance frequencies to identify location of mechanical load increases.
BRIEF DESCRIPTION OF DRAWINGS
[0032] Specific embodiments of the invention will be described in detail with reference to the following figures.
[0033] FIG. 1 illustrates a schematic of the servo control with feedback with the addition of continuous monitoring of position, velocity and acceleration time history to frequency domain transform analysis of multiple linkage robot system.
[0034] FIG. 2 shows a high level flow chart of the time and frequency domain analysis implementation using known equipment physical characteristics and parameters
[0035] FIG. 3 illustrates a time to frequency domain transform to highlight robot wear components and to identify high friction mechanical linkages.
[0036] FIG. 4 illustrates a schematic of the servo control with critical phase shift feedback loop in accordance with an embodiment of the invention.
[0037] FIG. 5 is typical time history plots showing the difference between the new and the worn robot component.
[0038] FIG. 6 is a transformed frequency domain plot showing location of worn components.
DETAILED DESCRIPTION
[0039] In the following detailed description of embodiments of the invention, numerous specific details are set forth in order to provide a more thorough understanding of the invention. However, it will be apparent to one of ordinary skills in the art that the invention may be practiced without these specific details. In other instances, well-known features have not been described in detail to avoid unnecessarily complicating the description.
[0040] Objects and Advantages
[0041] The present invention discloses failure predictive Monitoring and Analysis of A) a robot servo with associated multiple components system, B) Phase Shift in Servo Encoder Feedback near 0° and 180° phase shift angles and C) Servo Current/Voltage Drawn under Load Time Domain and Frequency Domain profiling,
[0042] Accordingly, it is an object of the present invention to provide more efficient and intelligent diagnostics for monitoring a robot mechanism having known physical attributes producing unique characteristic signatures, aiding in problem isolation and analysis in real-time.
[0043] It is an object of the present invention to install hardware and software to make automated judgments as to corrective actions, as well as executing them in real-time.
[0044] It is another object of the present invention to provide embodiments designed for monitoring servo current, voltage, and torque or motion profiles for healthy signatures which are stored in electronic medium for real-time comparison, signaling out-of-band or set limits where and when they occur in real-time.
[0045] It is another object of the present invention to provide methods to terminate manipulator motion when phase shift angles are out of specified band limits.
Embodiments of the Invention
[0046] FIG. 1 illustrates a schematic of the servo control and feedback with the addition of continuous monitoring of position, velocity and acceleration time and frequency domain analysis of a servo and associated multiple pulley arm robotic system in the radial dimension.
[0047] In an embodiment of the invention, a Controller 101 is serially coupled to a Digital-to-Analog Converter 103 and Amplifier 105 driver, serving to manipulate and control Servo motor 107 . The servo 107 is coupled to an Encoder 109 , Encoder sensors sending phase shift channel A and B digital data to Position Decoder & Counter 117 , and Current/Voltage/Torque signals from servo motor 107 are sent to Time and Frequency Domain analyzer unit 119 .
[0048] In an embodiment of the invention, the controller 101 , D/A converter 103 and amplifier 105 perform typical functions. The servo 107 current, voltage or torque signals are processed by the Time and Frequency Domain analyzer 107 which is provided the pulley ratios which are used to identify the current drawing components and out of limit signal amplitudes.
[0049] Pulley_ 1 drive belt 109 coupled to pulley rotating an adjacent drive belt 111 at a 1:m1 ratio is a known parameter, and installed in the program memory. This is also the case for belt 111 driving another coupled pulley_ 2 belt 113 , where the gear ratio from pulley_ 1 :pulley_ 2 is also a known parameter, 1:m2. A revolution of the servo will then have an m1×m2 revolution rotation affecting the manipulator end effecter in the radial dimension. Additional servos are likewise coupled to belts and pulleys and used to mechanically extend reach in alternate dimensions. Those servo signals can be processed similarly to provide the full X, Y, and Z or R, T, Z coordinate extensions.
[0050] Perturbations caused by manipulator motion will contain frequency and time signatures containing their resonant frequencies. Thus the servo 107 current/voltage/torque signals will contain the identifiable resonant frequencies of each belt, known by their corresponding pulley gear to gear ratio. Signals received and initiated by perturbations on pulley_ 2 belt 113 will contain the harmonics of the gear ratio multiplier because the high resistance will be encountered by any given component which will draw increased power and hence current from the servo. In translating the moments and forces to the servo, the servo current, voltage or torque sensed will likewise carry the identifiable component belt frequencies. These signals are sent to the Time-Frequency Domain Analyzer 119 unit for signal perturbation origination identification and amplitude magnitude assessment of perturbation against set normal parameters. Fourier transform converts time domain to frequency domain and many signal analysis techniques can be used and are known to those skilled in the art, and are applied to signals received.
[0051] FIG. 2 is a high level flow chart of the time-frequency domain analysis implementation using known equipment physical characteristics. Physical parameters, such as gear ratios for coupled pulleys, directly or indirectly transfer power to pulleys, belts and other manipulator components. As such, these components will draw power in accordance with their component power transfer relationships. Their increase in power consumption will be imposed ultimately on the source servo power consumption and hence the power and components and representations of power use, will also exhibit the increase in power drawn, at representative component transfer ratio resonances. The sink components of the power use will transfer their signature through the power transfer relationship. For example, a servo coupled to a pulley gear, will have a gear to gear rotation ratio. The belt driven by the pulley will affect the power drawn by the servo, through the gear coupling and to the ultimate source of the power, the servo. Thus the gear ratio will have a multiplier affect on the power drawn, and will identify the power sink component, pulley or belt, through the frequency or harmonics of the power drawn by the component.
[0052] Representatives of characteristic resonance frequencies or harmonics of the robotic manipulator components are stored 201 along with signal amplitude limits for triggering identified component and arm location warnings when power, current, voltage or other sensed signals are outside of preset margins at known resonant frequencies. Initial robotic manipulator characteristics and signal signatures are obtained by digitizing initial servo current, voltage and torque signal, performing time-frequency domain analysis on these signals and storing these data 203 . Once initial characteristics and signatures are stored and available, servo monitored signals can be input. The monitored signals are input from a known datum 205 , start position and time, similar to the algorithm used for obtaining the initial normal system parameters. These signals are digitized 207 for digital analysis and time-frequency domain analysis reveals any frequency content in the signals 209 . The monitored resultant frequency content is compared to the healthy initial system frequency parameters for out-of-band content 211 . Any out-of-band content matching known physical natural frequencies or harmonics of system parts such as belts and pulleys will be identified 211 immediately. Reoccurrence of these parametric matches within prescribed periods of time 213 will trigger errors, warnings, or immediate equipment stoppage depending on out-of-band limits exceeded 215 .
[0053] FIG. 3 illustrates a time to frequency domain transform to highlight robot wear and to and identifies high friction mechanical linkages, as they occur. In an embodiment of the invention, the gear ratios between the servo and pulleys in the manipulator are known. Given that the gear ratio in FIG. 1 , between the servo 107 and the pulley_ 1 111 belt, is 1:m1, and the gear ratio from pulley_ 1 111 belt to pulley_ 2 113 belt is 1:m2, the resonant frequencies which will transfer to the servo load will be a function of these gear ratios. These parameters are then stored in the analyzer 119 . The fundamental resonant frequencies of the individual linkage component servo, pulley_ 1 and pulley_ 2 will manifest as peaks at Ω 0 301 , Ω 1 303 , and Ω 2 305 frequencies 307 plotted verses
[0054] To capture the motor 407 position, typically a timer interrupt is used to sample the quadrature output from incremental rotary encoder 409 and to update the current position register. Normally, a hardware buffer counter is used for the encoder interface to reduce load of the sampling/reading process. Some servo controls currently sample the input signals directly with only software process to reduce external components.
[0055] If the phase shift exceeds the band limits, then this leaves the feedback loop blind, as quadrature counter cannot distinguish rise and fall voltage pulse edges.
[0056] Exclusive OR Circuit 411
[0057] In an embodiment of the inventions, an Exclusive OR circuit 411 and output phase shift pulse smoothing capacitor 421 provide a method of surviving current position feedback at blind or lost phase angles where the position counter register is unresponsive, 0°±50°. 180°±5°. As Channel A and Channel B pulse trains are continuously fed into the Exclusive OR circuit 411 , the output across the smoothing capacitor 421 will generally stay at midrange unless the channel A 413 and channel B 415 pulse trains are proximate to 0° or 180° poles, at which time the voltage will jump to the low range or high range voltage. A low range or high range voltage from signal processing 423 will signal bad quality phase shift angle, at which time the controller 401 will receive bad quality signal although the position decoder/counter 419 has lost count due to steep phase shift angle.
[0058] Currently, the encoder can remain faithful where the phase shift angle is not proximate to 0° or 180°. When the phase shift angle is 0°±5° or 180°±5° then the encoder position tracking is momentarily lost, giving a bad quality feedback. That is because counter circuitry cannot operate near 0 volts or 5 volts, corresponding to 0° or 180° phase shifts. Therefore when a positioning error occurs during these periods, the response cannot act quickly enough to stop a servo command position from going too far and colliding with a structure.
[0059] An embodiment of the invention receives channel A and channel B signals into Exclusive OR circuit, whose output is 2.5 volts at phase shift angles o±90°, and 0 volts or 5 volts when the phase shift angle is to 0° or 180° respectively. Thus when the feedback loop counter is lost or unable to determine position, near 0° or 180°, the invention embodiment acts to provide a signal which can be used to stop arm movement, averting a costly disaster.
[0060] FIG. 5 illustrates a typical time history plot, and FIG. 6 shows the frequency domain transformed from time domain in FIG. 5 . The time history plot in FIG. 5 shows the difference between the new and worn servo motors and robot component characteristics in the time domain. FIG. 6 shows worn component identification in accordance with an embodiment of the invention.
[0061] Given a time and position of servo performance can be obtained, a time history of a particular servos velocity 501 and Torque 503 verses time 511 is acquired at robot set up. The velocity data 509 provides a basis for comparison on a scheduled real-time basis, to monitor the servo performance over its usage life. Limits or bands 505 507 can be pre-set to trigger if the velocity or torque data strays outside the band. The bands can be multiple, giving indications of robot arm wear or problems well in advance of failures.
[0062] As in the time histories, a frequency domain plot with Frequency 523 verses signal amplitude 521 can be processed against preset limits 525 and preset margins triggering warnings when they are exceeded.
[0063] Current, voltage, torque, power, velocity profiles can be stored and used to monitor and diagnose potential problems with a robot components. The real-time data can be processed periodically, and resulting trends can also be predictive of cycles or time remaining on all components. Catastrophic failures can be reduced and possibly eliminated.
[0064] Therefore, while the invention has been described with respect to a limited number of embodiments, those skilled in the art, having benefit of this invention, will appreciate that other embodiments can be devised which do not depart from the scope of the invention as disclosed herein. Other aspects of the invention will be apparent from the following description and the appended claims.
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The present invention discloses a system and method for monitoring and diagnosing a robot mechanism. This requires adding intelligence to the diagnostics by parameters of physical robot arm linkages respecting component relative rotation or load transfer; storing rotation or translation relationship parameters characteristic of resonant frequencies between at least one mechanical link; receiving servo motor signals; digitizing and storing servo known normal data time histories; performing a time domain to frequency domain transformation on signal to identify components which are out-of band limit pre-sets.
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This application is a division of application Ser. No. 09/675,846, filed Sep. 29, 2000 now U.S. Pat. No. 6,454,992.
This invention was made with Government support under Contract No. 3637 by NASA. The Government has certain rights to the invention.
BACKGROUND OF THE INVENTION AND RELATED ART
The present invention relates to NiAl-based intermetallic composites, and more particularly, to a new NiAl—CoCrAlY bond coat optionally having particulate AlN dispersed therein. The bond coat has particular application as part of a thermal barrier coating for metallic components used in high temperature applications.
Multilayer thermal barrier coatings on superalloy substrates are comprised of an intermetallic bond coat, a thermal grown oxide layer and a zirconia top coat that provides thermal protection. Known bond coats include CoCrAlY and NiCrAlY. These bond coats are alumina formers and provide oxidation resistance. However, because of the low aluminum content of these bond coat materials, their oxidation resistance is limited to shorter times and lower temperatures then desired in many applications. Further, their coefficient of thermal expansion mismatch with the zirconia thermal barrier coating causes rapid degradation.
In accordance with the present invention, a bond coat with improved long-term oxidation resistance and coefficient of thermal expansion compatibility with the thermal barrier coating is provided.
SUMMARY OF INVENTION
It has now been found that NiAl and CoCrAlY may be combined to provide improved bond coats. The performance of the bond coat may be further enhanced with the dispersion therein of particulate AlN.
AlN is believed to operate to enhance oxidation resistance by providing an aluminum source useful to form alumina scale. In addition to enhancing oxidation resistance, AlN has also been found to reduce the coefficient of thermal expansion of the resulting composite to more closely match that of the ceramic thermal barrier coat, e.g. zirconia. Accordingly, the resulting composite is characterized by increased oxidation resistance and thermal fatigue properties.
The NiAl and CoCrAlY alloy may include 15 to 30 volume percent CoCrAlY, the balance being NiAl. The NiAl may be at 50 to 55 atom percent.
The NiAl—CoCrAlY—AlN composite may comprise about 10 to 15 volume percent AlN, 15 to 30 volume percent CoCrAlY and the balance is NiAl. Good results have been obtained with about 10 volume percent AlN and 15 volume percent CoCrAlY, the remainder being NiAl.
A further improvement provided by the AlN particulate is increased mechanical strength. More particularly, the modulus of the resulting composite is increased.
The NiAl—CoCrAlY—AlN composite is lightweight, tough and highly creep resistant. The composite also has good thermal conductivity.
Cryomilling may be used in the preparation of the composite. More particularly, NiAl and CoCrAlY may be mixed and cryomilled in liquid nitrogen with the use of a grinding media. During the subsequent forming and heating of the composite, the AlN is formed as a particulate dispersion within the NiAl—CoCrAlY matrix.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a micrograph showing extruded NiAl—CoCrAlY—AlN;
FIG. 1A is a micrograph similar to FIG. 1 showing various phases of the NiAl—CoCrAlY—AlN;
FIG. 2 shows a comparison of 1100° C. isothermal oxidation weight gain of NiAl—CoCrAlY—AlN and other MCrAlY bond coat alloys;
FIG. 3 shows an x-ray diffraction pattern of a specimen of oxidized NiAl—CoCrAlY—AlN;
FIG. 4 shows a comparison of the parabolic oxide growth rates of NiAl-0.1Zr and NiAl—CoCrAlY—AlN;
FIG. 5 shows a comparison of the cyclic oxidation of a CoCrAlY alloy with NiAl—CoCrAlY—AlN;
FIG. 6 shows a comparison of the coefficient of thermal expansion vs. temperature for NiAl—CoCrAlY—AlN and 16-12 alloy;
FIG. 7 shows dynamic Young's Modulus vs. temperature for NiAl—CoCrAlY—AlN, 16-6 alloy and partially stabilized zirconia; and
FIG. 8 shows a comparison of the thermal cycle lives of two layered thermal barrier coatings with 16-6 bond coat and NiAl—CoCrAlY—AlN bond coat.
DETAILED DESCRIPTION OF THE INVENTION
The NiAl—CoCrAlY alloy may be formed using conventional melting techniques and elemental constituients. Also, mechanical alloying may be used by mixing elemental constitutents or master alloy powders, NiAl and CoCrAlY, in proportion and milling it to form NiAl—CoCrAlY alloy. As noted above, the CoCrAlY may comprise 15 to 30 volume percent of the alloy. Also, an 85/15 volume percent ratio may be used. The NiAl—CoCrAlY alloy may be used as a bond coat for Ni-based superalloys, but its properties may be further improved with the addition of particulate AlN as discussed below.
The NiAl—CoCrAlY—AlN composite of the present invention is prepared using cryomilling. The component NiAl and CoCrAlY alloys may be prepared from elemental constituents in accordance with known techniques or purchased from commercial sources. In the following example, a prepared NiAl alloy is, combined with a commercially available CoCrAlY.
In preparation for cryomilling, about 85 percent by volume of prealloyed NiAl (50 atom percent) and 15 percent by volume of a commercially supplied CoCrAlY alloy were mixed and cryomilled in a Union Process 01-HDT attritor. The grinding media comprised 304 stainless-steel balls of ¼ inch diameter. The milling was carried out in the presence of liquid nitrogen for about 16 hours. The outer jacket of the vessel was also cooled with liquid nitrogen. The milled powder was consolidated by hot extrusion or by hot isostatic pressing.
Referring to FIG. 1, an SEM micrograph shows the NiAl—CoCrAlY—AlN composite as extruded. The elongated grains of NiAl are particularly illustrated. Referring to FIG. 1A, the light phase corresponds with the (NiCo)Al phase and a dark mantle region consists of nanosized AlN particles. The AIN particles range in size from 10 to 50 nanometers.
The consolidated material was used to form oxidation coupons, 4 point bend and tensile specimens. These were machined from the consolidated material.
Isothermal oxidation tests were carried out between 1100° C. and 1400° C. for 200 hours. Referring to FIG. 2, a plot of the specific weight gain vs. time for the NiAl—CoCrAlY—AlN composite of the invention and several other currently used MCrAlY bond coat alloys is shown. Only the 16-6 (16% Cr and 6% Al) alloy showed comparable performance with that of the inventive composite up to about 200 hours. Thereafter, the NiAl—CoCrAlY—AlN composite is characterized by a lower specific weight gain.
Referring to FIG. 3, an x-ray diffraction pattern for an oxidized specimen of NiAl—CoCrAlY—AlN is shown. The peak corresponds with alumina. SEM analysis showed that the alumina scale is continuous, very compact and thin. This agrees with the effective oxidation resistance displayed by the NiAl—CoCrAlY—AlN composite and the low specific weight gain observed.
Referring to FIG. 4, the Arrhanius plot shows the relationship of the parabolic scaling oxide constant (k p ) and 1/T for NiAl—CoCrAlY—AlN and NiAl0.1Zr. The k p values for NiAl—CoCrAlY—AlN are lower than those of NiAl0.1Zr alloy and indicate a lower rate of forming alumina for all temperatures.
Cyclic oxidation tests were performed at 1160° C. and 1200° C. for 200 cycles in air. Each cycle consisted of one-hour heating and 20 minutes of cooling. For purposes of comparison, the cyclic oxidation of CoCrAlY under these conditions was also tested. The results are reported in FIG. 5 .
Referring to FIG. 5, the CoCrAlY alloy displays a much lower specific weight gain at 50 cycles or higher indicating a greater degree of spallation. In comparison, NiAl—CoCrAlY—AlN at 200 cycles had a specific weight gain of −3 mg/cm2 at 1165° C. and −13 mg/cm2 at 1200° C.
The coefficient of thermal expansion of freestanding NiAl—CoCrAlY—AlN was measured at temperatures ranging from 20° C. to 1000° C. in an argon atmosphere. The average coefficient of thermal expansion is plotted against temperature in FIG. 6 . For comparison purposes, a commercially used 16-12 bond coat alloy (16% Cr and 12% Al) was also tested, and the results are included in FIG. 6 . As shown, the NiAl—CoCrAlY—AlN composite had a lower coefficient of thermal expansion. At temperatures of about 1150° C., the coefficient of thermal expansion is less than about 16 for the NiAl—CoCrAlY—AlN composite.
Tensile tests were carried out on butterhead type specimens between room temperature and 1000° C. The dynamic Young's modulus values were measured and correlated with temperature, the data being plotted in FIG. 7 . In addition to the NiAl—CoCrAlY—AlN alloy, similar measurements were made for a 16-12 alloy and a plasma sprayed, partially stabilized zirconia (PSA) alloy. As shown, both of the bond coats have a much higher modulus then in the thermal barrier coat which is porous. Since the elastic stress generated in the coating will be dominated by the lower modulus material, it is evident that the ceramic layer modulus will determine the stress in the thermal barrier coating up to the operating temperature.
The most important property of a bond coat is, of course, the thermal fatigue life of the thermal barrier coating system for that bond coat. The fatigue lives of thermal bond coatings having an air plasma sprayed ceramic top coat and a low pressure plasma spray applied NiAl—CoCrAlY—AlN bond coat or a 16-6 bond coat were evaluated using a jet-fuel fired Mach 0.3 burner rig to simulate gas turbine conditions. A JP-5 fuel was used in the burner. Samples were heated in the burner for six minutes to a steady state temperature of 1160° C. and then forced-air cooled for 4 minutes during each cycle.
The results of the thermal cycle testing are reported in FIG. 8 . As shown, the 16-6 alloy (16% Cr and 6% Al) had a cycle life of about 220 cycles and the NiAl—CoCrAlY—AlN composite of the invention had a cycle life of about 325 cycles. This corresponds to about a 50 percent increase in cycle life.
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A bond coat composition for use in thermal barrier coatings comprises a NiAl—CoCrAlY matrix containing particles of AlN dispersed therein. The bond coat composition is prepared by croymilling NiAl and CoCrAlY in liquid nitrogen.
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BACKGROUND OF THE INVENTION
1. Industrial Field of Utilization
The present invention relates to cold-rolled steel sheets or hot-dip galvanized cold-rolled steel sheets for deep drawing which have excellent resistance to cold-work embrittlement or bake hardenability and more particularly to hot-dip galvanized cold-rolled steel sheets for deep drawing which have excellent deep drawability and adhesion of galvanized coating.
2. Description of Prior Art
Cold-rolled steel sheets for use for automotive parts and outer panels of electrical equipment are required to have good press-formability and good corrosion resistance in recent years.
For manufacturing cold-rolled steel sheets which can meet the above-mentioned requirements, there has been proposed a process for the individual or compound addition of carbonitride forming elements such as Ti and Nb to ultra-low carbon steel for the purpose of stabilizing C and N in the steel, thereby developing (111) texture which is advantageous for deep drawing and for galvanizing of the steel.
However, ultra-low carbon steels in which C and N in the steels are sufficiently stabilized by the carbonitride forming elements such as Ti and Nb, have a problem that cracking due to brittle fracture occurs in cold-work after press-forming. Furthermore, P-added steels have a problem that P is segregated to the grain boundary promoting brittleness of the grain boundary. This is due to the stabilization of solid-solute C in the steel, resulting in nonsegregation of C into the ferrite grain boundary and accordingly in an embrittled grain boundary. Particularly in the case of the hot-dip galvanized steel sheet, molten zinc easily intrudes this embrittled grain boundary, thus further promoting brittleness.
This hot-dip galvanized steel sheet has the problem of powdering or flaking of the galvanized coating during press-forming, that is deteriorating adhesion of the galvanized coating.
As a means of solving the aforesaid problem of the embrittlement of grain boundary, there has been attempted to melt the steels by pre-controlling the addition of Ti and Nb so that solid-solute C and N may be left in the steels. According to this method, however, even if component steels having residual solid-solute C and N can be made, this solid-solute C and N substantially acts to deteriorate the r-value and ductility of the steels, unavoidably resulting in largely lowered press-formability. That is, the press-formability and the resistance to cold-work embrittlement cannot be compatible with each other. Besides, it is technologically impossible to leave such a slight amount of solid-solute C and N in steels at the stage of steel-making.
In connection with this respect, the following proposals have been made sofar; it is, however, difficult to obtain both excellent press-formability and excellent resistance to cold-work embrittlement.
For example for the purpose of improving the resistance to cold-work embrittlement in deep drawable steel sheets there has been proposed a method of forming a carburized layer at the surface of the steel sheets by stabilizing C in steels by adding Ti and Nb and, after cold-rolling, carburizing through open-coil annealing (laid-Open Japanese Patent Application No. Sho 63-38556). In this method, however, since carburizing is applied during a prolonged period of batch annealing, a high-concentration carburized layer is formed (an average amount of C in the carburized layer: 0.02 to 0.10%) at the surface layer of the steel, and there exists a difference in ferrite grain size between the surface layer and the central layer. Furthermore, the batch annealing process is naturally not highly productive and the mechanical properties of the steel are likely to be inhomogenous in the direction of rolling and in the direction of sheet width.
There has also been proposed a method for providing only an extremely thin surface layer with a very slight amount of solid-solute C and N for the purpose of improving phosphatability (Japanese Patent Publication No. Hei 1-4233I). According to this method, however, the resistance to cold-work embrittlement is not taken into consideration. Therefore, it is impossible to perform the carburizing step required for improving the resistance to cold-work embrittlement.
Similarly, for manufacturing steel sheets for deep drawing by addition of Ti and Nb there has also been proposed a method for further carburizing after applying recrystallization annealing after cold rolling (Laid-Open Japanese Patent Application No. Hei 1-96330). This method, however, has drawbacks in that it aims mainly at providing greater strength through the precipitation of a large amount of carbides or nitrides no consideration is taken for improvement in the resistance to cold-work embrittlement; prolonged batch carburizing and nitriding are carried out, which after annealing, causes the amount of carburizing and nitriding to become excessive and nonuniform, the producibility is low and the process is complicated.
Beside the aforementioned problem as to the improvement in the resistance to cold-work embrittlement, there is an increasing demand for the provision of properties capable of increasing yield stress of steel sheets after paint baking, that is so-called bake hardenability.
In relation to the aforementioned demand, there has been proposed a method of adding a smaller amount of Ti than atomic equivalent to C for the purpose of leaving the solid-solute C (Japanese Patent Publication No. Sho 61-2732). According to this method, however, the solid-solute C and N substantially acts to deteriorate the r-value of steel even if the component steel containing the residual solid-solute C and N can be made, with the result that the press-formability is largely lowered. That is, the press-formability and the bake hardenability are substantially incompatible with each other.
Furthermore, the aforesaid process utilizing carburizing in the annealing process (Laid-Open Japanese Patent Application No. Sho 63-38556) and the process for improving the phosphatability do not take the bake hardenability into consideration, and accordingly it is impossible to improve the bake hardenability.
Furthermore, in the case of the ultra-low carbon steels stabilizing C and N sufficiently with carbonitride forming elements such as Ti and Nb, the bake hardenability is not obtainable.
Furthermore, according to the process for containing the solid-solute C, a target value, if too high, deteriorates the ageing property, and, reversely if too low, can not obtain the bake hardenability. It is very difficult to control the optimum amount of residual solid-solute carbon in the steelmaking process.
SUMMARY OF THE INVENTION
The present invention has been accomplished in an attempt to solve the above-mentioned prior-art technological problems, and has as its object the provision of cold-rolled steel sheets or hot-dip galvanized cold-rolled steel sheets produced of ultra-low carbon steel with added Ti or Nb, which have both excellent deep drawability and excellent resistance to cold-work embrittlement or bake hardenability, and further the provision of hot-dip galvanized cold-rolled steel sheets having excellent deep drawability and excellent adhesion of galvanized coating.
In order to solve the above-mentioned problems, the inventor completed the present invention as a result of researches on chemical composition and the amount and distribution of solid-solute C contained in the steel.
The present invention discloses cold-rolled steel sheets or hot-dip galvanized cold-rolled steel sheets for deep drawing which have excellent resistance to cold-work embrittlement containing 0.01 mass % or less C, 0.2 mass % or less Si, 0.05 to 1.0 mass % Mn, 0.10 mass % or less P, 0.02 mass % or less S, 0.005 to 0.08 mass % sol.Al., and 0.006 mass or less N, further containing Ti (mass %) and/or Nb (mass %) solely or in combination within the range in which the relationship between the effective amount o Ti (hereinafter referred to as Ti*) defined by the following formula (1) and the amount of Nb with the amount of C satisfies the following formula (2), if necessary further containing 0.003 mass % or less B.
Ti*=total Ti-{(48/32)×S+(48/14)×N} (1)
1≦(Ti*/48+Nb/93)/(C/12)≦4.5 (2)
and the balance of Fe and inevitable impurities, the steel sheet has such a concentration gradient that, as a result of carburizing, the amount of solid-solute C decreases as it goes through the thickness direction from the sheet surface towards the center, with the maximum value of concentration of solid-solute C in a part of a one-tenth gage ratio of the surface layer set at 15 mass ppm and with the amount of solid-solute C in the entire part of the steel sheet set at 2 to 10 mass ppm.
Another embodiment of the present invention disclose cold-rolled sheets or hot-dip galvanized steel sheets for deep drawing which have excellent bake hardenability having the same chemical composition as described above and the concentration gradient that, as a result of carburizing, the amount of solid-solute C through the thickness direction decreases as it goes from the surface towards the center of the sheet, with the maximum value of concentration of solid-solute C in a part of a one-tenth gage ratio of the surface layer set at 60 mass ppm, and with the amount of solid-solute C in the entire part of the steel sheet set at 5 to 30 mass ppm.
Furthermore, the present invention discloses hot-dip galvanized cold-rolled steel sheets which have excellent deep drawability and excellent adhesion of galvanized coating, having the same chemical composition characterized by 10 to 100 mass ppm solid-solute C present in a part 100 μm deep from the sheet surface through the thickness direction.
Hereinafter the present invention will be explained in further detail.
First, reasons for defining the chemical composition f the steels in the present invention will be explained.
C
The amount of Ti and/or Nb to be added for stabilizing C increases with an increase in carbon content, resulting in an increased amount of TiC and/or NbC precipitation and hindered grain growth and accordingly deteriorated r-value. This will increase manufacturing cost. It is, therefore, necessary to hold the carbon content below 0.01 mass % or less. The lower limit value of this carbon content at the stage of steelmaking technology, though not specially limited, should be set at 0.0003 mass % from a practical steelmaking technological point of view. It is desirable that the carbon content be set at 0.01 mass % or less, and its lower limit value at 0.0003 to 0.01 mass %.
Furthermore, as described later, in order to provide excellent resistance to cold-work embrittlement, the steel sheet is required to have the concentration gradient that the amount of solid-solute C decreases as it goes through the thickness direction from the surface towards the center, with the maximum value of concentration of solid-solute C present in a part of a one-tenth gage ratio of the surface layer set at 15 mass ppm, and with the amount of solid-solute C in the entire part of the steel sheet set at 2 to 10 mass ppm. To impart excellent bake hardenability, however, the steel should be allowed to have, in addition to the above-mentioned concentration gradient, up to 60 mass ppm of the maximum concentration of solid-solute C in the part of a one-tenth gage ratio of the surface layer, maintaining 5 to 30 mass ppm solid-solute C in the entire part of the steel sheets. Furthermore, to obtain excellent adhesion of galvanized coating, the amount of solid-solute C present in a portion 100 μm deep from the sheet surface through the thickness direction must be set at 10 to 100 mass ppm. For the purpose of presenting such a suitable condition for the existence of the solid-solute C, any means may be adopted. It is, however, desirable, from the point of view of producibility, to provide an atmosphere having a carbon potential in the annealing process before galvanizing.
Si
Si is added mainly for the purpose of deoxidizing molten steels. However, excess addition deteriorates surface property, adhesion of galvanized coating, and phosphatability or paintability. The Si content, therefore, should be held to 0.2 mass % or less.
Mn
Mn is added mainly for the prevention of hot shortness. If, however, the addition is less than 0.05 mass %, the intended effect cannot be obtained. Reversely, if the addition is too much, the ductility is deteriorated. Therefore, it is necessary to hold the content within the range of 0.05 to 1.0 mass %.
P
P is effective to increase steel strength without deteriorating the r-value. In the case of ultra-low carbon steels, P has a similar effect as carbon in connection with the galvanization reaction to improve the adhesion of galvanized coating. However, it segregates to the grain boundary, being prone to cause cold-work embrittlement. Therefore, it is necessary to control the P content to 0.10 mass % of less.
S
S combines with Ti to form TiS. With an increase in the sulfur content, an increased amount of Ti necessary for stabilizing C and N is required. Also the amount of MnS series extended inclusions increases, thus deteriorating the local ductility. Therefore it is necessary to control the content to 0.02 mass % or less.
sol.Al
Al is added for the purpose of deoxidizing molten steels. The content sol.Al, if less than 0.005 mass %, can not achieve its aim. On the other hand, if the content exceeds 0.08 mass the deoxidation effect is saturated and the amount of Al 2 O 3 inclusion is increased to deteriorate formability. It is, therefore, necessary to hold the sol.Al content within the range of 0.005 to 0.08 mass %.
N
N combines with Ti to form TiN. Therefore, the amount of Ti required for stabilizing C increases with the increment of the N content. Besides the amount of TiN precipitation is increased to hinder the grain growth and deteriorate the r-value. Accordingly a smaller content is desirable. The N content should be controlled to 0.006% mass % or less.
Ti, Nb
These additives (mass %) are used to stabilize C and N for the purpose of increasing the r-value. To attain the aim of the present invention, therefore, it is necessary to contain them within the range that the relationship between the amount of Ti* and Nb content and the content of C satisfies the following formula (2).
1≦(Ti*/48+Nb/93)/(C/12)≦4.5 (2)
Ti combines S and N as described above, forming TiS and TiN respectively; the amount of the additive to be used, therefore, is given by converting to the effective amount of Ti (amount of Ti*) according to the formula (1).
Ti*=total Ti-{(48/32)×S+(48/14)×N} (1)
When the value of the formula (2) is smaller than 1, C and N can not be sufficiently stabilized with the result that the r-value will become deteriorated. Also, the value, if exceeding 4.5, will saturate the effect which will increase the r-value, and the solid-solute Ti and/or Nb will immediately stabilize the intruded carbon during atmospheric annealing in the subsequent process. The carbon stabilization will impede C segragation to the grain boundary and the presence of solid-solute C.
B
B is an effective element to provide resistance to cold-work embrittlement and may be added when required. Also the additive may be added to improve the resistance to cold-work embrittlement in an attempt to improve the bake hardenability. If, however, the additive exceeds 0.003 mass %, its effect will be saturated, deteriorating the r-value. It is necessary, therefore, to hold the B content to 0.003 mass % or less with economical efficiency taken into consideration. With a 0.0001 mass % or less content, the aimed effect of the B added is little. It is, therefore, desirable to add the B content within the range of 0.0001 to 0.003 mass %.
Next, although the steel sheets manufacturing method in relation with the present invention is not limited in particular, but one example of the method will be explained hereinafter. Steels having the above-mentioned chemical composition are hot-rolled by customary method, that is, in austenitic region after heating up to a temperature of 1000° to 1250° C. The temperature for coiling after hot-rolling desirably is within a range from 500° C. to 800° C. for stabilizing the solid-solute C and N in the steels as carbonitrides.
In cold rolling, it is desirable to apply at a total reduction of 60 to 90% in order to develop the (111) texture advantageous for the r-value. After this cold rolling, continuous annealing is performed in a carburizing atmospheric gas within a range of over the recrystallization temperature to form the (111) texture advantageous for the r-value.
As is already known, the r-value is dependent mainly on the (111) texture of steels, which is performed by completely stabilizing the solid-solute C and N by the coiling treatment before recrystallization annealing. However, once the recrystallization is completed and the texture is formed, C and N that subsequently intrude will not give an adverse effect to the r-value. The annealing atmosphere shall be a carburizing gas with controlled carbon potential. The carbon that has intruded from the carburizing atmosphere and not stabilized as TiC and NbC segregates to the grain boundary, thereby improving the resistance to cold-work embrittlement and the adhesion of galvanized coating; and the specific amount of solid-solute C improves bake hardenability.
According to the present invention, no overageing is required, but the overageing may be performed at a temperature near a coating bath temperature. To produce galvanized cold-rolled steel sheets, the sheets are subsequently dipped into a hot zinc coating bath, and an alloying treatment may further be applied when required.
In this case, as a method for manufacturing steel sheets to be annealed, any means including hot rolling in a ferritic region, hot charge rolling, and thin slab casting and rolling may be used.
Next, a relationship between the control of the amount of solid-solute C and the resistance to cold-work embrittlement, the bake hardenability, or adhesion of galvanized coating will hereinafter be explained.
Cold-work embrittlement is prone to occur, in Ti added ultra-low carbon steels because of high purity of grain boundary and the lowered Fe-Fe bond strength in the grain boundary. Furthermore, in the hot-dip galvanizing treatment, there takes place Zn diffusion into the grain boundary, further weakening the Fe-Fe bond. Therefore, the improvement of the resistance to cold-work embrittlement can be achieved by preventing the above-mentioned two factors of lowering the Fe-Fe bond. Both the former and latter problems can be solved by segregating carbon to the grain boundary. Particularly in the case of the latter, since the depth of Zn diffusion is equal to about several grains, or about 50 μm, the above-mentioned problem can effectively be solved by concentratedly carburizing as deep as the above-mentioned through the thickness direction. An effective method of obtaining the most excellent resistance to cold-work embrittlement is to provide steel sheets having the concentration gradient that the amount of solid-solute C decreases through the thickness direction as it goes from the surface towards the center, with the maximum value of concentration of the solid-solute C in the part of a one-tenth gage ratio of the surface layer set at 15 mass ppm. Further, brittle fracture after deep drawing occurs at the surface layer, and therefore it has been confirmed that if the grain boundary strength of the surface layer has been increased by the segregation of the solid-solute C to the grain boundary, a remarkable effect is obtainable despite of little or zero grain boundary segregation of C in the centor of sheet thickness. If the amount of the solid-solute C in the surface layer exceeds 15 mass ppm, the mean amount of the solid-solute C in the entire part of the steel sheet exceeds 10 mass ppm, with the result that the effect of improvement in the resistance to cold-work embrittlement is saturated. Also, if the mean amount of the solid-solute C in the entire part of the steel sheet is less than 2 mass ppm, it is impossible to sufficiently improve the resistance to cold-work embrittlement.
In the meantime, generally in the case of the ultra-low carbon Ti-added steels, it is impossible to obtain the bake hardenability because of the absence of a residual solid-solute C. The bake hardenability, however, can be obtained while maintaining a high r-value by introducing the solid-solute C after the completion of recrystallization and then the formation of a texture. Furthermore, by providing the concentration gradient that the amount of solid-solute C decreases through the thickness direction as it goes from the sheet surface towards the center, and by setting to 60 mass ppm the maximum concentration of the solid-solute C in the part of a one-tenth gage ratio of the surface layer at which the hardening of the surface layer is most accelerated, excellent characteristics are thereby provided to automobile outer panels such as greater fatigue strength, greater resistance to panel surface damage likely to be caused by stones hitting on the surface, and greater dent resistance. The amount of the solid-solute C in the surface layer exceeding 60 mass ppm is not desirable because it becomes impossible to decrease the amount of the solid-solute C in the entire part of the sheet below 30 mass ppm and accordingly causes a problem of deterioration on mechanical properties by age. Reversely, the solid solution of C in the entire part of the sheet, if less than 5 mass ppm, is insufficient, making it impossible to obtain the bake hardenability.
The present invention is intended to improve the adhesion of galvanized coating. Its information will be described hereinafter.
For the purpose of improving the adhesion of galvanized coating, an appropriate amount of Al is usually added to the bath of molten zinc according to the type of steel. In the bath of molten zinc, Fe and Al react first as the initial reaction of the galvanizing, a Fe-Al intermetallic compound layer being formed in the interface between the molten zinc and the surface of the steel sheet. Thereafter, the galvanizing reaction including the alloying of the galvanize coating proceeds while being affected by this intermetallic compound layer. In the case of forming a uniform Fe-Al intermetallic compound layer in the interface, this compound layer is prone to work as an obstacle to mutual diffusion between the galvanized coating and the base steel sheet, and the alloying of the galvanized coating proceeds uniformly to insure good adhesion of the galvanized coating.
However, where the grain boundary of the steel sheet has been purified, Al in the bath intrudes into an activated grain boundary to lower the Al concentration in the vicinity of the grain boundary. Therefore no Al-Fe compound layer is formed in the vicinity of the grain boundary of the steel sheet, from which the galvanized coating is rapidly alloyed, forming a so-called "outburst" structure. This means that the rapid and ununiform alloying of the galvanized coating proceeds, resulting in deteriorated adhesion of the galvanized coating.
This problem can be solved to some extent by increasing the amount of Al in the zinc bath; however, increasing the amount of Al develops dross in the bath and surface defects such as craters, and lowers producibility. Thus increasing the amount of Al, therefore, can not be a fundamental solution to the problem described above.
The deteriorated adhesion of a galvanized coating on an ultra-low carbon steel sheet such as the Ti-added steel sheet is caused by the absence of segregation of carbon in ferritic grain boundaries arising from the absence of the solid-solute C in steels, and purified at grain boundaries.
In order to solve this problem, it is necessary to carburize the steels so that carbon will exist in the grain boundary in the vicinity of the sheet surface, prevent Al diffusion throughout the grain boundary in the steel sheet as the base metal, and form a uniform Fe-Al compound layer in the interface between the molten zinc and the steel sheet, preventing the occurrence of an "outburst" structure for the purpose of uniform alloying.
The present invention can be realized by improving the adhesion of galvanized coating through carburizing in the annealing process without deteriorating the formability of the steel sheets as base metal.
The steels, however, are premised to be steels of special chemical composition. In this case, however, if the amount of the solid-solute C present in a part 100 μm deep from the surface of the steel sheet through the thickness direction is under 10 mass ppm, the adhesion of galvanized coating can not be sufficiently improved. Also if the amount of the solid-solute C exceeds 100 mass ppm, there occurs deterioration of ageing property, which requires the lowering of line speed to feed a sheet in the continuous annealing process. This will result in lowered producibility. To solve this problem, it is necessary to control the amount of the solid-solute C to the range of from 10 to 100 ppm in a part 100 μm deep from the surface of the steel sheet through the thickness direction.
These and other objects of the invention will be seen by reference to the description, taken in connection with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIGS. 1, 3, 5 and 7 are views each showing the distribution of solid-solute carbon through the thickness direction which is given by conversion from an internal friction value of a sample prepared by grinding in the direction of sheet thickness to the thickness of one-tenth the steel sheet of preferred embodiments 1 to 4, wherein:
FIG. 1 is a view for Steel No. 3 according to the embodiment 1;
FIG. 3 is a view for Steel No. 3 according to the embodiment 2;
FIG. 5 is a view for Steel No. 7 according to the embodiment 3;
FIG. 7 is a view for Steel No. 7 according to the embodiment 4;
FIGS. 2, 4, 6 and 8 are views showing a relationship between (Ti*/48+Nb/93)/(C/12) and mechanical properties as regards steel sheets containing 0.02% or less P additive in the embodiments 1 to 4, for Steels No. 1, No. 2, No. 3, No. 4, No. 5, No. 7 and No. 8 according to the embodiments; and
FIG. 9 is a view showing a relationship between the amount of solid-solute carbon up to 100 μm thick from the surface of steel through the thickness direction and the r-value and the adhesion of galvanized coating in the embodiment 5.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Hereinafter cold-rolled steel sheets or hot-dip galvanized cold-rolled steel sheets for deep drawing according to preferred embodiments of the present invention will be described. First, the description will be made on steel sheets having excellent resistance to cold-work embrittlement and bake hardenability.
EMBODIMENT 1
The ultra-low carbon steels having the chemical composition shown in Table 1 were heated for solution treatment at 1150° C. for a period of 30 minutes and hot-rolled at a finishing temperature of 890° C. and then coiled at 670° C. After pickling, the steels were cold-rolled at a reduction of 75%. The cold-rolled steel then underwent continuous annealing in carburizing atmosphere or (N 2 -H 2 ) gas at 780° C. for a period of 40 seconds for recrystallization annealing.
Thereafter the steels were subjected to hot-dip galvanizing at 450° C. and finally to 0.8% skin pass rolling.
The mechanical properties, amount of solid-solute C (a mean value in the direction of total sheet thickness), and critical temperature for the cold-work embrittlement of the hot-dip galvanized cold-rolled steel sheets thus obtained are shown in Table 2.
Brittleness tests were conducted to determine the critical temperature for the cold-work embrittlement of the steel sheets by trimming, to the height of 35 mm, cups prepared through cup forming at a total drawing ratio of 2.7, and then by pushing the cup placed in a refrigerant at various test temperatures, into a conical punch having an apex of 40° to measure a critical temperature at which no cracking would occur. The critical temperature thus measured is a critical temperature to be determined for embrittlement in secondary operation.
As is clear from Table 2, the steels according to the present invention have greater resistance to cold-work embrittlement than prior-art steels without contradicting requirements for the hot-dip galvanized cold-rolled steel sheets for deep drawing.
As a result of tests of the distribution of the solid-solute C through the thickness direction in Steel No. 3 of the present invention, it is seen from the concentration distribution thus tested that, in the case of a carburized steel, as shown in FIG. 1, the amount of solid-solute C decreases as it goes through the thickness direction from the surface to the center of the sheet. In addition, it has been confirmed that, in steels carburized within a gas B, the concentration of solid-solute C in the part of a one-tenth gage ratio of the surface layer is 15 mass ppm or less, and also as shown in FIG. 2, the resistance to cold-work embrittlement has been improved without deteriorating the r-value.
Meanwhile, as given in Table 2, comparison steels which do not have the chemical composition defined by the present invention and other comparison steels having the chemical composition defined by the present invention but not satisfying requirements as to the amount of solid-solute C, are both inferior either in the r-value or in the resistance to cold-work embrittlement.
TABLE 1__________________________________________________________________________Chemical composition of Test Steels (mass %)No. C Si Mn P S Ti Nb B sol.Al N X__________________________________________________________________________1 0.0030 <0.01 0.17 0.012 0.0081 0.031 -- -- 0.028 0.0035 0.57*2 0.0025 <0.01 0.19 0.008 0.0061 0.037 -- -- 0.024 0.0029 1.793 0.0015 <0.01 0.15 0.005 0.0040 0.042 -- -- 0.031 0.0045 3.434 0.0042 <0.01 0.31 0.011 0.010 0.130 -- -- 0.029 0.0032 6.19*5 0.0024 <0.01 0.21 0.009 0.0056 0.035 -- 0.0007 0.027 0.0028 1.746 0.0038 <0.01 0.24 0.044 0.0062 0.050 0.011 0.0018 0.037 0.0025 2.497 0.0013 <0.01 0.18 0.018 0.0026 0.028 -- -- 0.029 0.0031 2.598 0.0007 <0.01 0.20 0.015 0.0060 -- 0.010 -- 0.038 0.0021 1.849 0.0015 <0.01 0.22 0.072 0.0052 -- 0.025 -- 0.031 0.0025 2.1510 0.0031 <0.01 0.13 0.148* 0.0049 0.036 -- 0.0022 0.034 0.0030 1.47__________________________________________________________________________ (Note 1) "*" These values are out of scope of the present invention. (Note 2) X = (Ti*/48 + Nb/93)/(C/12)
TABLE 2__________________________________________________________________________Mechanical Properties and Critical Temperaturefor Cold-work Embrittlement Critical temperature amount ofSteel Annealing TS YS El r for cold-work solid-solute CNo. atmosphere (kgf/mm.sup.2) (kgf/mm.sup.2) (%) Value embrittlement (°C.) (mass ppm) Remarks__________________________________________________________________________1 (N.sub.2 --H.sub.2) gas 31.9 18.4 45.1 1.4 -140 15 Comparison steel2 (N.sub.2 --H.sub.2) gas 29.7 14.4 48.6 1.8 -75 -- Comparison steel Carburizing gas 30.2 15.2 48.9 1.8 -130 5 Steel produced in accordance with present invention3 (N.sub.2 --H.sub.2) gas 28.2 16.8 51.0 2.0 -65 -- Comparison steel Carburizing gas 28.8 15.8 50.6 2.0 -125 7 Steel produced in accordance with present invention4 Carburizing gas 30.4 14.6 49.0 2.1 - 40 1 Comparison steel5 (N.sub.2 --H.sub.2) gas 30.5 14.1 48.7 1.8 -85 -- Comparison steel Carburizing gas 30.3 15.5 47.6 1.8 -140 5 Steel produced in accordance with present invention6 (N.sub.2 --H.sub.2) gas 35.2 17.3 43.8 1.7 -20 -- Comparison steel Carburizing gas 35.4 19.6 42.5 1.6 -95 6 Steel produced in accordance with present invention7 (N.sub.2 --H.sub.2) gas 28.3 12.4 49.3 1.9 -55 -- Comparison steel Carburizing gas 29.5 12.9 48.1 1.9 -125 8 Steel produced in accordance with present invention8 (N.sub.2 --H.sub.2) gas 27.1 11.3 50.5 1.9 -30 -- Comparison steel Carburizing gas 27.9 12.4 50.1 2.0 -110 9 Steel produced in accordance with present invention9 (N.sub.2 --H.sub.2) gas 39.5 21.5 40.7 1.5 -10 -- Comparison steel Carburizing gas 39.8 22.0 40.5 1.5 -100 6 Steel produced in accordance with present invention10 Carburizing gas 45.2 24.1 35.4 1.5 -10 8 Comparison__________________________________________________________________________ steel
EMBODIMENT 2
The test steels having the chemical composition shown in Table 1, after recrystallization annealing in the carburizing atmosphere or in the N 2 -H 2 gas through the continuous annealing process in the embodiment 1, underwent 0.8% skin pass rolling, thereby obtaining cold-rolled steel sheets. Other conditions required are the same as the embodiment 1.
The mechanical properties and amount of solid-solute C (a mean value in the direction of total sheet thickness) and critical temperature for cold-work embrittlement of the cold-rolled steel sheets thus obtained are shown in Table 3.
As is clear from Table 3, the steels according to the present invention, have greater resistance to cold-work embrittlement than prior-art steels without contradicting requirements of cold-rolled steel sheets for deep drawing.
By the way, as a result of investigations of the distribution through the thickness direction of the amount of solid-solute C in Steel No. 3 according to the present invention given in Table 3, it is seen that, as shown in FIG. 3, the carburized steel indicates the distribution of concentration that the amount of solid-solute C decreases as it goes through the thickness direction from the surface towards the center. In addition, in the case of the carburizing treatment using the gas B, the amount of the solid-solute C in the part of a one-tenth gage ratio of the surface layer is 15 mass ppm or less, and it has been ascertained, as shown in FIG. 4, that the resistance to cold-work embrittlement has been improved without deteriorating the r-value.
On the other hand, as shown in Table 3, the comparison steels which do not have the chemical composition defined by the present invention and those having the same chemical composition as mentioned above but not satisfying requirements as to the amount of the solid-solute C of the present invention are inferior in either the r-value or the resistance to cold-work embrittlement.
TABLE 3__________________________________________________________________________Mechanical Properties and Critical Temperaturefor Cold-work Embrittlement Critical temperature amount ofSteel Annealing TS YS El r for cold-work solid-solute CNo. atmosphere (kgf/mm.sup.2) (kgf/mm.sup.2) (%) Value embrittlement (°C.) (mass ppm) Remarks__________________________________________________________________________1 (N.sub.2 --H.sub.2) gas 30.7 18.1 46.8 1.6 -150 16 Comparison steel2 (N.sub.2 --H.sub.2) gas 28.7 13.3 49.6 2.1 -85 -- Comparison steel Carburizing gas 29.4 14.8 49.5 2.1 -140 6 Steel produced in accordance with present invention3 (N.sub.2 --H.sub.2) gas 27.9 15.8 53.3 2.3 -70 -- Comparison steel Carburizing gas 28.2 15.4 52.6 2.4 -145 5 Steel produced in accordance with present invention4 Carburizing gas 28.4 14.2 54.2 2.4 - 60 1 Comparison steel5 (N.sub.2 --H.sub.2) gas 30.0 13.1 52.7 2.2 -100 -- Comparison steel Carburizing gas 30.7 13.5 52.6 2.2 -150 6 Steel produced in accordance with present invention6 (N.sub.2 --H.sub.2) gas 34.8 16.3 44.7 2.0 -50 -- Comparison steel Carburizing gas 35.0 18.6 44.2 2.0 -115 7 Steel produced in accordance with present invention7 (N.sub.2 --H.sub.2) gas 27.8 12.2 50.6 2.2 -70 -- Comparison steel Carburizing gas 28.2 12.2 50.1 2.2 -140 5 Steel produced in accordance with present invention8 (N.sub.2 --H.sub.2) gas 27.3 11.2 54.4 2.4 -45 -- Comparison steel Carburizing gas 27.9 11.5 53.6 2.3 -140 4 Steel produced in accordance with present invention9 (N.sub.2 --H.sub.2) gas 38.3 21.9 42.0 1.8 -30 -- Comparison steel Carburizing gas 39.0 22.4 41.8 1.8 -120 4 Steel produced in accordance with present invention10 Carburizing gas 44.6 23.7 35.9 1.9 -40 6 Comparison__________________________________________________________________________ steel
EMBODIMENT 3
The test steel having the chemical composition shown in Table 1 are subjected, after cold-rolling, to one-minute recrystallization annealing at 800° C. within the carburizing atmosphere or a (N 2 -H 2 ) gas in the annealing process prior to galvanizing, then to hot-dip galvanizing at 450° C., and finally to 0.8% skin pass rolling.
Mechanical properties, amount of solid-solute C (a mean value in the direction of total sheet thickness), ageing index (AI), and bake hardenability (BH) of hot-dip galvanized steel sheets are given in Table 4.
The aging property was evaluated at AI. AI was given, using AI=σ 2 -σ 1 , from a stress (σ 1 ) at the time of 10% stretching and a lower yield stress (σ 2 ) at the time of re-stretching after one hour aging at 100° C.
The bake hardenability was evaluated at BH. BH was obtained, using BH=σ 4 -σ 3 , from a stress (σ 3 ) at the time of 2% stretching and a lower yield stress (σ 4 ) at the time of re-stretching after 20 min. ageing at 170° C.
As is clear from Table 4, the steels produced in accordance with the present invention have excellent bake hardenability, as compared with prior-art steels, without contradicting requirements for hot-dip galvanized cold-rolled steel sheets for deep drawing. Also, these steels have good ageing property.
As a result of tests conducted on the distribution of the amount of solid-solute C through the thickness direction of sheets produced of Steel 7 of the present invention given in Table 4, the carburized steel shows the concentration distribution that the amount of solid-solute C decreases as it goes from the surface towards the center through the thickness direction as shown in FIG. 5. Moreover, in the case of steel carburized within the gas B, it has been ascertained that the concentration of the solid-solute C in the part of a one-tenth gage ratio of the surface layer is 60 mass ppm or less and that the bake hardenability has been improved without deteriorating the r-value.
In the meantime, as shown in Table 4, the comparison steels which do not have the chemical composition defined by the present invention, and the comparison steels having the chemical composition defined by the present invention but not satisfying requirements as to the amount of solid-solute C of the present invention are both inferior in either the r-value or the bake hardenability.
TABLE 4__________________________________________________________________________Mechanical Properties, Ageing Index (AI), and BakeHardenability (BH) amount ofSteel Annealing TS YS El r AI BH solid-solute CNo. atmosphere (kgf/mm.sup.2) (kgf/mm.sup.2) (%) Value (Kgf/mm.sup.2) (kgf/mm.sup.2) (mass ppm) Remarks__________________________________________________________________________1 (N.sub.2 --H.sub.2) gas 31.6 18.8 46.1 1.4 2.8 4.0 16 Comparison steel2 (N.sub.2 --H.sub.2) gas 29.7 14.3 49.0 1.8 0.0 0.2 -- Comparison steel Carburizing gas 30.5 15.0 48.2 1.9 2.0 3.7 13 Steel produced in accordance with present invention3 (N.sub.2 --H.sub.2) gas 28.5 15.8 50.0 2.0 0.0 0.0 -- Comparison steel Carburizing gas 29.8 16.2 49.6 2.0 1.9 3.3 10 Steel produced in accordance with present invention4 Carburizing gas 29.8 16.6 51.0 2.1 0.2 0.9 3 Comparison steel5 (N.sub.2 --H.sub.2) gas 31.1 14.9 47.7 1.8 0.0 0.0 -- Comparison steel Carburizing gas 31.9 16.0 47.1 1.8 2.1 4.0 15 Steel produced in accordance with present invention6 (N.sub.2 --H.sub.2) gas 35.2 17.7 43.5 1.7 0.0 0.0 -- Comparison steel Carburizing gas 35.9 19.0 42.5 1.7 2.0 3.7 12 Steel produced in accordance with present invention7 (N.sub.2 --H.sub.2) gas 29.3 13.4 47.3 1.9 0.0 0.0 -- Comparison steel Carburizing gas 30.5 14.0 47.1 1.9 1.9 3.0 8 Steel produced in accordance with present invention8 (N.sub.2 --H.sub.2) gas 29.1 14.3 50.1 2.0 0.0 0.1 -- Comparison steel Carburizing gas 29.6 15.0 50.0 2.0 2.5 4.5 18 Steel produced in accordance with present invention9 (N.sub.2 --H.sub.2) gas 38.9 23.3 40.6 1.5 0.0 0.0 -- Comparison steel Carburizing gas 40.0 24.7 40.0 1.5 1.7 3.1 7 Steel produced in accordance with present invention10 Carburizing gas 45.8 27.9 35.0 1.5 5.3 6.5 33 Comparison__________________________________________________________________________ steel
EMBODIMENT 4
The test steels having the chemical composition in Table 1, in the embodiment 3, were continuously annealed for recrystallization annealing within a carburizing atmosphere or an (N 2 -H 2 ) gas, cooled down to 400° C. at a cooling rate of about 80° C./s, then overaged for 3 min. at 400° C., and finally subjected to I% skin pass rolling, thereby obtaining cold-rolled steel sheets. Other conditions are the same as those of the embodiment 3.
Mechanical properties, amount of solid-solute C (a mean value in the direction of total sheet thickness), ageing index (AI), and bake hardenability (BH) of the cold-rolled steel sheets thus prepared are shown in Table 5.
As is clear from Table 5, the steels produced in accordance with the present invention are provided with excellent bake hardenability, as compared with prior-art steels, without contradicting requirements for the cold-rolled steel sheets for deep drawing, and also with good ageing property.
By the way, as a result of tests of the distribution of the amount of solid-solute C through the thickness direction of Steel No. 7 of the present invention given in Table 5, the steel carburized, as shown in FIG. 7, has the concentration distribution that the amount of solid-solute C decreases through the thickness direction from the surface towards the center. Furthermore, it has been ascertained that, in steels carburized in the gas B, the concentration of solid-solute C in the part of a one-tenth gage ratio of the surface layer is 60 mass ppm or less, and that the steels are provided with improved bake hardenability without deteriorating the r-value.
Meanwhile, as shown in Table 5, comparison steels not having the chemical composition defined by the present invention, and comparison steels having the chemical composition but not satisfying requirements as to the amount of solid-solute of the present invention are inferior in either the r-value or the bake hardenability.
TABLE 5__________________________________________________________________________Mechanical Properties, Ageing Index (AI) Proparty, andBake Hardenability (BH) amount ofSteel Annealing TS YS El r AI BH solid-solute CNo. atmosphere (kgf/mm.sup.2) (kgf/mm.sup.2) (%) Value (Kgf/mm.sup.2) (kgf/mm.sup.2) (mass ppm) Remarks__________________________________________________________________________1 (N.sub.2 --H.sub.2) gas 30.6 17.8 47.1 1.6 2.5 4.0 15 Comparison steel2 (N.sub.2 --H.sub.2) gas 28.7 13.3 49.6 2.1 0.0 0.1 -- Comparison steel Carburizing gas 30.2 15.2 48.2 2.1 2.2 4.0 15 Steel produced in accordance with present invention3 (N.sub.2 --H.sub.2) gas 28.2 14.8 53.0 2.3 0.0 0.0 -- Comparison steel Carburizing gas 28.8 15.2 52.6 2.2 2.1 3.5 12 Steel produced in accordance with present invention4 Carburizing gas 28.4 14.6 53.0 2.4 0.1 0.2 2 Comparison steel5 (N.sub.2 --H.sub.2) gas 30.1 14.4 51.7 2.2 0.0 0.0 -- Comparison steel Carburizing gas 30.9 16.5 49.6 2.1 2.5 4.8 18 Steel produced in accordance with present invention6 (N.sub.2 --H.sub.2) gas 34.2 17.3 44.8 1.9 0.0 0.1 -- Comparison steel Carburizing gas 34.9 19.6 44.5 1.9 2.4 3.8 16 Steel produced in accordance with present invention7 (N.sub.2 --H.sub.2) gas 28.3 13.4 52.3 2.3 0.0 0.0 -- Comparison steel Carburizing gas 28.5 14.3 51.1 2.3 1.9 3.2 10 Steel produced in accordance with present invention8 (N.sub.2 --H.sub.2) gas 28.1 14.3 53.5 2.4 0.0 0.1 -- Comparison steel Carburizing gas 28.6 15.7 52.8 2.3 2.9 5.5 25 Steel produced in accordance with present invention9 (N.sub.2 --H.sub.2) gas 38.6 22.3 42.6 1.8 0.0 0.0 -- Comparison steel Carburizing gas 40.3 24.5 41.8 1.8 1.4 3.0 7 Steel produced in accordance with present invention10 Carburizing gas 45.3 26.9 35.7 1.7 5.5 6.8 36 Comparison__________________________________________________________________________ steel
Next, the hot-dip galvanized cold-rolled steel sheets having excellent adhesion of galvanized coating according to another embodiment of the present invention will hereinafter be described.
EMBODIMENT 5
Ultra-low carbon steel sheets having the chemical composition shown in Table 6 were heated at 1150° C. for a period of 30 minutes for solution treatment, hot-rolled at a finishing temperature of 890° C., coiled at 720° C., and then, after pickling, cold-rolled at a reduction of 75%, to the sheet thickness of 0.8 mm.
Subsequently, in a hot-dip galvanizing line, the steel sheets were continuously annealed at 780° C. for 40 sec for recrystallization annealing within a carburizing atmosphere or a N 2 -H 2 atmosphere, cooled down to 500° C., then hot-dipped for galvanizing, and finally processed at 600° C. for 40 sec for alloying treatment.
Table 7 shows the mechanical properties and ageing property, adhesion of coating and the amount of solid-solute C, of hot-dip galvanized cold-rolled steel sheets thus obtained.
To evaluate the adhesion of galvanized coating, the sheet was formed to a height of 60 mm with a 5 mm high bead, using a 50 mm wide punch and a 52 mm wide die, and the adhesion was evaluated by classifying the state of peeled off tape into three stages: Good (o), slightly poor (Δ) and poor (x) from the amount of coating peeled off by tape.
To measure the amount of solid-solute C, the amount of carbide and the amount of free carbon in the steel were separated. That is, the amount of free carbon was found of a sample where both faces were ground for the thickness of 100 μm from the surface and a sample not ground, and a half of a difference between the two samples was determined as the amount of solid-solute C included in the depth of 100 μm measured in the direction of sheet thickness from the surface.
The ageing property was evaluated at AI. AI was found, using the equation AI=σ 2 -σ 1 , from the stress (σ 1 ) at the time of 10% stretching and the lower yield stress (σ 2 ) at the time of re-stretching after 1 hr ageing at 100° C.
As is clear from Table 7, all examples of the present invention, as compared with prior-art steels, have provided excellent adhesion of galvanized coating without contradicting requirements for hot-dip galvanized cold-rolled steel sheets for deep drawing.
FIG. 9 shows a relationship between the amount of solid-solute C present in the steels in Table 7 up to the depth of 100 μm from the surface of the steel sheet through the thickness direction and the r-value, and the adhesion of the galvanized coating.
From Table 7 and FIG. 9, it is understood that the steels defined by the present invention have improved the adhesion of galvanized coating without deteriorating the r-value by the carburizing treatment.
TABLE 6__________________________________________________________________________Chemical Composition of Test Steels (mass %)No. C Si Mn P S Ti Nb B sol.Al N X__________________________________________________________________________1 0.0016 0.18 0.012 0.0048 0.027 -- -- 0.025 0.0024 1.812 0.0029 0.21 0.009 0.0038 0.050 -- -- 0.030 0.0040 2.643 0.0025 0.14 0.012 0.0032 0.038 0.024 0.0024 0.034 0.0028 3.604 0.0044 0.19 0.046 0.0061 0.052 -- -- 0.036 0.0028 1.895 0.0021 <0.2 0.26 0.011 0.0038 0.065 -- -- 0.027 0.0030 2.116 0.0026 0.17 0.012 0.0056 0.038 -- -- 0.025 0.0030 1.867 0.0027 0.22 0.081 0.0053 -- 0.036 -- 0.029 0.0032 1.728 0.0042 0.20 0.016 0.0058 -- 0.020 -- 0.030 0.0036 0.619 0.0021 0.26 0.011 0.0068 0.080 -- -- 0.027 0.0030 7.09__________________________________________________________________________ (Note) X = (Ti*/48 + Nb/93)/(C/12) where Ti* = total Ti((48/32) × S + (48/14) × N)
TABLE 7__________________________________________________________________________ Adhesion amount ofSteel Annealing TS YS El r AI of solid-solute CNo. atmosphere (kgf/mm.sup.2) (kgf/mm.sup.2) (%) Value (Kgf/mm.sup.2) coating (mass ppm) Remarks__________________________________________________________________________1 (N.sub.2 --H.sub.2) gas 28.3 13.1 52.3 2.2 0.0 Δ -- Example of comparison steel Carburizing gas 28.9 16.6 50.9 2.1 3.9 O 97 Example of steel according to present invention2 (N.sub.2 --H.sub.2) gas 29.8 12.9 53.2 2.3 0.0 X -- Example of comparison steel Carburizing gas 29.7 15.8 51.4 2.2 1.8 O 23 Example of according to present invention3 (N.sub.2 --H.sub.2) gas 31.5 15.2 48.4 2.0 0.0 X -- Example of comparison steel Carburizing gas 31.7 15.9 47.7 1.9 1.1 O 13 Example of according to present invention4 (N.sub.2 --H.sub.2) gas 34.6 17.1 44.6 1.9 0.0 X -- Example of comparison steel Carburizing gas 35.4 18.3 43.8 1.8 1.9 O 31 Example of according to present invention5 (N.sub.2 --H.sub.2) gas 30.8 13.9 49.3 2.2 0.0 X -- Example of comparison steel Carburizing gas 30.5 14.1 48.9 2.1 2.4 O 67 Example of according to present invention6 (N.sub.2 --H.sub.2) gas 29.3 14.5 51.3 2.1 0.0 Δ -- Example of comparison steel Carburizing gas 28.8 16.6 50.7 2.1 0.7 Δ 6 Example of comparison steel7 (N.sub.2 --H.sub.2) gas 38.8 21.0 42.1 1.8 0.0 Δ -- Example of comparison steel Carburizing gas 39.2 21.5 42.0 1.7 5.1 O 133 Example of comparison steel8 (N.sub.2 --H.sub.2) gas 29.4 17.6 47.2 1.5 4.8 O 114 Example of comparison steel9 Carburizing gas 30.8 13.9 48.3 2.2 0.3 Δ 3 Example of comparison steel__________________________________________________________________________
According to the present invention, as described in detail, the chemical composition of the ultra-low carbon steel was adjusted and the amount of solid-solute C and its distribution through the thickness direction were regulated, thereby enabling improved production and provision of steel sheets having excellent resistance to cold-work embrittlement and/or bake hardenability without contradicting requirements for the cold-rolled steel sheets or hot-dip galvanized cold-rolled steel sheets for deep drawing. Furthermore, according to the present invention, it is possible to obtain hot-dip galvanized cold-rolled steel sheets for deep drawing having excellent deep drawability and excellent adhesion of galvanized coating.
It is to be understood that the above description of the present invention is susceptible to various modifications, changes and adaptations and the same are intended to be comprehended within the meaning and range of equivalents of the appended claims.
|
Cold-rolled steel sheets or hot-dip galvanized steel sheets for deep drawing which have excellent resistance to cold-work embrittlement, containing, all by mass, 0.01% or less C, 0.2% or less Si, 0.05-1.0% Mn, 0.10% or less P, 0.02% or less S, 0.005-0.08% sol.Al, and 0.006% or less N, containing Ti (%) and/or NB (%) solely or in combination within the range in which a relationship between the effective amount of Ti (hereinafter referred to as Ti*) defined by the following formula (1) and the amounts of Nb and C satisfies the following formula (2), and further containing 0.003% or less B when required.
Ti*=total Ti-{(48/32)×S+(48/14)×N}TM (1)
1≦(Ti*/48+Nb/93)/(C/12)≦4.5 (2)
And the balance of Fe and inevitable impurities, the steel sheets have a concentration gradient as a result of carburizing.
| 2 |
RELATED APPLICATIONS
[0001] This patent application is a continuation in part of U.S. patent application Ser. No. 13/784,252, filed Mar. 4, 2013, which claims priority from U.S. Provisional Application No. 61/617,565, filed Mar. 29, 2012, the contents of which are hereby incorporated by reference.
FIELD OF THE INVENTION
[0002] This specification proposes a Radio-Immuno-Modulation (RIM) treatment for patients with advanced cancer, a method of evaluating patients' tolerance to the treatment and the cellular immune responses at the tumor site.
BACKGROUND
[0003] Advanced lung cancer is a disease driven by numerous oncogenic mutations, which are very heterogeneous between patients, as well as between each individual patient's primary tumor and metastases. These cancers are refractory to chemotherapy either from the beginning or after a limited period of response to the treatment.
[0004] Some current treatment approaches are based on stimulating the patient's immune system. The involvement of the immune system in the anti-tumor response has long been suspected and finally shown in more recent works. For example, lung cancer vaccines use the immune system to generate an anti-tumor response.
[0005] A first category of vaccines target the tumor associated antigens (TAA), like melanoma associated antigen (MAGE)-A3, Mucin-1, or epidermal growth factor (EGF). A second category of vaccines are prepared from tumor cells, like granulocyte macrophage colony stimulating factor, gene engineered tumor vaccine (GVAX), or Lucanix. The prime components of such vaccines are the TAA, which the immune system is supposed to target.
[0006] Another result that a vaccine must induce is that of a co-stimulatory effect on the responder T cells. This is achieved by either adding an immuno-adjuvant product to the first category of vaccines, or by genetically modifying the lung cancer cells in the second category of vaccines, in order to generate immune stimulating cytokines. Tumor responses have been noted after vaccination. However, lung cancer cells have several ways to turn down such an immune response in the tumor microenvironment. These include a low expression of human leukocyte antigen (HLA) molecules, and the presence of local regulatory T cells associated with immunosuppressive cytokines, i.e. transforming growth factor (TGF)-beta, interleukin (IL)-10, or cytotoxic T lymphocyte antigen (CTLA)-4.
[0007] Another way of stimulating the immune system is through ionizing radiation, which has a known systemic effect outside of the irradiation field, termed ‘abscopal’, or “off-target” effect. It is known from pre-clinical models, that low, or non-cytolytic doses of radiation produce so-called “danger signals”. Danger signals up-regulate major histocompatibility complex (MHC) molecules presenting TAA on the surface of the tumor cells. This is accompanied by a local secretion of chemokines which enhance the immune cell traffic through the vascular endothelium. The stromal cells situated within the irradiated field contribute to the secretion of inflammatory cytokines that activate the antigen presenting cells (APC). The latter present TAA and stimulate the generation of cytotoxic T cells targeted towards these TAA.
[0008] In some cancer treatment trials on animals, low dose radiation has been combined with various forms of immunotherapy like TAA vaccines, CTLA-4 blockade, or adoptive cell therapy. A synergistic effect was observed with all mentioned approaches, producing significantly higher immunologic changes in the tumor microenvironment when radiation was combined with immunotherapy, compared to radiation or immunotherapy alone. For example, the MHC mean fluorescence intensity (MFI) on the tumor cells increased by 100 units and T cells infiltrating the tumor increased their density by 30%. Also, a significantly higher number of animals resolved their tumors with the combined approach compared to either radiation or immunotherapy alone.
[0009] This synergy has also been suspected from clinical trials. Butts et al. treated patients with stage III non-small cell lung cancer in a randomized manner with either a Mucin-1 targeted vaccine or with placebo ( Lancet Oncol 2014; 15:59). Out of the 806 patients who had received prior concurrent chemotherapy and radiotherapy, those who received the vaccine reached a 50% survival probability at 31 months, compared to only 21 months for the patients who received the placebo, as seen in FIG. 2 .
[0010] In another trial, Chi et al. treated 12 liver cancer patients with a low dose radiation of 8 Gy to their tumors, followed by an APC injection (J Immunother 2005;28:129). The autologous APC were harvested by leukapheresis and the injection was given intratumorally. An immune response specific to alpha fetoprotein was observed. In this trial, the treatment was well tolerated and tumor regression was noted in 6 patients.
[0011] Yet in another trial, Gulley et al. randomized 30 men with hormone resistant prostate cancer in a 2/1 ratio to receive either standard radiotherapy in combination with a prostate specific antigen (PSA) targeted vaccine, or radiotherapy alone for the control group ( Clin Cancer Res 2005;11:3353). A T cell response targeted towards PSA was observed on 13 out of 17 evaluable patients in the vaccine group compared to no response in the control group.
[0012] Another form of immunotherapy is allogeneic hematopoietic stem cell transplantation (HSCT). This approach has been used for 40 years and relies on the activity of allogeneic (another person's) immune cells, obtained from a healthy donor. Patients with hematologic malignancies that were refractory to chemotherapy were treated with HSCT, in order to obtain the graft-versus-leukemia effect. So far, this immune mediated anti-tumor approach is the only one to offer patients a chance for a long term cure and survival.
[0013] Phase I and II studies using allogeneic cellular immunotherapy, with no hematopoietic engraftment, are also known. The patients included in these studied received a total body irradiation dose of 1 Gy, followed by peripheral blood mononuclear cells (PBMC) from an HLA identical family donor. In order to expand eligibility, a subsequent study was done in the haplo-identical setting, as 95% of patients had 3/6 HLA-compatible donors. Those patients who were not heavily pre-treated did not present donor chimerism and the side effects were acceptable.
[0014] Depending on their ethnic origin, approximately 40-80% of patients will not have a suitable adult donor of PBMC for hematopoietic transplantation. For these situations, a newer source of cells has been explored, Umbilical Cord Blood (UCB). These cells are obtained through a volunteer donation at the baby's birth, from the placental blood, and stored in cord blood banks.
[0015] They have many advantages over stem cells coming from a volunteer donor, such as faster availability, lower incidence of graft-versus-host disease and no risk for the donor. The disadvantages of UCB transplants have mainly derived from their lower numbers of stem cells, relative to an adult recipient. This will not be a concern in our study, as we are not looking for a complete replacement of the patient's hematopoietic system; our hypothesis is that the immunoreactive donor cells will home to the tumoral sites and develop their anti-tumor activity.
SUMMARY
[0016] The present specification describes a therapy for cancer patients conveniently associating the immune adjuvant effect of targeted radiation with infusions of allogeneic hematopoietic cells from a compatible donor. The advantage of using allogeneic cells rather than the patient's own immune system resides in the fact that the patient's immune system has already shown anergy towards the tumor cells through some of the above mentioned mechanisms. This includes the presence of the patient's own regulatory T cells. In the first embodiment, the allogeneic cells are PBMC from a volunteer donor.
[0017] According to the method described herein, patients with cancer still progressing after chemotherapy, are treated with radio-immuno-modulation (RIM). No additional chemotherapy regimens or immunosuppressants like in the HSCT need to be administered. Therefore, hematopoietic engraftment or presence of donor cells outside of the tumor bed and/or the regional lymph nodes is not anticipated. Consequently, the complications typically associated with allogeneic HSCT are not expected.
[0018] The first stage of the proposed RIM method uses radiotherapy as an immuno-stimulant. A low dose radiation is targeted on one tumor site. The tumor site is one that has not previously received radiation, to promote immunologically activating changes, as described previously. The fastest growing tumor and/or the largest of the metastases are/is chosen for irradiation in order to direct the immune response towards the most aggressive clones.
[0019] Optionally, the patient may be administered a non-cytotoxic amount of an immuno-modulator, in a sufficient amount to trigger an immunomodulation activity, while avoiding cytotoxicity. Cyclophosphamide may be used as the immuno-modulator; a proposed amount is preferably in the range of 200 mg/m 2 to 300 mg/m 2 .
[0020] In the second stage of the proposed RIM method, immunotherapy is used to start an allogeneic reaction by injecting the recipient with T-cells from a donor. In the first embodiment, the T-cells are PBMC obtained from a first degree genetic relative of the patient.
[0021] These will migrate to the inflammation zone and destroy the tumor. The donor selection is relevant; the donor should present at least 50% HLA compatibility with the recipient and should preferably be related to the recipient. The donor cells may be obtained from a first degree genetic relative of the patient, in relatively good health according to selection criteria described later.
[0022] In a preferred embodiment, the allogeneic stem cell source is the UCB cells obtained from a compatible donor.
[0023] The evolution of the tumor is then surveyed preferably for six months, as described in detail below.
[0024] The methods described here are preferably applicable in cases of advanced or metastatic cancer, where the disease progressed after at least one chemotherapy treatment. In other words, the described methods are applicable preferably for treatment of chemo-resistant cancers. Preferably, the treatment is recommended for chemo-resistant lung cancers.
[0025] The low dose radiation generates local secretion of adhesion molecules as well as chemokines, stimulating chemotaxis. Chemotaxis refers to migration of the immune cells through the vascular endothelium towards the irradiated tumor.
[0026] On the other hand, the stromal cells in the tumor contribute to the local secretion of inflammatory cytokines and co-stimulation molecules. As such, the APC become activated, and this in turn stimulates production of the cytotoxic T cells directed towards the specific TAA, as illustrated in FIG. 1 .
[0027] By combining radiotherapy with immunotherapy, a synergetic effect is obtained compared to radiotherapy or donor cells alone. Immune cells from the systemic circulation, especially the donor cytotoxic T cells, migrate to the tumor site, triggering a neoplastic rejection process.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] FIG. 1 illustrates danger signals following a low dose radiation;
[0029] FIG. 2 illustrates an increase in the survival time for stage III lung cancer patients receiving anti-tumor vaccination after concurrent chemo-radiotherapy;
[0030] FIG. 3 illustrates a treatment plan for the recipient and donor below and above the time line, according to an embodiment of the RIM method;
[0031] FIG. 4 illustrates an example of the immune related response criteria used by the RIM method; and
[0032] FIG. 5 illustrates an embodiment of the preconditioning and post treatment schedule according to the RIM method.
DETAILED DESCRIPTION
[0033] The following detailed description, given by way of example and not intended to limit the present invention solely thereto, will best be appreciated in conjunction with the accompanying drawings FIGS. 1-5 .
[0034] The terms used in this specification are defined as follows:
[0035] “Patient tolerance”: refers to how significant are the post-treatment side effects following RIM; as used herein, this term does not refer to immunologic tolerance;
[0036] “Conformal radiation therapy”: is a three dimensional therapy designed to conform the field of radiation to the exact volume of the tissue treated;
[0037] “Modulation”: refers to immune modulation representing a change in the direction of an immune reaction towards cancer;
[0038] “Human leukocyte antigens (HLA)”: are an important factor in transplantation, while “major histocompatibility antigens (MHC)”, are the equivalent of the HLA in animals;
[0039] “Chimerism”: refers to a mixture of patient and donor T cells;
[0040] “Abscopal effect”: refers to an immunologic effect of radiation outside of the irradiated zone;
[0041] “Performance status”: is a scale which quantifies patients' general well-being and activities of daily life. A performance status of 2 refers to a patient confined to his bed less than 50% of the daytime, and is not considered bedridden;
[0042] “Non-cytolytic radiation dose”: refers to a radiation dose insufficient to kill a significant number of tumor cells
[0043] FIG. 1 shows the response of a tumor receiving a low dose of radiation. As indicated above, it is known from pre-clinical models, that the danger signals produced after low or non-cytolytic doses of radiation, up-regulate major histocompatibility complex (MHC) molecules presenting tumor associated antigens (TAA) on the surface of the tumor cells, # 1 in FIG. 1 . The stromal cells situated within the irradiated field contribute to the secretion of inflammatory cytokines, step # 2 , which, in turn activate the antigen presenting cells (APC), shown at # 3 in FIG. 1 . The latter present TAA, step # 4 , and stimulate the generation of cytotoxic T cells targeted towards these TAA. Chemokines are also secreted, and this enhances the immune cell traffic through the vascular endothelium. Cytotoxic T cells migrate to the irradiated tumor, step # 5 in FIG. 1 .
[0044] FIG. 2 illustrates an increase in the survival time for stage III lung cancer patients receiving anti-tumor vaccination according to Butts et al. ( Lancet Oncol 2014; 15:59). As indicated above, in this study, the patients were treated in a randomized manner with either a Mucin-1 targeted vaccine or with placebo, after having received combination chemo-radiotherapy. Out of the 806 patients who had received concurrent chemo-radiotherapy, median survival was 31 months with the vaccine, compared to only 21 months with the placebo.
[0045] The RIM methods are now described in conjunction with FIGS. 3-5
[0046] Pre-Treatment
[0047] A comprehensive physical examination the patient should be initially performed before commencing the treatment. The patient evaluation is shown in FIG. 5 . Patients that are more likely to benefit from this method are selected based on inclusion and exclusion criteria.
[0048] Preferably, the patient selection inclusion criteria include:
patients with advanced lung cancer documented by a histo-pathological analysis; patients who received at least one line of chemotherapy; patients with least one measurable tumor mass (≧1 cm) not previously irradiated and situated in the lymph nodes, soft tissue, lung, or skeleton; patients presenting a performance status less or equal to 2 and a life expectancy greater than 3 months; availability of a compatible allogeneic hematopoietic cell source, either from a PBMC, or UCB donor is also necessary.
[0054] Patients for whom the treatment is not recommendable are excluded based on the following exclusion criteria:
Presence of a second active cancer requiring treatment; Corticosteroid dependency; Presence of vertebral metastases as the only tumors that could be irradiated; Decreased diffusion capacity below 40% if a lung tumor was the only metastasis that could be irradiated; Patients needing urgent radiotherapy.
[0060] Patient HLA typing is done for the A, B and DR alleles, as recommended in the setting of allogeneic HSCT.
[0061] Donor Evaluation and Selection Criteria
[0062] Donor evaluation and selection are described next.
[0063] For the embodiment that uses peripheral blood mononuclear cells, the donor should be a first degree genetic relative of the patient, in relatively good health. The donor selection process starts preferably one month prior to the planned treatment, and includes evaluation of the donor health and compatibility.
[0064] Donor evaluation includes medical history, physical exam, HLA typing, complete blood count (CBC), electrolytes, glycemia, uric acid, Ca, P, Albumin, lactate dehydrogenase (LDH), liver enzymes, renal, coagulation, blood group, electro cardiogram (EKG) and chest x-ray.
[0065] Donor evaluation also includes serology for Human Immunodeficiency Virus (HIV), Hepatitis A, B and C, Herpes Simplex Virus (HSV), Varicella-Zoster Virus (VZV), Epstein-Barr Virus (EBV) and Cyto Megalo Virus (CMV).
[0066] Every active medical condition shall be evaluated and stabilised before the PBMC collection, i.e., diabetes, hypertension, chest pain, weight loss, fever, etc.
[0067] Aspirin is stopped for one week before and one week after collection, if it is safe to do so. For donors on Aspirin or Plavix needing a central catheter, we favour a femoral line. Donors on anticoagulation medication (Coumadin) who require a central line for collection are switched to low molecular weight heparin.
[0068] Donors are considered based on the following donor inclusion criteria: they should be a first degree relative with the patient (parent, sibling or child); have a HLA compatibility of ≧50%; and a performance status of 0 or 1.
[0069] Donors are excluded based on the following donor exclusion criteria: a HLA incompatibility in the graft versus host direction (donor homozygous and patient heterozygous for the shared haplotype); a positive serology for HIV, Hepatitis B or C; and an active medical condition that cannot be improved within a month.
[0070] For the alternative embodiment when the Umbilical Cord Blood (UCB) cell are used rather than an adult donor (i.e. a first degree genetic relative of the patient), an UCB unit with at least 4 of 6 allele compatibility and at least 2×10 7 total nucleated cells per kg patient weight should be identified.
[0071] Treatment
[0072] In the first stage, the patient receives a dose of external radiation of preferably 15 Gy. This dose is divided in three equal fractions of 5 Gy, on Days −3, −2 and −1. Optionally, Cyclophosphamide, 250 mg/m 2 may be administered on Day −2.
[0073] In the second stage of RIM, immunotherapy is used to start an allogeneic reaction by injecting the recipient with a sufficient amount of donor cells. These contain donor T-cells, which are expected to reject the tumor by migration to the inflammation zone.
[0074] The day of UCB or PBMC infusion is referred to as ‘Day 0’ and the n th day before that is referred to as ‘Day −n’ (see FIG. 3 )
[0075] In the embodiment that uses PBMC, donors receive five doses of granulocyte colony stimulating factor (GCSF), each dose calculated as 10 μg/kg, by subcutaneous injection. The GCSF injections are administered from Day −4 to Day 0. PBMC collection is preferably performed through a standard leukapheresis procedure, 2 to 3 hours after the last GCSF injection on Day 0.
[0076] Aliquots from the UCB or the PBMC will be stained for flow cytometry with CD34 and CD3 antibodies, in order to measure their respective concentrations. As the optimal cell populations are unknown, these cells will not be selected, but infused entirely; this approach aims to avoid the inadvertent depletion of such cells.
[0077] Normally, the patients do not need to receive any pre-medication, unless they have already reacted to previous blood transfusions, necessitating a specific medication. In this case, the same pre-medication is administered prior to PBMC, with the exception of corticosteroids, which should be avoided wherever possible.
[0078] PBMC are administered intravenously fresh and unmodified. Donor PBMC should be infused within 24 hours after collection. Preferably, this is performed within 1 hour, in which case the collection bag is kept at room temperature (20-24° C.). If the infusion cannot be performed within 1 hour, the bag is kept in the refrigerator at 4° C. until the infusion.
[0079] By combining radiotherapy with immunotherapy, a synergistic effect is obtained, compared to radiotherapy or donor cell administration alone. Immune cell from the systemic circulation, especially the donor cytotoxic T cells, migrate to the tumor site, triggering a neoplastic rejection process.
[0080] Post-Treatment
[0081] The post-treatment refers to a methodology of monitoring the cellular immune response at the tumor site and the patients' adverse events. Recipients are evaluated preferably during 6 months post-treatment. The patient post-treatment evaluations are shown in FIG. 5 .
[0082] Each patient is evaluated regarding the post-treatment immune condition, the phenotype of the neoplastic cell, and the degree of T cell infiltration. Paired T tests will be used to compare HLA MFI on tumor cells and T cell density between pre and post treatment samples. Tumor response is evaluated using the Immune-Related Response Criteria (irCR) as illustrated in FIG. 4 . The survival period without progression is calculated starting from Day 0 until cancer progression, if any. A chimerism analysis is performed for determining the presence of donor cells in the recipient. Adverse events are collected according to the Common Terminology Criteria for Adverse Events (CTCAE) from the National Cancer Institute, version 3.0, and a grade, i.e. mild, moderate, or severe, is attributed to each toxicity. (http://ctep.cancer.qov/protocol Development/electronic applications/docs/ctcaev3.p df).
[0083] Treatment tolerance is evaluated by follow-up clinic visits scheduled twice a week for the first 2 weeks, then once a week for the following 2 weeks, then every 2 weeks for 2 months, and every month for the following 3 months, for a total of 6 months, as shown in FIG. 5 .
[0084] The visits will end either after the 6 months follow-up period, or at the time of disease progression, or whenever the consent of the patient has been waved, if that occurred earlier. Beyond 6 months, standard care will be offered to the patient, according to established clinical guidelines.
[0085] The immune response is assessed using tumor biopsies done before and after the treatment for immunological comparisons. The tumor block slides could be stained with CD4 and CD8 antibodies in order to assess the T cell density under the microscope. This will be expressed as T cell numbers on a 400× power field (0.292 mm 2 ), relative to the number of tumoral cells, as well as to the weight of tumoral tissue.
[0086] Flow cytometry analysis may be used to determine the presence of immunologic markers like HLA, Fas (CD95) and ICAM-1 (CD54) (tumor cells), CD3, CD4, CD8, CD25 and Foxp3 (T cells). The percentage of the positive cells in these markers as well as their fluorescence intensity will be determined.
[0087] The tumor infiltrating T cells are preferably sorted and isolated by fluorescence-activated cell sorting (FACS), from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks by density gradient centrifugation. The origins of all these cell populations are determined with polymerase chain reaction (PCR) techniques, quantifying patient and donor specific variable number of tandem repeats (VNTR) bands.
[0088] Tumor responses can be assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria are applied, as seen in FIG. 4 .
[0089] Symptoms attributable to lung cancer are collected monthly according to the FACT/NCCN Lung Symptom Index (FLSI)-12.
EXAMPLE 1
[0090] In this example the radiation is administered to the primary tumor of the recipient. The dose of external radiation is 15 Gy and divided in 3 fractions, on Days −3, −2 and −1.
[0091] Cyclophosphamide, 250 mg/m 2 is administered on Day −2.
[0092] Donors receive 5 doses of GCSF, each dose of 10 pg/kg from Day −4 to Day 0. PBMC collection is performed through a standard leukapheresis procedure on Day 0.
[0093] The PBMC are administered intravenously, fresh and unmodified, starting at a rate of 40 cc/hour for 15 minutes and increasing with 20 cc/hour every 15 minutes as tolerated, up to a maximum of 100 cc/hour. At the same time, the body temperature, vital signs, and oxygen saturation are monitored every 15 minutes, until a stable flow of perfusion is reached. Thereafter, monitoring is performed every 30 minutes.
[0094] The immune responses are assessed using tumor biopsies done before and after the treatment. Flow cytometry is used to assess the following cell surface markers: HLA, Fas, ICAM-1 on tumor cells, and CD3, CD4, CD8, CD25 and Foxp3 on tumor infiltrating T cells.
[0095] The tumor block slides are stained with CD4 and CD8 antibodies in order to assess the T cell density on a 400× magnitude power field.
[0096] The tumor infiltrating T cells are isolated by FACS from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks with a density gradient centrifugation. The origin of all these cell populations is determined with PCR techniques, quantifying patient and donor specific VNTR bands.
[0097] Tumor responses are assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria irCR are applied (see FIG. 4 ).
EXAMPLE 2
[0098] This example refers to administering radiation to the largest metastatic site.
[0099] The dose of external radiation is 15 Gy and divided in 3 fractions, on Days −3, −2 and −1.
[0100] Cyclophosphamide, 250 mg/m 2 is administered on Day −2.
[0101] Donors receive 5 doses of GCSF, each dose of 10 pg/kg from Day −4 to Day 0. PBMC collection is performed through a standard leukapheresis procedure on Day 0. The PBMC are administered intravenously, fresh and unmodified.
[0102] The immune responses are assessed using tumor biopsies done before and after the treatment. Flow cytometry is used to assess the following cell surface markers: HLA, Fas, ICAM-1 on tumor cells, and CD3, CD4, CD8, CD25 and Foxp3 on tumor infiltrating T cells.
[0103] The tumor block slides are stained with CD4 and CD8 antibodies in order to assess the T cell density on a 400× magnitude power field.
[0104] The tumor infiltrating T cells are isolated by FACS from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks with a density gradient centrifugation. The origin of all these cell populations is determined with PCR techniques, quantifying patient and donor specific VNTR bands.
[0105] Tumor responses are assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria irCR are applied (see FIG. 4 ).
EXAMPLE 3
[0106] This is an example where the radiation is administered to the primary tumor of the recipient. The dose of external radiation is 15 Gy and divided in 3 fractions, on Days −3, −2 and −1.
[0107] No Cyclophosphamide is administered in this example.
[0108] Donors receive 5 doses of GCSF, each dose of 10 pg/kg from Day −4 to Day 0. PBMC collection is performed through a standard leukapheresis procedure on Day 0. The PBMC are administered intravenously, fresh and unmodified.
[0109] The immune responses are assessed using tumor biopsies done before and after the treatment. Flow cytometry is used to assess the following cell surface markers: HLA, Fas, ICAM-1 on tumor cells, and CD3, CD4, CD8, CD25 and Foxp3 on tumor infiltrating T cells.
[0110] The tumor block slides are stained with CD4 and CD8 antibodies in order to assess the T cell density on a 400× magnitude power field.
[0111] The tumor infiltrating T cells are isolated by FACS from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks with a density gradient centrifugation. The origin of all these cell populations is determined with PCR techniques, quantifying patient and donor specific VNTR bands.
[0112] Tumor responses are assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria irCR are applied (see FIG. 4 ).
EXAMPLE 4
[0113] This example provides for a method where the radiation is administered to the largest metastatic site. The dose of external radiation is 15 Gy and divided in 3 equal fractions, on Days −3, −2 and −1.
[0114] No Cyclophosphamide is administered in this example.
[0115] Donors will receive 5 doses of GCSF, each dose of 10 pg/kg from Day −4 to Day 0. PBMC collection is performed through a standard leukapheresis procedure on Day 0.The PBMC are administered intravenously, fresh and unmodified.
[0116] The immune responses are assessed using tumor biopsies done before and after the treatment. Flow cytometry is used to assess the following cell surface markers: HLA, Fas, ICAM-1 on tumor cells, and CD3, CD4, CD8, CD25 and Foxp3 on tumor infiltrating T cells.
[0117] The tumor block slides are stained with CD4 and CD8 antibodies in order to assess the T cell density on a 400× magnitude power field.
[0118] The tumor infiltrating T cells are isolated by FACS from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks with a density gradient centrifugation. The origin of all these cell populations is determined with PCR techniques, quantifying patient and donor specific VNTR bands.
[0119] Tumor responses are assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria irCR are applied (see FIG. 4 ).
[0120] The following Examples 5 - 8 refer to UCB embodiment
EXAMPLE 5
[0121] In this example the radiation is administered to the primary tumor of the recipient and UCB is used as an allogeneic cell source. The dose of external radiation is 15 Gy and divided in 3 fractions, on Days −3, −2 and −1.
[0122] Cyclophosphamide, 250 mg/m 2 is administered on Day −2.
[0123] The UCB unit had been cryopreserved by the cord blood bank. It is thawed and administered intravenously on day 0.
[0124] The immune responses are assessed using tumor biopsies done before and after the treatment. Flow cytometry is used to assess the following cell surface markers: HLA, Fas, ICAM-1 on tumor cells, and CD3, CD4, CD8, CD25 and Foxp3 on tumor infiltrating T cells.
[0125] The tumor block slides are stained with CD4 and CD8 antibodies in order to assess the T cell density on a 400× magnitude power field.
[0126] The tumor infiltrating T cells are isolated by FACS from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks with a density gradient centrifugation. The origin of all these cell populations is determined with PCR techniques, quantifying patient and donor specific VNTR bands.
[0127] Tumor responses are assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria irCR are applied (see FIG. 4 ).
EXAMPLE 6
[0128] This example refers to administering radiation to the largest metastatic site and using UCB as an allogeneic cell source. The dose of external radiation is 15 Gy and divided in 3 fractions, on Days −3, −2 and −1.
[0129] Cyclophosphamide, 250 mg/m 2 is administered on Day −2.
[0130] The UBC unit is thawed and administered intravenously on day 0.
[0131] The immune responses are assessed using tumor biopsies done before and after the treatment. Flow cytometry is used to assess the following cell surface markers: HLA, Fas, ICAM-1 on tumor cells, and CD3, CD4, CD8, CD25 and Foxp3 on tumor infiltrating T cells.
[0132] The tumor block slides are stained with CD4 and CD8 antibodies in order to assess the T cell density on a 400× magnitude power field.
[0133] The tumor infiltrating T cells are isolated by FACS from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks with a density gradient centrifugation. The origin of all these cell populations is determined with PCR techniques, quantifying patient and donor specific VNTR bands.
[0134] Tumor responses are assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria irCR are applied (see FIG. 4 ).
EXAMPLE 7
[0135] This is an example where the radiation is administered to the primary tumor of the recipient and UCB is used as an allogeneic cell source. The dose of external radiation is 15 Gy and divided in 3 fractions, on Days −3, −2 and −1.
[0136] No Cyclophosphamide is administered in this example.
[0137] The UCB unit is thawed and administered intravenously on day 0.
[0138] The immune responses are assessed using tumor biopsies done before and after the treatment. Flow cytometry is used to assess the following cell surface markers: HLA, Fas, ICAM-1 on tumor cells, and CD3, CD4, CD8, CD25 and Foxp3 on tumor infiltrating T cells.
[0139] The tumor block slides are stained with CD4 and CD8 antibodies in order to assess the T cell density on a 400× magnitude power field.
[0140] The tumor infiltrating T cells are isolated by FACS from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks with a density gradient centrifugation. The origin of all these cell populations is determined with PCR techniques, quantifying patient and donor specific VNTR bands.
[0141] Tumor responses are assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria irCR are applied (see FIG. 4 ).
EXAMPLE 8
[0142] This example provides for a method where the radiation is administered to the largest metastatic site and UCB is used as an allogeneic cell source. The dose of external radiation is 15 Gy and divided in 3 equal fractions, on Days −3, −2 and −1.
[0143] No Cyclophosphamide is administered in this example.
[0144] The UCB unit is thawed and administered intravenously on day 0.
[0145] The immune responses are assessed using tumor biopsies done before and after the treatment. Flow cytometry is used to assess the following cell surface markers: HLA, Fas, ICAM-1 on tumor cells, and CD3, CD4, CD8, CD25 and Foxp3 on tumor infiltrating T cells.
[0146] The tumor block slides are stained with CD4 and CD8 antibodies in order to assess the T cell density on a 400× magnitude power field.
[0147] The tumor infiltrating T cells are isolated by FACS from the post treatment biopsy specimen. Blood granulocytes and mononuclear cells are isolated every 2 weeks with a density gradient centrifugation. The origin of all these cell populations is determined with PCR techniques, quantifying patient and donor specific VNTR bands.
[0148] Tumor responses are assessed through radiologic imaging after 6, 12 and 18 weeks. This is done by CT-scanning and the immune related response criteria irCR are applied (see FIG. 4 ).
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A combination therapy for treating advanced cancer, comprises, first, performing targeted low dose radiation therapy on a recipient tumoral site to generate an inflammation zone and an immuno-stimulant effect, including release of cytokines and chemokines. Secondly, hematopoietic cells from a suitable donor are administered intravenously in order to initiate an allogeneic reaction. These cells could be collected either as PBMC from an adult donor, or from an UCB donation. The post-radiotherapy inflammation zone will attract the newly injected donor cells to the tumor bed, triggering an immunological cancer cell rejection. The cellular response in the recipient is monitored and post-treatment evaluation for recipients' side effects is also provided.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to apparatus and process for plasmapheresis, and, more especially, to such apparatus/process employing a membrane separator.
2. Description of the Prior Art
Plasmapheresis is a known operation consisting of separating the whole blood of a donor into two fractions, the first fraction constituting the plasma phase and the second fraction constituting the cellular component phase, which is typically injected back into the donor. The plasma phase is a complex aqueous solution containing proteins in particular, while the cellular component phase, which still contains plasma, comprises the red corpuscles (or erythrocytes), the white corpuscles (or leucocytes) and the platelets.
The technique of plasmapheresis has long been used in animal experiments. Compare, for example, the article by John J. Abel et al entitled "Plasma Removal With Return Of Corpuscles" published at J. Pharmacol. Exp. Ther., No. 5, pages 625 to 641 (1914), in which dog's blood is centrifuged in order to perform the separation. There may also be mentioned the article by A. Geiger published in J. Phys., 71, pages 111-120 (1931) and entitled "Method Of Ultrafiltration In Vivo", which describes a continuous plasmapheresis operation on dogs, the separating apparatus employed being a membrane separator, and the membrane being arranged in a spiral and being selected such that it is possible, if desired, to obtain a plasmatic solution comprising the entirety of the proteins from the blood treated.
Plasmapheresis has also been applied to man for a certain number of years, as indicated by the article "La plasmapherese--Technique--Indications" ("Plasmapheresis--Technique--Indications") by Fr. Oberling et al, published at J. Med. Strasbourg, pages 277-279 (March, 1968). Thus, plasmapheresis now tends to replace the total donation of blood, because this technique has the advantage of enabling larger amounts of plasma to be withdrawn from a human donor without serious drawbacks. Because the formed elements of the blood are returned to the donor, the withdrawal sessions can be carried out at shorter intervals of time than for the donation of blood.
Thus, plasmapheresis is an old technique and the subsequent improvements which have been made thereto involve either improved centrifugation apparatus or improved membrane apparatus therefor. In the patent literature featuring improvements in membrane apparatus, reference is made to Amicon's German Patent No. 2,100,209 which describes a vessel comprising a membrane forming a spiral, for the circulation of whole blood withdrawn from a donor, and in which a pressure is exerted on the blood contained in the vessel, either by means of a gas or by means of the piston of a syringe, subjected to the action of a leaf spring. Compared with the apparatus of Geiger described above, this apparatus, by its very design, has the disadvantage of not permitting a continuous operation to be performed on the donor.
Also representative is Hemotherapy's U.S. Pat. No. 4,191,182 which describes membrane apparatus and in which blood continuously withdrawn from the donor is separated into plasma and into a cellular fraction continuously returned to the donor, such apparatus having the particular characteristic of allowing a portion of the cellular fraction to recirculate in the upstream compartment of the membrane apparatus and of allowing the plasma fraction to recirculate in the downstream compartment of the same apparatus. Cf. the International Application of Friedman et al published under International Publication No. WO 79/01121, which also deals with apparatus enabling the withdrawal of blood from the donor and injection back into the donor of the fraction which has not passed through the membrane, in a continuous operation.
However, the types of equipment described above, which permit continuous plasmapheresis, display the particular disadvantage of requiring the donor to be injected at two separate points, which is rather unpleasant for the donor.
SUMMARY OF THE INVENTION
Accordingly, a major object of the present invention is the provision of improved apparatus/process employing a membranous seperator which is well adapted for plasmapheresis operations on a donor, while entailing injecting the subject at but a single point with a blood withdrawal needle.
Another object of the present invention is the provision of improved plasmapheresis apparatus/process enabling subjecting the blood from the donor to a first separation by passage of same over a filtration membrane, and then to a second separation over the same membrane, as it is returned to the donor.
Another object of this invention is specially designed plasmapheresis apparatus enabling obtainment of plasma of very good quality and under the best conditions of filtration efficency, while at the same time guaranteeing virtually zero haemolysis of the blood.
Yet another object of this invention is the provision of improved plasmapheresis apparatus enabling the user to regulate the pressure at which the cellular component fraction exits the upstream compartment of the membrane apparatus to relative pressure values which are typically between 0 and 20 mm of mercury, the downstream compartment being at atmospheric pressure.
Still another object of this invention is the provision of plasmapheresis apparatus making it possible to withdraw about 600 ml of plasma from a donor in about 45 minutes.
And yet another object of this invention is the provision of plasmapheresis apparatus/process for the withdrawal of plasma in which the operational strategy can easily by adapted according to the donor, the requirements of the operator and the characteristics of the membrane apparatus employed.
Briefly, the present invention features improved plasmapheresis apparatus comprising, and with reference to the attached Figures of Drawing:
(i) means 1 for withdrawing blood from a donor;
(ii) a membrane filtration cell 2 separating the blood into a fraction which has passed through the membrane and which consists of plasma, and into a fraction which has not passed through the membrane;
(iii) a first conduit 5 connecting the withdrawal means 1 to the inlet 6 of the upstream compartment 3 of the membrane filtration cell 2;
(iv) a pump 7 situated along said conduit 5;
(v) a pressure sensor 14 for the blood circulating in the conduit 5, said sensor being located between the pump 7 and the inlet 6 of the upstream compartment 3;
(vi) an inflatable tourniquet 21;
(vii) means enabling inflation or deflation of the tourniquet 21;
(viii) a second conduit 16 connecting the outlet 15 of the upstream compartment 3 of the membrane filtration cell 2 to a vessel 17 for collecting the fraction of the blood which has not been filtered through the membrane;
(ix) a pump 18 situated along the second conduit 16 and rotating in the same direction as the pump 7;
(x) a second pressure sensor 19 situated along the conduit 16 between the said pump 18 and the outlet 15 of the upstream compartment 3 of the membrane filtration cell 2;
(xi) a vessel 20 for collecting the plasma which has been filtered through the membrane, such vessel 20 being in communicating relationship with the outlet of the downstream compartment 4 of the membrane filtration cell 2;
(xii) means for measuring the volume of blood withdrawn from the donor during the withdrawal stage, at the beginning of which the tourniquet 21 is inflated or tightened about the limb of the donor;
(xiii) means for reversing the direction of rotation of the pumps 7 and 18 when the desired amount of blood has been withdrawn during the withdrawal stage, and thus ensuring the return of the blood from the vessel 17 to the donor, passing through the lines 16 and 5 and through the upstream compartment 3 of the membrane filtration cell 2, the tourniquet 21 being deflated upon commencement of the return stage; and
(xiv) means 27 enabling monitoring or determining when the completion of the return stage has been reached, and ensuring that a return stage switches to a withdrawal stage.
The present invention also features a plasmapheresis technique utilizing the aforesaid apparatus.
BRIEF DESCRIPTION OF THE DRAWINGS
The description of the apparatus according to the present invention will be understood more clearly with reference to the attached Figures of Drawing, which illustrates, in a simplified manner, by way of non-limiting examples and with no fixed scale, particular embodiments of said apparatus.
FIG. 1 is a schematic diagram of one embodiment of apparatus according to the present invention; and
FIG. 2 is a schematic diagram of one embodiment of apparatus according to the invention, illustrating, in particular, the operative connections to a monitoring and control device.
DETAILED DESCRIPTION OF THE INVENTION
More particularly according to this invention, and with specific reference to FIG. 1, there is illustrated device for withdrawing blood from a donor patient comprising a needle 1 for the withdrawal of blood. By way of example, such needle can have an external diameter of 1.65 mm and an internal diameter of 1.45 mm, such as those typically employed in blood transfusion centers and conventially designated as 16 G needles. A membrane filtration cell 2, comprising an upstream compartment 3 and a downstream compartment 4, is operably connected to the needle 1 by a first conduit 5 extending from the needle 1 to the inlet 6 of the upstream compartment 3 of the membrane cell. This conduit 5 typically comprises a plastic tube, for example, made of polyvinyl chloride. Along this conduit 5, there is situated a pump 7 capable of rotating in either direction, which is advantageously of the peristaltic pump type. Such pumps are marketed, for example, by Hospal under the trademark RP 01. Between the pump 7 and the needle 1, there is a device 8 for injecting an anticoagulant into the blood emanating from the donor, for example, a glucose solution containing 35.6 g/liter of trisodium citrate, marketed as AB 16 from Bieluz. This device 8 comprises, for example, a reservoir 9 of anticoagulant, a conduit 11 operably connected to the conduit 5 and to the reservoir 9, and a pump 10, for example, of peristaltic type, situated along the conduit 11. This conduit 11 is connected to the conduit 5 as close as possible to the needle 1. A bubble detector 12 and a pressure sensor 13 operably communicate with the conduit 5 between the point of connection of the conduits 11 and 5 and the pump 7. A pressure detector 14 is also arranged between the pump 7 and the inlet 6 of the upstream compartment 3 of the membrane filtration cell 2. The outlet 15 of the upstream compartment 3 of the membrane filtration cell 2 is connected by a conduit 16 to a vessel 17 for collecting the fraction of the blood which has come into contact with the membrane separator without passing therethrough. This conduit 16 can be made of the same material and can have the same diameters as the conduit 5, while the vessel 17 is advantageously comprised of a flexible plastic bag. A pump 18 is situated along the conduit 16 and can rotate in either direction, this pump advantageously also being of peristaltic type. Between the outlet 16 of the upstream compartment 3 of the membrane filtration cell 2 and the pump 18, there is located a pressure sensor 19 along the conduit 16. The downstream compartment 4 of the separator is connected to a vessel 20 for collecting the plasma which has passed through the membrane, this vessel 20 being, for example, a plastic bag, the interior of which is in communication with atmospheric pressure, for example, via a sterile plug located at its upper end. This vessel 20 can also be a flexible plastic bag such as those marketed by Fenwal as "transfer-pack" R-2022.
The membrane, per se, comprising the filtration cell 2 referred to above can be in planar form, in spiral form or in the form of small thin tubes such as hollow fibers. If the membrane comprises a plurality of hollow fibers, the blood advantageously circulates inside the hollow fibers, the internal portions of the fibers together defining the upstream compartment 3 of the separator. If the membrane is in the planar or spiral form, the blood advantageously circulates between two membranes or groups of two membranes defining the upstream compartment 3 of the separator 2.
The membranes employed are preferably those which make it possible to collect a plasma in which all of the proteins in the initial blood are found again in the same proportions, in which the protein concentration is more than 55.5 g/liter, in which there are no red corpuscles and in which the platelet concentration is less than 15,000 platelets per mm 3 . The membranes selected are those which also make it possible to avoid haemolysis of the blood circulating in contact with same, while at the same time permitting good filtration efficiencies.
These membranes advantageously have a latex rejection level of less than 75% for particles of a size of 0.27 micron and they have a latex rejection level of more than 15% for particles of a size of 0.64 micron. Preferably, the rejection level for particles of a size of 0.27 micron is less than 30% and the rejection level for latex particles of a size of 0.64 micron is more than 90%.
If the membranes are planar, this measurement of the latex rejection level is carried out by the following procedure:
50 ml of a suspension of sized polystyrene particles having a diameter of 0.27-0.4 or 0.64 micron (marketed by Rhone-Poulenc under the trademark Estapor), diluted to 0.1% strength with distilled water treated with 1% of a surface-active agent (an alkylarylsulfonate marketed as SINOZON NAS 60 by Sinnova), are introduced into a cell of the type Amicon Model 52.
The Amicon cell is fitted with a sample of membrane strengthened by a web. An air pressure corresponding to 20 cm of water is established. The first six milliliters of filtrate are recovered and the concentration (cf) of sized particles therein is determined.
The rejection level is determined according to the formula: ##EQU1##
Membranes having the above characteristics are typically fabricated from a synthetic polymer, for example, of cellulose esters (cellulose nitrate or the like), regenerated cellulose, polycarbonate or the like. These membranes can also be based on polyether-urethanes comprising heparin-modified ammonium groups, or can be made from an acrylonitrile copolymer. Advantageously, these membranes are strengthened by a web if they are in the form of planar membranes and have a thickness ranging from 50 to 200 microns.
The apparatus depicted in FIG. 1 also comprises an inflatable tourniquet 21 of a type which is in itself known, it being possible for this tourniquet to be inflated, if desired, by a device (which is also in itself known) comprising an electrovalve connected to a cylinder of pressurized gas, for example, nitrogen or freon. In FIG. 1, the dashed lines including arrows, between the pressure sensors 13, 14 and 19 and the pumps 7 and 18, indicate that the said sensors act on the pump in accordance with the set values which they have been given beforehand. Thus, the operation of the pumps is controlled by the set values of the sensors. The same applies to the tourniquet 21, the inflation (or deflation) of which is controlled by the direction of rotation of the pump 7.
In FIG. 2 apparatus is shown which is equivalent to that of FIG. 1, but including the electrical connections from the various elements to a logic unit 22 for control and monitoring, the electric leads being shown in dashed lines and the unit 22 being operably associated with a current supply (not shown).
The apparatus described above is used in the following manner. Initially, the conduit 11 is filled with citrate solution and, as the junction between the conduit 11 and the conduit 5 is in fact very close to the needle 1, it can be considered that the needle 1 is at least partially filled with this citrate solution. With the tourniquet inflated beforehand to the desired pressure (about 60 mm of mercury) using the cylinder 23 and the contact manometer 24, by opening the electrovalve 25 (these latter two elements being connected to the logic unit 22), the needle 1 is inserted into one of the donor's veins once the intended point of injection, which is located between the tourniquet and the end of the limb, has been sterilely prepared in conventional fashion. At this moment, the pump 10 injects citrate into the conduit 5, and the two pumps 7 and 18 rotate in the same direction and cause the blood to flow from the donor to the vessel 17, flowing through the upstream compartments 3 of the membrane filtration cell 2, where a portion of the plasma passes through the membrane separator and into the downstream compartment 4 connected to the bag 20. The pressure sensor 13 controls the pump 7 such that the pressure measured at this point along the conduit 5 always remains above a certain value, which is generally close to 0 mm of mercury and is designated the threshold pressure, in order to ensure that the pump 7 does not "draw" the blood directly from the donor's vein. If the pressure in this section of the conduit becomes less than the set value given to the sensor 13, the logic unit 22 acts automatically and momentarily stops or slows down the rotation of the pump 7 for as long as the desired pressure is not restored. The pressure sensor 14 is adjusted such that a pressure at the inlet 6 of the upstream compartment 3 which is greater than a maximum value, for example, a relative value ranging from 40 to 100 mm of mercury, preferably ranging from 60 to 90 mm of mercury, is automatically detected. If this desired maximum value is exceeded, the logic unit 22 automatically stops the pump 7. The sensor 19 makes it possible to ensure a relative pressure value ranging from 0 to 20 mm of mercury at the outlet 15 of the upstream compartment 3 of the separator 2, while the downstream compartment 4 is at atmospheric pressure. If the pressure at the outlet 15 of the upstream compartment 3 exceeds the desired maximum pressure, the logic unit 22 for control and monitoring automatically acts on the pump 18 to accelerate the rotation of its motor, namely, to increase its throughput.
The period during which the blood is exiting the donor's vein is called the withdrawal stage. This stage is terminated, for example, according to the predetermined volume of blood which it is desired to withdraw from the donor, this volume of course always being less than the volume of the vessel 17 for collecting the blood. Advantageously, a tachometric device is connected to the pump 7 and, when the desired volume of blood has been withdrawn from the donor, the logic unit 22 acts and stops the pumps 7, 10 and 18. The logic unit then acts simultaneously on the electrovalve 25, which takes up a position such that the tourniquet 21 deflates, and it causes the pumps 7 and 18 to rotate in the opposite direction to that of the preceding so-called withdrawal stage. The so-called "return of the blood to the donor" stage then starts and, during this stage, the blood contained in the bag 17 again passes through the upstream compartment 3 of the membrane filtration cell 2. In the course of the return stage, during which the citrate pump 11 is at rest, the sensor 19 performs a safety function and is adjusted such that the relative pressure does not exceed a certain value fixed in advance, for example, ranging from 40 to 100 mm of mercury, preferably ranging from 60 to 90 mm of mercury, when the blood enters the compartment 3 of the membrane separator 2; the blood then enters the separator via the conduit 15 noted in FIGS. 1 and 2. If this predetermined pressure value is exceeded, the logic unit 22 acts on the pump 18 and stops it, at least momentarily. The sensor 14 ensures that the blood leaving the separator via the line 6 is at a relative pressure ranging from 0 to 20 mm of mercury, while the downstream compartment 4 of the separator is at atmospheric pressure. If the fixed value is exceeded, the logic unit 22 immediately acts to accelerate the rotation of the pump 7, namely, to increase its throughput. During the return stage, the blood emanating from the vessel or bag 17, and from which a fraction of the plasma has already been removed, is filtered again by passage in contact with the membrane, and an additional fraction of its plasma is removed and passes into the downstream compartment 4 of the separator 2 and then into the bag 20. The blood then passes through the bubble detector 12. If bubbles are detected by the bubble detector 12, the logic unit 22 immediately stops the pumps 7 and 18 and, if necessary, acts on a clamp 26, or blocking device, which closes the conduit 5. During the return stage, the pressure sensor 13 performs a safety function in the sense that it is adjusted such that the pressure of the blood does not exceed a certain predetermined value. If this value is exceeded, for example, as a result of obstruction of the needle 1, the logic unit 22 immediately intervenes to stop the pump 7. During the return stage, the blood may pass through a conventional filter provided in the bubble detector 12, in order to prevent undesirable particles from being returned to the donor. This filter can, for example, move aside during the withdrawal stage, and it falls back onto a seat, provided in the bubble detector, during the return stage. The completion of the return stage is detected, for example, by an optical detector 27 provided along the conduit 5. When no more blood (from which a portion of the plasma has been removed) is passing through at the point where the detector 27 is located, the logic unit 22 intervenes to stop the return stage and to cause the equipment to revert to a withdrawal stage. Thus, the pumps 7 and 18 are stopped and are re-started such that they both rotate in the same direction, but in the opposite direction to that of the return stage, while the tourniquet 21 is inflated and the citrate pump 10 is activated. When, upon completion of a return stage, it is seen that the plasma bag 20 contains a sufficient amount of plasma, the operation is stopped completely.
In general, the throughput of the pump 10 is adjusted such that, during the so-called withdrawal stage, there is one volume of citrate per 8 volumes of blood, or preferably 1 volume of citrate per 16 volumes of blood, the ratio being selected by the user. This dilution ratio is advantageously obtained by bringing the speed of rotation of the pump 10 under the control of the speed of rotation of the pump 7.
It is readily apparent that a very high level of automation can be imparted to the apparatus according to the present invention. Thus, as is shown more paricularly in FIG. 2, the logic unit 22 for control and monitoring can be connected to a keyboard 28 and a display unit 29. Likewise, the logic unit 22 can be connected to a synoptic table (not shown), on which the location of any anomaly is indicated to the operator by a signal lamp, for example, at the same time as a sound signal is actuated. On the keyboard 28, it is possible to select the volume of blood which it is desired to circulate during the withdrawal stage (for example, 300, 350, 400, 450 cm 3 of blood) by pressing the corresponding key. It is also possible to select the volume of plasma which it is desired to withdraw during the session (for example, 400, 500 or 600 cm 3 ) by pressing the corresponding key. Thus, a device 30 is advantageously provided on the plasma bag 20 such as to give an instantaneous measurement of the volume (or the weight) of plasma withdrawn during a particular session, this device 30, which is in itself known, being connected to the logic unit 22. A key for the automatic actuation of the conduit 11, before the donor is injected, can also be provided on the keyboard 28. By pressing this key, the pump 10 starts, and it stops automatically when the citrate solution is detected, for example, at the junction 31 between the two conduits 11 and 5. The keyboard 28 can also be provided, for example, with a key for indicating, on the display unit 29, a measurement of the instantaneous volume of plasma in the bag 20 at any time, a key for indicating, on the display unit 29, a measurement of the flow of blood from the pump 7, a key for indicating a measurement of the time for which the present session has been running, and so on. The apparatus can comprise, linked to the logic unit 22 and the values displayed on the keyboard 28 concerning the volume of blood desired during the withdrawal stage and the total volume of plasma desired, an integrating system acting during the last withdrawal stage, such that the withdrawal volume makes it possible to obtain the desired total volume of plasma upon completion of the last return stage.
Numerous variations of the apparatus described above will be apparent to those skilled in the art. By way of example, the apparatus can include a collapsible balloon along the conduit 5 between the junction 31 and the clamp 26. This balloon then performs a dual safety function with the pressure sensor 13 in the sense that it blocks itself when the throughput of the pump 7 is greater than that of the vein, if the sensor has not functioned during the withdrawal stage. If appropriate, this collapsible balloon can be substituted for the sensor 13.
Likewise, the device 8 for injecting the anticoagulant may be omitted insofar as the interior of the needle 1, of the bubble detector 12 and of the conduits 5 and 16 is covered, for example, with a polymer based on polyether-urethanes containing heparin-modified ammonium groups, such as those described, in particular, in U.S. Pat. No. 4,046,725. If appropriate, the conduits 5 and 16 can be made of a polymer such as those described in the abovementioned U.S. patent, or of a mixture of polyvinyl chloride and a polyether-urethane containing heparin-modified ammonium groups, such as those mixtures referred to in published European patent application No. 12,701. The microporous membrane can also be prepared from a mixture of polymers according to European patent application No. 12,701.
Utilizing the apparatus such as shown in FIGS. 1 and 2 and described above, plasmapheresis operations have been carried out on a donor using, by way of example, a membrane filtration cell 2 having a total membrane surface area of 600 cm 2 and comprising two microporous membranes arranged face-to-face (forming the upstream compartment 3), between which the blood circulates. The membranes each have a length of 30 cm and a width of 10 cm and are strengthened by a web, as described more clearly below. The average thickness of the film of blood is 370 microns. The withdrawal device 1 is a needle having an external diameter of 1.65 mm and an internal diameter of 1.45 mm. The conduits 5 and 6 are made of polyvinyl chloride (PVC) and have an internal diameter of 3.5 mm. The conduit 11 is made of PVC and has an internal diameter of 0.9 mm. The pump 10 is a peristaltic pump (reference RP 04, marketed by Hospal), the said pump having a pump casing made of silicone.
The pumps 7 and 18 are peristaltic pumps (reference RP 01, marketed by Hospal), the said pumps having a pump casing made of silicone. The vessels 17 and 18 have a capacity of 1,000 cm 3 and are made of PVC.
The sensor 13 is a sensor marketed by National Semiconductor under the trademark LX 1801 GB, of which the displayed pressure is set at 10 mm of mercury during the withdrawal stage and of which the maximum pressure value is set at 100 mm of mercury during the return stage. The sensors 14 and 19 are sensors marketed under the same trademark and the same reference as the sensor 13. The sensor 14 is set at a maximum relative pressure of 80 mm of mercury for the withdrawal stage and at a minimum relative pressure of 10 mm of mercury during the return stage, while the sensor 19 is set at a relative pressure of 10 mm of mercury for the withdrawal stage and at a relative pressure of 80 mm of mercury for the return stage. Thus, the pressure of the blood in circulation is greater than the pressure of the plasma collected in the downstream compartment 4 of the membrane cell, which is at atmospheric pressure. The average trans-membrane pressure is equal to ##EQU2## of mercury.
During each withdrawal stage, the tourniquet is inflated to 60 mm of mercury and the flow of the citratetreated blood at the inlet of the separator is 85 ml/minute on average.
The membrane employed is a woven membrane obtained from a solution of polymer in an organic solvent, which is poured over a web rotating in contact with a strip having a very smooth surface. This solution comprises 8% by weight, in an N-methylpyrrolidone/glycerol mixture (70.8/21.2%), of an acrylonitrile/methyl methacrylate/sodium methallylsulfonate copolymer comprising 7.75% by weight of methyl methacrylate and 80 milliequivalents/kg of acid sites. This polymer has a specific viscosity of 0.3 at 20° C. in a dimethylformamide solution containing 2 g/liter.
The web used is a single-filament fabric made of polyethyleneglycol terephthalate, of which the mesh size is 75 microns, the filament diameter is 55 microns and the proportion of voids is 33%. The weight of this web is 55 g/m 2 .
The microporous woven membrane obtained has a thickness of 120 microns and its weight is 10 g of polymer per m 2 of dry membrane. The microstructure of the polymer phase of the membrane is spongy and uniform. Its porosity is 80%, the porosity being defined as the ratio (multiplied by 100) of the volume of the pores to the total volume of the membrane (polymer+pores).
The flow of water (treated with 1% of a surfaceactive agent) through this woven membrane is 4.5 ml/hour.
cm 2 . mm Hg. The latex rejection level of this membrane is:
(a) 5% to 15% for a latex having a particle size of 0.27 micron;
(b) 65% to 80% for a latex having a particle size of 0.4 micron; and
(c) 98% to 100% for a latex having a particle size of 0.64 micron.
Using the apparatus described above, and fixing a blood volume of 350 cm 3 during the withdrawal stage, a total of volume of 600 cm 3 of plasma to be collected, and a ratio of volume of anticoagulant solution/volume of blood of 1/16, during each withdrawal stage, the plasmapheresis operation was completed in 44 minutes after having carried out 6 withdrawal stages and 6 return stages.
The plasma collected is virtually non-cellular. It contains no contamination by red corpuscles and contains only 3,000 platelets per mm 3 . The protein concentration of the plasma is 57 g/liter.
The apparatus described above can quite obviously be used on animals (dogs, horses and the like), in particular for plasmapheresis operations.
In general, this apparatus can be used whenever it is desired to inject a subject (human or aminal) at only one point, with a simple needle (having only one internal channel), the liquid withdrawn from the subject, which is generally blood, being circulated firstly in one direction (withdrawal stage) and then in the opposite direction (return stage), in contact with a microporous membrane comprising a membrane filtration cell, there being means for controlling the desired pressures at which the blood enters and leaves the membrane cell during the two stages. Thus, with this apparatus, it is possible to remove elements from the blood in circulation, a first time during the withdrawal stage and a second time during the return stage, when the fraction of the blood which has not passed through the membrane is returned to the patent. Thus, the apparatus described above can be used for applications other than plasmapheresis. According to the separation characteristics (such as, for example, the level of rejection of sized latex particles) of the membranes used, it will thus be possible, for example, to remove only a portion of the proteins or only a portion of the other constituent elements of the plasma from the blood in circulation. It is thus also possible, with the apparatus described above, to perform haemofiltration sessions, for example, by means of re-injection with a substitute liquid, this re-injection being controlled by the amount of filtered liquid collected in the vessel 20.
The subject apparatus can also be used for plasmatic exchange operations, namely, by re-injecting a patient with a plasma in an amount equivalent to that which has been withdrawn from said patient, by means of a pump (not shown) and a conduit (not shown) connected, for example, to the conduit 5 between the inlet 6 of the separator and the sensor 14, the said pump operating during each return stage. The subject apparatus can also be used in peritoneal dialysis, in which case the tourniquet is no longer necessary.
To be suitable for all of the possible uses noted above, the subject apparatus can of course include variants as regards certain of its structural elements. By way of example, the pump 18, although used preferentially, may be replaced by equivalent means performing the same functions, namely, in particular, ensuring a certain maximum desired pressure during the return stage.
While the invention has been described in terms of various preferred embodiments, the skilled artisan will appreciate that various modifications, substitutions, omissions, and changes may be made without departing from the spirit thereof. Accordingly, it is intended that the scope of the present invention be limited solely by the scope of the following claims.
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Apparatus/process for the withdrawal and return of liquid materials from a donor source, comprising means for withdrawing whole blood from a mammalian donor; a membranous blood filtration cell which includes a membrane separator/filter, a compartment downstream therefrom for receiving a blood plasma fraction and a compartment upstream thereof for receiving a blood cellular component fraction; conduit means for communicating the withdrawal means and an inlet end of the upstream compartment; a collection vessel; conduit means for communicating an outlet end of said upstream compartment and said collection vessel; means for determining the volume of liquid material withdrawn from the donor source during a withdrawal stage; means for back-filtering and returning liquid material from said collection vessel to the donor source; a second collection vessel; and conduit means for communicating an outlet end of the downstream compartment and the second collection vessel.
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BACKGROUND
[0001] Tensioned belts are sometimes employed to transfer rotational power from a rotating shaft to another object, such as an item coupled to the belt or to a pulley. Having a high belt tension may be problematic in that the high belt tension may lead to motor heating and rapid wear of motor bushings for the motor driving the rotating shaft. Having a low belt tension may also be problematic in that slipping may occur between the belt and the shaft or pulley.
BRIEF DESCRIPTION OF THE DRAWINGS
[0002] FIG. 1 schematically illustrates an inkjet printing system in accordance with an example embodiment.
[0003] FIG. 2 is a side view of a portion of a carriage drive assembly, in accordance with an example embodiment.
[0004] FIG. 3 is a side view of a portion of a carriage drive assembly in accordance with another example embodiment.
DETAILED DESCRIPTION
[0005] FIG. 1 illustrates an example embodiment of a portion of an inkjet printing system 100 . Inkjet printing system 100 includes an inkjet printhead assembly 102 , an ink supply assembly 104 , a carriage assembly 106 , a media transport assembly 108 , and an electronic controller 120 . Inkjet printhead assembly 102 includes a printhead that ejects drops of ink through a plurality of orifices or nozzles 122 toward a print medium 126 so as to print onto print medium 126 . Print medium 126 may comprise any type of suitable media, such as, but not limited to, paper, cardstock, transparencies, and the like. In some embodiments, nozzles 122 are arranged in one or more columns or arrays such that properly sequenced ejection of ink from nozzles 122 causes characters, symbols, and/or other graphics or images to be printed upon print medium 126 as inkjet printhead assembly 102 and print medium 126 are moved relative to each other.
[0006] Ink supply assembly 104 supplies ink to printhead assembly 102 and includes a reservoir 130 for storing ink. As such, ink flows from reservoir 130 to inkjet printhead assembly 102 . In some embodiments, inkjet printhead assembly 102 and ink supply assembly 104 are housed together in an inkjet print cartridge or pen as defined by dashed line 140 . In other embodiments, ink supply assembly 104 and/or reservoir 130 are separate from ink printhead assembly 102 and supply ink to inkjet printhead assembly 102 from an off-axis position. In some embodiments, the reservoir 130 of ink supply assembly 104 may be removed, replaced, and/or refilled.
[0007] Carriage assembly 106 positions inkjet printhead assembly 102 relative to media transport assembly 108 , and media transport assembly 108 positions print medium 126 relative to the inkjet printhead assembly 102 . Thus, a print zone 132 is defined adjacent to nozzles 122 in an area between inkjet printhead assembly 102 and print medium 126 . In a scanning-type printing system, carriage assembly 106 moves inkjet printhead assembly 102 relative to media transport assembly 108 to scan print medium 126 . As such, carriage assembly 106 includes a carriage and a carriage drive assembly, as described below. Thus, in some embodiments, the entire print cartridge 140 is positioned in and supported by the carriage and the carriage drive assembly moves print cartridge 140 , including inkjet printhead assembly 102 , back and forth across print medium 126 . In other embodiments, the printhead assembly 102 is positioned in and supported by the carriage while the ink supply assembly 104 and reservoir 130 are not carried by the carriage.
[0008] Electronic controller 120 communicates with the inkjet printhead assembly 102 , carriage assembly 106 , and media transport assembly 108 . Electronic controller 120 receives data 122 from a host system, such as a computer, and may include a memory for temporarily storing data 122 . Data 122 represents, for example, a document and/or file to be printed. As such, data 122 forms a print job for inkjet printing system 100 and may include one or more print job commands and/or command parameters.
[0009] Electronic controller 122 provides control of inkjet printhead assembly 102 including timing control for ejection of ink drops from nozzles 122 . Electronic controller 122 also provides control of carriage assembly 106 including timing and a direction of movement relative to print medium 126 . As such, electronic controller 120 defines a pattern of ejected ink drops which form characters, symbols, and/or other graphics or images on print medium 126 .
[0010] FIG. 2 illustrates a portion of an example carriage assembly 200 that may be used in an imaging device, such as the inkjet printing system 100 . As shown, the carriage assembly 200 includes a carriage 202 , a drive pulley 204 , an idler pulley 206 , and a belt 210 disposed about the pulleys 204 , 206 . The drive pulley 204 and the idler pulley 206 are shown in this embodiment as being spaced from each other by a fixed distance and generally disposed in the same plane. The drive pulley 204 is coupled to a motor (not shown) by shaft 208 in a manner than permits the motor to transfer rotational power to the drive pulley 204 via the shaft 208 . The motor thus drives the drive pulley 204 in different directions in response to control signals received from a suitable controller, such as the electronic controller 120 ( FIG. 1 ).
[0011] The belt 210 comprises an elongated flexible member and, in some embodiments, comprises a timing belt. In the embodiment shown in FIG. 2 , the belt 210 includes teeth 214 formed therein and sized to engage grooves (not shown) formed on the periphery of the pulleys 204 , 206 . In alternative embodiments, the belt 210 may comprise a flat belt disposed about pulleys without grooves formed therein. The belt 210 , in alternate embodiments, may comprise an endless belt.
[0012] The belt 210 may be formed any of a variety of suitable materials, including, for example, a nylon fabric. In some embodiments, the belt 210 does not significantly stretch axially under loads common to the assembly 200 .
[0013] FIG. 2 also illustrates the belt 210 being split and having ends 216 , 218 . The carriage 202 is elastically or resiliently coupled to the belt 210 via tensioning members 226 , 228 . The tensioning members 226 , 228 may comprise springs or other suitable elastic tensioning members. In some embodiments, the tensioning members 226 , 228 may comprise, for example, leaf springs, coil springs, wave springs, or the like and serve to tension the belt 210 .
[0014] The carriage 202 is shown as being adapted to carry and support a printhead assembly 222 therein. The printhead assembly 222 may be configured and may operate in a manner similar to the printhead assembly 102 described above.
[0015] The tensioning members 226 , 228 serve to tension the belt 210 and to filter vibrations from the belt 210 , according to some embodiments. Pursuant to some embodiments, vibrations, such as those that may originate at the motor may be transferred to the belt 210 via the shaft 208 and the pulley 204 . The tensioning members 226 , 228 , in some of these embodiments may serve to at least partially reduce, or dampen, these vibrations such that these vibrations have less effect on the carriage 202 and printhead assembly 222 .
[0016] In the configuration shown in FIG. 2 , the tensioning members 226 , 228 act substantially independently and provide for similar belt tensions regardless of the direction of motion of the belt 210 . Since the tension of the belt 210 is not significantly dependent upon the direction of motion of the belt, low belt tensions can be employed. These low belt tensions may also permit usage of a smaller motor to drive the pulley 204 .
[0017] The tensioning members 226 , 228 may be coupled to the carriage 202 by any of a variety of suitable ways. For example, in some embodiments the tensioning members 226 , 228 may be coupled to the carriage 202 by coupling an end of each of the tensioning members 226 , 228 to the carriage 202 by a suitable respective fastener (not shown). Clips, adhesives, or other coupling members or materials may alternatively be used to couple the tensioning members 226 , 228 to the carriage 202 .
[0018] Similarly, the tensioning members 226 , 228 may be coupled to the belt 210 by any of a variety of suitable ways. The tensioning members 226 , 228 may be coupled to the belt 210 at or adjacent the ends 216 , 218 . In some embodiments, the tensioning members 226 , 228 are coupled to the ends 216 , 218 of the belt 210 . Further, as shown in FIG. 2 , the carriage 202 is substantially centered between the tensioning members 226 , 228 .
[0019] In an example inkjet printing implementation, the carriage 202 may have a mass in the range of about 20 grams to 1 kilogram and may nominally have a mass of about 90 grams. Moreover, in this example embodiment, the tensioning members 226 , 228 may have a spring constant rate of about 0.75 Newton/mm. The spring constant rate may be in the range of about 0.1 to 7.5 Newton/mm in other inkjet printing embodiments. Further, the belt 210 may have a tension of about 2.5 Newtons. In other inkjet printing embodiments, the belt 210 may have a tension in the range of about 1 to 25 Newtons. Linear acceleration of the carriage 202 may be about 1.2 g in this example embodiment. In other inkjet printing embodiments, the linear acceleration of the carriage may be in the range of about 0.5 to 5.0 g. It should be understood that embodiments of the present subject matter may be outside these example ranges. These ranges are provided by way of example and are non-limiting. Further, embodiments of the present subject matter may be used in applications other than inkjet printing.
[0020] FIG. 3 illustrates a portion of an example carriage assembly 300 that may be used in an imaging device, such as the inkjet printing system 100 . The carriage assembly 300 is configured the same as the carriage assembly 200 described above, except as follows. The carriage 202 is coupled to the belt 210 via leaf springs 326 , 328 . The leaf springs 326 , 328 may be formed of sheet metal or other suitable material and serve to tension the belt 210 .
[0021] Although the present disclosure has been described with reference to example embodiments, workers skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope thereof. For example, although different example embodiments may have been described as including one or more features providing one or more benefits, it is contemplated that the described features may be interchanged with one another or alternatively be combined with one another in the described example embodiments or in other alternative embodiments. The present subject matter described with reference to the example embodiments and set forth in the following claims is manifestly intended to be broad. For example, unless specifically otherwise noted, the claims reciting a single particular element also encompass a plurality of such particular elements.
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Several embodiments of apparatus and methods are disclosed. One or more of the disclosed example devices includes a flexible member having first and second tensioning members.
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FIELD OF INVENTION
The invention is directed to a system for shredding scrap materials located in a flume.
DESCRIPTION OF RELATED TECHNOLOGY
In the course of a machine operation, scrap material, generally in the form of helical or other shaped metal chips are generated. The chips, referred to as wet chips, also are coated with a lubricant that is applied to the metal material during the course of a machining operation. Often, it is required to transport the scrap material from one or more machine locations to a shredder station where undesired bales of scrap material or other undesired large pieces of material are shredded. Following shredding, the scrap material or wet chips pass to a chip processing system where the wet chips are centrifuged during which lubricant is separated from the chips. The separated fluid is recaptured while the dry chips are blown to a dry chip container or collection site.
There are various systems for conveying wet chip material from a machine center (a center generally comprising one or more machine stations). In some instances, mechanical conveyors are utilized to transport the scrap material from a machine center to a shredder. In other instances, important to the present invention, the scrap material is transported in a flume from the machine center to a shredder. A flume is defined as a fluid or liquid conveyor system in which wet chips are transported through a fluid flow to at least a shredder station.
Heretofore, systems incorporating a flume as a means for conveying wet chips, employed a trough disposed in the floor of a building or structure. Liquid coolant was pumped through the trough. As wet chips passed from a machine discharge chute into the trough, they mixed with the liquid and were pumped along the length of the trough to a receiving tank. There the wet chips would drop on to a conventional drag filter mechanical conveyor partially disposed in the tank. The wet chips would be mechanically conveyed to a wet chip centrifugal separator processing system where fluid would be removed from the chips and recirculated back into the system while dry chips would be directed to a dry chip collection.
While this wet chip transport system is satisfactory for a number of applications, it is not particularly suitable in all instances. In some situations, it is not desired or convenient to place a trough in the floor of a building. It has been found that environmental concerns exist in properly maintaining unwanted debris from building up in the trough. Further, once a trough is formed in a flume transport system, it becomes more difficult to later relocate a machine center or flume transport.
Further, it has been found that, in some instances, as the wet chips travel in the flume, helical scrap pieces intertwine with one another forming bales of material. The bales can clog the pump which pumps the liquid and wet chips in the flume generally at a rate of about five to ten feet per second. Accordingly, a shredder is incorporated in the system ahead of the pump station for the purpose of shredding wet chip bales and any other undesired material into smaller pieces. Previously, the shredder was positioned at a location outside the trough. The wet chips would enter the shredder and, following a shredding operation, shredded wet chips were dropped or reintroduced into the flume and thereafter transported to the chip processing or other workstation(s).
What is desired is to have a wet chip transport system in which the flume is not located in the floor of a structure. Rather, the trough is positioned above ground so that, if necessary, the trough can be disassembled and a new trough positioned as desired thereby allowing flexibility in locating wet chip flume systems.
Additionally, it is desired to have a shredder assembly disposed directly in the trough path in order that wet chips need not be diverted from the flume. It is desired to have the wet chips in the flume pass directly into a shredder without the wet chips having to be removed from the liquid containing trough for shredding purposes.
SUMMARY OF INVENTION
The invention disclosed and claimed herein serves to obviate the above identified problems and achieve the above stated desires while at the same time achieving proper wet chip flow in the flume. Shredding of wet chips can occur without removing wet chips or bales of wet chips from the flume during shredding. The shredder is positioned within the trough whereby bales of wet chips or other unwanted large metal pieces pass through the shredder whose shredding mechanism is at least partially disposed in and traverses the trough. Further, the trough containing the fluid coolant preferably is positioned above ground.
These and other features, advantages, and objects of the present invention will be further understood and appreciated by those skilled in the art by reference to the following specification, drawings and claims.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a schematic elevation view of a first embodiment of a shredder assembly disposed in a trough of a flume system of the present invention;
FIG. 2 shows a partial perspective view of the embodiment of FIG. 1 with the combs and sizing members of the shredder disposed in a trough of the present invention and the shredder shaft is positioned substantially parallel to the longitudinal axis of the trough in an inline position with the fluid/material flow;
FIG. 3 shows an elevation view of the shredder disposed in the trough shown in FIG. 1 with the trough flange removed;
FIG. 4 shows a plan view of the shredder of FIG. 3 with the drive assembly removed;
FIG. 5 shows a side elevation view taken along the right side of FIG. 3 with the drive assembly removed;
FIG. 6 shows a side elevation view taken along the left side of FIG. 3 with the drive assembly and shredder faceplate removed for illustration; and
FIG. 7 shows a second embodiment of the shredder assembly disposed in a trough with the shredder shaft positioned in a radial position substantially perpendicular to both the longitudinal axis of the trough and the flow.
DETAILED DESCRIPTION
Referring to the drawings, FIG. 1 illustrates a schematic view of a machine center 10 where wet chips are generated by a lathe or other type of metal working machine. Wet chips pass from the machine center through discharge chute 11 where the wet chips drop into a trough 12 containing liquid coolant. The wet chips along with coolant fluid disposed in trough 12 travel along the length of trough 12 , the wet chips and fluid being pumped along in the direction of the longitudinal axis of the trough by means of a conventional pump assembly 13 .
Prior to the wet chips entering pump assembly 13 , the wet chips pass through shredder 14 , which has a shredder assembly 15 , at least a portion of which is disposed in the trough. As wet chips, which sometimes cling together in the form of stringy bales, pass into shredder assembly 15 , the wet chips or bales thereof, as well as other unwanted metal objects, are shredded into individual wet chip pieces which are capable of passing through pump assembly 13 .
Upon exiting shredder assembly 15 , the shredded wet chips pass through pump assembly 13 where the wet chips and coolant then are pumped through conduit 16 into collection tank 17 . Here the coolant fluid is recovered as the coolant passes into conduit 19 . The coolant is pumped through pump assembly 20 into coolant conduit 21 where it then is recovered either at machine center 10 for reuse as a coolant or in a suitable collection tank, not shown. The shredded wet chips are conveyed by means of a suitable mechanical conveyor 22 , such as a drag/filter conveyor, into a conventional parts separator and centrifugal separator, neither of which is shown.
FIG. 2 illustrates shredder assembly 15 disposed within trough 12 so that as the wet chips travel along trough 12 , they will automatically engage shredder assembly 15 . In this manner, any wet chips which have formed into bales or the like will pass through shredder assembly 15 without need of removing the wet chips or bales thereof from the trough for shredding purposes.
As illustrated in FIGS. 1, 2 and 3 , shredder 14 includes motor 25 mounted on motor bracket 26 . Drive shaft 27 extends from motor 25 with drive sprocket 28 mounted on the outboard end of shaft 27 . Trough 12 is illustrated as including a U shaped base 32 with two ends terminating as spaced substantially vertical tough side walls 33 , 34 . Side wall 33 is flanged at the top to provide flange 37 while side wall 34 is flanged at the top to provide flange 38 . Shredder housing face plates 40 , 41 , shown in FIG. 3, serve to enclose shredder sizing members and combs, and preferably are welded at their edges to the side walls of trough 12 .
Bearing assembly 42 is seated in an opening in face plate 40 while bearing assembly 43 is seated in an opening in face plate 41 . A rotatable drive shaft 44 is seated for rotation in bearings 45 , 46 of bearing assemblies 42 , 43 . Sprocket 48 is attached to one end of drive shaft 44 and is connected to sprocket 28 through a suitable roller chain, not shown.
Drive shaft 44 in this particular shredder assembly embodiment is positioned so that it extends in the direction of the longitudinal axis of trough 12 and is substantially in line with the flow of material and fluid in trough 12 .
Referring to FIGS. 2-6, a plurality of spaced sizing members or wheels 50 are fixedly seated on rotatable shaft 44 . Each sizing member 50 includes a central hub 51 . A plurality of spaced sizing arms 52 extend outwardly from hub 51 . As shown in FIG. 2, four sizing arms 52 extend outwardly from hub 51 , each arm being positioned at approximately 90° to an adjacent arm.
As shown in FIGS. 2, 3 , 5 and 6 adjacent sizing members 50 are located combs 54 , each comb being formed of a metal plate. There are three different size comb sets 55 , 56 , 57 each set preferably comprising three like combs 54 . Combs 54 each comprise a substantially flat metal plate. The majority of the combs are sandwiched between adjacent sizing members 50 . Each side edge of a comb 54 preferably is contoured to substantially conform to an adjacent inner surface of trough side members 33 and 34 . Illustratively, comb 54 includes a comb side edge 58 adapted to abut or be contiguous to the inner surface of trough side member 33 . Comb side edge 59 is adapted to abut or be contiguous to the inner surface of trough side member 34 .
Combs 54 are each flanged at 60 , 61 . Comb flange 60 as shown in FIG. 6, is adapted to seat on trough flange 38 while flange 61 is adapted to seat on flange 37 .
Each comb 54 includes a pair of fingers 62 , 63 . Finger 63 depends downward (FIG. 6) the same distance for each comb in each comb set; however, fingers 62 depend downward varying distances for each comb set. Comb fingers 62 extend further downward for the combs of set 57 than the comb fingers for set 56 . Similarly, comb fingers 62 of comb set 56 depend further downward than the fingers for comb set 55 .
Each comb 54 as shown in FIGS. 2 and 6, also includes recesses 65 , 66 in the top edge of the comb. A pressure plate 67 is adapted to seat in comb recesses 65 while pressure plate 68 is adapted to seat in comb recesses 66 . Bolts 70 , 71 extend through respective openings located at the opposite ends of pressure plate 67 while Bolts 72 , 73 extend through openings located at the opposite ends of pressure plate 68 . Each bolt extends downwardly through a corresponding opening in a trough flange 37 or 38 . A compression spring 74 is mounted on each bolt and retained in place by a suitable washer and nut assembly 75 . When nut assemblies 75 are tightened, combs 54 are maintained in place under spring pressure.
In operation, wet chips, often in the form of relatively long flexible helical strips are discharged from machine center 10 into fluid located in trough 12 of a flume. The wet chips often form into bales of material. As the bales of wet chips and fluid travel along in trough 12 , upon actuation of pump in assembly 13 , the materials approach shredder 14 whose combs 54 and sizing members 50 are positioned at least partially in the trough liquid directly in the path of the bales and chips. As the bales and chips enter shredder assembly 14 , actuation of the shredder causes sizing members 50 to rotate on shaft 44 relative to combs 54 thereby engaging the combs in a scissors like cutting operation to shred the bales and wet chips relatively into small shredded pieces. The shredded wet chips and coolant fluid then continue on in the trough through pump assembly 13 and conduit 16 where they are deposited in collection tank 17 . The coolant then is pumped out of tank 17 via pump 20 . The coolant passes through conduit 21 and is recycled for use as a machine tool coolant and/or wet chip transfer medium. Simultaneously, the shredded wet chips transfer onto conveyor 22 where the wet chips are transported to a wet chip collection site or a wet chip centrifugal separator system where the wet chips are centrifuged and dry chips are recovered.
While the particular embodiment of the invention has been illustrated showing the shredder combs and sizing fingers disposed in a trough, it is appreciated the shredder could be made in which the shredder contains a separate trough section adapted to seat within a trough. In this embodiment, the shredder and trough section could be assembled at one location and then shipped to a job site when the shredder and trough section would be installed within the trough already in place at the site or the trough section could be joined to other trough sections at the job site.
Similarly, while the trough has been shown to include a preferred U-shaped base, it is appreciated that the trough, if desired, could utilize another shape, e.g., box-like, and the fingers and combs formed to fit properly within such other shape.
FIG. 7 shows a further embodiment of the invention. In this particular embodiment, the shredder assembly is located in a radial position so that rotatable shaft 44 and the sizing members and combs are positioned substantially perpendicular to the fluid flow in the trough, unlike the embodiment of FIG. 1 where shaft 44 is positioned in line with the fluid flow in the trough. In the embodiment of FIG. 7, sizing members 50 are fixed for rotation on shaft 44 . Comb members 54 have flange members 60 , 61 which seat on spaced cross members which extend over the trough. One end of each cross member seats on trough flange 37 which the remaining cross member end seats on trough flange 38 . Comb members 54 are disposed between sizing members 50 and resiliently maintained in place on the cross beams utilizing the same type spring assembly as described above with respect to the embodiment of FIG. 1 .
The foregoing detailed description is given for clearness of understanding only, and not unnecessary limitation should be understood therefrom as modification within; the scope of the invention will be apparent to those skilled in the art.
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A shredder system and method in which wet chips travel in a flume. The wet chips in a fluid transport travel in a trough to a shredder having a shredder assembly made up of a plurality of combs that cooperate with a plurality of sizing members with at least a portion of the combs and members being positioned within the trough. The trough preferably is located above ground and the wet chips can be shredded in the trough without removal of the wet chips form the trough.
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BACKGROUND OF THE INVENTION
The present invention relates to a method for expanding perlite. The expanded product of the invention has advantageous properties for numerous uses and particularly as a filteraid.
Perlite is a silicious material of volcanic origin, which has a silica content greater than 65% by weight and a combined water content of about 2 to 5% by weight. In addition to silica and water, perlite contains variable quantities of compounds of aluminum, sodium and potassium among others.
When perlite in the form of particles is introduced into a flame, it is subjected to expansion, or "bursts" into a material of lighter weight and density. Generally speaking, the expansion or "bursting" is observed when perlite is heated to a temperature on the order of 760° to 1315° C., according to the origin of the perlite and its particle size. For purposes of the present invention, temperatures on the order of about 870° to 1150° C. are used.
As a general rule, unexpanded perlite ore has a density on the order of about 0.96 to 1.28 kg/dm 3 while after expansion, this density is on the order of about 0.032 to 0.16 kg/dm 3 .
Various techniques are known for expansion of perlite and these conventional methods have met with varying degrees of success. By reason of the continuing rise in demand for expanded perlite of better quality at a lower cost, it is desirable to substantially increase the capacity of known expansion installations, without a substantial investment of capital.
One object of the present invention is to considerably increase the production of expanded perlite and also to improve the quality thereof.
Another object is to provide a method yielding products with improved water-permeability.
Still another object of the invention is to provide a method reducing normal losses to a minimum and diminishing the quantity of floating material produced.
Additional objects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention. The objects and advantages of the invention may be realized and attained by means of the combinations particularly pointed out in the appended claims.
SUMMARY OF THE INVENTION
To achieve the foregoing objects and in accordance with the purpose of the invention, as embodied and broadly described herein, the present invention comprises a method of expanded unexpanded particulate perlite.
The unexpanded particulate perlite is mixed with a combustible gas, air and oxygen. The amount of combustible gas in the mixture is on the order of 1 volume of combustible gas for 2 to 6 volumes of air. Oxygen is introduced to the mixture in an amount comprising 1.5 to 16 weight percent of air in the mixture. The mixture is ignited, effecting combustion of the combustible gas which expands substantially all of the unexpanded particulate perlite.
Preferably, the combustible gas is natural gas which is included in the mixture in an amount on the order of 1 volume of natural gas for 2 to 4 volumes of air. In this preferred method, the oxygen is introduced to the mixture in an amount comprising 2.5 to 10 weight percent of air in the mixture. It is also preferred that the unexpanded particulate perlite have a particle size less than 575 microns and a particle size distribution of:
297 microns--20 to 30%
150 microns--30 to 50%
100 microns--5 to 20%
74 microns--5 to 12%
less than 74 microns--5 to 15%
DESCRIPTION OF THE PREFERRED EMBODIMENTS
In disclosing the invention set out in the appended claims, reference will be made to preferred methods of practicing the invention.
The unexpanded perlite used in the present invention is ground, generally speaking, to a particle size of less than 2.5 cm and is dried to a moisture content of less than 0.2% by weight, by treatment at about 26°-94° C. for 10 minutes. This constitutes a method frequently used in practice.
This conventionally treated material is then ground more finely and subjected to sorting or classification. Preferably, the starting material used in the processing according to the invention should pass through a screen with a mesh opening of 595 microns. It is preferable that the greater part of the material be retained on a screen with a mesh opening of 100 microns, a large part being retained on a screen with openings of 297 or 150 microns. It is advantageous, in order to achieve maximal results according to the invention, that appreciable quantities of the material be of a size smaller than 74 microns, for examples 2 to 20%. A typical analysis of the particle sizes (A.S.T.M. E 11-61) of a starting material which we can use appears as follows:
595 microns and less--100%
297 microns--20 to 60%
150 microns--20 to 60%
100 microns--2 to 20%
74 microns--2 to 20%
less than 74 microns--2 to 20%
A particularly advantageous starting material will have the following approximate percentages of screen retention:
297 microns--20 to 30%
150 microns--30 to 50%
100 microns--5 to 20%
74 microns--5 to 12%
less than 74 microns--5 to 15%
The unexpanded perlite is fed to the expansion apparatus by conventional methods, and it is introduced therein at such a rate that practically all of this perlite will undergo an expansion under the conditions which will be explained more completely below.
According to the ordinary methods of expansion of a perlite, air is mixed with a combustible gas, such as natural gas, and the mixture fed to the burner of the expansion apparatus. The flow of rates and the quantities of air and natural gas (principally methane) vary according to the ordinary requirements of the known methods, and characteristics of the burner and the expansion apparatus.
It is frequently desirable, in order to direct and control the process, and to be able to achieve the advantages of a heat exchange, to augment the initial air feed by an additional or secondary air feed. If this technique is used, ordinarily secondary air is fed at a point in the expansion apparatus different from the feed point of primary air. In the conventional expansion apparatus of the vertical type, a secondary air feed is ordinarily introduced at a point lying well above the position of the burner.
In the process according to the present invention, natural gas is mixed with primary air and oxygen, and this mixture is fed to the burner. Other combustible gases such as propane, butane, etc. can also be satisfactorily used in the process. One critical characteristic of the present invention is the quantity of oxygen which is added in relation to the primary air feed. On the basis of percentages by weight, it is necessary to feed oxygen to the combustible gas mixture going to the burner at the rate of about 1.5 to 16% relative to the air present in this gas mixture. It is more particularly preferable to use from about 2.5 to about 10% oxygen relative to the quantity of air existing in the initial gas mixture.
Another characteristic which is vital to the success of the process according to the invention is the ratio of combustible gas to primary air fed to the burner. This ratio, when given in volumes, is on the order of 1 volume of combustible gas for 2 to 6 volumes of normal air and preferably 1 volume of combustible gas for 2 to 4 volumes of normal air.
Secondary air is preferably fed into the mixture to insure complete combustion of the combustible gas. This secondary air can be introduced in any conventional manner known to those skilled in the art. The embodiment of the invention disclosed herein provides for the use of a vertical expansion apparatus in which the secondary air is introduced into a double or tripe-walled structure to be pre-heated by heat exchange. The pre-heated secondary air is then preferably introduced into the burner zone close to its base.
Preferred results were obtained according to the method of the invention, by using about 25% normal primary air, necessary for the total combustion of the natural gas used, with an introduction of oxygen in quantities varying from 1.5 to 16% by weight relative to the quantity of primary air used.
Particular success has been experienced using a vertical expansion apparatus, employing a mixture of:
235 m 3 /hours of natural gas;
540 m 3 /hour of normal primary air; and
25 to 60 m 3 /hour of oxygen.
To this mixture 1680 m 3 /hour of secondary air was introduced at the base of the burner.
An additional successful embodiment of the invention used a vertical expansion apparatus employing a mixture of:
100 m 3 /hour of natural gas;
230 m 3 /hour of normal primary air; and
25 m 3 /hour of oxygen.
Secondary air was introduced to this embodiment at the rate of 1680 m 3 /hour at the base of the burner.
A high yield of product was obtained from this latter embodiment which constituted a filteraid with improved air permeability and low weight. The product also exhibited a low filter cake density and yielded a minimum quantity of floating material and waste.
This same embodiment was used under identical conditions except that oxygen was not added to the mixture of natural gas and normal primary air. The operation of the process in this manner resulted in the production of only 75% of the quantity of material produced by operation of the present invention as previously described.
Typical yields obtained with the use of the method of the invention are compared with yields obtained with conventional techniques as follows:
______________________________________ Conventional Method of theProduct Technique Invention______________________________________Flow at medium speed 92% 96%Flow at medium speed 90% 95%Flow at high speed 76% 85%Flow at high speed 70% 90%______________________________________
In addition to the noted improvements in yield, rejected material is reduced by at least 50% using the process of the invention. The products described in the preceding table relate to the desired primary product. Corresponding small quantities of low yield filteraid material were also collected according to known methods.
In addition to the advantages of the invention disclosed above, it will be evident to one skilled in the art that the invention, by increasing the effective capacity of the present apparatus, reduces depreciation of such apparatus. In addition, the present invention also reduces the cost of operation of such processes, even in the face of the increasing cost of natural gas.
The invention has been disclosed in terms of preferred embodiments and it should be understood that the scope of the invention is not to be limited thereto. The scope of the invention is to be determined by the appended claims as read in light of the preceding disclosure.
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Particulate unexpanded perlite is introduced to an expansion apparatus that utilizes the combustion of a gas as a source of heat. The particulate perlite is mixed with a combustible gas, air from a first source and oxygen and thereafter introduced to a burner section. The amount of oxygen introduced is in the range of from 1.5 to 16 weight percent of the amount of air introduced. The amount of combustible gas in the mixture is related to the air input from the first source, being in the range of 1 volume of combustible gas to 2 to 6 volumes of air.
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SUMMARY OF THE INVENTION
In the prior art, notching woven fabric, pliable or other thin material required that two separate, angular intersecting, cuts be made in two separate cutting operations. It is an object of my invention to create a hand operated notch cutting tool that will cut a complete notch in a single cutting action.
In the drawing, the single FIGURE illustrates a perspective of the notch cutting tool.
DESCRIPTION OF THE INVENTION
The tool is fabricated from a single blank of stock tool material. It is shaped in manufacture to feature an upper tool element 2 over a lower tool element 3 with space 4 between the two elements to place therein the workpiece material that is intended to be notched. The end of the lower tool element is tapered as indicated at 13 in a manner to facilitate sliding the lower tool element underneath workpiece material that may be at rest on a flat surface; however, be it known that the tool may be efficiently operated in any direction or plane and no mobility or directional limitation is imposed on either the tool or the workpiece material. The lower tool element has a portion of tool material removed in manufacture leaving in it's place an aperture 5 a part of which is in form of a notch shape, said shape being triangular. The edges 6 and 7 of the aperture that define the notch shape are then beveled to create sharp cutting edges. Indices 8 are etched on the upper surface of the lower tool element to aid in the alignment of the workpiece material permitting the operator to control the size of the notch that is cut in the workpiece material when the tool is operated. Located above the lower tool element is an upper tool element 2 with space 4 between the upper and lower tool elements to place workpiece material to be notched. The periphery 9 of the upper tool element is formed in the notch shape, said shape being triangular, that features at it's apex 10 a very sharp point for the purpose of penetrating through workpiece material, when the tool is operated, at the point on the material that the operator selects as the notch apex, thence passing through the apex 1 of the notch aperture in the lower tool element. The upper tool element edges 11 and 12 are beveled to create sharp cutting edges that extend rearwardly from the sharp point and are designed to coact with the cutting edges of the lower tool element to provide a shearing cut. Upon operating the tool in the notch cutting process a relative coaction is commenced between the upper and lower tool elements whereby the sharp point of the upper tool element penetrates through the workpiece material continuing to enter and pass through the apex of the aperture in the lower tool element wherepon the sharp cutting edges of the upper tool element commences to move downward between and presses laterally against while sliding alongside the sharp cutting edges of the lower tool element thereby gripping the workpiece material caught therebetween and in continuation severs the notch plug from the workpiece material by scissors type cuts in a single action of the tool.
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My invention relates to a hand operated notch cutting tool that will notch woven fabric, pliable or other thin material.
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This application is a continuation-in-part of application Ser. No. 807,331, filed 12/10/85, now U.S. Pat. No. 4,664,400, issued 5/12/87.
BACKGROUND OF THE INVENTION
The present invention pertains to new and useful improvements in velocipedes, and may be embodied in two-wheeled or three-wheeled exercise or recreational cycles propelled by the rider's muscular forces.
More particularly, the cycle or vehicle is drivable by means of pitman rods acting upon a crank by the coordinated action of the occupant's body weight, arm force and footleg action.
The novel two or three-wheeled vehicle is operated by the occupant-rider in a manner similar to the action of rowing a boat. This is highly desirable, because it is well known that the exercise by a human being when rowing a boat is a complete exercise in which most of the principle muscles of the body make a concerted effort and are thereby substantially fully exercised.
SUMMARY OF THE INVENTION
It is an object of the invention to provide a cycle construction to bring into action all of the muscles of the rider's body, and focus them in the propulsion of the vehicle.
Another object of the invention is to assemble the parts of the vehicle so that one set of the rider's muscles are rested while another set reciprocally performs the work of propelling the vehicle, and vice versa.
A still further object is to devise a construction whereby the cycle will accommodate itself to different positions assumed by the rider, to insure comfort.
Toward these ends, the invention contemplates providing exercise for the rider's hands, arms, back, legs, and upper body, while utilizing the extension and contraction actions of these organs to propel the vehicle forward.
In particular, the invention relates to a cycle of the velocipede type having as a system or propulsion, the reciprocating motion of the rider's hands, arms, legs and body in place of the system operated by the feet and legs used in the 360 degree cycling or pedalling process for propelling a vehicle forward.
The novel vehicle and system of propulsion of the present invention is based firstly upon the coordinated simultaneous extension action of both legs in combination with body-weight depression of the seat, while pulling the handle bar towards the body. The first coordinated action of body weight, arm pull and leg extension acts to push a lever connected to a lengthy crank rotatably connected to the rear wheel.
Propulsion of the present invention is based secondly upon the coordinated simultaneous standing action of both legs in combination with removing the body-weight from the seat, while pushing the handle bar forward away from the body, thereby allowing the seat to ascend to its original height. This second coordinated action operates to pull a lever connected to the short crank rotatably connected to the rear wheel.
The novel features of the invention consists of the construction and combination of parts hereinafter set forth and described.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side perspective view of the vehicle in partial cut away, showing the structure and arrangement.
FIG. 2 is a side perspective view showing the points around which the parts of the vehicle pivot.
FIG. 3 is a side elevational view showing the seat at its highest elevation, the handle bar in the forward-most position, and the foot-treadle in the lowest position to accomodate a standing occupant.
FIG. 4 is a side elevational view showing the seat, handle bar, and foot-treadle at points after commencing the coordicated action of sitting, pulling the handle bar, and extending the legs.
FIG. 5 is a side elevational view showing the seat fully depressed, the handle bar pulled in the utmost position towards the body, and the foot-treadles extended in the utmost position towards the front wheel of the vehicle.
FIG. 6 is a side elevational view showing the positions of the seat, handle bar, and foot-treadles after commencing the coordinated action of pushing the handle bar forward to begin assumption of the standing position, and allowing the seat to ascend towards its highest elevation.
FIG. 7 is an enlarged view of the curved fork direction controlling means at the power-lever-handle bar base.
FIG. 8 is an enlarged view of the raised hinged assembly means connecting the upper vehicle frame portion and the base area of the power lever.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to FIG. 1 of the drawings, it is seen that the vehicle of the present invention comprises a frame indicated in general at 1, having a lower frame portion 2 which extends rearwardly in forked mounting relationship with rear wheel axle 4 of cranks 8 and 9, and upper frame portion 3 which extends in a rotatably connected manner to the A frame-mounting column 5, having downwardly projecting forked arms 6, through which treadle-shaft crank means extend, and onto which treadles 7 are solidly or non-rotatably attached.
In order for the occupant to combine the power derived from his weight with that from his muscular forces, connecting-rods or pitman 10 and 11 attach treadle-lever 12 and seat-mounting column lever 13 respectively to short crank 8 and long crank 9.
Main shaft or axle 4 rotates in harmonious accord due to the movement of the treadle-shaft crank 14, which is connected to treadle-lever 12 by a pitman, and the combined handle bar-seat movement through their connection with the seat-mounting column lever 13. The angles through which the ascent and descent of the seat-mounting column swings does not always align or cause synchronizing of the push on the long crank from the seat descent with the pull on the short crank from the treadle extension. Such deviation in the lack of alignment or synchronization is compensated for by treadle-shaft crank 14, which is flexibly rotatably attached to downwardly projecting forked arms 6, of the A frame-mounting column 5, in order to allow smooth continuous revolution of the wheels and prevent gaps or "jam-ups" in the operation of the vehicle.
The angular range between the short crank 8 and long crank 9, measured longitudinally from crankshaft 4, must be from about 135° to about 155° and the ratio of the length of the long crank to the length of the short crank must be from about 1.5:1 to about 2:1.
With these angles and ratios, the novel recreation-exercise vehicle of the invention can be made to accomodate the ratio of leg to body and arm lengths of most occupants, and also prevent a jam-up of harmonious flowing action between the first coordinated simultaneous extension action of both legs in combination with body-weight depression of the seat, while pulling the handle bar towards the body; and the second coordinated simultaneous standing action of both legs in combination with removal of the body-weight from the seat, while pushing the handle bar forward away from the body.
Handle bar 15, is connected to a power lever indicated in general at 16, which is mounted in hinged assemblage 17 through a curved fork direction controlling means on the upper member 19A constituted by the front fork 19. This connection allows the dual functions of steering the vehicle and transmitting the arm-pulling force through longitudinal cross bar 18 in combination with depression of the seat to provide part of the force needed to push seat-mounting lever 13, which is connected through pitman rod 11 to long crank 9, as shown in FIGS. 4 and 5.
Hinged assembly 17 is raised in fixed relationship to the base of the power lever 16 at a point closely above the generally circular upper washer portion 17A, which is in fixed relationship to the base of power lever 16.
Upper washer portion 17A is integral to curved fork direction controlling means 17B, in that it extends from the generally circular periphery of the washer. The curved fork direction controlling means is projected at all times through the looped extensions 17C from the lower washer, which is in fixed relationship to the upper-most part of the member constituted by front fork 19.
As shown in FIG. 3, when treadles 7, which can be rotatably connected with ball-bearing journals, are in the position to accomodate a standing occupant, and the arm-pushing force has handle bar 15 in the forward-most position, the seat is at its highest elevation and short crank 8 is in the static position after having received the pulling force from treadle-lever 12. Strap or other foot securing means 7A are positioned on the treadle to prevent foot slippage in the standing position. In this position, the upper washer portion 17A is in full contact with lower washer portion 17C, and the curved fork direction controlling means 17B is fully extended through the looped extensions 17C on the lower washer.
After commencing the coordinated action of sitting, pulling the handle bar, and extending the legs, as shown in FIG. 4, the seat beings its descent, thereby giving a pushing action to long crank 9 through seat-mounting column lever 13, and positions short crank 8 for the forthcoming pulling action from treadle lever 12 upon further extension of the occupant's legs and more pulling force exerted on handle bar 15.
In FIG. 5, the front portion of the vehicle seat is shown very close to, but not in actual contact with the longitudinal cross bar 18 connecting power lever 16 and the upper portion of seat-mounting column lever 13.
FIG. 6 shows the positions of the seat, handle bar, and foot treadles at points after full extension of the rider's legs, and at a point immediately prior to beginning resumption of seat ascent. In these positions, the pushing action on the long crank is about completely spent.
FIG. 7 shows an enlarged view of the raised hinged assembly portion and the curved fork direction controlling means of the steering mechanism, which allows steering of the vehicle from whichever position the power lever-handle bar is situated.
FIG. 8 shows an enlarged view of the raised hinged assembly connecting means and the position of the curved fork direction controlling means through the looped extensions of the lower washer.
While the invention has been described with reference to a tricycle suitable for use in a manner similar to the action of rowing a boat, a bicycle made in accordance with the invention is also operable by mounting a single rear wheel on the axle which extends from the short and long cranks, where the angle between the cranks and the ratio of length of the cranks are observed, together with the basic structural connections of the invention.
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A recreational and exercise cycle characterized by a propulsion system which derives its transmission force from the coordinated rowing action of the occupant's body weight, arm force, and foot-leg action comprising rotatable cranks, treadle and seat levers connected to and cranks, and a handle bar-power lever combination connected to a seat.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a process of the preparation of D(-)αphenylglycine by resolution of DLαphenylglycine by means of D(+)camphorsulfonic acid in the presence of a strong acid in a reaction vessel, wherein the crystallized salt of the D(-)αphenylglycine is filtrated and then it is subjected to hydrolysis by the addition of a base whereby the D(-)αphenylglycine precipitates and finally said D(-)αphenylglycine is recovered and the obtained filtrate containing the salt of the D(-)camphorsulfonic acid dissolved in water, is introduced again into the reaction vessel, whereas the filtrate, obtained after filtration of the salt of the D(-)αphenylglycine, which filtrate contains L(+)αphenylglycine, is subjected to an alkaline racemization by means of a base, wherein the obtained DLαphenylglycine is also introduced into the reaction vessel.
2. Brief Description of the Prior Art
The preparation of D(-)αphenylglycine by resolution of a racemic mixture of DLαphenylglycine into the D and L isomers by means of D(+)camphorsulfonic acid is known.
Also the alkaline racemization of the undesired L isomer in the racemic DL mixture is known.
The known process for the preparation of D(-)αphenylglycine, wherein subsequent to the racemization the mixture is neutralized and filtrated, whereas the solid DLαphenylglycine is introduced again into the reaction vessel and the filtrate is removed as effluent water, has as disadvantages that together with the filtrate salts, very expensive DLαphenylglycine and especially D(+)camphorsulfonic acid are discarded, which means, that the known process on the one hand is uneconomical because of the loss of expensive starting materials, which from time to time have to be supplemented and otherwise said process causes pollution of the environment.
An object of the present invention is to eliminate the above mentioned disadvantages efficiently.
SUMMARY OF THE INVENTION
In accordance with the invention H 2 SO 4 is used as strong acid, whereas the L(+)αphenylglycine without separation from the racemization mixture is subjected to racemization in the presence of the D(+)camphorsulfonic acid by means of KOH or NaOH, wherein during the racemization, which is carried out at increased temperatures, water is removed by distillation which water is used for the hydrolysis whereupon the racemization mixture is chilled under crystallization of K 2 SO 4 or Na 2 SO 4 , which is recovered by crystallization and the obtained filtrate, containing the K- or Na-salt of the DLαphenylglycine and the K- or Na-salt of the camphorsulfonic acid, dissolved in water, is introduced again into the reaction vessel, whereupon the DLαphenylglycine is supplemented and additional sulphuric acid is added, obtaining a mixture to be resoluted again.
BRIEF DESCRIPTION OF THE DRAWING
The accompanying drawing is a flow sheet showing schematically the process of the invention.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present process essentially any loss of D(-)αphenylglycine and D(+)camphorsulfonic acid is prevented, whereas furthermore no process effluent water is discarded, which means that no pollution of the environment occurs.
The according to the present process obtained solid salts, such as K 2 SO 4 in use of KOH or Na 2 SO 4 in use of NaOH, are separated from the racemic mixture by filtration and may be used for other purposes, for instance as fertilizer in the agriculture in case of K 2 SO 4 .
The process of the invention is illustrated by means of the enclosed working scheme.
To the starting resolution mixture in the reaction vessel H 2 SO 4 is added besides the DLαphenylglycine in order to convert the recovered K- or Na-salt of D(+)camphorsulfonic acid into the free acid, to neutralize the alkaline racemization mixture and to dissolve the newly added DLαphenylglycine.
To the crystallized salt of D(-)αphenylglycine and D(+)-camphorsulfonic acid KOH or NaOH and water are added after separation from the resolution mixture, wherein the D(-)αphenylglycine is precipitated and the K- or Na-salt of D(+)camphorsulfonic acid is dissolved.
After precipitation of the desired D(-)αphenylglycine, the solution of the K- or Na-salt of D(+)camphorsulfonic acid is introduced again into the reaction vessel and therein it is used again for a subsequent resolution.
The filtrate of the resolution mixture contains the excess of D(+)camphorsulfonic acid, D(+)αphenylglycine and KHSO 4 or NaHSO 4 . By addition of KOH or NaOH the pH of the mixture is adjusted to a value of 11 or higher, preferably on a value of 11-13.
The mixture is cooked during 1.5-4 hours at a temperature of 100°-120° C. in order to racemize the L isomer into DL. Simultaneously a part of the water from the racemization mixture is removed by distillation in order to prevent the volume increase of the process liquid. The distilled water is used for the washing of the several filtrated solid materials and for the hydrolysis of the salt of D(-)αphenylglycine and D(+)camphorsulfonic acid.
By chilling the racemization mixture to 18°-30° C. the K 2 SO 4 or Na 2 SO 4 present in the process liquid surprisingly crystallizes essentially quantitatively and may be separated by means of a simple filtration. The Na 2 SO 4 crystals contain 10 mol of crystallization water. The liquid containing DLαphenylglycine and the K- or Na-salt of D(+)camphorsulfonic acid is introduced again into the reaction vessel and it is used again in the subsequent resolution.
The process of the invention is illustrated in more detail by means of the following examples.
EXAMPLE I
1st resolution (KOH)
In a reaction vessel the following mixture is stirred:
1200 ml of water
2 mole (302 g) of DLαphenylglycine
1.2 mol (278.5 g) of D(+)camphorsulfonic acid
0.8 mole (78.4 g) of H 2 SO 4 .
The resolution mixture was heated under stirring to 90°-100° C., wherein the DLαphenylglycine is dissolved.
Then the solution is cooled to 15°-30° C. under stirring, wherein the salt of D(-)αphenylglycine has been crystallized.
The crystals were filtrated and washed with a slight amount of water. Yield of the salt was about 300 g.
Hydrolysis
The salt formed during the resolution was stirred in 500 ml of water. By addition of circa 42 g of KOH dissolved in 60 ml of water, the pH of the mixture is adjusted on a value of 3.5-6. The reaction mixture was cooled and the crystallized D(-)αphenylglycine was filtrated.
The crystals were washed on the filter by means of a slight amount of water.
The product was dried. Yield: 118 g; content via acid-base titration amounts 99%. Specific rotation [α] D/20=-160°.
Racemization
The filtrate of the resolution mixture plus the wash liquid were stirred and made alkaline to a pH more than 11 by means of circa 3.22 mol (185 g) of KOH.
For the racemization the mixture is then heated to 100°-120° C. during 3 hours, wherein sufficient water is distilled off in order to decrease the volume to ±900 ml. Then the mixture was cooled to 20° C. under stirring. Herein K 2 SO 4 crystallized and by filtration separated. The crystals were washed by means of a slight amount of water, which has been distilled off during the racemization.
Yield of K 2 SO 4 circa 136 g.
The filtrate circa 750 ml was introduced again into the reaction vessel and used again during the following resolution.
EXAMPLE II
2nd and following resolution
In the reaction vessel of Example I the following mixture is stirred:
the filtrate obtained after the hydrolysis in Example I, which filtrate contained 0.8 mol (217 g) of K-salt of D(+)camphorsulfonic acid in water and a slight amount of D(-)αphenylglycine. Volume circa 1400 ml.
the filtrate, obtained after the filtration of the racemization mixture in Example I, which filtrate contained 1.2 mol (181.4 g) of DLαphenylglycine, 0.4 mol (108.5 g) of K-salt of D(+)camphorsulfonic acid, 1.22 mol (68.4 g) of KOH dissolved in water. Total volume circa 750 ml.
8.8 mol (120.9 g) of DLαphenylglycine, (a new portion).
4.4 mol (431.2 g) of H 2 SO 4 . (a new portion).
The resolution mixture was heated under stirring to 90°-100° C., whereas the DLαphenylglycine is dissolved.
Then the solution was cooled to 15°-30° C. under stirring, whereas the salt of D(-)αphenylglycine crystallized out. The crystals were filtrated and washed by means of a slight amount of water, which has been distilled off during the former racemization. Yield of salt circa 307 g.
Hydrolysis
The salt formed during the resolution was stirred in 500 ml of water which has been distilled off during the previous racemization. By addition of circa 45 g of KOH dissolved in 60 ml of water the pH of the mixture has been adjusted on 3.5-6. The reaction mixture was cooled to 15°-35° C., whereas the crystallized D(-)αphenylglycine was filtrated.
The crystals were washed on the filter with a slight amount of water, which has been distilled off during the previous racemization. The product was dried. Yield: 121 g; content via acid-base titration 99%. Specific rotation [α] D/20=-160°.
Racemization
The filtrate of the resolution mixture plus the wash liquid were stirred and made alkaline to a pH of more than 11 by means of 8 mol (449 g) of KOH.
Prior to the racemization the mixture was heated to 100°-120° C. during 3 hours, wherein sufficient water was distilled off in order to obtain a volume of circa 950 ml. Then the mixture was cooled off to 20° C. under stirring. Herein K 2 SO 4 crystallized out, which was separated by filtration. The crystals were washed with a slight amount of water, which has been distilled off during the racemization.
Yield of K 2 SO 4 after drying circa 766 g.
The filtrate circa 750 ml was introducted again into the reaction vessel and used again in the following resolution.
EXAMPLE III
1st Resolution
In a reaction vessel the following mixture is stirred:
1200 ml of water
2 mol (302 g) of DLαphenylglycine
1.2 mol (278.5 g) of D(+)camphorsulfonic acid
0.8 mol (78.4 g) of H 2 SO 4 .
The resolution mixture was heated under stirring to 90°-100° C., wherein the DLαphenylglycine is dissolved.
Then the solution was cooled off to 15°-30° C. under stirring, wherein the salt of D(-)αphenylglycine crystallized out.
The crystals were filtered and washed with a slight amount of water. Yield of salt circa 300 g.
Hydrolysis
The salt formed during the resolution was stirred in 500 ml of water. By addition of circa 31 g of NaOH dissolved in 55 ml of water the pH of the mixture was adjusted on 3.5-6. The reaction mixture was cooled off and the crystallized D(-)αphenylglycine was filtrated.
The crystals were washed on the filter with a slight amount of water. The product was dried. Yield: 118 g; content via acid-base titration 99%. Specific rotation [α] D/20=-160°.
Racemization
The filtrate of the resolution mixture plus the wash liquid were stirred and made alkaline to a pH of more than 11 by means of 3.22 mol of NaOH (129 g).
For the racemization the mixture is heated to 100°-120° C. during 3 hours, wherein sufficient water has been distilled off in order to decrease the volume to circa 850 ml. Then the mixture was cooled off to 20° C. under stirring. Herein Na 2 SO 4 .10H 2 O crystallized out, which material was separated by filtration. The crystals were washed with a slight amount of water, which has been distilled off during the racemization. Yield: NaSO 4 .10H 2 O circa 259 g.
The filtrate circa 750 ml was introduced into the reaction vessel and used again during the following resolution.
EXAMPLE IV
2nd and following resolution
In a reaction vessel the following mixture was stirred:
the filtrate obtained during the hydrolysis in Example III, which filtrate contained 0.8 mol (203.2 g) of Na-salt of D(+)camphorsulfonic acid in water and a slight amount of D(-)αphenylglycine. Volume circa 700 ml.
the filtrate, obtained after the filtration of the racemization mixture in the previous preparation, which filtrate contained 1.2 mol (181.4 g) of DL(α)phenylglycine, 0.4 mol (101.6 g) of Na-salt of D(+)camphorsulfonic acid, 1.22 mol (48.8 g) of NaOH dissolved in water. Total volume circa 750 ml.
0.8 mol (120.9 g) of DLαphenylglycine (a new portion)
4.4 mol (431.2 g) H 2 SO 4 (a new portion)
The resolution mixture was heated to 90°-100° C., under stirring, wherein the DLαphenylglycine is dissolved.
Subsequently the solution was cooled off to 15°-30° C. under stirring, wherein the salt of D(-)αphenylglycine and D(+)-camphorsulfonic acid crystallized out. The crystals were filtrated and washed with a slight amount of water. Yield of salt circa 307 g.
Hydrolysis
The salt formed during the resolution was stirred in 500 ml of water, which has been distilled off during the previous racemization. By addition of circa 32 g of NaOH dissolved in 54 ml water the pH of the mixture has been adjusted to 3.5-6.
The reaction mixture was cooled off to 15°-35° C. and the crystallized D(-)αphenylglycine was filtrated.
The crystals were washed on the filter with a slight amount of water. The product was dried. Yield: 121 g; content via acid-base titration 99%. Specific rotation [α]D/20=-160°.
Racemization
The filtrate of the resolution mixture plus the wash liquid were stirred and made alkaline to a pH of more than 11 by means of circa 8 mol (320 g) of NaOH.
For the racemization the mixture is heated to 100°-120° C. during 3 hours, wherein sufficient water was distilled off in order to decrease the volume to 1500 ml. Then the mixture was cooled off to 18° C. under stirring. Herein Na 2 SO 4 .10H 2 O crystallized out, which salt has been separated by filtration. The crystals were washed with a slight amount of water. Yield of Na 2 SO 4 .10H 2 O circa 1416 g.
The filtrate circa 750 ml was introduced again into the reaction vessel and used again during the following resolution.
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The invention provides a process for the preparation of D(-)αphenylglycine by resolution of DLαphenylglycine by means of D(+)camphorsulfonic acid. The present process enables the preparation of D(-)αphenylglycine at a minimum loss of the very expensive starting materials, such as DLαphenylglycine and D(+)camphorsulfonic acid. The salts produced in this process are precipitated from the resolution filtrate and the filtrate may be discarded as effluent water without any danger to the environment.
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RELATED APPLICATION
[0001] This application is a divisional of co-pending U.S. patent application Ser. No. 11/166,411, filed Jun. 24, 2005 entitled “Endovascular Aneurysm Repair System,” which is a divisional of Ser. No. 10/271,334 filed Oct. 15, 2002 (now U.S. Pat. No. 6,960,217), which claims the benefit of U.S. provisional application Ser. No. 60/333,937 filed Nov. 28, 2001.
BACKGROUND OF THE INVENTION
[0002] The invention relates generally to the attachment of a vascular prosthesis to a native vessel, and in particular, to a method and system of devices for the repair of diseased and/or damaged sections of a vessel.
[0003] Description of Related Art. The weakening of a vessel wall from damaged or diseased can lead to vessel dilatation and the formation of an aneurysm. Left untreated, an aneurysm can grow in size and will eventually rupture.
[0004] For example, aneurysms of the aorta primarily occur in abdominal region, usually in the infrarenal area between the renal arteries and the aortic bifurcation. Aneurysms can also occur in the thoracic region between the aortic arch and renal arteries. The rupture of an aortic aneurysm results in massive hemorrhaging and has a high rate of mortality.
[0005] Open surgical replacement of a diseased or damaged section of vessel can eliminate the risk of vessel rupture. In this procedure, the diseased or damaged section of vessel is removed and a prosthetic graft, made either in a straight of bifurcated configuration, is installed and then permanently attached and sealed to the ends of the native vessel by suture. The prosthetic grafts for these procedures are usually unsupported woven tubes and are typically made from polyester, ePTFE or other suitable materials. The grafts are longitudinally unsupported so they can accommodate changes in the morphology of the aneurysm and native vessel. However, these procedures require a large surgical incision and have a high rate of morbidity and mortality. In addition, many patients are unsuitable for this type of major surgery due to other co morbidities.
[0006] Endovascular aneurysm repair has been introduced to overcome the problems associated with open surgical repair. The aneurysm is bridged with a vascular prosthesis, which is placed intraluminally. Typically these prosthetic grafts for aortic aneurysms are delivered collapsed on a catheter through the femoral artery. These grafts are usually designed with a fabric material attached to a metallic scaffolding (stent) structure, which expands or is expanded to contact the internal diameter of the vessel. Unlike open surgical aneurysm repair, intraluminally deployed grafts are not sutured to the native vessel, but rely on either barbs extending from the stent, which penetrate into the native vessel during deployment, or the radial expansion force of the stent itself is utilized to hold the graft in position. These graft attachment means do not provide the same level of attachment when compared to suture and can damage the native vessel upon deployment.
[0007] Accordingly, there is a need for an endovascular aneurysm repair system that first provides a prosthetic graft, which can adapt to changes in aneurysm morphology and be deployed without damaging the native vessel and second, a separate endovascular fastening system that provides permanent graft attachment to the vessel wall.
SUMMARY OF THE INVENTION
[0008] The methods and apparatus for implanting radially expandable prostheses in body lumens are described. In particular, the present invention provides improved methods and systems for implanting vascular stents and stent-grafts into blood vessels, including both arterial and venous systems. In the exemplary embodiments, stent-grafts are placed in vasculature to reinforce aneurysms, particularly abdominal aortic aneurysms.
[0009] One aspect of the invention provides systems and methods for introducing a tissue fastener applier to apply tissue-piercing fasteners to a prosthesis sequentially along a path established by the directing device that, between fastener applications, is manipulated into orientation with different desired fastening sites, until a plurality of tissue-piercing fasteners are placed, one-at-a-time, in the prosthesis.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] The invention will be understood from the following detailed description of preferred embodiments, taken in conjunction with the accompanying drawings, wherein:
[0011] FIG. 1 is a perspective view of one embodiment of an endovascular graft delivery device shown positioned within an abdominal aortic aneurysm;
[0012] FIG. 2 is a perspective view of one embodiment the deployment of an endovascular graft within the aneurysm of FIG. 1 ;
[0013] FIG. 3 is a perspective view of a fully deployed straight endovascular graft of FIG. 2 ;
[0014] FIG. 4 is a perspective view of a fully deployed bifurcated endovascular graft broken away to show an anchoring scaffold at one end;
[0015] FIG. 5 is a perspective view similar to FIG. 5 showing an alternative scaffold structure;
[0016] FIG. 6 is a perspective view showing one embodiment of a device for directing the fastener applier;
[0017] FIG. 7 is a perspective view showing the device of FIG. 6 upon insertion within the deployed endovascular graft of FIG. 3 with both the graft and scaffolding broken away;
[0018] FIG. 8 is a perspective view of the device of FIG. 6 showing activation of one embodiment of a stabilizing device attached to the directing device;
[0019] FIG. 9 is a perspective view of the control assembly in FIG. 8 articulating the directing device of FIG. 6 ;
[0020] FIG. 10 is a perspective view of an alternative embodiment of the stabilization device of FIG. 8 ;
[0021] FIG. 11 is a perspective view showing the activation of the alternative stabilization device of FIG. 10 ;
[0022] FIG. 12 is a perspective view showing another embodiment of the stabilization device of FIG. 8 ;
[0023] FIG. 13 is a perspective view showing activation of the stabilization device of FIG. 12 ;
[0024] FIG. 14 is one embodiment of the fastener applier;
[0025] FIG. 15 is a perspective view of the fastener applier of FIG. 14 being positioned within directing device of FIG. 6 ;
[0026] FIG. 16 is an enlarged cross-sectional view of one embodiment of the fastener applier of FIG. 14 ;
[0027] FIG. 17 is an enlarged cross-sectional view of the attachment applier showing one embodiment of the proximal end of the helical fastener and the drive mechanism;
[0028] FIG. 18 is a enlarged perspective view of one embodiment of the helical fastener of FIG. 16 ;
[0029] FIG. 19 is an enlarged view of the attachment applier showing one embodiment of the control assembly that activates the fastener applier;
[0030] FIG. 20 is an enlarged view of the attachment applied activated with a fastener implanted into the graft and vessel wall;
[0031] FIG. 21 is an enlarged view of the completed attachment of the proximal graft of FIG. 3 to the vessel wall with fasteners;
[0032] FIG. 22 is a perspective view of the graft of FIG. 4 completely attached to the vessel.
DETAILED DESCRIPTION OF THE INVENTION
[0033] FIG. 1 depicts an endovascular graft delivery catheter 10 being positioned within an abdominal aortic aneurysm 11 over a guidewire 12 . FIG. 2 depicts the initial stage of graft deployment within a vessel. The delivery catheter 10 has a movable cover 13 over the graft. When the cover is pulled proximally the graft 14 expands to contact the internal walls of the vessel. It is contemplated that the graft could be self-expanding or utilize an expanding member such as a balloon or mechanical expander. The process of graft deployment is continued until the graft is fully deployed within the vessel. It is contemplated that the graft could be in either a straight or bifurcated form. FIG. 3 depicts a completely deployed straight graft 14 and FIG. 4 depicts a completely deployed bifurcated graft 15 . The guidewire 11 used to deliver and position the graft remains within the vessel for access of the fastener attachment system. One embodiment of the graft scaffolding 16 (stent) is illustrated in the area broke away in FIG. 4 . The stent is in the form of a simple zigzag pattern, however it is contemplated that the stent design could involve more complex patterns 17 as depicted in FIG. 5 . Although only one stent structure within the graft is depicted, in FIGS. 4 and 5 , it is contemplated that multiple independent stent structures could be incorporated into the graft. 1391 FIG. 6 depicts one embodiment of the directing device 18 with an obturator 19 positioned within the lumen of the directing device and extending past the distal of the tip of the directing device. The obturator has a lumen to allow for delivery over a guidewire. FIG. 7 depicts the directing device being positioned within the deployed endovascular graft over a Quidewire 12 . The directing device has an incorporated stabilizing device 20 to aid in maintaining position of the directing device within the vessel. In one embodiment, the stabilizing device 20 is spring-loaded and is positioned for use when the obturator in the directing device is removed FIG. 8 . The directing device is activated though a control assembly 21 as seen in FIG. 8 . In one embodiment the control assembly 21 features a movable wheel or lever 22 , which deflects the distal tip 23 of the directing device 18 to the desired location as seen in FIG. 9 . It is contemplated that the control assembly for the directing device could be activated mechanically, electrically, hydraulically or pneumatically. The control assembly has a through lumen to allow for the passage of the obturator and fastener applier. FIG. 10 depicts another embodiment the stabilizing device as a movable strut assembly 24 . The movable strut assembly is activated through a lever 25 on the control assembly FIG. 11 . In both embodiments ( FIG. 7 and 10 ) the stabilizing device is distal to the end of the directing device. In another embodiment the stabilizing device could be in the form of an expandable member 26 adjacent to the distal tip of the directing device FIG. 12 . In one embodiment, the expandable member 26 is shown activated through a lever 25 on the control assembly FIG. 13 . However it also contemplated that this type of stabilizing device could also be inflatable. In all embodiments the stabilizing device could be use to stabilize the directing member either concentrically or eccentrically within the vessel.
[0034] In another embodiment of the invention a separate tubular device could be used in cooperation with the directing device and to access the vessel. This separate tubular device could incorporate the stabilizing devices used above with the directing device.
[0035] FIG. 14 depicts one embodiment of the fastener applier 27 . FIG. 14A is a detail view of the distal end of the fastener applier. FIG. 15 depicts the fastener applier being positioned through the lumen of the directing device to the site where a fastener will be installed.
[0036] FIG. 16 is an enlarged cross-sectional view of fastener applier 27 and directing device 18 . In one embodiment of the fastener applier the helical fastener 28 is rotated via a fastener driver 29 through a drive shaft 30 that is connected to the control assembly 31 . The drive shaft 30 can be made of any material that allows for both bending and rotation. The drive shaft is connected to the fastener driver 29 , which engages and imparts torque to the helical fastener. FIG. 16 illustrates the coils of the helical fastener 28 engaged with internal grooves 32 within the fastener applier. It is contemplated that the grooves could be positioned along the entire length of the fastener or within a portion of its length. FIG. 17 is an enlarged cross-sectional view of the fastener applier 27 with a cross-section of the fastener driver 29 depicting one embodiment of engagement between the fastener driver and helical fastener 28 . In this embodiment the proximal coil of the helical fastener is formed to produce a diagonal member 33 , which crosses the diameter of the helical fastener. Similar helical fasteners are described in U.S. Pat. No. 5,964,772; 5,824,008; 5,582,616; and 6,296,656, the full disclosures of which are incorporated herein by reference.
[0037] FIG. 18 depicts one embodiment of the helical fastener 28 showing the diagonal member 33 . FIG. 19 depicts one embodiment of the fastener applier 27 during activation of the fastener applier control assembly. Activation of the control assembly rotates the drive shaft, faster driver and helical fastener. This rotation causes the helical fastener 28 to travel within the internal grooves 32 of the fastener applier and into the graft 14 and vessel wall 34 FIG. 20 . It is contemplated that the control assembly for the fastener applier could be activated mechanically, electrically, hydraulically or pneumatically.
[0038] FIG. 21 illustrates a completed helical fastener 28 attachment of the graft 14 to the vessel wall 34 . It is contemplated that one or more fasteners will be required to provide secure attachment of the graft to the vessel wall.
[0039] FIG. 22 illustrates a perspective view of a graft prosthesis attached to the vessel wall both proximally and distally. It is contemplated that the present invention can be used for graft attachment of both straight and bifurcated grafts 15 within the aorta and other branch vessels.
[0040] It will be appreciated that the components and/or features of the preferred embodiments described herein may be used together or separately, while the depicted methods and devices may be combined or modified in whole or in part. It is contemplated that the components of the directing device, fastener applier and helical fastener may be alternately oriented relative to each other, for example, offset, bi-axial, etc. Further, it will be understood that the various embodiments may be used in additional procedures not described herein, such as vascular trauma, arterial dissections, artificial heart valve attachment and attachment of other prosthetic device within the vascular system and generally within the body.
[0041] The preferred embodiments of the invention are described above in detail for the purpose of setting forth a complete disclosure and for the sake of explanation and clarity. Those skilled in the art will envision other modifications within the scope and sprit of the present disclosure.
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Systems and methods introduce a tissue fastener applier to apply tissue-piercing fasteners to a prosthesis sequentially along a path established by the directing device that, between fastener applications, is manipulated into orientation with different desired fastening sites, until a plurality of tissue-piercing fasteners are placed, one-at-a-time, in the prosthesis.
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This application is a continuation of Ser. No 10/411,565 filed Apr. 10, 2003 now U.S. Pat. No. 6,830,009 and, claims the benefit of U.S. Provisional Application No. 60/372,267, filed 11 Apr. 2003, titled “Solar Powered Bird Feeder.”
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to bird feeders. In particular, the present invention relates to bird feeders having electrical power sources.
2. Description of Related Art
Solar energy systems that collect solar energy and convert it into electrical energy have been around for many years. However, only recently have these solar energy systems been developed to the point where they are small enough, efficient enough, and economical enough, to allow their widespread use in small electrical devices. One use of these small solar energy systems is to recharge rechargeable batteries in small household devices.
One example of a small household electrical device with rechargeable batteries that can be recharged by one of these small solar energy systems is an outdoor landscaping lighting system. The rechargeable batteries provide power to illuminate the lighting elements during darkness, and the solar energy system collects and converts solar energy and recharges the rechargeable batteries during daylight.
Although the use of small solar energy systems in outdoor landscaping lighting systems represents great strides in the development and use of solar energy systems, there is a need for these miniaturized solar energy systems in other small electrical household devices.
BRIEF SUMMARY OF THE INVENTION
There is a need for solar powered bird feeder.
Therefore, it is an object of the present invention to provide a solar powered bird feeder.
This object is achieved by providing a bird feeder having a rechargeable electrical power source and a solar energy system that collects solar energy, converts it into electrical energy, and uses the electrical energy to recharge the rechargeable electrical power source. The rechargeable electrical power source can be used to power lights, radios, cameras, and a wide variety of other electrical devices operably associated with the bird feeder.
The solar powered bird feeder according to the present invention provides significant advantages, including: (1) the rechargeable electrical power source can be recharged by the solar energy system; (2) the rechargeable electrical power source can provide power to a wide variety of electrical devices operably associated with the bird feeder; and (3) the lighting elements allow the bird feeder to be viewed and enjoyed at night. Other objects and advantages of the present invention will be evident from the following detailed description of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a is a perspective view of the solar powered bird feeder according to the present invention.
FIG. 2 is a front view of the solar powered bird feeder of FIG. 1 .
FIG. 3 is a right side view of the solar powered bird feeder of FIG. 1 .
FIG. 4 is a rear view of the solar powered bird feeder of FIG. 1 .
FIG. 5 is a left side view of the solar powered bird feeder of FIG. 1 .
FIG. 6 is a top plan view of the solar powered bird feeder of FIG. 1 .
FIG. 7 is a bottom view of the solar powered bird feeder of FIG. 1 .
FIG. 8 is an exploded longitudinal cross-sectional view of the solar powered bird feeder of FIG. 1 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Although the present invention will be described herein with reference to a bird feeder having a particular configuration, it should be understood that the methods and apparatuses of the present invention can be used on bird feeders and bird houses of almost any shape or design, as well as on other small animal feeders and houses. Thus, it will be appreciated that the rechargeable electrical power source and solar recharging system of the present invention is well suited for use on any decorative outdoor accessory.
Referring to FIGS. 1-8 in the drawings, the preferred embodiment of a solar powered bird feeder 11 according to the present invention is illustrated. Bird feeder 11 is adapted to be hung on a stand 13 , in a tree, on a hanging bracket, from a rope or cable, or by any of a wide variety of conventional hanging means. Stand 13 is shown in dashed lines to indicated that stand 13 may be of any suitable design.
In the preferred embodiment, bird feeder 11 has a hanging means 15 , an upper cap member 17 , an upper canopy 19 , a main canopy 21 , a food reservoir 23 , a perch 25 , a lower portion 27 , and a lower finial 29 . Hanging means 15 , upper cap member 17 , upper canopy 19 , main canopy 21 , food reservoir 23 , perch 25 , lower portion 27 , and lower finial 29 are coupled together by a rod 31 (see FIG. 8 ) that passes along a central longitudinal axis 33 of bird feeder 11 and that is releasably connected to lower finial 29 and upper cap member 17 . It should be understood that rod 31 may also be a chain, wire, cable, or any other type of connecting means which aids in holding the components of bird feeder 11 together.
Upper cap member 17 , upper canopy 19 , main canopy 21 , perch 25 , lower portion 27 , and lower finial 29 are preferably made of a suitable material that is treated, finished, and/or coated to prevent rust, wear, and exposure to the environment. It should be understood that hanging means 15 , upper cap member 17 , upper canopy 19 , and main canopy 21 may be integrally combined into one or more component parts, depending on their shape, the application in which they are used, or the ornamental design that they are intended to represent. For example, these components may include embossed figurines or cut-out shapes that enhance the appearance or motif of bird feeder 11 .
Food reservoir 23 includes at least one outlet port 32 through which birds may gather the bird food. Outlet ports 32 may be located on food reservoir 23 at various locations and heights, such as at low locations near perch 25 or high locations near main canopy 21 . Outlet ports 32 may also include flanges (not shown) that extend into or out of food reservoir 23 to prevent the bird food from spilling out of outlet ports 32 unnecessarily. Bird feeder 11 may also include additional perches that extend outwardly from food reservoir 23 for birds to use while gathering the bird food. Such additional perches are particularly useful for outlet ports 32 that are located well above perch 25 .
Food reservoir 23 may include a liner portion 23 a , preferably made of transparent glass or plastic, and a decorative lattice portion 23 b , preferably made of a suitable material that is treated, finished, and/or coated to prevent rust, wear, and exposure to the bird food or the environment. Liner portion 23 a may be beveled, etched, colored, tinted, or otherwise treated, depending upon the effect desired. For example, food reservoir 23 may be formed from leaded glass or stained glass having a decorative appearance or motif. Furthermore, it should be understood that the liner portion 23 a and lattice portion 23 b may be integrally combined to form a single component. For instances in which liner portion 23 a and lattice portion 23 b are separate components, it will be appreciated that lattice portion 23 b may be disposed on either the inside or the outside of liner portion 23 a.
A food access port 28 is disposed in main canopy 21 to allow a user to fill food reservoir 23 with bird food without disassembling bird feeder 11 . Food access port 28 is preferably covered by a cap 30 (see FIGS. 4 and 8 ) to protect the bird food in food reservoir 23 from the weather. Cap 30 may be attached to bird feeder 11 by a wide variety of attachment means. It should be understood that food access port 28 may be located in several locations on bird feeder 11 , depending upon the application in which bird feeder 11 is used, and the effect that is desired.
A rechargeable electrical power source 41 is operably associated with bird feeder 11 to provide electrical power to bird feeder 11 . In the preferred embodiment, rechargeable electrical power source 41 is disposed within upper canopy 19 . It will be appreciated that rechargeable electrical power source 41 may also be disposed in other components of bird feeder 11 , such as perch 25 or lower portion 27 , and may be disposed in multiple components of bird feeder 11 . Rechargeable electrical power source 41 is preferably two 1.2 Volt rechargeable AA NiCd batteries providing about 600 milliamps of current, but may be any of a wide variety of rechargeable batteries. An electrical charging system 43 (see FIG. 8 ) is conductively coupled to rechargeable electrical power source 41 . Electrical charging system 43 may include an electrical access port (not shown) to receive an adapter or transformer (not shown) that allows rechargeable electrical power source 41 to be recharged by a conventional AC power source, such as an AC wall outlet. It will be understood that rechargeable electrical power source 41 may be used to power a wide variety of electrical devices, such as microphones, radio receivers or transmitters, cameras, audio recording and playback devices, video recording and playback devices, loud speakers, lighting elements, timing devices, remote controls, motors, etc.
At least one conventional solar collector 45 is operably associated with bird feeder 11 to collect solar energy. In the preferred embodiment, at least one solar collector 45 is disposed on the upper surface of upper canopy 19 . Solar collectors 45 either include or are conductively coupled to a conventional solar energy conversion system 47 that converts the solar energy to electrical energy. Electrical charging system 43 uses the electrical energy from the solar energy conversion system 47 or the AC power outlet to recharge rechargeable electrical power source 41 . An optional photoresistor 49 disposed on the upper surface of upper canopy 19 is conductively coupled to rechargeable electrical power source 41 to detect the amount of light hitting bird feeder 11 and to provide a corresponding electrical signal that can be used to determine whether power is supplied to certain electrical components.
In the preferred embodiment, the electrical power from rechargeable electrical power source 41 is used to illuminate at least one lighting element 51 . It is preferred that lighting element 51 be positioned to cast light on and/or through food reservoir 23 , perch 25 , and as many other components of bird feeder 11 as possible. In the preferred embodiment, lighting elements 51 are disposed beneath main canopy 19 . Lighting elements 51 preferably illuminate food reservoir 23 and perch 25 in a decorative fashion. Thus, it will be appreciated that the configuration and choice of materials for food reservoir 23 may produce a distinctive effect on the appearance of bird feeder 11 while being illuminated by lighting elements 51 . In the preferred embodiment, lighting elements 51 comprise one or more LED's. It should be understood that lighting elements may also be fluorescent lighting elements, cold cathode ray tube lighting elements, and/or any other suitable lighting elements.
In the preferred embodiment, lighting elements 51 are carried by an alignment disk 53 . Alignment disk 53 is disposed between main canopy 21 and food reservoir 23 . It should be understood that alignment disk 53 may be integral with either main canopy 21 or food reservoir 23 , or both main canopy 21 and food reservoir 23 . Alignment disk 53 includes a plurality of tabs 55 which provide spacing and a means of attaching alignment disk 53 to main canopy 21 . Alignment disk 53 may include an annular flange 56 that extends downward from a central aperture 58 . Flange 56 preferably has an outside diameter that is slightly smaller that the inside diameter of food reservoir 23 , such that flange 56 may protrude slightly into the interior of food reservoir 23 . This aligns and centers food reservoir 23 about axis 33 . It should be understood that the functions of alignment disk 53 may be achieved by other means, such as tabs, spacers, posts, or clips coupled to main canopy 19 . Alignment disk 53 , or its functional equivalent, may include conduits or clips for aligning and/or holding and protecting any electrical wiring that is necessary for any electrical components that are operable on bird feeder 11 .
An optional on/off switch 61 may be disposed on bird feeder 11 and conductively coupled to rechargeable electrical power source 41 to provide a means to manually activate and deactivate the power from rechargeable electrical power source 41 , the power to lighting elements 51 , and/or any other electrical components that may be operably associated with bird feeder 11 . On/Off switch 61 is preferably disposed beneath main canopy 21 on alignment disk 53 . In the preferred embodiment, on/off switch 61 overrides the switching functions of photoresistor 49 . It should be understood that one or more on/off switches 61 and their corresponding control circuitry may be utilized to control the various electrical components on bird feeder 11 .
It will be appreciated that an invention with significant advantages has been described. Although the present invention is shown in a limited number of forms, it is not limited to just these forms, but is amenable to various changes and modifications without departing from the spirit thereof.
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A bird feeder having a rechargeable electrical power source and a solar energy system that collects solar energy, converts it into electrical energy, and uses the electrical energy to recharge the rechargeable electrical power source is disclosed. The rechargeable electrical power source can be used to power an LED lighting system which illuminates at least a portion of said bird feeder so that said bird feeder is visible in low light conditions.
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The present invention relates to toys. More particularly, the present invention relates to a toy that functions both as a jump rope and as a sidewalk chalk holder.
BACKGROUND OF THE INVENTION
Jump ropes have been used by children for generations. Jump ropes ordinarily consist of a flexible cord or rope with a handle at each end. Typically, the handles of the jump rope are used to twirl the rope while one or more children jump over the twirling rope. Through the years numerous games and activities have been conceived and improvised using a basic jump rope.
Another common children's toy is sidewalk chalk. Sidewalk chalk typically consists of a stick or cylinder of material which can mark concrete or asphalt. Sidewalk chalk is often used to draw pictures on asphalt or concrete. A sidewalk chalk holder typically comprises a plastic case which covers and protects the chalk on all sides except the drawing tip.
SUMMARY OF THE INVENTION
The present invention relates to a new toy which integrates both a jump rope and a sidewalk chalk holder into a single toy. This new jump rope and sidewalk chalk holder toy provides the functionality and use of these previously separate toys in a single unit, thereby facilitating and encouraging new games and play.
In a preferred embodiment of the present invention, a flexible rope or cord has a pair of handles mounted at each end. Each of the handles comprises a body which is attached on one end to the rope, and which has a aperture or opening on the opposite end for inserting and retaining a stick of chalk. Preferably the chalk is in the form of a slightly tapered cylinder which can be easily and snugly inserted into the aperture of the handle.
A more complete appreciation of the present invention and its scope can be obtained by reference to the following detailed description of presently preferred embodiments of the invention taken in connection with the accompanying drawings, which are briefly summarized below, and by reference to the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a combination jump rope/sidewalk chalk holder toy which embodies the present invention.
FIG. 2 is an enlarged perspective view of the right handle of the combination jump rope and sidewalk chalk holder toy shown in FIG. 1.
FIG. 3 is a vertical sectional view of the handle shown in FIG. 2.
FIG. 4 is a cross sectional view of the handle taken in the plane of line 4--4 in FIG. 3.
FIG. 5 is a perspective view of the handle shown in FIG. 2 in an open configuration set to receive a stick of chalk which is shown in an exploded relationship to the handle.
FIG. 6 is a perspective view of the handle shown in FIG. 5 in an intermediate configuration with the chalk inserted in the handle.
FIG. 7 is a perspective view of the handle shown in FIG. 6 with the handle in a closed configuration.
DETAILED DESCRIPTION
A combination jump rope and sidewalk chalk holder toy 10 which embodies the present invention is generally illustrated in FIG. 1. The toy 10 comprises two identical handles 12 and 14 and an elongated cord or rope 16 which extends between the handles 12 and 14. The toy 10 can be used as a conventional jump rope where, for example, the handles 12 and 14 are used to twirl the rope 16 while one or more children jump over the twirling rope 16. The handles 12 and 14 of the toy 10 can also be used as conventional sidewalk chalk holders for holding sticks of chalk 18 and 20, respectively, which are used for drawing on asphalt or concrete. The flexible rope 16 does not restrict the movement of the handles 12 and 14 when drawing with the sticks of chalk 18 and 20. Combining a jump rope and sidewalk chalk holder in this way provides the features of two separate toys in one light and portable toy 10 which facilitates the use and interaction of both individual toys.
The rope 16 which extends between the two handles 12 and 14 may be constructed of any number of natural or synthetic substances which provide sufficient textile strength, flexibility, and durability to function as a jump rope. The rope 16 will preferably be between five and seven feet in length, however, a variety of rope lengths outside of this range may be employed. The length of the rope 16 extends between its opposite ends 22 and 24, located at the handles 12 and 14, respectively.
Each of the handles 12 and 14 is preferably identical. As shown in FIGS. 2 and 3, the handle 14 preferably comprises a tubular main body 26, an annular clamping sleeve 28, an annular stop ring 30, and a substantially hemispherical end piece 32. As shown in FIG. 3, a hole 34, located in the center of the end piece 32, allows the passage of the end 24 of the rope 16 into the interior 33 of the end piece 32 and the hollow main body 26 of the handle 14. A sufficiently large knot 36 or fastener is fixed on the end 24 of the rope 16 to prevent the end 24 of the rope 16 from exiting the handle 14 through the hole 34, thereby securing the end 24 of the rope 16 in the handle 14.
The main body 26 comprises a cylindrical portion 38 and a pair of tines 40 and 42 extending integrally from the cylindrical portion 38. The tines 40 and 42 are semicircular in cross-sectional shape as shown in FIG. 4. A pair of diametrically opposed slots 39 and 41 extend along a portion of the main body 26, as shown in FIGS. 2, 3, and 4. The slots 39 and 41 divide the main body 26 into the tines 40 and 42. The cylindrical portion 38 together with the tines 40 and 42 form the elongated, hollow, substantially tubular aperture 43 or opening of the main body 26 into which the stick of chalk 20 is received (FIGS. 5 and 6). The main body 26 has an inner surface 44 at the aperture 43, an outer surface 46, an end 48 that is closed by the end piece 32, and an opposite open end 50 that circumscribes the aperture 43.
Extending outward from the outer surface 46 of the main body 26 and centrally positioned along the length of the tines 40 and 42 are two inclined ridges 52 and 54, respectively. The inclined ridges 52 and 54 preferably begin at about the locations where the tines 40 and 42 join the cylindrical portion 38 of the main body 26. Each ridge 52 and 54 gradually increases in height relative to the outer surface 46 until it reaches the open end 50 of the main body 26. Located at the open end 50 of the main body 26 on each ridge 52 and 54 is a raised shoulder 56 and 58, respectively.
Also extending outward from the outer surface 46 of the main body 26 parallel to the length of the tines 40 and 42 are four spacing bars 60, 62, 64, and 66, as shown in FIG. 4. Two spacing bars are positioned on each tine, one on each opposite side of and running parallel with the inclined ridges 52 and 54. The spacing bars 60, 62, 64, and 66 extend from the outer surface 46 of the main body 26 at a uniform height or, preferably, they begin flush with the outer surface 46 of the main body 26 and gradually increase in height until they reach the open end 50 of the main body 26, in a manner similar to the inclination of the ridges 52 and 54.
The entire main body 26, including the cylindrical portion 38, the tines 40 and 42, the inclined ridges 52 and 54, and the spacing bars 60, 62, 64, and 66, is preferably molded as a single integral plastic or polypropylene unit, although a variety of synthetic or natural materials and fabrication techniques could be employed in constructing the main body 26.
The annular stop ring 30 is positioned coaxially around the closed end 48 of the main body 26 where it is permanently attached to the outer surface 46 of the main body 26, such as with an adhesive or by plastic welding. The clamping sleeve 28 is formed as an integral cylinder which surrounds the main body 26. The clamping sleeve 28 moves axially along the outer surface 46 of the main body 26.
The annular clamping sleeve 28 is initially positioned on the main body 26 by pressing the tines 40 and 42 together at the outer ends of the slots 39 and 41 until the distance between the shoulders 56 and 58 is less than the inside diameter of the clamping sleeve 28. The clamping sleeve 28 is then slid axially over the shoulders 56 and 58. The tines are then released and the clamping sleeve 28 is free to slide axially along the outer surface 46 of the main body 26 between the stop ring 30 and the shoulders 56 and 58.
The end piece 32 is positioned coaxially within the closed end 48 of the main body 26 where it is permanently attached to the inner surface 44 of the main body 26, such as with an adhesive or by plastic welding. While the stop ring 30 and the end piece 32 have been described as being permanently attached to the main body 26, the main body 26, stop ring 30, and end piece 32 could be molded together into one integral unit.
As shown in FIGS. 5, 6, and 7, a stick of chalk 20 is inserted into and held within the handle 14 of the toy 10. Preferably the chalk 20 is in the form of a slightly tapered cylinder as shown in FIG. 5. The chalk 20 may consist of any material or combination of materials which are typically used in the construction of chalk 20. The chalk 20 may come in a variety of colors and is usually larger than conventional blackboard chalk.
Before inserting the chalk 20 into the handle 14, the clamping sleeve 28 is slid back toward the closed end 48 of the main body 26 until it abuts the stop ring 30, thus allowing the tines 40 and 42 to become fully separated and placing the handle 14 in its open configuration, as shown in FIG. 5. Next, the chalk 20 is inserted between the tines 40 and 42 and into the main body 26 as shown in FIG. 6. The clamping sleeve 28 is then slid forward along the main body 26 toward the shoulders 56 and 58 located at the open end 50 of the main body 26. As the clamping sleeve 28 moves away from the stop ring 30 it engages the inclined ridges 52 and 54, as shown in FIG. 5, thus forcing the tines 40 and 42 towards one another and applying frictional force on the chalk 20 to hold the chalk 20 in the handle 14. When the clamping sleeve 28 abuts the shoulders 56 and 58, as shown in FIG. 7, the tines 40 and 42 are completely closed around the chalk 20 and the handle 14 is in its closed configuration. The spacing bars 60, 62, 64, and 66 function to evenly guide and position the clamping sleeve 28 on the main body 26 as it moves between the stop ring 30 and the shoulders 56 and 58, and to assist in preventing the clamping sleeve 28 from binding on the main body 26 due to misalignment.
When a new stick of chalk 20 is placed in the handle 14 in the manner described above, an exposed portion 68 (FIG. 7) of the chalk 20 will extend beyond the open end 50 of the main body 26 permitting the exposed portion 68 of the chalk 20 to be used to write or draw on the sidewalk or pavement. As the exposed portion 68 of the chalk 20 wears down, the chalk 20 may be further extended from the handle 14. The clamping sleeve 28 is slid back along the main body 26 until it abuts the stop ring 30, the chalk 20 is repositioned in the handle 14 to more fully expose a larger exposed portion 68 of the chalk 20, and the clamping sleeve 28 is slid forward to abut the shoulders 56 and 58 and hold the chalk 20 in its new position.
The combination jump rope and sidewalk chalk holder toy 10 can be used both as a conventional jump rope or as a convenient holder for sidewalk chalk. Toy 10 may be used in a way that combines jumping rope with the use of sidewalk chalk 20. For example, jumping games may be played which require a pattern or playing area to be drawn on the ground, over or through which one jumps using the rope. In jump rope games which require scoring, scoring may be kept by marking the scores on the sidewalk with the sidewalk chalk 20 held in the handle 14. The rope can also be positioned as a border around objects drawn on the sidewalk in non-jumping games, for example. Accurate circles or arcs may be made on the sidewalk or pavement by firmly holding one end of the rope 16 as a center point, pulling the rope 16 taut, and circumscribing a line with the chalk held in the handle 14. Combining a jump rope and sidewalk chalk holder in this way provides all of these features in one light and portable toy and also facilitates and encourages new games and play.
Presently preferred embodiments of the invention and its improvements have been described with a degree of particularity. This description has been made by way of preferred example. It should be understood that the scope of the present invention is defined by the following claims, and should not be unnecessarily limited by the detailed description of the preferred embodiment set forth above.
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An elongated flexible rope has a pair of handles connected at opposite ends of the rope, and at least one of the handles retains a stick of sidewalk chalk. The handle is a chalk holder, and the resulting combination facilitates new forms of games and play involving jumping rope and marking with the chalk.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a method for surface treatment of a sliding portion, and in particular, to a method for surface treatment of a sliding portion, in which lubricativeness is given to the sliding portion of a tool, a die, a piston of an engine, a bearing, a shaft, and in addition hereto, an article including a portion (a sliding portion) sliding on another member as an object to be treated.
2. Description of the Prior Art
In many cases, fluid lubricant such as oil or grease is used in lubricating the sliding portion. However, responding to the case where the fluid lubricant cannot be used for reason of the design of the sliding portion, or the case where fluid and adsorptive air are evaporated and desorbed due to restrictions in the use environment, for example, like the case of use in vacuum, and further, and by the social demand for reducing as much as possible the use of fluid lubricant, accompanied by the recent trend of more sensitive reaction to environmental problems or the like, various solid lubricants have been proposed.
As one example of such solid lubricants, graphite(C), molybdenum disulfide (MoS 2 ), tungsten disulfide (WS 2 ), boron nitride (BN), or the like is used.
In addition, there is a method of forming a wear resistance layer on the sliding portion by use of the solid lubricant, by injecting particles of the solid lubricant onto the surface of the object to be treated at a predetermined injection pressure or speed or more to diffuse and penetrate elements in the solid lubricant composition into the surface thereof (refer to Japanese Patent KOKAI (LOPI) No. 11-131257).
In addition, there has been proposed a method in which solid lubricant powder and soft metal are mechanically contacted with each other for forming solid lubricant-containing soft metal powder, and a low-friction layer is formed by causing this solid lubricant-containing soft metal to contact with the surface of a metal member by use of mechanical means such as a shot blast, a barrel, and a ball mill (Japanese Patent KOKAI (LOPI) No. 2000-282259).
In a shot blast or shot peening of injecting the injection particles together with compressed air, when the compressed air is injected toward the object to be treated with an injection nozzle as shown in FIG. 1 (B), the compressed air which has collided with the surface of the object to be treated is reflected back by the object to be treated, thereby causing a layer made of the compressed air to be formed on the surface of the object to be treated, and together therewith the compressed air which has been interrupted in going straight to the object to be treated to change its flow into the direction along the surface of the object to be treated.
Therefore, in a case where the injection are smaller and lighter in relative relation to the injection pressure or the like of the compressed air, the injection particles get caught up in the flow of the compressed air, and the injection particles together with the compressed air are forced to change the flying direction thereof. As a result, the amount of injection particles colliding with the surface of the object to be treated is reduced. Further, collision energy of the injection particles is reduced due to the change in the flying direction as described above, or due to the layer of the compressed air formed on the surface of the object to be treated, and it becomes impossible to efficiently perform the diffusion/penetration of the injection particles into the object to be treated, and in turn, the formation of the wear resistance layer.
Therefore, as injection particles used in the shot blast or the shot peening, the injection particles having a particle size which enables the injection particles to effectively collide with the surface of the object to be treated is selected in light of the degree and purpose of working or in the relative relation to the working condition such as the injection pressure, and in the case where the injection particles once injected are used again, the fragmentized particles are removed out of the collected injection particles, thereby to make an adjustment so that their size is in a predetermined range.
By the way, graphite(C), molybdenum disulfide (MoS 2 ), tungsten disulfide (WS 2 ), or boron nitride (BN) exemplified as the solid lubricant is a layer-structure solid lubricant. In explanation of graphite as one example, graphite is of a hexagonal plate-crystal layered structure, wherein a carbon-carbon bond is formed on the surface of each layer constituting the layered structure by strong covalent bonding, whereas an inter-layer bond is formed by a relatively weak force. And the sliding occurs between the layers when a load is applied to the layered structure, which provides the lubricativeness.
Therefore, as shown in Japanese Patent KOKAI (LOPI) No. 11-131257, in the case of using the layered-structure solid lubricant as an injection particle, the impact at the time of colliding with the object to be treated incurs inter-layer peeling and causes the injection particles to be finely fragmentized so that many injection particles cannot be reused after one time-injection, which leads to an increase in a wear-out rate and hence in the cost of this kind of surface treatment.
As one example, when the layered-structure solid lubricant having an average particle diameter of 20 μm is injected onto the surface of the object to be treated as injection particles, the injection particles collected after the one-time injection have been fragmentized to pieces, each having an average particle diameter equal to or less than 10 μm. Even in the case of using any layered-structure solid lubricant as injection particles, it has been confirmed that when the injection particle is equal to or less than 5 μm in a diameter, an efficiency of the diffusion/penetration deteriorates, and when it is equal to or less than 1 μm in diameter, the efficiency thereof deteriorates extremely.
In addition, calculation of the expense of molybdenum disulfide required in the treatment based upon the wear-out rate of the injection particle in an attempt where a piston of an engine for an automobile is used as an object to be treated and the wear resistance layer is formed by use of molybdenum disulfide as an injection particle demonstrates that it is more costly by 100 yen or more per piston.
In a case where graphite, which is less expensive as compared with molybdenum disulfide, is used as an injection particle, the cost can be decreased to a low level. However, when graphite as carbon is fragmentized at the time of collision with the object to be treated to produce powder dust, there is a danger that powder dust fire or the like may possibly occurs. In addition, even when any one of the layered-structure solid lubricants is used, the powder dust produced due to the fragmentation pollutes and deteriorates the working environment.
In contrast, in the method described in Japanese Patent KOKAI (LOPI) No. 2000-282259 in which the solid lubricant-containing soft metal powder formed by mechanically contacting with the solid lubricant powder and the soft metal each other is used as injection particles, even in the case where the layered-structure solid lubricant is used as the solid lubricant powder, this solid lubricant powder is difficult to fragmentize because it is carried by the soft metal. Accordingly, it is thought that the problem with deterioration in the working environment caused by the powder dust is improved, as compared to the case of independently injecting the layered-structure solid lubricant.
However, according to the method described in Japanese Patent KOKAI (LOPI) No. 2000-282259 listed above, in order to obtain the injection particles, it is necessary that the solid lubricant powder and the soft metal are mechanically contacted with each other in advance to obtain the solid lubricant-containing soft metal powder, which is a complicated process.
Since the solid lubricant-containing soft metal powder obtained as described above is one obtained by carrying the solid lubricant powder on the particle surface of the soft metal, when the solid lubricant-containing soft metal powder is collided with the surface of the object to be treated, and the solid lubricant carried on the surface is adhered to the object to be treated, the amount of the solid lubricant equivalent to the one that has adhered to the object to be treated is lost from the surface of the solid lubricant-containing soft metal powder. Accordingly, using this repeatedly results in that the solid lubricant powder is transformed into one that cannot adhere to the object to be treated by a necessary amount.
Therefore, in the case of adopting the method described in Japanese Patent KOKAI (LOPI) No. 2000-282259, when the injection particle once injected is collected for reuse, unless the procedure is performed of causing the collected injection particles and the solid lubricant powder to mechanically contact with each other again, and of causing the solid lubricant powder to adhere to the surface of the soft metal, the layer with a stable quality cannot be formed.
Additionally, the layer formed with the solid lubricant or the like is used in place of the fluid lubricant such as oil or grease under the foregoing vacuum environment, but it is used under normal-pressure environment together with the fluid lubricant in many cases, and there are also many cases where it is provided for purpose of protecting the sliding portion from wearing in the event of the accidental loss of the oil layer in the sliding portion.
In the case of use of the layer with the fluid lubricant thus, it is preferable in a point of making generation of seizing etc. difficult all the more that minute concavities, which have the effect of an oil reservoir which makes it difficult that the oil layer loss occurs on the sliding portion of the object to be treated, are formed a lot.
However, in any method described above as the prior art, the concavity to achieve the effect of an oil reservoir like this cannot be formed simultaneously with the formation of the layer.
Thereupon, the present invention has been made for solving the problems in the above-mentioned prior art, and an object of the present invention is to provide a method for surface treatment of the sliding portion, which enables the surface treatment to be carried out economically for the sliding portion even in the case of using the layered-structure solid lubricant as an injection particle, the risk of pollution for the working environment, a powder dust fire, or the like is reduced, yet high lubricativeness is achieved, and moreover many concavities are formed on the sliding portion simultaneously with giving the lubricativeness.
SUMMARY OF THE INVENTION
In order to achieve the object, the method for surface treatment of the sliding portion according to the present invention includes the steps of injecting the injection particles obtained by blending the soft-metal solid lubricant particles of which the surface has been oxidized and the layered-structure solid lubricant particles onto the surface of the sliding portion at an injection speed of 150 m/sec or more, diffusing and penetrating an oxide of the soft-metal solid lubricant and the layered-structure solid lubricant into the surface of the sliding portion of the product to be treated to form the layer thereon, and forming many concavities, which are minute and substantially arc in cross section, on the surface of the sliding portion.
In the method for surface treatment of the sliding portion mentioned above, it is preferable that the concavity is formed to have an average diameter of 0.1 to 10 μm and an average depth of 0.1 to 5 μm.
In addition, the particle diameter of the solid lubricant particle is preferably in the range of 20 to 100 μm, and one having a particle diameter of 50 μm or so is used more preferably. In addition, the layered-structure solid lubricant particle having a particle diameter of 20 μm or less may be used, and even when fragmentized to a particle diameter of 5 μm or less, the layer can be stably formed by use of the fragmentized particle.
Further, the layered-structure solid lubricant particles comprising one or more of particles selected from a group of, for example, graphite(C), molybdenum disulfide (MoS 2 ), tungsten disulfide (WS 2 ), and boron nitride (BN) is blended with the soft-metal solid lubricant particles at a ratio of 5 to 30% by weight, preferably at a ratio of 10% or so by weight
According to the arrangement of the present invention as described above, the method for surface treatment of the sliding portion of the present invention makes it possible to stably form the layer even in the case where the fragmentized layered-structure solid lubricant is used repeatedly as it is without removal thereof notwithstanding use of the layered-structure solid lubricant, which is easily fragmentized by collision with the object to be treated, as injection particles and to form many concavities functioning as an oil reservoir etc. on the surface of the sliding portion of the object to be treated at the same time with formation of the layer caused by the diffusion/penetration of the solid lubricant, and moreover to decrease the occurrence of the powder dust at the time of the treatment.
BRIEF DESCRIPTION OF THE DRAWINGS
The objects and advantages of the invention will become apparent from the following detailed description of preferred embodiments thereof provided in connection with the accompanying drawings in which:
FIGS. 1(A)-1(B) are explanatory views showing the relation between the flow of compressed air and the flying direction of the injection particles, wherein FIG. 1(A) shows the case where the soft-metal solid lubricant particles and the layered-structure solid lubricant particles are blended for injection, and FIG. 1(B) shows the case of independently injecting the layered-structure solid lubricant particles;
FIGS. 2(A)-2(C) are photomicrographs (×400) of a surface of an aluminum plate as an object to be treated, wherein FIG. 2(A) shows the case of an untreated aluminum plate, FIG. 2(B) shows the state after treatment of an embodiment 1-1 in which the method of the present invention is applied directly to the untreated aluminum plate, and FIG. 2(C) shows the state after treatment of an embodiment 1-2 in which the method of the present invention is applied after a blast treatment;
FIGS. 3(A)-3(C) are photomicrographs (×400) of a surface of a stainless plate as an object to be treated, wherein FIG. 3(A) shows the case of an untreated stainless plate, FIG. 3(B) shows the state after treatment of an embodiment 2-1 in which the method of the present invention is applied directly to the untreated stainless plate, and FIG. 3 (C) shows the state after treatment of an embodiment 2-2 in which the method of the present invention is applied after a blast treatment,
FIGS. 4(A)-4(C) are photomicrographs (×400) of a surface of a titanium plate as an object to be treated, wherein FIG. 4(A) shows the case of an untreated titanium plate, FIG. 4(B) shows the state after treatment of an embodiment 3-1 in which the method of the present invention is applied directly to the untreated titanium plate, and FIG. 4(C) shows the state after treatment of an embodiment 3-2 in which the method of the present invention is applied after a blast treatment;
FIGS. 5(A)-5(B) are photomicrographs (× 400 ) of a surface of an aluminum plate as an object to be treated, wherein FIG. 5(A) shows the case of an untreated aluminum plate, and FIG. 5(B) shows the state after treatment of the comparative example 1;
FIGS. 6(A)-6(B) are photomicrographs (×400) of a surface of a stainless plate as an object to be treated, wherein FIG. 6(A) shows the case of an untreated stainless plate, and FIG. 6(B) shows the state after treatment of the comparative example 2;
FIGS. 7(A)-7(B) are photomicrographs (×400) of a surface of a titanium plate as an object to be treated, wherein FIG. 7(A) shows the case of an untreated titanium plate, and FIG. 7(B) shows the state after treatment of the comparative example 3;
FIGS. 8(A)-8(C) are photomicrographs (×400) of a surface of a glass plate as an object to be treated, wherein FIG. 8(A) shows the case of an untreated glass plate, and FIG. 8(B) shows the state after treatment by the method of the present invention; and
FIGS. 9(A)-9(B) are photomicrographs (×400) of a surface of a glass plate as an object to be treated, wherein FIG. 9(A) shows the case of an untreated glass plate, and FIG. 9(B) shows the state after injection of molybdenum disulfide alone.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Next, embodiments of the present invention will be hereinafter explained.
Entire Arrangement
The method for surface treatment of the sliding portion according to the present invention includes the steps of injecting the injection particles obtained by blending the soft-metal solid lubricant particles of which the surfaces have been oxidized and the layered-structure solid lubricant particles onto the surface of the object to be treated at an injection speed of 150 m/sec or more, diffusing and penetrating an oxide of the soft-metal solid lubricant and the layered-structure solid lubricant into the surface of the object to be treated to form the layer thereon, and simultaneously therewith, forming numberless concavities, which are minute and substantially arc in cross section, on the sliding portion.
Note that the injection of the injection particles may be carried out after performing the blast treatment of the object to be treated. In this case, this blast treatment may be performed by injecting, for example, alumina having a particle diameter of 74 to 37 μm, silica beads, alundum (A), and carbon (C) (polygonal) at an injection pressure of 0.3 to 0.1 MPa, or at an injection speed of 150 to 50 m/sec.
When a material hardness of the sliding portion is high, it is difficult to form the concavities by the surface-oxidized soft metal. Especially with regard to the sliding portion having a material hardness exceeding HV600, forming the concavities in advance leads to reduction in work time.
Note that with regard to an abrasive material, a spherical abrasive material as a metal, a ceramic or a blended article thereof, or a polygonal abrasive material as a ceramic, A, white alundum (WA), C, or the like may be used and the particle diameter of both of the abrasive materials is preferably equal to or less than #220.
Treatment Object
As an object to be treated in the present invention, various articles having the portion (sliding portion), which slides on another member etc., can be treatment objects, and mechanical elements such as a piston of an engine, a bearing or a rotating shaft, a gear and a shaft, a cutting tool, and a die are exemplified as an object to be treated.
The method for the treatment of the present invention can be applied to a metal, ceramic or general blended article thereof as the material of the object to be treated. In addition, even in the case of use of glass as an object to be treated, the layer of the solid lubricant can be formed.
Injection Particle
The injection particles used in the method of the present invention is a blended one of the surface-oxidized soft metal solid lubricant particles and the layered-structure solid lubricant particles as mentioned above.
Soft-Metal Solid Lubricant Particle
The particles of tin (Sn) and zinc (Zn) can be used as a soft-metal solid lubricant particles, and this surface-oxidized soft-metal solid lubricant particles are used as injection particles together with the layered-structure solid lubricant to be described later.
Note that as the surface-oxidized soft-metal solid lubricant particles, besides the above, silver (Ag), indium (In), lead (Pb), etc. are thought to be used, but since silver (Ag) and indium (In) are expensive and lead (Pb) is harmful, they are not suitable for use.
Oxidization of the surface of the soft-metal solid lubricant particles may be performed with any method, and in this embodiment, the surface of the soft-metal solid lubricant particles is oxidized with a liquid atomization method.
The soft-metal solid lubricant particle of which the surface has been oxidized thus is relatively soft because the oxidized surface portion is high in hardness and the inside is of the soft metal that has not been oxidized.
The particle diameter of the soft-metal solid lubricant particle to be used is in the range of 20 to 100 μm, and one having a particle diameter of 50 μm or so is used preferably.
Layered-Structure Solid Lubricant Particle
As a layered-structure solid lubricant particle, the layered structure of graphite(C), molybdenum disulfide (MoS 2 ), tungsten disulfide (WS 2 ), boron nitride (BN), phthalocyanine or the like is used.
The layered-structure solid lubricant particle having a particle diameter of 20 μm or less may be used, and even when fragmentized to a particle diameter of 5 μm or less, the fragmentized particle may be used as it is by collecting the injected injection particle and using it repeatedly.
Blending Ratio
With regard to a blending ratio of the surface-oxidized soft-metal solid lubricant particles to the layered-structure solid lubricant particles, the layered-structure solid lubricant grain of 5 to 30% by weight, preferably 10% or so by weight is blended with the surface-oxidized soft-metal solid lubricant particles, which are used as the injection particles.
Operation
When the injection particles obtained as described above are injected onto the sliding portion of the object to be treated at an injection speed of 150 m/sec or more, both surfaces of the object to be treated and the injection particles have heat energy generated, in consideration of the law of conservation of energy based upon the speed change between before and after the collision of the injected injection particles with the sliding portion of the object to be treated.
Since the conversion of energy is performed only at deformed portions with which the injection particles have collided, temperature rises locally in the injection particles and in the vicinity of the surface of the sliding portion of the object to be treated.
Since this temperature rise is in proportion to the speed prior to the collision of the injection particles, making the injection speed of the injection particles high makes it possible to increase the temperature of the injection particles and the surface of the sliding portion of the object to be treated.
Accordingly, it is thought that the oxide formed on the surface of the soft-metal solid lubricant constituting the injection particles and the layered-structure solid lubricant particles are heated due to colliding with the sliding portion of the object to be treated, the injection particles are activated and adsorbed into the surface of the sliding portion of the object to be treated, whereby they diffuse/penetrate. As a result, a layer made of the oxide of the soft-metal solid lubricant and the layered-structure solid lubricant is formed on the surface of the sliding portion of the object to be treated.
The oxide formed on the surface of the soft-metal solid lubricant particles are activated and adsorbed into the sliding portion of the object to be treated due to the foregoing collision, and diffuse and penetrate, and the oxide on the surface of the soft-metal solid lubricant particles partly disappear due to activation and adsorption by the sliding portion of the object to be treated, but since the portion where the surface oxide has disappeared is instantaneously oxidized due to the heat at the collision time, the soft-metal solid lubricant particles maintain the state where the surface has been oxidized without re-oxidization with the water atomized method or the like.
In addition, since the oxidized surface of the soft-metal solid lubricant particle has a hardness of HV1000 or more due to the oxidization, many concavities, which is substantially arc in cross section, are formed on the sliding portion of the object to be treated, and also, compressive residual stress is provided on the surface of the sliding portion.
The oxidized surface of the soft-metal solid lubricant particle shows a high hardness as described above, but the inside thereof is of the soft metal which has not been oxidized. Therefore, the soft metal in the inside serves as a cushion and the formed concavities are relatively shallow, which makes it difficult that the sliding portion of the object to be treated will be surface-roughed.
Each of the concavities thus formed, which has a diameter of substantially 0.1 to 10 μm and a depth of 0.1 to 5 μm or so, has an idealistic shape as an oil reservoir.
When the injection particles are thus injected onto the object to be treated, the layered-structure solid lubricant particles in the injection particle are relatively easily fragmentized due to impact at the time of the collision and the particle diameter is reduced.
Therefore, as explained with reference to FIG. 1(B) , in the case of injecting only the layered-structure solid lubricant particles independently, reduction in the particle diameter caused by this fragmentation allows the amount of the layered-structure solid lubricant particles colliding with the sliding portion of the object to be treated to be reduced, or energy at the time of the collision to be reduced, thereby making the diffusion/penetration of the particle into the sliding portion difficult together with reduction in the particle diameter.
However, in the case of injecting the layered-structure solid lubricant particles together with the soft-metal solid lubricant particles having a particle diameter of 20 to 100 μm, preferably 50 μm or so, it is possible to stably perform the diffusion/penetration of the layered-structure solid lubricant into the sliding portion of the object to be treated regardless of reduction in the particle diameter of the layered-structure solid lubricant particle.
It is considered that the diffusion/penetration into the sliding portion of the object to be treated can be stably performed in such a manner although the particle diameter of the layered-structure solid lubricant particle is reduced, and the layered-structure solid lubricant particle, which has been fragmented and has reduced in the particle diameter, is pushed by the soft-metal solid lubricant particle, which is difficult to fragmentize and maintains the initial particle diameter, to reach the surface of the sliding portion of the object to be treated where the stable diffusion and penetration are performed (refer to FIG. 1(A) ).
As a result, even in the case where the layered-structure solid lubricant particle of which the initial particle diameter was 20 μm or so is fragmentized to have a particle diameter of 5 μm or less, it is possible to stably perform the formation of the layer, and even in the case of collecting the injection particle, which was used once, and of which the layered-structure solid lubricant particle was fragmentized, and of using it repeatedly, it is possible to stably perform the formation of the layer, which enables the surface treatment of the present invention to be economically performed.
Embodiments
Next, embodiments of the method for surface treatment of the sliding portion will be explained using comparative examples.
Surface Treatment Test
An aluminum plate, a stainless plate, and a titanium plate are respectively prepared as an object to be treated and the results obtained by performing the surface treatment to each treatment object are shown below.
1. Embodiment 1, Comparative Example 1
Treatment object; aluminum plate (50×50×1 mm)
Embodiment 1 (Embodiment 1-1, Embodiment 1-2); the tin particles of 2 kg the surfaces of which were oxidized with the water atomized method and the molybdenum disulfide particles of 200 g were blended, which were injected onto the aluminum plate (50×50×1 mm) as an injection particle at conditions shown in Table 1.
Note that as Embodiment 1, the above-mentioned injection particles were injected directly onto the untreated aluminum plate (Embodiment 1-1) and also the injection particles were injected onto the aluminum plate for which the blast treatment was performed by injecting spherical alumina and silica beads having a particle diameter of 55 μm at an injection pressure of 0.2 MPa as a pre-treatment (Embodiment 1-2).
Comparative example 1; only the molybdenum disulfide particles were injected as the injection particles onto the aluminum plate (50×50×1 mm) at conditions shown in Table 1.
TABLE 1 Treatment conditions and treatment results of Embodiment 1 and Comparative example 1 Embodiment Comparative 1 (1-1, 1-2) example 1 Injection pressure Fine powder type Fine powder type 0.6 Mpa 0.6 Mpa Injection time 100 mm 100 mm Injection time 15 sec 15 sec Injection nozzle diameter Diameter 9 mm Diameter 9 mm Surface-oxidized metal Tin (water atomized) particle 50 μm Solid lubricant particle MoS 2 5 μm or less MoS 2 20 μm Treatment conditions Working Possible to confirm Product to be treated atmosphere treatment object visually cannot be seen at all due to powder dust Condition of Concavity exists on Layer adheres to surface surface. surface thickly. Layer adheres to surface thinly and equally. Use amount Average 0.8 g per one Average 2.0 g per (consumption plate one plate amount) of MoS 2
2. Embodiment 2, Comparative Example 2
Treatment object; stainless plate (50×50×1 mm)
Embodiment 2 (Embodiment 2-1, Embodiment 2-2); the zinc particles of 2 kg the surfaces of which were oxidized with the water atomized method and the molybdenum disulfide particles of 200 g were blended, which were injected onto the stainless plate (50×50×1 mm) as the injection particles at conditions shown in Table 2.
Note that as Embodiment 2, the injection particles were injected directly onto the untreated stainless plate (Embodiment 2-1) and also the injection particles were injected onto the stainless plate for which the blast treatment was performed by injecting spherical alumina and silica beads having a particle diameter of 55 μm at an injection pressure of 0.3 MPa as a pre-treatment (Embodiment 2-2).
Comparative example 2; only the molybdenum disulfide particles were injected as the injection particles onto the stainless plate (50×50×1 mm) at conditions shown in Table 2.
TABLE 2 Treatment Conditions and treatment results of Embodiment 2 and Comparative example 2 Embodiment Comparative 2 (2-1, 2-2) example 2 Injection pressure Fine powder type Fine powder type 0.6 Mpa 0.6 Mpa Injection distance 100 mm 100 mm Injection time 15 sec 15 sec Injection nozzle diameter Diameter 9 mm Diameter 9 mm Surface-oxidized metal Zinc (water atomized) particle 50 μm Solid lubricant particle MoS 2 5 μm or less MoS 2 20 μm Treatment conditions Working Possible to confirm Product to be treated atmosphere treatment object visually cannot be seen at all due to mine dusts Condition of Concavity exists on Layer adheres to surface surface. Layer adheres surface thickly. to surface thinly and Difficult for layer to equally. adhere to surface. Use amount Average 1.0 g per one Average 2.5 g per (consumption plate one plate amount) of MoS 2
3. Embodiment 3, Comparative Example 3
Treatment object; titanium plate (50×50×1 mm)
Embodiment 3 (Embodiment 3-1, Embodiment 3-2); the tin particles of 2 kg the surfaces of which were oxidized with the water atomized method and the molybdenum disulfide particles of 200 g were blended, which were injected onto the titanium plate (50×50×1 mm) as the injection particles at conditions shown in Table 3.
Note that as Embodiment 3, the injection particles were injected directly onto the untreated titanium plate (Embodiment 3-1) and also the injection particles were injected onto the titanium plate for which the blast treatment was performed by injecting spherical alumina and silica beads having a particle diameter of 55 μm at an injection pressure of 0.3 MPa as a pre-treatment (Embodiment 3-2).
Comparative example 3; only the molybdenum disulfide particles were injected as an injection particle onto the titanium plate (50×50×1 mm) at conditions shown in Table 3.
TABLE 3
Treatment conditions and treatment results of Embodiment 3 and
Comparative example 3
Embodiment
Comparative
3 (3-1, 3-2)
example 3
Injection pressure
Fine powder type
Fine powder type
0.6 Mpa
0.6 Mpa
Injection distance
100 mm
50 mm*
Injection time
15 sec
15 sec
Injection nozzle diameter
Diameter 9 mm
Diameter 9 mm
Surface-oxidized metal
Tin (water atomized)
particle
50 μm
Solid lubricant particle
MoS 2 5 μm or less
MoS 2 20 μm
Treatment conditions
Working
Possible to confirm
Product to be
atmosphere
treatment object visually
treated cannot be
seen at all by
powder dusts
Condition of
Concavity exists on
Layer adheres to
surface
surface. Layer adheres
surface thickly.
to surface thinly and
Difficult for
equally.
layer to adhere to
surface.
Use amount
Average 1.0 g per one
Average 3.0 g per
(consumption
plate
one plate
amount) of MoS 2
*Since it was difficult for the injection particle to adhere to the surface, the injection distance was set as 50 mm.
As a result of the above, the surface treatment of each of Embodiments 1 to 3 enabled the consumption amount of molybdenum disulfide (MoS 2 ) to be reduced as compared to that of Comparative examples 1 to 3 and, in details, enabled the consumption amount to be reduced in the aluminum plate and stainless plate each by 60%, and in the titanium plate by 67%, respectively.
In addition, it was confirmed that the concavity was formed on the surface of the object to be treated in Embodiments 1 to 3 (refer to FIGS. 2 to 4 ).
In contrast, although it was confirmed that in Comparative examples 1 to 3 where only the molybdenum disulfide (MoS 2 ) particles were injected, the molybdenum disulfide adhered to the surface of the object to be treated, the adherence amount was great so that a dimensional accuracy of the product to be treated might be impaired, and although the surface of treatment object became rugged, the concavity suitable for an oil reservoir was not formed because this ruggedness was produced due to uneven adherence of the molybdenum disulfide (refer to FIGS. 5 to 7 ).
Further, in Embodiments 1 to 3, an improvement in the compressive stress on the surface was confirmed, and an increase in the hardness also was confirmed such that that the hardness of the aluminum plate was increased by HV100 or so, and that of the stainless plate and the titanium plate was increased by HV100 or more, respectively.
Note that in Comparative examples, the higher the hardness of the object to be treated was, the more difficult it was to form the layer, and in Comparative example 3 of using the titanium plate as an object to be treated, the injection distance had to be set close to 50 mm which was half of that in Embodiment because it was difficult to form the layer at the same conditions as that of the Embodiment. On the other hand, in the surface treatment of each of Embodiments 1 to 3, it was possible to stably form any layer at the same conditions despite the material of the object to be treated.
4. Others
In addition, according to the method of the surface treatment of the present invention, the layer of the solid lubricant can be formed on not only the foregoing metal materials but also ceramics or glass.
When, as one example, the surface treatment was performed to the glass plate as an object to be treated at the same conditions as that of the Embodiment 1, it was confirmed that it was possible to form a layer of the solid lubricant on the surface of the glass as well (refer to FIG. 8 ).
On the other hand, also in the case of injecting the molybdenum disulfide particles onto the glass plate as an object to be treated likewise, it was found out that it was possible that the solid lubricant was adhered to the surface of the glass plate, but the adherence was thick and rough (refer to FIG. 9 ).
Endurance Test
The product of the embodiment treated with the method of the surface treatment of the present invention and the product of the comparative example treated by using only the layered-structure solid lubricant particle as an injection particle were compared in terms of durability (life time). The result is shown below.
1. Embodiment 4, Comparative Example 4 (Lifetime Measurement of Fine-Blanking Punch)
The endurance test result of the fine-blanking punch (Embodiment 4) surface-treated with the method of the present invention and the fine-blanking punch (Comparative example 4) surface-treated by injecting only the layered-structure solid lubricant particles is shown in Table 4.
Note that the work conditions in Embodiment 4 and Comparative example 4 are as shown in Table 4, and the treatment conditions not shown in Table 4 are the same as that of Table 1.
In addition, the injection pressure was increased to 0.7 MPa in Comparative example 4 because the diffusion/penetration amount of the solid lubricant is reduced when the injection pressure is set to the same amount as that of Embodiment 4.
TABLE 4
Embodiment 4
Comparative example 4
Treatment time
Approximately
Approximately 1.5 min
1.5 min
at a pressure of 0.7 Mpa
Use amount of MoS 2
2.0 g
10.0 g
(consumption amount)
Average lifetime of die
405,000 pieces
135,000 pieces
Treatment object
Fine-blanking punch
(Working a high tensile steel sheet SANH60)
Average lifetime of untreated one
(27,000 pieces)
Material: YXR 3
Surface treatment: TiCN
Work material
High tensile steel sheet SANH60
(thickness: 2.0 mm)
As a result of the above, it was confirmed that a lifetime of the fine-blanking punch in Embodiment 4 was three times that of the fine-blanking punch in Comparative example 4. Moreover, in comparison to the untreated fine-blanking punch, it was confirmed that the lifetime was 15 times and the method of the surface treatment of the present invention allowed the friction resistance to be largely reduced.
2. Embodiment 5, Comparative Example 5 (Lifetime Measurement of Trimming Punch)
The endurance test result of the trimming punch (Embodiment 5) surface-treated with the method of the present invention and the trimming punch (Comparative example 5) surface-treated by injecting only the layered-structure solid lubricant particles is shown in Table 5.
Note that the work conditions in Embodiment 5 and Comparative example 5 are as shown in Table 5, and the treatment conditions not shown in Table 5 are the same as that of Table 1.
In addition, the injection pressure was increased to 0.7 MPa in Comparative example 5 because the diffusion/penetration amount of the solid lubricant is reduced when the injection pressure is set to the same amount as that of Embodiment 5.
TABLE 5
Embodiment 5
Comparative example 5
Treatment time
Approximately 15 sec
Approximately 15 sec
at a pressure of 0.7 Mpa
Use amount of MoS 2
1.0 g
4.0 g
Average lifetime of die
175,000 pieces
125,000 pieces
Treatment object
Trimming punch
Average lifetime of the untreated one
(25,000 pieces)
Material: SKH51
Surface treatment: TiN
Size 15 × 15 × 75 L (mm)
Work material
SUS 301 (thickness: 0.31 mm)
As a result of the above, it was confirmed that the lifetime of the trimming punch in Embodiment 5 was 1.4 times that of the trimming punch in Comparative example 5. Moreover, in comparison to the untreated trimming punch, it was confirmed that the lifetime was seven times and the method of surface treatment of the present invention allowed the friction resistance to be largely reduced.
3. Embodiment 6, Comparative Example 6 (Lifetime Measurement of Drawing Die)
The endurance test result of the drawing die (Embodiment 6) surface-treated by the method of the present invention and the drawing die (Comparative example 6) surface-treated by injecting only the layered-structure solid lubricant particles is shown in Table 6.
Note that the work conditions in Embodiment 6 and Comparative example 6 are as shown in Table 6, and the treatment conditions not shown in Table 6 are the same as that of Table 1.
In addition, the injection pressure was increased to 0.9 MPa in Comparative example 6 because the diffusion/penetration amount of the solid lubricant is reduced when the injection pressure is set to the same amount as that of Embodiment 6.
TABLE 6
Embodiment 6
Comparative example 6
Treatment time
Approximately 2 min
Approximately 2 min at
only for inner diameter
pressure of 0.9 Mpa
of φ50
Use amount of MoS 2
3.0 g
15.0 g
Average lifetime of die
560,000 pieces
210,000 pieces
Treatment object
Drawing die
Average lifetime of untreated one (70,000 pieces)
Material: YXR 3
Surface treatment: TiCN
Size: outer diameter 150 × inner diameter
50 × 100 L (mm)
Work material
High tensile steel sheet SANH60P
(thickness: 5.0 mm)
As a result of the above, it was confirmed that the lifetime of the drawing die in Embodiment 6 was 2.7 times that of the drawing die in Comparative example 6. Moreover, in comparison to the untreated drawing die, it was confirmed that the lifetime was eight times and the method of surface treatment of the present invention allowed the friction resistance to be largely reduced.
As accompanied by the weight saving of automobiles in recent years, the steel sheet to be used has become thin in thickness, and the high tensile steel sheet has been used for strength guarantee. However, the situation is that tools for working these steel sheets have not been improved in terms of strength in response thereto, and many problems have occurred caused by the reduction in lifetime or the like.
It was confirmed that also in the test for the drawing die used under such harsh conditions, the die surface-treated with the method of the present invention improved remarkably in lifetime and was able to respond to the foregoing demand in the market.
Review
From the above test result, the method of the surface treatment of the present invention enables countless concavities to be formed in good working conditions and yet simultaneously while compensating for the defect of high fragmentation rate in the case of independently using the layered-structure solid lubricant particles.
In addition, from the test result, the lubricating effect can be obtained in the die etc. operating under the harsh condition such as the high surface pressure, and for this reason, it is thought that the effect of remarkable lifetime extension is obtained due to a synergy effect of the oxide of the soft-metal solid lubricant and the layered-structure solid lubricant.
It will thus be seen that the objects set forth above, and those made apparent from the foregoing description, are efficiently attained. Also, since certain changes may be made in the above construction without departing from the scope of the invention, it is intended that all matters contained in the foregoing description or shown in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.
It is also to be understood that the following claims are intended to cover all of the generic and specific features of the invention herein described, and all statements of the scope of the invention which, as a matter of language, might be said to fall therebetween.
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There is provided a method for surface treatment of a sliding portion of a product, which is an economical method, has less risk of polluting the working environment, or causing a fire by the powder dust, and yet enables high lubricativeness to be achieved, and many concavities to be formed on the sliding portion while simultaneously providing lubricativeness. Injection particles, obtained by blending soft-metal solid lubricant particles the surfaces of which have been oxidized and layered-structure solid lubricant particles, are injected onto a surface of the sliding portion of the product to be treated at an injection speed of 150 m/sec or more, thereby to diffuse and penetrate the surface to form a layer of the injection particles, and to form many concavities on the surface of the sliding portion.
| 2 |
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to catalysts suitable for use particularly in the cracking of mineral oils.
2. Description of the Prior Art
Middle distillates, typified by kerosine and light gas oil, have recently been in strong and growing demand. These distillates are derived generally by atmospheric distillation of crude oil and alternatively by hydrocracking of mineral oils such as crude oil, liquefied coal gas, deasphalted oil, shale oil, vacuum gas oil, and residual oils including atmospheric residues, vacuum residues and the like.
Hydrocracked lubricant base oils have also received high credit for their greater values of viscosity index and higher rates of yield.
Hydrocracking converts mineral oils, because of their varying fractions, to a number of petroleum products by the use of many different catalysts. Most commonly employed are catalysts made up of porous inorganic oxides such as alumina and silica-alumina, and active metals of Group VI such as molybdenum and tungsten and of Group VIII such as cobalt and nickel. To attain improved hydrogenation and cleavage qualities, this catalyst system has been fluorinated by impregnation or coprecipitation in aqueous solution as disclosed for instance in Japanese Patent Publication No. 46-6507, or by deposition in gaseous phase as taught in U.S. Pat. No. 3,457,188. Such prior catalysts, however, are not wholly satisfactory as they are catalytically not so active and less selective.
SUMMARY OF THE INVENTION
The present invention turns on the discovery that catalysts of enhanced catalytic activity and selectivity characteristics can be obtained by solid-phase modification of inorganic oxide carriers with a selected class of fluorine compounds without resorting to aqueous impregnation and coprecipitation or to gaseous deposition.
It is the primary object of the invention to provide novel and improved catalysts which are highly capable of hydrocracking mineral oils with optimum selectivity and at maximum yield, thus contributing to the formation of kerosine, light gas oil and lubricant base oil of good qualities. The catalyst according to the invention is particularly useful in the treatment of atmospheric residue, vacuum gas oil, vacuum residue, liquefied coal gas, deasphalted oil, shale oil and crude oil.
Many other objects and advantages of the invention will be better understood from the following description taken in connection with the accompanying drawing in which a preferred embodiment of the invention is shown by way of illustrative example.
According to the invention, thus is provided a catalyst for use in hydrocracking mineral oils which comprises (a) a carrier resulting from solid-phase modification of at least one porous inorganic oxide with one or more solid fluorine compounds, the inorganic oxide being in an amount of 10 to 90 percent by weight of the total catalyst, the fluorine compounds being in an amount of 2.5 to 85 percent by weight of the total catalyst, and (b) at least one metal component in an amount of 5 to 50 percent by weight of the total catalyst.
BRIEF DESCRIPTION OF THE DRAWING
The accompanying drawing is a graphic representation of the pore size distributions of the catalyst provided in accordance with the present invention and of a comparative catalyst.
DETAILED DESCRIPTION OF THE INVENTION
Porous inorganic oxides useful in the present invention are materials resulting from oxidation of Groups II, III and IV elements of the Periodic Table. Typical examples include simple oxides such as alumina, silica, boria, zirconia and the like, and composite oxides such as silica-alumina, silica-magnesia, alumina-magnesia, alumina-titania, silica-titania, alumina-boria, alumina-zirconia and the like. These oxides, simple or composite, may be used alone or in combination. Alumina and silica-alumina are particularly preferred.
The amount of the oxide to be used should be in the range of 10 to 90 percent by weight, preferably 30 to 60 percent by weight of the total catalyst. The oxide has a surface area of 150 to 700 m 2 /g and a pore volume of 0.3 to 1.5 cc/g. Where silica-alumina is used, the alumina content usually ranges from 5 to 95 percent by weight, preferably 10 to 40 percent by weight.
According to an important aspect of the invention, the inorganic oxide should be modified with one or more fluorine compounds. Eligible fluorides are in solid form and may be selected from ammonium fluoride and metallic fluorides. Specific examples of the metallic fluorides include AlF 3 , (NH 4 ) 3 AlF 6 , KF, CrF 2 , CrF 3 , CaF 2 , CoF 2 , SrF 2 , FeF 3 , CuF, CUF 2 , LiF, NaF, NiF 2 , BaF 2 , AgF, AgF 2 , UF 3 and the like. Particularly preferred among these modifiers are AlF 3 and (NH 4 ) 3 AlF 6 .
The amount of the fluorine compound to be added should be between 2.5 and 85 percent by weight, preferably between 3 and 50 percent by weight of the total catalyst.
Active metal components used herein include for example metals classified in Groups VI and VIII. Group VI metals are typically tungsten (W) and molybdenum (Mo), whereas Group VIII metals are for example nickel (Ni) and cobalt (Co). Such metals may be used singly or put together and may be as they are or in oxide or sulfide form. Either of the two metals of both groups when employed in combination has an atomic ratio of Group VIII metal to Group VI metal in the range of 0.5:1 to 6:1, preferably 1:1 to 5:1.
The amount of the metal component to be deposited should range from 5 to 50 percent by weight, preferably 10 to 40 percent by weight, in terms of the oxide, based on the total catalyst.
In the production of the catalyst according to the invention, one or more selected inorganic oxides and one or more selected fluorine compounds are contact-molded in solid phase to give a carrier. Contact molding may be effected by blending the starting materials on any suitable known kneader and then by forming the blend by extrusion or pressure molding into a spherical, cylindrical, pellet or other suitable shape, followed by calcination at a predetermined temperature. The blend, though sufficiently extrudable with use of water, may be added with an alumina or silica sol. The sol acts as a binder, rendering the finished catalyst mechanically strong. This additive is used in an amount of 0.5 to 5 parts by weight, preferably 1 to 3 parts by weight per 10 parts of the carrier.
The resulting molded article is air-dried, dried and calcined with heat to thereby provide a desired catalyst carrier. Drying conditions are at from 50° to 250° C., preferably 90° to 150° C., for 1 to 48 hours. Calcination is carried out in a stream of air at 250° to 1,000° C., preferably 400° to 800° C., for 0.5 to 24 hours.
The catalyst carrier thus modified has now been found to possess a surface area of 100 to 700 m 2 /g and a pore volume of 0.2 to 1.5 cc/g. This is taken to mean that the surface areas and pore volumes of modified carriers will in many instances be substantially identical to, or smaller than, those of the corresponding inorganic oxides unmodified.
Subsequently, the modified carrier is dipped overnight in an impregnating solution containing one or more selected metal components and air-dried on a filter paper for 24 hours. After being dried at 60° to 250° C. for 24 hours, the metal-deposited carrier is calcined for 30 minutes or longer at 250° to 1,000° C., preferably 400° to 800° C., with gradual temperature rise up to 250° C.
The invention contemplates hydrocracking atmospheric residue, vacuum gas oil, vacuum residue, liquefied coal gas, deasphalted oil, shale oil and crude oil. Hydrocracking conditions are at a temperature of 320° to 480° C., preferably 370° to 430° C., at a hydrogen pressure of 70 to 350 kg/cm 2 , preferably 140 to 230 kg/cm 2 , and at a liquid hourly space velocity (LHSV) of 0.1 to 10.0, preferably 0.1 to 2.0.
The catalyst of the invention, as shown in the drawing, has a unique pore size distribution; that is, the pore volume of an AlF 3 -modified alumina-silica carrier is small in a region of about 40 to 80 A and great in a region of about 80 to 150 A contrasted to a similar carrier unmodified. The physical properties of the carriers appearing in the drawing are given below.
______________________________________ Inorganic Surface Area Pore Volume Pore SizeSymbol Oxide (m.sup.2 /g) (cc/g) (A)______________________________________ ##STR1## silica- alumina 352.74 0.763204 43.2729 ##STR2## AlF.sub.3 modified silica- alumina 300.173 0.620588 41.3487______________________________________
The following examples are provided to further illustrate the present invention, but should not be regarded as limiting the invention.
EXAMPLE 1
To 10 parts of particulate silica-alumina (Al 2 O 3 content: 29%) was added 3.27 parts of aluminum fluoride, followed by kneading on an automatic mortar for 1.5 hours. The resulting mixture was combined with 26.5 parts of an alumina sol (Al 2 O 3 content: 10%) and then extrusion-molded. After being air-dried overnight, the extrudate was dried at 120° C. for 2 hours and air-calcined at 500° C. for 4 hours, giving a modified carrier.
The carrier was put into an impregnating solution and disposed overnight. The solution was prepared using ammonium tungstate and nickel nitrate such that metal concentrations were 7.3% Ni and 13% W, respectively, based on the total weight of the catalyst.
The metal-deposited carrier was air-dried for 24 hours, dried at 120° C. for 24 hours and air-calcined at 550° C. for 3 hours, thereby providing Catalyst A according to the invention.
The procedure for Catalyst A was followed except that fluorination was omitted, after which Catalyst B was obtained. Catalyst C was fluorinated by simultaneously placing silica-alumina and ammonium fluoride in aqueous solution, the amount of the fluoride being similar to Catalyst A. A commercially available catalyst was used as Catalyst D. All the test catalysts were formulated with the same level of metal deposition.
Catalysts A to D were examined for catalytic activity and selectivity under the conditions given below and with the results shown in Table 1.
deasphalted oil
specific gravity (15/4° C.): 0.9269
sulfur content: 1.90 wt. %
nitrogen content: 540 ppm
initial boiling point: above 540° C.
reaction
temperature: 410° C.
hydrogen pressure: 171 kg/cm 2
LHSV: 1.0
selectivity ##EQU1## 540° C. + : fraction boiling above 540° C.
Catalyst A has proved quite effective in selectively hydrocracking the test oil, producing at high yield a 177°-260° C. fraction equivalent to kerosine and a 260° C.-330° C. fraction equivalent to light gas oil.
Catalyst A also enables a SAE-10 oil, whose boiling range is at 330°-460° C., to be efficiently processed as shown in Table 2. This catalyst improves viscosity index (VI) and aniline point (AP) and hence makes the resulting fraction highly paraffinic. As evidenced by ndm analysis, the catalyst excels in hydrogenating aromatic rings and also in cleaving naphthenic rings.
EXAMPLE 2
Catalysts A to D of Example 1 were applied to the treatment of vacuum gas oil under the conditions given below and with the results shown in Table 3.
vacuum gas oil
specific gravity (15/4° C.): 0.922
sulfur content: 1.80 wt. %
nitrogen content: 1,000 ppm
initial boiling point: 268° C.
10 wt. % distillation point: 360° C.
reaction
temperature: 380° C.
hydrogen pressure: 100 kg/cm 2
LHSV: 0.6
hydrogen/oil ratio: 600 Nl/1
cracking activity
10 wt. % distillation point: 360° C. ##EQU2## 360° C. + : fraction boiling above 360° C.
selectivity ##EQU3## 360° C. - : fraction boiling below 360° C.
As appears clear from the test results, Catalyst A is highly satisfactory both in catalytic activity and in selectivity of kerosine and light gas oil.
TABLE 1______________________________________Deasphalted OilCatalyst A B C D______________________________________Conversion 79.9 67.6 72.0 69.5of 540° C..sup.+ (wt. %)Yield (wt. %)C1-C4 2.4 1.7 2.2 1.8C5-177° C. 12.3 7.9 9.5 7.8-260° C.*.sup.(1) 15.2 11.3 12.6 11.9-330° C.*.sup.(2) 13.6 10.5 12.0 11.7-460° C. 19.4 17.0 17.8 15.9-540° C. 17.1 19.9 17.9 19.3540° C. 20.1 32.4 28.0 30.5Selectivity 36.0 32.2 34.2 34.0of *(1) and *(2)______________________________________ *.sup.(1) Kerosine *.sup.(2) Light gas oil
TABLE 2______________________________________SAE-10 OilCatalyst A B C D______________________________________VI 118 112 113 105AP (%) 106 102 105 102ndm Analysis% CP 71.0 68.5 69.8 67.5% CN 26.6 27.5 27.2 28.7% CA 2.4 3.9 3.0 3.8RN 1.14 1.29 1.14 1.18RA 0.10 0.16 0.12 0.15RT 1.24 1.45 1.26 1.33______________________________________
TABLE 3______________________________________Vacuum Gas OilCatalyst A B C D______________________________________Conversion 22.1 16.5 18.9 18.0of 360° C..sup.+ (wt. %)Yield (wt. %)C1-C4 1.8 2.3 2.7 2.3C5-177° C. 3.3 2.7 3.2 3.0-260° C.*.sup.(1) 6.4 4.3 5.2 5.3-360° C.*.sup.(2) 20.8 16.4 17.8 17.3360° C..sup.+ 70.1 75.1 73.0 73.8Selectivity of 84.2 80.5 79.6 81.0(*1) and (*2)______________________________________ *.sup.(1) Kerosene *.sup.(2) Light gas oil
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Hydrocracking catalysts are disclosed which comprise specified amounts of selected inorganic oxides and specified amounts of selected metal components carried thereon. The carrier is essentially derived from solid-phase modification with specified amounts of a selected class of fluorine compounds. Mineral oils are selectively processable with high catalytic activity and at maximum yield.
| 1 |
FIELD OF THE INVENTION
The invention pertains to mounts for outboard engines. More particularly, the invention pertains to adjustable mounts intended for use with pontoon boats.
BACKGROUND OF THE INVENTION
Pontoon boats include a pair of elongated pontoons which support a platform spanning between the pontoons. An outboard engine or outboard motor (terms used interchangeably) is supported from the platform at a position intermediate the pontoons at a rear of the boat.
An engine mount is connected to an underside of the platform. The engine mount comprises an elongated hollow body or trough which extends longitudinally and rearwardly of the rear end (stern end) of the platform. The body is exposed to the water beneath the boat. The engine mount is substantially closed except for a top opening at a rear of the boat. A fuel tank is held within the body, accessed through the top opening. The outboard motor is bolted to the rear wall of the body. The prior known mount is non-adjustably fixed to the platform. No range of vertical adjustment for the outboard engine is provided by the mount.
The present inventors have recognized that it would be desirable to provide a vertical adjustability at the engine mount such that outboard engines could be optimized for depth below waterline. Additionally, the present inventors have recognized the desirability of providing a vertical adjustability at the engine mount so that a variety of commercially available outboard engines can be attached to the boat, and the boat tuned to the engine by adjusting the depth of the motor beneath the waterline.
SUMMARY OF THE INVENTION
An adjustable engine mount is provided that includes a tapered, elongated body which is couplable to, and vertically adjustable relative to, the hull of a watercraft. The body has a first, smaller end oriented toward the bow of the watercraft and a second, wider end positioned adjacent to the stem of the craft. An engine-mounting wall or mounting plate is attached to the second end of the body. An outboard motor or outboard engine can be attached to the mounting plate. By vertically adjusting the body with respect to the hull, the elevation of the outboard motor with respect to the watercraft or with respect to the waterline, can be adjusted. The adjustment can be utilized to optimize performance of an outboard motor. The adjustment provides flexibility for the use of different model outboard motors on the watercraft.
In one aspect of the invention, the body is substantially hollow and extends rearwardly from a back edge of the watercraft, defining a top opening. An elongated fuel tank can be placed within the body to be connected by a fuel line to the outboard motor. By having an elevation-adjustable body, access for installing and removing the fuel tank is improved. The body can be lowered to provide more clearance for maneuvering the fuel tank partially beneath the back edge of the watercraft.
In another aspect, the body can be formed with a multi-sided, generally U-shaped cross section. The planar sides are tapered and extend smoothly without protrusions between the ends.
Two exterior elongated rails or supports, rigidly coupled to the craft, extend axially therealong and provide support for the body. The body is attached to the rails at a plurality of longitudinal positions between the bow end and stem end of the craft.
In another aspect, the rails, at the stem end, can include a plurality of spaced apart bolt holes or, alternately, protrusions. The stern end of the body can be releasably locked into a selected vertical position by using bolts that extend through the holes, or alternately by using holes which receive the protrusions.
An engine can be coupled to the mounting plate. The mounting plate will in turn support the engine at the vertical position relative to the craft.
In yet another aspect, the body can be formed with four planar tapered sides. Two of the sides extend generally parallel to one another along and beneath the craft. In this embodiment, the mounting plate extends between the parallel sides generally perpendicular thereto.
In a further aspect of the invention, the braces can include a bottom flange having a downturned lip which acts as a splash guard to help prevent water from splashing into the engine mount body.
Numerous other advantages and features of the present invention will become readily apparent from the following detailed description of the invention and the embodiments thereof, from the claims and from the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a watercraft utilizing the engine mount of the present invention, wherein an outboard motor is not shown for clarity of view of the engine mount;
FIG. 2 is a sectional view taken generally along line 2 — 2 of FIG. 1, with an outboard motor installed;
FIG. 3 is an enlarged sectional view taken generally along lines 3 — 3 of FIG. 2;
FIG. 4 is a perspective view of a body portion of the engine mount of FIG. 1;
FIG. 5 is an elevational view of one of two retainer plates, to be attached to portions of the body portion shown in FIG. 4;
FIG. 6 is a perspective view of one of two braces which are each attached to a region of the body portion of FIG. 4;
FIG. 7 is an enlarged elevational view of the engine mount of FIG. 1, separated from the watercraft; and
FIG. 8 is an enlarged, fragmentary, top perspective view of a stern end of the mount separated from the watercraft, as shown in FIG. 7; and
FIG. 9 is an enlarged, fragmentary, rear perspective view of the watercraft shown in FIG. 1 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
While this invention is susceptible of embodiment in many different forms, there are shown in the drawings and will be described herein in detail specific embodiments thereof with the understanding that the present disclosure is to be considered as an exemplification of the principles of the invention and is not intended to limit the invention to the specific embodiments illustrated.
FIG. 1 illustrates a watercraft 20 . The watercraft 20 includes a platform 26 supported on parallel pontoons 30 , 32 . For simplicity, the platform is shown as a plain floor surrounded by a railing, but the platform could be adapted to provide seating for people, or storage for cargo, or structure for a houseboat, as only a few examples. Mounted to the platform 26 , between the pontoons 30 , 32 , is an elongated engine mount 36 . The engine mount 36 includes a trough-like hollow body 40 , closed at a rear end (stem end) by an engine-mounting wall or plate 44 . An outboard motor is coupled to the wall 44 as described below. The body 40 is connected intermittently along its length to support rails 50 , 52 . The support rails 50 , 52 are connected intermittently along lengths thereof to an underside of the platform 26 . The engine mount 36 extends rearwardly of a back edge 56 of the platform 26 , defining a top opening 58 .
FIG. 2 illustrates the engine mount 36 beneath the watercraft 20 . The rail 52 is connected to the body 40 by five bolted connections 62 , 64 , 66 , 68 , 70 . An end plate 74 substantially closes a front end (bow end) of the mount body 40 . A motor plate 80 supports an outboard motor 82 . The motor plate 80 is bolted to the engine-mounting wall 44 using bolts 83 . The mounting wall 44 includes a top channel portion 45 which reinforces the top free edge of the wall 44 and also provides a guiding retainer for a fuel line, control cables or other like devices. Two inside reinforcing channels 44 a , 44 b are disposed facing against the inside surface of the mounting wall 44 . The lower channel 44 a is welded to the body 40 . The upper channel 44 b can be held to the wall 44 by the bolts 83 which penetrate through the wall 44 and a respective channel 44 a , 44 b . The channels 44 a , 44 b provide additional strength to the wall 44 .
The bolted connection 62 includes a bolt 62 a penetrating a circular hole 62 b . The connections 64 , 66 include bolt 64 a , 66 a each penetrating through a slot 64 b , 66 b respectively, which allows for rotation of the body 40 about the bolted connection 62 during adjustment. Although three connections 62 , 64 , 66 are shown, it is also encompassed by the invention to use a different number of connections such as one or more than three, depending on the requirements of a particular design.
The bolted connections 68 , 70 , include bolts 68 a , 70 a , that penetrate through two holes selected from a plurality of holes 69 , spaced at different elevations. The holes 69 are arranged along a circle having its center point at the connection 62 . With the connections 62 , 64 , 66 loosened, and before the bolts 68 a , 70 a are installed, by pivoting the body 40 about the connection 62 , different holes 69 can be selected to change or adjust the elevation of the mounting wall 44 . In this regard the elevation of the motor 82 can be changed as shown dashed in FIG. 2 .
After adjustment, all the connections 62 , 64 , 66 , 68 , 70 can be tightened. Although two bolts 69 a , 70 a are shown, a different number of bolts can be used such as one or more than two, depending on the requirements of a particular design. Although a plurality of holes 69 are shown, it is also encompassed by the invention that the holes 69 are replaced by a curved slot arranged on a circular path having its center on the connection 62 .
The connections 68 , 70 are illustrated in FIG. 3 . The bolts 68 a , 70 a are inserted through two selected holes of the plurality of holes 69 . The rails are substantially channel-shaped in cross-section, having a continuous top flange 86 , a web 87 and a bottom flange 88 . The rails 50 , 52 are connected to the deck 26 by a plurality of longitudinally spaced bolted connections 84 , extending through the top flange 86 of the rails, respectively. Alternatively, the rails can be connected to the deck by brackets and/or by welding. The bottom flange 88 has a downturned end portion or deflector lip 92 which acts as a splash guard. The deflector lip 92 helps to keep water out of the engine mount body 40 . The body 40 includes retainer plates 96 which have hexagonal holes for receiving, and restricting rotation of, hexagonal bolt heads 98 of the fasteners 68 , 70 . Thus, the bolts can be loosened from the outside without the need to grip the bolt heads 98 with a tool to prevent rotation of the bolt heads.
The retainer plates 96 are each respectively welded to inside surfaces of sidewalls 106 , 108 of the body 40 . The retainer plate 96 is also preferably composed of aluminum and is 0.250 inches thick. The sidewalls 106 , 108 are connected to angled bottom walls 112 , 114 . Together, the walls 106 , 108 , 112 , 114 form a generally U-shaped cross-section of the body.
FIG. 4 illustrates the body 40 having side walls 106 , 108 and bottom walls 112 , 114 . The four walls 106 , 108 , 112 , 114 can be formed by bending a single sheet of aluminum. The sheet is preferably 0.170 inches thick. Each of the side walls 106 , 108 has a region 106 a , 108 a (shown in phantom) which receives one retainer plate 96 attached thereto by welding. Each sidewall 106 , 108 includes a plurality of spaced apart circular holes 120 for receiving the shank of bolts 62 a , 64 a , 66 a , respectively.
FIG. 6 illustrates one of the rails 50 . The rail 52 is mirror image identical. The rail 50 is configured in a channel shape having a tapering height from stem end to bow end. The top flange 86 also includes a downturned flange lip 121 for added rigidity. The rail is also preferably composed of aluminum and is 0.170 inches thick. The rail 50 includes the plurality of holes 69 arranged substantially vertically along the circular arc having its center at the connection hole 62 b . The bolts 68 a , 70 a are arranged to also be along the same circular arc, such as to be positionable within select ones of the holes 69 , for adjusting the elevation of the engine-mounting wall 44 . The slots 64 b , 66 b are arranged extending along circular arcs also having centers at the centerline of the connection hole 62 b . The bottom flange 88 of the rail 50 includes the angled lip 92 which is turned at an angle A, preferably being about 55 degrees at the stern end.
FIG. 7 illustrates the body 40 and the rail 52 assembled, but shown without bolts for clarity of view. The angle A of the lip 92 is gradually straightened out toward a front of the rail 52 , i.e., the angle A gradually diminishes to zero degrees, wherein the lip blends into the rest of the bottom flange 88 . The lip 92 blends into the rest of the bottom flange 88 , at a point p about midway between the slot 64 b and the hole 62 b . A reinforcing, rectangular gusset plate 130 is welded to the upper and lower flanges 86 , 88 and to the web 89 to reinforce the rail adjacent to the bolted connections 68 , 70 .
The mount 36 is tapered from its stem end toward its bow end, tapered both in plan and in elevation, to provide a streamlined profile to reduce splashing and water resistance or drag as the watercraft moves through the water. In this regard the preferred dimensions (in inches), as indicated in FIGS. 4 through 7, are: a=9¼; b=13½; c=74; d=4; e=2; f=4¾; g=3¼; h=3½; i=68; j={fraction (15/16)}; k=8¼; m=3; n={fraction (15/16)}; q=68; r=15½; s=71; t=1.
FIG. 8 illustrates the mount 36 with the fuel tank 59 within the body 40 . The mounting wall 44 is welded all around with a bead 127 to the sidewalls 106 , 108 , and the bottom walls 112 , 114 . A small gap 128 in the weld at the intersection of the bottom walls provides a drain for water which enters the body 40 . The channel portion 45 extends above the side walls 106 , 108 and is welded thereto via prone L-shaped pieces 131 , 133 .
FIG. 9 illustrates the inside of the body 40 at the stem end. The L-shaped pieces 131 , 133 are further connected to the sidewalls 106 , 108 by horizontal triangular reinforcing plates 141 , 143 . The channel 44 a is connected to, and overlies, a bottom half of the inside of the mounting wall 45 . Two L-shaped spacers 145 , 147 protrude from the inside wall 145 toward the bow end and act to retain the fuel tank 59 . A triangular notch 151 through the channel 44 a provides fluid communication with the gap 128 for draining the body 40 . Bolt holes 155 , 157 are used for mounting the outboard motor. The upper channel 44 b is not shown in FIG. 9 but is substantially similar to the lower channel 44 a.
From the foregoing, it will be observed that numerous variations and modifications may be effected without departing from the spirit and scope of the invention. It is to be understood that no limitation with respect to the specific apparatus illustrated herein is intended or should be inferred. It is, of course, intended to cover by the appended claims all such modifications as fall within the scope of the claims.
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An adjustable engine mount for a pontoon boat makes it possible to adjust the relative position of an outboard engine relative to the waterline of the boat. The mount has an elongated, tapered, four-sided body which is attached to the bottom of the hull of the boat by a pair of spaced apart, elongated mounting rails. The body is a substantially U-shaped, continuously changing cross section with an engine-mounting wall located adjacent the stern of the boat. The bow end of the body is pivotably attached to the mounting rails. The stem ends of the rails have a plurality of vertically disposed bolt holes. The vertical position of the body can be adjusted by selecting which vertically disposed bolt holes in the rails to use.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to the collection of bodily waste. More particularly, the invention relates to urine collection bags worn by persons who are incontinent.
2. Background
Incontinence afflicts many persons, especially many who are confined to wheelchairs. Typically, such persons have a urine collection bag that is worn on the leg, commonly at or near the calf. Conventional collection bags have a drain tube to permit emptying of the contents. For many incontinent persons, particularly paraplegic and quadriplegic individuals, considerable effort is required to empty a collection bag. Often, the assistance of an attendant is required.
Because the difficulties associated with emptying conventional collection bags may reduce a person's independence and may also cause embarrassment, efforts have been made to provide incontinent persons, particularly those confined to wheelchairs, with a means for more conveniently draining a collection bag. For example, U.S. Pat. No. 3,931,650 discloses a disposal device for wheelchairs in which the collection bag drain tube is connected to a valve mounted on the wheelchair. The valve may be manually operated, as by a lever within reach of the wheelchair occupant, or may be electrically operated using a solenoid. The valve and control mechanism, being mounted to the wheelchair, is inherently conspicuous.
SUMMARY OF THE INVENTION
The present invention provides a discreet apparatus for draining a urine collection bag worn by an incontinent person, particularly such a person who is confined to a wheelchair. An electrically operated drain valve is coupled to a drain tube of the urine collection bag. A control device for remotely controlling the drain valve is adapted to be worn by the person. The control device is preferably disguised with an outward configuration resembling an article that is ordinarily carried or worn for other purposes, thereby concealing the true function of the device. Examples of such articles include a personal electronic device, such as a pager, cell phone or the like, a key fob, a belt buckle, a pen, a broach, a decorative pin, etc.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 illustrates the general configuration of a remote control valve in accordance with the present invention.
FIG. 2 is a detailed view of the control device in FIG. 1 .
FIGS. 3A-3D illustrate alternative control device configurations.
DETAILED DESCRIPTION OF THE INVENTION
In the following description, for purposes of explanation and not limitation, specific details are set forth in order to provide a thorough understanding of the present invention. However, it will be apparent to one skilled in the art that the present invention may be practiced in other embodiments that depart from these specific details. In other instances, detailed descriptions of well-known methods and devices are omitted so as to not obscure the description of the present invention with unnecessary detail.
FIG. 1 generally illustrates the present invention as it may be employed by a person 10 confined to a wheelchair 12 . A urine collection bag 14 , commonly called a “legbag”, is worn on the person's leg and is secured by strap 16 . A catheter or other collection device drains into bag 14 through tube 18 . Bag 14 drains through tube 20 , which is connected to valve 22 . A fine mesh filter may be incorporated within tube 20 or valve 22 to capture any stray materials.
Valve 22 is conveniently worn about the ankle and may be secured by an adjustable strap 24 . Valve 22 is preferably enclosed within a soft padded case to prevent irritation of the person's skin. Strap 24 is also preferably made of a soft pliable material and may employ a hook and loop or other type of conventional closure device. An outlet tube 26 extends downwardly from valve 22 to a point just below the sole of the person's shoe.
Valve 22 is actuated by means of a low voltage solenoid. An electrical signal to operate the solenoid is sent from control device 28 through electrical cable 30 . Cable 30 is preferably a flexible flat wire cable, which is able to withstand the daily abuse of being worn and protects the skin of the wearer by not leaving a “wire mark” on the skin, particularly near the waistband where cable 30 connects to control device 28 . As will be explained more fully below, control device 28 may be disguised as a pager or similar personal electronic device that is commonly worn on a person's belt or waistband. Cable 30 preferably connects to device 28 at the rear thereof and is threaded over the belt or waistband to be routed through the pants leg to valve 22 . It should be noted that the wheelchair-bound person would typically wear full-length pants, thereby concealing collection bag 14 and valve 22 . Only outlet tube 26 would be visible below the pant cuff.
Valve 22 is preferably operated by a low voltage solenoid so that a suitable power source can be readily carried within control device 28 or within the enclosure for valve 22 . The power source may comprise a disposable or rechargeable battery. For example, a 3.6 volt NiMH rechargeable battery may be used. Recharging may be accomplished with a conventional external charger or by means of a solar cell on device 28 .
The fluid conducting portions of valve 22 are preferably constructed of materials that will not be corroded or otherwise degraded when conducting caustic fluids. Furthermore, the valve mechanism should be configured so that its sealing capability is not compromised by crystallization of the conducted fluid. The actuating solenoid should, of course, be compatible with the power source. The solenoid should also have a low holding current to maximize battery life. Assuming collection bag 14 has a capacity of 32 ounces and is elevated about one foot above valve 22 , the valve is exposed to approximately 8.5 pounds of pressure. Thus, a relatively low force valve closure spring may be employed, thereby reducing the power required for actuation of the valve.
FIG. 2 is a detailed view of control device 28 . As mentioned, the control device may be disguised as an article that a person might carry or wear for other purposes, such as a pager, cell phone or similar personal electronic device. Thus, the device may have a simulated display window 32 . If a solar cell is used to maintain the charge of the power supply battery, the cell may be disposed within window 32 . The device is secured to a belt or waistband with a clip 34 or other suitable means. Device 28 , including clip 34 , should be free of any sharp edges that might cause skin irritation or other discomfort.
Control device 28 includes a valve actuation control, such as a push button 36 . A determined effort should be required to operate control 36 so that valve 22 is not inadvertently actuated, but the effort should not be so great as to be difficult for persons with limited manual strength or dexterity.
When it becomes necessary to empty to contents of collection bag 14 , wheelchair 12 is maneuvered so that outlet tube 26 is positioned over a floor drain other suitable receptacle. Control 36 is then depressed to energize the solenoid for actuating valve 22 . The dimensions of the fluid conducting path through valve 22 are preferably large enough to allow the contents of the collection bag, up to about 32 ounces, to completely drain within a reasonable period of time, such as 60 seconds or less.
In the foregoing description, control device 28 communicates with valve 22 via a wired connection 30 . It will be appreciated that a wireless connection may also be employed using a radio frequency (RF) signal or other suitable means. In such case, control device 28 incorporates a small wireless transmitter and valve 22 incorporates a cooperating wireless receiver. Suitable transmitters and receivers for operating over short distances are well known. For example, a transmitter and receiver using the “Bluetooth” protocol may be employed. A wireless control device may be configured to resemble any of a variety of articles that are commonly carried or worn. For example, in addition to a personal electronic device as described above, the control device could be configured to resemble a key fob, belt buckle, pen, broach or decorative pin as shown in FIGS. 3A-3D , respectively.
It will be recognized that the above-described invention may be embodied in other specific forms without departing from the spirit or essential characteristics of the disclosure. Thus, it is understood that the invention is not to be limited by the foregoing illustrative details, but rather is to be defined by the appended claims.
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A discreet apparatus for draining a urine collection bag worn by an incontinent person has an electrically operated drain valve coupled to a drain tube of the urine collection bag. A control device for remotely controlling the drain valve is adapted to be worn by the person. The control device is preferably disguised with an outward configuration resembling an article that is ordinarily carried or worn for other purposes.
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CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] Not applicable
STATEMENT REGARDING FEDERALLY SPONSORED R&D
[0002] Not applicable
REFERENCE TO MICROFICHE APPENDIX
[0003] Not applicable
FIELD OF THE INVENTION
[0004] The present invention pertains to processes involving the deposition of one or more fluid materials onto a substrate, especially in those cases where the accurate positioning of the fluids on the substrate is important, or where blending or coalescence between discrete fluid droplets or pools is undesirable. Examples of items with manufacturing processes that may benefit from this invention include color filters for liquid crystal displays (LCD), organic light emitting diode displays (OLED), and liquid semi-conducting polymer devices.
BACKGROUND OF THE INVENTION
[0005] There are many industrial processes where accurate or controlled deposition of fluid substances is desirable. While this is true for the printing industry, especially with respect to inkjet printing, it also applies to other manufacturing processes, particularly in the electronics and microelectronics industry. Examples include processes involved in the manufacture of display screens and other electronic components.
[0006] Recent advances in inkjet printing technologies have vastly improved inkjet printing as a means for the precise deposition of liquid droplets. Because inkjet printing makes it possible to deposit very small measures of fluid very accurately and cheaply, and because inkjet deposition typically requires fewer steps and less equipment than conventional methods such as photolithography, it is a very attractive candidate for many precision-manufacturing applications outside of conventional printing. Outside of the graphic arts, examples of proposed applications of inkjet printing include manufacture of color filters for flat panel displays, manufacture of OLED devices, deposition of microlenses on the tips of optical fibers, deposition of conductive ink in the manufacture of circuit boards, and the manufacture of 3-dimensional objects.
[0007] In many of the proposed applications, the precise placement of the fluid substance, whether ink or polymer or other material, is critical. In the case of color filter manufacture for conventional flat panel displays or OLED devices, many such precisely placed fluid droplets must be placed very close to other such droplets without coalescing. This is particularly important in situations in which different kinds of fluids are being deposited on the same substrate, such as differently colored inks on a color filter substrate. In the case of color filters, it is vital to the quality of the filter to prevent blending between discrete ink droplets, as differently colored filter elements are typically situated adjacent to one another on a clear substrate, separated only by a minute barrier on the order of some microns across. In the case of organic light emitting diodes (OLED) and semiconducting polymers, the actual active device materials also need to be deposited with great accuracy and circumspection in order to ensure that the various sections of the devices remain well delineated.
[0008] The use of fluid droplet deposition techniques, such as inkjet, for precision manufacturing applications, however, does present a number of difficulties. Firstly, inkjet technology typically has a spatial accuracy of approximately 40 microns while the display screen and semiconductor industries require accuracies at least an order of magnitude better. Secondly, there are particular problems with respect to controlling the position of the fluids once they have been deposited upon a substrate.
[0009] For example, in the case where the fluid material is intended to adhere to the substrate, problems arise because the ability of the fluid to adhere to a surface is related to its ability to wet a surface, and the fact that a fluid capable of wetting a surface will also tend to spread upon that same surface. This can cause undesirable effects such as coalescence of adjacent droplets as well as blending of the fluids in adjacent droplets. Droplet spreading can also lead a non-uniform thickness of the layer on the substrate, as the fluid droplet layer may tend to be thinner at its boundaries when it spreads.
[0010] In applications where it is necessary to deposit a pattern of one or more fluid substances that need to be contained within specific areas, the wetting of the substrate will prevent accurate and uniform placement of droplets, as well as non-uniform thicknesses in layers created with the fluid droplets. At the same time, the droplets are generally required to adhere well to the substrate upon which they are deposited.
[0011] One area in which the specific aforementioned problem can be an issue is the manufacture of color filters for flat panel displays. Manufacturers are faced with a stringent requirement for the accurate placement of fluid substances without being able to tolerate any coalescence or blending between fluid droplets from adjacent patterned cells. Filter layer thickness and the distribution of colorant in the layer are also important to ensure that each colored region transmits light uniformly.
[0012] The color filter of a liquid crystal display is typically fabricated with alternating cells of red, green, and blue material deposited on a transparent substrate at the same matrix spacing as the panel. The colored materials act as filters and therefore transmit light. To enhance contrast, a light-shielding region, known as a black matrix, usually demarcates the color cells. This black matrix typically has an optical density of greater than 3.0 in order to adequately block stray light from adjacent cells. It is also used to mask non-emitting areas such as LCD cell electrodes.
[0013] Many different methods have been used or proposed for forming the partition walls. Typically, photolithography is used. However, other methods such as electrodeposition, screen offset printing, gravure printing, flexographic printing, and inkjet printing have also been suggested in the art.
[0014] Most of these methods suffer from a number of deficiencies. In general the very precise methods are expensive and complicated, and often require additional processing steps or expensive equipment. The printing based methods tend to be cheaper, but tend to suffer the fact that the partitions are being made by applying a liquid to a surface, with the same attendant problems of liquid spreading and coalescence. Conventional manufacturing techniques like photolithography are costly due to the need for complex processes like vacuum chamber deposition as well as the multiple steps which are required to produce a finished color filter. On the other hand, currently available alternative methods are either just as complex, or lack the required precision. The resulting high fabrication costs have thus prevented flat panel displays from replacing conventional CRT displays in applications where cost is a primary concern. This has happened despite their many desirable characteristics, such as compact size and low radiation emissions.
[0015] Other types of display devices, based on OLEDs, have requirements slightly different from conventional color filters. For example, because OLEDs are light emitting, the optical density required for the partition walls may not be as severe and hence controlling the thickness of the fluid layers may be less important. However, accurate placement is still needed. For example, an OLED display may be made up of OLED cells of different colours, which again would require that closely placed fluid droplets be prevented from mixing or coalescing.
[0016] A number of methods of addressing this problem have been proposed, and the concept of using the surface energy characteristics of the fluids, substrates, and the partition barriers to control the placement of inkjetted droplets has specifically been suggested. Again, as with previously mentioned approaches to fabricating partition walls in general, the various approaches proposed for producing a desirable pattern of surface energy variations on a substrate of a colour filter have tended to be either expensive or complex. Additionally, they frequently require many processing steps, including post-processing steps, or lack the precision required for the manufacture of devices such as color filters for flat panel displays or OLED displays.
[0017] The incorporation of conventional printing techniques has been proposed in various approaches, as the conventional printing industry has extensive experience with methods to produce large numbers of precisely patterned objects at low cost. However, the use conventional printing techniques requiring the use of liquid ink to produce precisely patterned surface energy variations on a substrate suffers the same problems mentioned earlier with regard to adhesion, wettability, and liquid spreading.
[0018] One well-known printing technique that does not involve the deposition of a fluid in order to create a precise pattern on a surface is thermal transfer. This technology is employed extensively in the printing and imaging field for the purposes of proofing. In applying this technology to the filter, OLED and polymeric semiconductor devices addressed here, it has the benefit of not employing liquids that could spread or coalesce.
[0019] In thermal transfer, a donor material layer is disposed on a carrier sheet. This medium is then either placed in close proximity with a substrate or in contact with that substrate, such that the donor layer faces the substrate. The donor layer is then transferred from the carrier sheet to the required areas of the substrate by a variety of means. These include illumination with a laser or another thermal source. When a laser is employed in this fashion, the process is referred to as laser induced film transfer.
[0020] The mechanism of transfer varies from essentially explosive heating of the interlayer between the donor and carrier to detach a minute amount of donor material, to phase change processes. When a phase change is employed, the process is known as phase change transfer. All the mechanisms have the net result of transferring donor material in a precisely defined fashion from the carrier sheet to the substrate on which the image or pattern is required. Provided a well-defined laser-beam is used, images or patterns may be imagewise written onto the carrier to transfer the donor material imagewise to the substrate. This technology provides a method to obtain very well-defined edge structures and is inherently capable of the precision required for the devices discussed here.
[0021] Unfortunately, there has to date been no simple method proposed for incorporating thermal transfer into an inkjet-based method for manufacturing colour filters, OLED devices or semiconducting polymer devices.
OBJECTS AND ADVANTAGES OF THE INVENTION
[0022] It is a principle object of the present invention to provide a method for fabricating a surface comprising a pattern of varying surface energy that is useful in any device fabrication application where a fluid substance is to be accurately deposited onto a substrate.
[0023] A more particular object of the present invention is to provide a method for fabricating a partition layer that is useful in any the manufacture of color filters for liquid crystal displays (LCD) and in the manufacture of organic light emitting diode displays (OLED) and liquid semi-conducting polymer devices.
[0024] Yet another object of the present invention is to provide a method for fabricating a partition layer using materials which are commonly available from graphic arts media vendors.
[0025] Yet a further object of the present invention is to provide a method for forming a partition pattern on a substrate using imaging techniques well established in the area of graphic arts industry.
[0026] A further object of the present invention is to provide a simple method for fabricating on a surface a pattern to partition liquids such that the pattern requires no post-processing to impart the desired surface energy characteristics.
[0027] It is another object of the present invention to allow fabrication of color filters, OLEDs, and other devices whose manufacture may require the precise deposition of fluids using transfer media that are substantially similar to the media used extensively in the graphic arts industry.
[0028] A further object of the present invention is to allow the use of commonly available imaging systems in order to implement the methods of the invention, which once again has the advantage of reducing costs.
[0029] Yet a further object of the invention is to allow for a simple two-step process with no required wait time between steps, requiring no post processing of the deposited partition material.
[0030] Another object of the present invention is to provide a two-step process that may advantageously be performed on the same imaging platform.
[0031] The method disclosed in this application for letters patent has several advantages over conventional methods of forming partition layers
[0032] Beyond the obvious advantages provided by the attainment of the above objects, a further significant advantage of this approach is that it offers the advantage of economy of scale and results in a lower cost than would be achievable with a fully customized process. It also allows the process to benefit from developmental efforts for a larger market.
SUMMARY OF THE INVENTION
[0033] A method for forming a partition layer on a substrate by imaging a thermal or laser transfer medium onto the substrate using a imagewise controlled radiation source is described. A matrix of partition cells is created on the substrate that can, in a further step, be selectively filled with fluid. The selective filling of partition cells can be accomplished using an inkjet printing technique. The partition layer, the substrate, and fluids to be deposited are selected so that the fluids wet the substrate but not the partitions, preventing unwanted interactions between fluids in adjacent cells. An apparatus for implementing this method is also described.
BRIEF DESCRIPTION OF THE DRAWINGS
[0034] [0034]FIGS. 1 a - 1 d show the process steps of the present invention.
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0035] FIGS. 1 - a through 1 - d show cross sectional views of the process for forming partition barriers on a substrate according to the preferred embodiment of the present invention. It is to be understood that the present invention is executed in at least two dimensions to create a two-dimensional pattern to be used to control the placement of fluids. In general the material being deposited may have any desired surface energy to affect the subsequent placement of liquid droplets on the surface on which the material is deposited. In the preferred embodiment of the present invention, the invention is demonstrated at the hand of a low surface energy material that is transferred to a surface.
[0036] In FIG. 1- a a media donor sheet 10 , comprising carrier layer 11 and a low surface energy partition material layer 12 initially adhering to carrier layer 11 , is positioned above a substrate 13 . In the preferred embodiment of the present invention the transfer media fixture (not shown) serves to maintain donor sheet 10 in position above substrate 13 .
[0037] In an alternative embodiment of the present invention, the use of phase change media requires that donor sheet 10 be maintained in contact with substrate 13 .
[0038] Substrate 13 can be glass, chromium, or any other material to which the low surface energy partition material of layer 12 will adhere. Substrate 13 is mounted on a stage (not shown) that may be fixed or movable in one or more dimensions. Imagewise controllable radiation source 20 is attached to a translation stage (not shown) that can be translated over the area of the substrate. By way of example, the translation stage may be similar to those employed in flatbed printers.
[0039] In an alternative embodiment of the present invention the imagewise controllable radiation source is affixed to a non-translating fixture.
[0040] In yet a further embodiment of the present invention, transfer of the low surface energy partition material of layer 12 is performed not via laser or on a point-by-point basis, but rather by using area illumination through a mask that has been provided with the pattern desired.
[0041] Returning to the preferred embodiment of the present invention, the radiation from imagewise controllable radiation source 20 is modulated in response to a data source (not shown) that determines the partition pattern to be formed. In the preferred embodiment of the present invention the lasers are switched on and off in response to the data source. The depth of modulation and functional form of the modulation may be adapted to suit the particular low surface energy partition material being used. On exposure to the radiation from imagewise controllable radiation source 20 , the low surface energy partition material of layer 12 is transferred to substrate 13 in the areas where the radiation impinges on donor sheet 10 .
[0042] In selecting materials for the substrate, partition material and the fluid to be deposited as part of the preferred embodiment of the present invention, careful attention is paid to the relative surface energy of the materials as this determines the degree to which the fluid will wet the substrate and the partition material. The selection requirement is that the surface energy of substrate 13 is chosen to be greater than the surface energy of the fluid to be deposited on it, which should in turn be greater than the surface energy of the material of low surface energy partition material layer 12 . Under these conditions, the fluid adheres to the substrate but does not spread past the partition layers.
[0043] An example of a thermal transfer medium that demonstrates properties for application in the preferred embodiment of the present invention, is available from Imation Corp of Oakdale Minn., and is sold under the trade name Imation Matchprint Digital Halftone Proofing System. The Imation Matchprint medium works through a laser induced thermal film transfer. The laser transfers the pigment as a film from the donor sheet 10 to substrate 13 resulting in clean edges.
[0044] Another example of a similar medium is Dupont WaterProof®, available from Dupont Company of Wilmington, Del. This medium works slightly differently in that the donor sheet 10 and substrate 13 are in closer contact and the laser effects a phase change transfer, melting the low surface energy partition material layer 12 , which then sticks to the receiver layer.
[0045] Other transfer media are available which operate through a laser ablation transfer where the donor undergoes an explosive decomposition and propulsion from donor to receiver. These commercially available media are primarily targeted at the color proofing market for the printing industry. Typically proofing media are available in a multitude of colors and a number of different formulations to suit various imaging devices. These media, with little customisation, can be used in forming partition layers on a substrate for applications that require accurate placement of fluids. In order to form good partition layers, the medium is not wettable by the fluid to be contained in the partition. At present, inks used in color filter production typically have a surface tension of the order of 29 mN/meter and typically include butyl carbitol acetate as solvent. The medium chosen should also be chemically stable in the presence of the solvent. Furthermore, the medium has sufficient exposure sensitivity to allow it be imaged using conventional imaging methods.
[0046] A suitable imagewise controllable radiation source for exposing the transfer media and creating the partitions is the SQUAREspot™ thermal imaging head, produced by CreoScitex of Burnaby, British Columbia, Canada. The SQUAREspot™ thermal imaging head is used in many areas of graphic arts imaging including digital proofing and is capable of imaging at a resolution up to 5080 dots per inch, with 20W of available imaging power divided into more than 200 independent channels. The radiation source is a laser diode bar with a wavelength of 830 nm. This imaging head is particularly suited to imaging features with very clean edges due to the substantially square profile of the laser beams it produces. Advantageously the SQUAREspot™ thermal imaging head is available with a beam size appropriate for writing the partitions, The CreoScitex imaging system is available with a 5 um spot size that is well suited to form these thin partitions.
[0047] In the present application for letters patent the term “imagewise controllable radiation source” is used to describe any radiation source that is imagewise controllable and which controllably emits radiation capable of transferring a medium imagewise from a carrier sheet to a substrate.
[0048] Referring now to FIG. 1- b, the imaging is partially completed and partition walls 2 have been deposited forming a cell 3 on the substrate 13 . FIG. 1- c shows the imaging completed. At this stage a 2-dimensional grid partition pattern will have been formed.
[0049] Referring now to FIG. 1- d, on completion of imaging, the donor sheet is removed and the substrate 13 is ready to have fluid droplets 5 deposited into the cells forming areas of fluid 21 . Fluid 21 may comprise a colorant such as a pigment or dye, or may be another type of fluid such as the active materials employed in making an organic light emitting diode (OLED) or a liquid semiconducting polymer. In the present application for letters patent, the term active materials is used to describe materials that play an active role in the functioning of an optoelectronic or electronic device. The roles include, but are not limited to, the formation of the p-n junction of a diode, the emission of light upon stimulation and the creation of free electrons in response to the absorption of photons. It is also clear that a plurality of different fluids may be deposited in droplet form in the same cell to create more complex structures or mixtures for electronic devices.
[0050] In the present application for letters patent the term electronic device is used to describe all devices of which the operation is based on the manipulation or behaviour of electrons, including specifically, but not limited to, those that absorb or emit light. This in particular includes all diodes, including specifically light emitting devices, and any optical filters, such as those employed by liquid crystal displays or organic light emitting devices (OLED).
[0051] In the preferred embodiment of the present invention a translation stage typical of commercial flatbed plotters is used to allow the imaging head to move in one axis whereas the substrate moves on an orthogonal axis, thus allowing the entire surface to be traversed. In addition, in the preferred embodiment of the present invention, an integrated imaging unit is used, such that the imagewise controllable radiation source 20 and fluid deposition unit 4 share the same translation stage. This combination allows the step of imagewise transferring the partition medium and the step of depositing fluid to be performed in succession on the same platform. In the preferred embodiment of the present invention, fluid deposition unit 4 is an inkjet head.
[0052] In an alternative embodiment, the imaging arrangement may consist of separate translation stages. It is clear to those skilled in the art that different arrangements may be employed to achieve the relative translation of the substrate and imagewise controllable radiation source 20 . Similarly, a variety of arrangements to obtain the relative translation of substrate 13 and fluid deposition unit 4 are known in the art.
[0053] A particular alternative embodiment employs a flexible substrate mounted on a cylinder or drum. The cylinder rotates while the imagewise controllable radiation source traverses across the length of the cylinder. The motion of the imagewise controllable radiation source may be continuous, such that it writes a spiral swath around the cylinder, or it may be stepped, such that it writes circular swaths. These mechanical arrangements are well-established in the printing industry and will not be discussed in further detail here. The same arrangement may be applied to fluid deposition unit 4 . Fluid deposition unit 4 and imagewise controllable radiation source 20 may also be mounted on the same stage.
[0054] In an alternative embodiment of the present invention, the fluid is deposited by a process other than ink-jetting. By way of example, the fluid may be deposited by a syringing method. In yet another example the fluid may be deposited by passing the substrate containing the partition cells through a bath of the fluid.
[0055] It should be understood that the above descriptions of the simple and preferred embodiments are intended for illustrative purposes only, and are not intended to limit the scope of the present invention in any way. Those skilled in the art will appreciate that various modifications can be made to the embodiments discussed above without departing from the spirit of the present invention.
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A method and apparatus for forming a partition layer on a substrate by imaging a thermal or laser transfer medium onto the substrate using a imagewise controlled radiation source. A matrix of partition cells are created on the substrate that can, in a further step, be selectively filled with fluid or ink using an inkjet printing technique. The partition layer, the substrate, and fluids to be deposited are selected so that the fluids wet the substrate but not the partitions, preventing bending between adjacent cells.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part application of U.S. application Ser. No. 09/850,482 filed May 7, 2001.
BACKGROUND OF THE INVENTION
[0002] [0002] 1 . Field of the Invention
[0003] The present invention relates to the local administration of drug/drug combinations for the prevention and treatment of vascular disease, and more particularly to intraluminal medical devices for the local delivery of drug/drug combinations for the prevention and treatment of vascular disease caused by injury and methods for maintaining the drug/drug combinations on the intraluminal medical devices. The present invention also relates to medical devices having drugs, agents or compounds affixed thereto to minimize or substantially eliminate a biological organism's reaction to the introduction of the medical device to the organism.
[0004] 2. Discussion of the Related Art
[0005] Many individuals suffer from circulatory disease caused by a progressive blockage of the blood vessels that profuse the heart and other major organs with nutrients. More severe blockage of blood vessels in such individuals often leads to hypertension, ischemic injury, stroke, or myocardial infarction. Atherosclerotic lesions, which limit or obstruct coronary blood flow, are the major cause of ischemic heart disease. Percutaneous transluminal coronary angioplasty is a medical procedure whose purpose is to increase blood flow through an artery. Percutaneous transluminal coronary angioplasty is the predominant treatment for coronary vessel stenosis. The increasing use of this procedure is attributable to its relatively high success rate and its minimal invasiveness compared with coronary bypass surgery. A limitation associated with percutaneous transluminal coronary angioplasty is the abrupt closure of the vessel which may occur immediately after the procedure and restenosis which occurs gradually following the procedure. Additionally, restenosis is a chronic problem in patients who have undergone saphenous vein bypass grafting. The mechanism of acute occlusion appears to involve several factors and may result from vascular recoil with resultant closure of the artery and/or deposition of blood platelets and fibrin along the damaged length of the newly opened blood vessel.
[0006] Restenosis after percutaneous transluminal coronary angioplasty is a more gradual process initiated by vascular injury. Multiple processes, including thrombosis, inflammation, growth factor and cytokine release, cell proliferation, cell migration and extracellular matrix synthesis each contribute to the restenotic process.
[0007] While the exact mechanism of restenosis is not completely understood, the general aspects of the restenosis process have been identified. In the normal arterial wall, smooth muscle cells proliferate at a low rate, approximately less than 0.1 percent per day. Smooth muscle cells in the vessel walls exist in a contractile phenotype characterized by eighty to ninety percent of the cell cytoplasmic volume occupied with the contractile apparatus. Endoplasmic reticulum, Golgi, and free ribosomes are few and are located in the perinuclear region. Extracellular matrix surrounds the smooth muscle cells and is rich in heparin-like glycosylaminoglycans which are believed to be responsible for maintaining smooth muscle cells in the contractile phenotypic state (Campbell and Campbell, 1985).
[0008] Upon pressure expansion of an intracoronary balloon catheter during angioplasty, smooth muscle cells within the vessel wall become injured, initiating a thrombotic and inflammatory response. Cell derived growth factors such as platelet derived growth factor, basic fibroblast growth factor, epidermal growth factor, thrombin, etc., released from platelets, invading macrophages and/or leukocytes, or directly from the smooth muscle cells provoke a proliferative and migratory response in medial smooth muscle cells. These cells undergo a change from the contractile phenotype to a synthetic phenotype characterized by only a few contractile filament bundles, extensive rough endoplasmic reticulum, Golgi and free ribosomes. Proliferation/migration usually begins within one to two days post-injury and peaks several days thereafter (Campbell and Campbell, 1987; Clowes and Schwartz, 1985).
[0009] Daughter cells migrate to the intimal layer of arterial smooth muscle and continue to proliferate and secrete significant amounts of extracellular matrix proteins. Proliferation, migration and extracellular matrix synthesis continue until the damaged endothelial layer is repaired at which time proliferation slows within the intima, usually within seven to fourteen days post-injury. The newly formed tissue is called neointima. The further vascular narrowing that occurs over the next three to six months is due primarily to negative or constrictive remodeling.
[0010] Simultaneous with local proliferation and migration, inflammatory cells adhere to the site of vascular injury. Within three to seven days post-injury, inflammatory cells have migrated to the deeper layers of the vessel wall. In animal models employing either balloon injury or stent implantation, inflammatory cells may persist at the site of vascular injury for at least thirty days (Tanaka et al., 1993; Edelman et al., 1998). Inflammatory cells therefore are present and may contribute to both the acute and chronic phases of restenosis.
[0011] Numerous agents have been examined for presumed anti-proliferative actions in restenosis and have shown some activity in experimental animal models. Some of the agents which have been shown to successfully reduce the extent of intimal hyperplasia in animal models include: heparin and heparin fragments (Clowes, A. W. and Karnovsky M., Nature 265: 25-26, 1977; Guyton, J. R. et al., Circ. Res., 46: 625-634,1980; Clowes, A. W. and Clowes, M. M., Lab. Invest. 52: 611-616, 1985; Clowes, A. W. and Clowes, M. M., Circ. Res. 58: 839-845, 1986; Majesky et al., Circ. Res. 61: 296-300,1987; Snow et al., Am. J. Pathol. 137: 313-330, 1990; Okada, T. et al., Neurosurgery 25: 92-98, 1989), colchicine (Currier, J. W. et al., Circ. 80: 11-66,1989), taxol (Sollot, S. J. et al., J. Clin. Invest. 95: 1869-1876,1995), angiotensin converting enzyme (ACE) inhibitors (Powell, J. S. et al., Science, 245: 186-188, 1989), angiopeptin (Lundergan, C. F. et al. Am. J. Cardiol. 17(Suppl. B):132B-136B, 1991), cyclosporin A (Jonasson, L. et al., Proc. Natl., Acad. Sci., 85: 2303,1988), goat-anti-rabbit PDGF antibody (Ferns, G. A. A., et al., Science 253: 1129-1132, 1991), terbinafine (Nemecek, G. M. et al., J. Pharmacol. Exp. Thera. 248: 1167-1174,1989), trapidil (Liu, M. W. et al., Circ. 81: 1089-1093,1990), tranilast (Fukuyama, J. et al., Eur. J. Pharmacol. 318: 327-332,1996), interferongamma (Hansson, G. K. and Holm, J., Circ. 84: 1266-1272, 1991), rapamycin (Marx, S. O. et al., Circ. Res. 76: 412-417,1995), steroids (Colburn, M. D. et al., J. Vasc. Surg. 15: 510-518, 1992), see also Berk, B. C. et al., J. Am. Coll. Cardiol. 17: 111 B-117B, 1991), ionizing radiation (Wein berger, J. et al., 1 nt. J. Rad. Onc. Biol. Phys. 36: 767-775,1996), fusion toxins (Farb, A. et al., Circ. Res. 80: 542-550,1997) antisense oligonucleotides (Simons, M. et al., Nature 359: 67-70,1992) and gene vectors (Chang, M. W. et al., J. Clin. Invest. 96: 2260-2268,1995). Anti-proliferative action on smooth muscle cells in vitro has been demonstrated for many of these agents, including heparin and heparin conjugates, taxol, tranilast, colchicine, ACE inhibitors, fusion toxins, antisense oligonucleotides, rapamycin and ionizing radiation. Thus, agents with diverse mechanisms of smooth muscle cell inhibition may have therapeutic utility in reducing intimal hyperplasia.
[0012] However, in contrast to animal models, attempts in human angioplasty patients to prevent restenosis by systemic pharmacologic means have thus far been unsuccessful. Neither aspirin-dipyridamole, ticlopidine, anti-coagulant therapy (acute heparin, chronic warfarin, hirudin or hirulog), thromboxane receptor antagonism nor steroids have been effective in preventing restenosis, although platelet inhibitors have been effective in preventing acute reocclusion after angioplasty (Mak and Topol, 1997; Lang et al., 1991; Popma et al., 1991). The platelet GP IIb /IIIa receptor, antagonist, Reopro is still under study but has not shown promising results for the reduction in restenosis following angioplasty and stenting. Other agents, which have also been unsuccessful in the prevention of restenosis, include the calcium channel antagonists, prostacyclin mimetics, angiotensin converting enzyme inhibitors, serotonin receptor antagonists, and anti-proliferative agents. These agents must be given systemically, however, and attainment of a therapeutically effective dose may not be possible; anti-proliferative (or anti-restenosis) concentrations may exceed the known toxic concentrations of these agents so that levels sufficient to produce smooth muscle inhibition may not be reached (Mak and Topol, 1997; Lang et al., 1991; Popma et al., 1991).
[0013] Additional clinical trials in which the effectiveness for preventing restenosis utilizing dietary fish oil supplements or cholesterol lowering agents has been examined showing either conflicting or negative results so that no pharmacological agents are as yet clinically available to prevent post-angioplasty restenosis (Mak and Topol, 1997; Franklin and Faxon, 1993: Serruys, P. W. et al., 1993). Recent observations suggest that the antilipid/antioxident agent, probucol may be useful in preventing restenosis but this work requires confirmation (Tardif et al., 1997; Yokoi, et al., 1997). Probucol is presently not approved for use in the United States and a thirty-day pretreatment period would preclude its use in emergency angioplasty. Additionally, the application of ionizing radiation has shown significant promise in reducing or preventing restenosis after angioplasty in patients with stents (Teirstein et al., 1997). Currently, however, the most effective treatments for restenosis are repeat angioplasty, atherectomy or coronary artery bypass grafting, because no therapeutic agents currently have Food and Drug Administration approval for use for the prevention of post-angioplasty restenosis.
[0014] Unlike systemic pharmacologic therapy, stents have proven useful in significantly reducing restenosis. Typically, stents are balloon-expandable slotted metal tubes (usually, but not limited to, stainless steel), which, when expanded within the lumen of an angioplastied coronary artery, provide structural support through rigid scaffolding to the arterial wall. This support is helpful in maintaining vessel lumen patency. In two randomized clinical trials, stents increased angiographic success after percutaneous transluminal coronary angioplasty, by increasing minimal lumen diameter and reducing, but not eliminating, the incidence of restenosis at six months (Serruys et al., 1994; Fischman et al., 1994).
[0015] Additionally, the heparin coating of stents appears to have the added benefit of producing a reduction in sub-acute thrombosis after stent implantation (Serruys et al., 1996). Thus, sustained mechanical expansion of a stenosed coronary artery with a stent has been shown to provide some measure of restenosis prevention, and the coating of stents with heparin has demonstrated both the feasibility and the clinical usefulness of delivering drugs locally, at the site of injured tissue.
[0016] As stated above, the use of heparin coated stents demonstrates the feasibility and clinical usefulness of local drug delivery; however, the manner in which the particular drug or drug combination is affixed to the local delivery device will play a role in the efficacy of this type of treatment. For example, the processes and materials utilized to affix the drug/drug combinations to the local delivery device should not interfere with the operations of the drug/drug combinations. In addition, the processes and materials utilized should be biocompatible and maintain the drug/drug combinations on the local device through delivery and over a given period of time. For example, removal of the drug/drug combination during delivery of the local delivery device may potentially cause failure of the device.
[0017] Accordingly, there exists a need for drug/drug combinations and associated local delivery devices for the prevention and treatment of vascular injury causing intimal thickening which is either biologically induced, for example atherosclerosis, or mechanically induced, for example, through percutaneous transluminal coronary angioplasty. In addition, there exists a need for maintaining the drug/drug combinations on the local delivery device through delivery and positioning as well as ensuring that the drug/drug combination is released in therapeutic dosages over a given period of time.
SUMMARY OF THE INVENTION
[0018] The drug/drug combinations and associated local delivery devices of the present invention provide a means for overcoming the difficulties associated with the methods and devices currently in use, as briefly described above. In addition, the methods for maintaining the drug/drug combinations on the local delivery device ensure that the drug/drug combinations reach the target site.
[0019] In accordance with one aspect, the present invention is directed to a local drug delivery apparatus. The local drug delivery apparatus comprises a medical device for implantation into a treatment site of a living organism and at least one agent in therapeutic dosages releasable affixed to the medical device for the treatment of reactions by the living organism caused by the medical device or the implantation thereof. The local delivery apparatus also comprises a material for preventing the at least one agent from separating from the medical device prior to implantation of the medical device at the treatment site, the material being affixed to at least one of the medical device or a delivery system for the medical device.
[0020] In accordance with another aspect, the present invention is directed to a local drug delivery apparatus. The local drug delivery apparatus comprises a medical device for implantation into a treatment site of a living organism and at least one agent in therapeutic dosages releasably affixed to the medical device for the treatment of reactions by the living organism caused by the medical device or the implantation thereof, the at least one agent being incorporated into a polymeric matrix. The local drug delivery apparatus also comprises a material for preventing the at least one agent from separating from the medical device prior to implantation of the medical device at the treatment site, the material being affixed to at least one of the medical device or a delivery system for the medical device.
[0021] In accordance with another aspect, the present invention is directed to a local drug delivery apparatus. The local drug delivery apparatus comprises a medical device for implantation into a treatment site of a living organism and at least one agent in therapeutic dosages releasably affixed to the medical device for the treatment of reactions by the living organism caused by the medical device or the implantation thereof, the at least one agent being incorporated into a polymeric matrix. The local drug delivery apparatus also comprises a material for preventing the polymeric matrix from adhering to itself when parts of the medical device make contact with one another.
[0022] In accordance with another aspect, the present invention is directed to a drug delivery device. The drug delivery device comprises a medical device for implantation into a treatment site of a living organism, and therapeutic dosages of one or more anti-proliferatives, one or more anti-inflammatories, one or more anti-coagulants, and one or more immunosuppressants releasably affixed to the medical device for the treatment of reactions by the living organism caused by the medical device or the implantation of the medical device at the treatment site.
[0023] In accordance with another aspect, the present invention is directed to a method for maintaining agents on a medical device during implantation into a treatment site of a living organism. The method comprises releasably affixing one or more agents in therapeutic dosages to the medical device, treating one of the medical device or the delivery device with a material for preventing the one or more agents from separating from the medical device during delivery and implantation of the medical device at the treatment site, and loading the medical device into a delivery device.
[0024] In accordance with another aspect, the present invention is directed to a method for maintaining agents on a medical device during implantation into a treatment site of a living organism. The method comprises releasably affixing one or more agents in therapeutic dosages to the medical device by incorporating the one or more agents in at least one polymer, treating the medical device with a material for preventing the polymer from adhering to itself when parts of the medical device make contact, and loading the medical device into a delivery device.
[0025] In accordance with another aspect, the present invention is directed to a method for maintaining agents on a medical device during implantation into a treatment site of a living organism. The method comprises coating at least a portion of the medical device with a primer layer, coating the primer layer with a first polymer layer including cross-linking moieties, cross-linking the first polymer layer to the primer layer, and releasably affixing one or more agents in therapeutic dosages to the medical device by incorporating the one or more agents in at least one polymer, the polymer being similar in chemical composition to the first polymer.
[0026] The local drug delivery devices and methods for maintaining the drug coatings thereon of the present invention utilizes a combination of materials to treat disease, and reactions by living organisms due to the implantation of medical devices for the treatment of disease or other conditions. The local delivery of drugs, agents or compounds generally substantially reduces the potential toxicity of the drugs, agents or compounds when compared to systemic delivery while increasing their efficacy.
[0027] Drugs, agents or compounds may be affixed to any number of medical devices to treat various diseases. The drugs, agents or compounds may also be affixed to minimize or substantially eliminate the biological organism's reaction to the introduction of the medical device utilized to treat a separate condition. For example, stents may be introduced to open coronary arteries or other body lumens such as biliary ducts. The introduction of these stents cause a smooth muscle cell proliferation effect as well as inflammation. Accordingly, the stents may be coated with drugs to combat these reactions.
[0028] In order to be effective, the drugs, agents or compounds should preferably remain on the medical devices during delivery and implantation. Accordingly, various coating techniques for creating strong bonds between the drugs, agents or compounds may be utilized. In addition, various materials may be utilized as surface modifications to prevent the drugs, agents or compounds from coming off prematurely.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] The foregoing and other features and advantages of the invention will be apparent from the following, more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings.
[0030] [0030]FIG. 1 is a view along the length of a stent (ends not shown) prior to expansion showing the exterior surface of the stent and the characteristic banding pattern.
[0031] [0031]FIG. 2 is a perspective view of the stent of FIG. 1 having reservoirs in accordance with the present invention.
[0032] [0032]FIG. 3 is a cross-sectional view of a band of the stent of FIG. 1 having drug coatings thereon in accordance with a first exemplary embodiment of the invention.
[0033] [0033]FIG. 4 is a cross-sectional view of a band of the stent of FIG. 1 having drug coatings thereon in accordance with a second exemplary embodiment of the invention.
[0034] [0034]FIG. 5 is a cross-sectional view of a band of the stent of FIG. 1 having drug coatings thereon in accordance with a third exemplary embodiment of the present invention.
[0035] [0035]FIG. 6 is a cross-sectional view of a balloon having a lubricious coating affixed thereto in accordance with the present invention.
[0036] [0036]FIG. 7 is a cross-sectional view of a band of the stent in FIG. 1 having a lubricious coating affixed thereto in accordance with the present invention.
[0037] [0037]FIG. 8 is a cross-sectional view of a self-expanding stent in a delivery device having a lubricious coating in accordance with the present invention.
[0038] [0038]FIG. 9 is a cross-sectional view of a band of the stent in FIG. 1 having a modified polymer coating in accordance with the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0039] The drug/drug combinations and delivery devices of the present invention may be utilized to effectively prevent and treat vascular disease, and in particular, vascular disease caused by injury. Various medical treatment devices utilized in the treatment of vascular disease may ultimately induce further complications. For example, balloon angioplasty is a procedure utilized to increase blood flow through an artery and is the predominant treatment for coronary vessel stenosis. However, as stated above, the procedure typically causes a certain degree of damage to the vessel wall, thereby potentially exacerbating the problem at a point later in time. Although other procedures and diseases may cause similar injury, the present invention will be described with respect to the treatment of restenosis and related complications following percutaneous transluminal coronary angioplasty.
[0040] While the invention will be described with respect to the treatment of restenosis and related complications following percutaneous transluminal coronary angioplasty, it is important to note that the local delivery of drug/drug combinations may be utilized to treat a wide variety of conditions utilizing any number of medical devices, or to enhance the function and/or life of the device. For example, intraocular lenses, placed to restore vision after cataract surgery is often compromised by the formation of a secondary cataract. The latter is often a result of cellular overgrowth on the lens surface and can be potentially minimized by combining a drug or drugs with the device. Other medical devices which often fail due to tissue in-growth or accumulation of proteinaceous material in, on and around the device, such as shunts for hydrocephalus, dialysis grafts, colostomy bag attachment devices, ear drainage tubes, leads for pace makers and implantable defibrillators can also benefit from the device-drug combination approach. Devices which serve to improve the structure and function of tissue or organ may also show benefits when combined with the appropriate agent or agents. For example, improved osteointegration of orthopedic devices to enhance stabilization of the implanted device could potentially be achieved by combining it with agents such as bonemorphogenic protein. Similarly other surgical devices, sutures, staples, vertebral disks, bone pins, suture anchors, hemostatic barriers, clamps, screws, plates, clips, vascular implants; tissue adhesives and sealants, tissue scaffolds, various types of dressings, bone substitutes, intraluminal devices, and vascular supports could also provide enhanced patient benefit using this drug-device combination approach. Essentially, any type of medical device may be coated in some fashion with a drug or drug combination which enhances treatment over use of the singular use of the device or pharmaceutical agent.
[0041] As stated previously, the implantation of a coronary stent in conjunction with balloon angioplasty is highly effective in treating acute vessel closure and may reduce the risk of restenosis. Intravascular ultrasound studies (Mintz et al., 1996) suggest that coronary stenting effectively prevents vessel constriction and that most of the late luminal loss after stent implantation is due to plaque growth, probably related to neointimal hyperplasia. The late luminal loss after coronary stenting is almost two times higher than that observed after conventional balloon angioplasty. Thus, inasmuch as stents prevent at least a portion of the restenosis process, a combination of drugs, agents or compounds which prevents smooth muscle cell proliferation, reduces inflammation and reduces coagulation or prevents smooth muscle cell proliferation by multiple mechanisms, reduces inflammation and reduces coagulation combined with a stent may provide the most efficacious treatment for post-angioplasty restenosis. The systemic use of drugs, agents or compounds in combination with the local delivery of the same or different drug/drug combinations may also provide a beneficial treatment option.
[0042] The local delivery of drug/drug combinations from a stent has the following advantages; namely, the prevention of vessel recoil and remodeling through the scaffolding action of the stent and the prevention of multiple components of neointimal hyperplasia or restenosis as well as a reduction in inflammation and thrombosis. This local administration of drugs, agents or compounds to stented coronary arteries may also have additional therapeutic benefit. For example, higher tissue concentrations of the drugs, agents or compounds can be achieved utilizing local delivery, rather than systemic administration. In addition, reduced systemic toxicity may be achieved utilizing local delivery rather than systemic administration while maintaining higher tissue concentrations. Also in utilizing local delivery from a stent rather than systemic administration, a single procedure may suffice with better patient compliance. An additional benefit of combination drug/agent/compound therapy may be to reduce the dose of each of the therapeutic drugs, agents or compounds, thereby limiting their toxicity, while still achieving a reduction in restenosis, inflammation and thrombosis. Local stent-based therapy is therefore a means of improving the therapeutic ratio (efficacy/toxicity) of anti-restenosis, anti-inflammatory, anti-thrombotic drugs, agents or compounds.
[0043] There are a multiplicity of different stents that may be utilized following percutaneous transluminal coronary angioplasty. Although any number of stents may be utilized in accordance with the present invention, for simplicity, one particular stent will be described in exemplary embodiments of the present invention. The skilled artisan will recognize that any number of stents may be utilized in connection with the present invention. In addition, as stated above, other medical devices may be utilized.
[0044] A stent is commonly used as a tubular structure left inside the lumen of a duct to relieve an obstruction. Commonly, stents are inserted into the lumen in a non-expanded form and are then expanded autonomously, or with the aid of a second device in situ. A typical method of expansion occurs through the use of a catheter-mounted angioplasty balloon which is inflated within the stenosed vessel or body passageway in order to shear and disrupt the obstructions associated with the wall components of the vessel and to obtain an enlarged lumen.
[0045] [0045]FIG. 1 illustrates an exemplary stent 100 which may be utilized in accordance with an exemplary embodiment of the present invention. The expandable cylindrical stent 100 comprises a fenestrated structure for placement in a blood vessel, duct or lumen to hold the vessel, duct or lumen open, more particularly for protecting a segment of artery from restenosis after angioplasty. The stent 100 may be expanded circumferentially and maintained in an expanded configuration, that is circumferentially or radially rigid. The stent 100 is axially flexible and when flexed at a band, the stent 100 avoids any externally-protruding component parts.
[0046] The stent 100 generally comprises first and second ends with an intermediate section therebetween. The stent 100 has a longitudinal axis and comprises a plurality of longitudinally disposed bands 102 , wherein each band 102 defines a generally continuous wave along a line segment parallel to the longitudinal axis. A plurality of circumferentially arranged links 104 maintain the bands 102 in a substantially tubular structure. Essentially, each longitudinally disposed band 102 is connected at a plurality of periodic locations, by a short circumferentially arranged link 104 to an adjacent band 102 . The wave associated with each of the bands 102 has approximately the same fundamental spatial frequency in the intermediate section, and the bands 102 are so disposed that the wave associated with them are generally aligned so as to be generally in phase with one another. As illustrated in the figure, each longitudinally arranged band 102 undulates through approximately two cycles before there is a link to an adjacent band 102 .
[0047] The stent 100 may be fabricated utilizing any number of methods. For example, the stent 100 may be fabricated from a hollow or formed stainless steel tube that may be machined using lasers, electric discharge milling, chemical etching or other means. The stent 100 is inserted into the body and placed at the desired site in an unexpanded form. In one embodiment, expansion may be effected in a blood vessel by a balloon catheter, where the final diameter of the stent 100 is a function of the diameter of the balloon catheter used.
[0048] It should be appreciated that a stent 100 in accordance with the present invention may be embodied in a shape-memory material, including, for example, an appropriate alloy of nickel and titanium or stainless steel. In this embodiment after the stent 100 has been formed it may be compressed so as to occupy a space sufficiently small as to permit its insertion in a blood vessel or other tissue by insertion means, wherein the insertion means include a suitable catheter, or flexible rod. On emerging from the catheter, the stent 100 may be configured to expand into the desired configuration where the expansion is automatic or triggered by a change in pressure, temperature or electrical stimulation.
[0049] [0049]FIG. 2 illustrates an exemplary embodiment of the present invention utilizing the stent 100 illustrated in FIG. 1. As illustrated, the stent 100 may be modified to comprise one or more reservoirs 106 . Each of the reservoirs 106 may be opened or closed as desired. These reservoirs 106 may be specifically designed to hold the drug/drug combinations to be delivered. Regardless of the design of the stent 100 , it is preferable to have the drug/drug combination dosage applied with enough specificity and a sufficient concentration to provide an effective dosage in the lesion area. In this regard, the reservoir size in the bands 102 is preferably sized to adequately apply the drug/drug combination dosage at the desired location and in the desired amount.
[0050] In an alternate exemplary embodiment, the entire inner and outer surface of the stent 100 may be coated with drug/drug combinations in therapeutic dosage amounts. A detailed description of a drug for treating restenosis, as well as exemplary coating techniques, is described below. It is, however, important to note that the coating techniques may vary depending on the drug/drug combinations. Also, the coating techniques may vary depending on the material comprising the stent or other intraluminal medical device.
[0051] Rapamycin is a macroyclic triene antibiotic produced by streptomyces hygroscopicus as disclosed in U.S. Pat. No. 3,929,992. It has been found that rapamycin among other things inhibits the proliferation of vascular smooth muscle cells in vivo. Accordingly, rapamycin may be utilized in treating intimal smooth muscle cell hyperplasia, restenosis, and vascular occlusion in a mammal, particularly following either biologically or mechanically mediated vascular injury, or under conditions that would predispose a mammal to suffering such a vascular injury. Rapamycin functions to inhibit smooth muscle cell proliferation and does not interfere with the re-endothelialization of the vessel walls.
[0052] Rapamycin reduces vascular hyperplasia by antagonizing smooth muscle proliferation in response to mitogenic signals that are released during an angioplasty induced injury. Inhibition of growth factor and cytokine mediated smooth muscle proliferation at the late GI phase of the cell cycle is believed to be the dominant mechanism of action of rapamycin. However, rapamycin is also known to prevent T-cell proliferation and differentiation when administered systemically. This is the basis for its immunosuppresive activity and its ability to prevent graft rejection.
[0053] As used herein, rapamycin includes rapamycin and all analogs, derivatives and congeners that find FKBP12 and possesses the same pharmacologic properties as rapamycin.
[0054] Although the anti-proliferative effects of rapamycin may be achieved through systemic use, superior results may be achieved through the local delivery of the compound. Essentially, rapamycin works in the tissues, which are in proximity to the compound, and has diminished effect as the distance from the delivery device increases. In order to take advantage of this effect, one would want the rapamycin in direct contact with the lumen walls. Accordingly, in a preferred embodiment, the rapamycin is incorporated onto the surface of the stent or portions thereof. Essentially, the rapamycin is preferably incorporated into the stent 100 , illustrated in FIG. 1, where the stent 100 makes contact with the lumen wall.
[0055] Rapamycin may be incorporated into or affixed to the stent in a number of ways. In the exemplary embodiment, the rapamycin is directly incorporated into a polymeric matrix and sprayed onto the outer surface of the stent. The rapamycin elutes from the polymeric matrix over time and enters the surrounding tissue. The rapamycin preferably remains on the stent for at least three days up to approximately six months, and more preferably between seven and thirty days.
[0056] Any number of non-erodible polymers may be utilized in conjunction with the rapamycin. In the exemplary embodiment, the polymeric matrix comprises two layers. The base layer comprises a solution of ethylene-co-vinylacetate and polybutylmethacrylate. The rapamycin is incorporated into this base layer. The outer layer comprises only polybutylmethacrylate and acts as a diffusion barrier to prevent the rapamycin from eluting too quickly. The thickness of the outer layer or top coat determines the rate at which the rapamycin elutes from the matrix. Essentially, the rapamycin elutes from the matrix by diffusion through the polymer molecules. Polymers are permeable, thereby allowing solids, liquids and gases to escape therefrom. The total thickness of the polymeric matrix is in the range from about 1 micron to about 20 microns or greater.
[0057] The ethylene-co-vinylacetate, polybutylmethacrylate and rapamycin solution may be incorporated into or onto the stent in a number of ways. For example, the solution may be sprayed onto the stent or the stent may be dipped into the solution. Other methods include spin coating and RF-plasma polymerization. In one exemplary embodiment, the solution is sprayed onto the stent and then allowed to dry. In another exemplary embodiment, the solution may be electrically charged to one polarity and the stent electrically changed to the opposite polarity. In this manner, the solution and stent will be attracted to one another. In using this type of spraying process, waste may be reduced and more precise control over the thickness of the coat may be achieved.
[0058] Since rapamycin acts by entering the surrounding tissue, it s preferably only affixed to the surface of the stent making contact with one tissue. Typically, only the outer surface of the stent makes contact with the tissue. Accordingly, in a preferred embodiment, only the outer surface of the stent is coated with rapamycin.
[0059] The circulatory system, under normal conditions, has to be self-sealing, otherwise continued blood loss from an injury would be life threatening. Typically, all but the most catastrophic bleeding is rapidly stopped though a process known as hemostasis. Hemostasis occurs through a progression of steps. At high rates of flow, hemostasis is a combination of events involving platelet aggregation and fibrin formation. Platelet aggregation leads to a reduction in the blood flow due to the formation of a cellular plug while a cascade of biochemical steps leads to the formation of a fibrin clot.
[0060] Fibrin clots, as stated above, form in response to injury. There are certain circumstances where blood clotting or clotting in a specific area may pose a health risk. For example, during percutaneous transluminal coronary angioplasty, the endothelial cells of the arterial walls are typically injured, thereby exposing the sub-endothelial cells. Platelets adhere to these exposed cells. The aggregating platelets and the damaged tissue initiate further biochemical process resulting in blood coagulation. Platelet and fibrin blood clots may prevent the normal flow of blood to critical areas. Accordingly, there is a need to control blood clotting in various medical procedures. Compounds that do not allow blood to clot are called anti-coagulants. Essentially, an anticoagulant is an inhibitor of thrombin formation or function. These compounds include drugs such as heparin and hirudin. As used herein, heparin includes all direct or indirect inhibitors of thrombin or Factor Xa.
[0061] In addition to being an effective anti-coagulant, heparin has also been demonstrated to inhibit smooth muscle cell growth in vivo. Thus, heparin may be effectively utilized in conjunction with rapamycin in the treatment of vascular disease. Essentially, the combination of rapamycin and heparin may inhibit smooth muscle cell growth via two different mechanisms in addition to the heparin acting as an anti-coagulant.
[0062] Because of its multifunctional chemistry, heparin may be immobilized or affixed to a stent in a number of ways. For example, heparin may be immobilized onto a variety of surfaces by various methods, including the photolink methods set forth in U.S. Pat. Nos. 3,959,078 and 4,722,906 to Guire et al. and U.S. Pat. Nos. 5,229,172; 5,308,641; 5,350,800 and 5,415,938 to Cahalan et al. Heparinized surfaces have also been achieved by controlled release from a polymer matrix, for example, silicone rubber, as set forth in U.S. Pat. Nos. 5,837,313; 6,099,562 and 6,120,536 to Ding et al.
[0063] In one exemplary embodiment, heparin may be immobilized onto the stent as briefly described below. The surface onto which the heparin is to be affixed is cleaned with ammonium peroxidisulfate. Once cleaned, alternating layers of polyethylenimine and dextran sulfate are deposited thereon. Preferably, four layers of the polyethylenimine and dextran sulfate are deposited with a final layer of polyethylenimine. Aldehyde-end terminated heparin is then immobilized to this final layer and stabilized with sodium cyanoborohydride. This process is set forth in U.S. Pat. Nos. 4,613,665; 4,810,784 to Larm and 5,049,403 to Larm et al.
[0064] Unlike rapamycin, heparin acts on circulating proteins in the blood and heparin need only make contact with blood to be effective. Accordingly, if used in conjunction with a medical device, such as a stent, it would preferably be only on the side that comes into contact with the blood. For example, if heparin were to be administered via a stent, it would only have to be on the inner surface of the stent to be effective.
[0065] In an exemplary embodiment of the invention, a stent may be utilized in combination with rapamycin and heparin to treat vascular disease. In this exemplary embodiment, the heparin is immobilized to the inner surface of the stent so that it is in contact with the blood and the rapamycin is immobilized to the outer surface of the stent so that it is in contact with the surrounding tissue. FIG. 3 illustrates a cross-section of a band 102 of the stent 100 illustrated in FIG. 1. As illustrated, the band 102 is coated with heparin 108 on its inner surface 110 and with rapamycin 112 on its outer surface 114 .
[0066] In an alternate exemplary embodiment, the stent may comprise a heparin layer immobilized on its inner surface, and rapamycin and heparin on its outer surface. Utilizing current coating techniques, heparin tends to form a stronger bond with the surface it is immobilized to then does rapamycin. Accordingly, it may be possible to first immobilize the rapamycin to the outer surface of the stent and then immobilize a layer of heparin to the rapamycin layer. In this embodiment, the rapamycin may be more securely affixed to the stent while still effectively eluting from its polymeric matrix, through the heparin and into the surrounding tissue. FIG. 4 illustrates a cross-section of a band 102 of the stent 100 illustrated in FIG. 1. As illustrated, the band 102 is coated with heparin 108 on its inner surface 110 and with rapamycin 112 and heparin 108 on its outer surface 114 .
[0067] There are a number of possible ways to immobilize, i.e., entrapment or covalent linkage with an erodible bond, the heparin layer to the rapamycin layer. For example, heparin may be introduced into the top layer of the polymeric matrix. In other embodiments, different forms of heparin may be directly immobilized onto the top coat of the polymeric matrix, for example, as illustrated in FIG. 5. As illustrated, a hydrophobic heparin layer 116 may be immobilized onto the top coat layer 118 of the rapamycin layer 112 . A hydrophobic form of heparin is utilized because rapamycin and heparin coatings represent incompatible coating application technologies. Rapamycin is an organic solvent-based coating and heparin is a water-based coating.
[0068] As stated above, a rapamycin coating may be applied to stents by a dip, spray or spin coating method, and/or any combination of these methods. Various polymers may be utilized. For example, as described above, polyethylene-co-vinyl acetate and polybutyl methacrylate blends may be utilized. Other polymers may also be utilized, but not limited to, for example, polyvinylidene fluoride-co-hexafluoropropylene and polyethylbutyl methacrylate-co-hexyl methacrylate. Also as described above, barrier or top coatings may also be applied to modulate the dissolution of rapamycin from the polymer matrix. In the exemplary embodiment described above, a thin layer of heparin is applied to the surface of the polymeric matrix. Because these polymer systems are hydrophobic and incompatible with the hydrophilic heparin, appropriate surface modifications may be required.
[0069] The application of heparin to the surface of the polymeric matrix may be performed in various ways and utilizing various biocompatible materials. For example, in one embodiment, in water or alcoholic solutions, polyethylene imine may be applied on the stents, with care not to degrade the rapamycin (e.g., pH<7, low temperature), followed by the application of sodium heparinate in aqueous or alcoholic solutions. As an extension of this surface modification, covalent heparin may be linked on polyethylene imine using amide-type chemistry (using a carbondiimide activator, e.g. EDC) or reductive amination chemistry (using CBAS-heparin and sodium cyanoborohydride for coupling). In another exemplary embodiment, heparin may be photolinked on the surface, if it is appropriately grafted with photo initiator moieties. Upon application of this modified heparin formulation on the covalent stent surface, light exposure causes cross-linking and immobilization of the heparin on the coating surface. In yet another exemplary embodiment, heparin may be complexed with hydrophobic quaternary ammonium salts, rendering the molecule soluble in organic solvents (e.g. benzalkonium heparinate, troidodecylmethylammonium heparinate). Such a formulation of heparin may be compatible with the hydrophobic rapamycin coating, and may be applied directly on the coating surface, or in the rapamycin/hydrophobic polymer formulation.
[0070] It is important to note that the stent may be formed from any number of materials, including various metals, polymeric materials and ceramic materials. Accordingly, various technologies may be utilized to immobilize the various drugs, agent, compound combinations thereon. In addition, the drugs, agents or compounds may be utilized in conjunction with other percutaneously delivered medical devices such as grafts and profusion balloons.
[0071] In addition to utilizing an anti-proliferative and anti-coagulant, anti-inflammatories may also be utilized in combination therewith. One example of such a combination would be the addition of an anti-inflammatory corticosteroid such as dexamethasone with an anti-proliferative, such as rapamycin, cladribine, vincristine, taxol, or a nitric oxide donor and an anti-coagulant, such as heparin. Such combination therapies might result in a better therapeutic effect, i.e., less proliferation as well as less inflammation, a stimulus for proliferation, than would occur with either agent alone. The delivery of a stent comprising an anti-proliferative, anti-coagulant, and an anti-inflammatory to an injured vessel would provide the added therapeutic benefit of limiting the degree of local smooth muscle cell proliferation, reducing a stimulus for proliferation, i.e., inflammation and reducing the effects of coagulation thus enhancing the restenosis-limiting action of the stent.
[0072] In other exemplary embodiments of the inventions, growth factor or cytokine signal transduction inhibitor, such as the ras inhibitor, R115777, or a tyrosine kinase inhibitor, such as tyrphostin, might be combined with an antiproliferative agent such as taxol, vincristine or rapamycin so that proliferation of smooth muscle cells could be inhibited by different mechanisms. Alternatively, an anti-proliferative agent such as taxol, vincristine or rapamycin could be combined with an inhibitor of extracellular matrix synthesis such as halofuginone. In the above cases, agents acting by different mechanisms could act synergistically to reduce smooth muscle cell proliferation and vascular hyperplasia. This invention is also intended to cover other combinations of two or more such drug agents. As mentioned above, such drugs, agents or compounds could be administered systemically, delivered locally via drug delivery catheter, or formulated for delivery from the surface of a stent, or given as a combination of systemic and local therapy.
[0073] In addition to anti-proliferatives, anti-inflammatories and anti-coagulants, other drugs, agents or compounds may be utilized in conjunction with the medical devices. For example, immunosuppressants may be utilized alone or in combination with these other drugs, agents or compounds. Also modified genes in viral and non-viral gene introducers may also be introduced locally via a medical device.
[0074] As described above, various drugs, agents or compounds may be locally delivered via medical devices. For example, rapamycin and heparin may be delivered by a stent to reduce restenosis, inflammation, and coagulation. Various techniques for immobilizing the drugs, agents or compounds are discussed above, however, maintaining the drugs, agents or compounds on the medical devices during delivery and positioning is critical to the success of the procedure or treatment. For example, removal of the drug, agent or compound coating during delivery of the stent can potentially cause failure of the device. For a self-expanding stent, the retraction of the restraining sheath may cause the drugs, agents or compounds to rub off the stent. For a balloon expandable stent, the expansion of the balloon may cause the drugs, agents or compounds to simply delaminate from the stent through contact with the balloon or via expansion. Therefore, prevention of this potential problem is important to have a successful therapeutic medical device, such as a stent.
[0075] There are a number of approaches that may be utilized to substantially reduce the above-described problem. In one exemplary embodiment, a lubricant or mold release agent may be utilized. The lubricant or mold release agent may comprise any suitable biocompatible lubricious coating. An exemplary lubricious coating may comprise silicone. In this exemplary embodiment, a solution of the silicone base coating may be introduced onto the balloon surface, onto the polymeric matrix, and/or onto the inner surface of the sheath of a self-expanding stent delivery apparatus and allowed to air cure. Alternately, the silicone based coating may be incorporated into the polymeric matrix. It is important to note, however, that any number of lubricious materials may be utilized, with the basic requirements being that the material be biocompatible, that the material not interfere with the actions/effectiveness of the drugs, agents or compounds and that the material not interfere with the materials utilized to immobilize the drugs, agents or compounds on the medical device. It is also important to note that one or more, or all of the above-described approaches may be utilized in combination.
[0076] Referring now to FIG. 6, there is illustrated a balloon 200 of a balloon catheter that may be utilized to expand a stent in situ. As illustrated, the balloon 200 comprises a lubricious coating 202 . The lubricious coating 202 functions to minimize or substantially eliminate the adhesion between the balloon 200 and the coating on the medical device. In the exemplary embodiment described above, the lubricious coating 202 would minimize or substantially eliminate the adhesion between the balloon 200 and the heparin or rapamycin coating. The lubricious coating 202 may be attached to and maintained on the balloon 200 in any number of ways including but not limited to dipping, spraying, brushing or spin coating of the coating material from a solution or suspension followed by curing or solvent removal step as needed.
[0077] Materials such as synthetic waxes, e.g. diethyleneglycol monostearate, hydrogenated castor oil, oleic acid, stearic acid, zinc stearate, calcium stearate, ethylenebis (stearamide), natural products such as paraffin wax, spermaceti wax, carnuba wax, sodium alginate, ascorbic acid and flour, fluorinated compounds such as perfluoroalkanes, perfluorofatty acids and alcohol, synthetic polymers such as silicones e.g. polydimethylsiloxane, polytetrafluoroethylene, polyfluoroethers, polyalkylglycol e.g. polyethylene glycol waxes, and inorganic materials such as talc, kaolin, mica, and silica may be used to prepare these coatings. Vapor deposition polymerization e.g. parylene-C deposition, or RF-plasma polymerization of perflouroalkenes can also be used to prepare these lubricious coatings.
[0078] [0078]FIG. 7 illustrates a cross-section of a band 102 of the stent 100 illustrated in FIG. 1. In this exemplary embodiment, the lubricious coating 300 is immobilized onto the outer surface of the polymeric coating. As described above, the drugs, agents or compounds may be incorporated into a polymeric matrix. The stent band 102 illustrated in FIG. 7 comprises a base coat 302 comprising a polymer and rapamycin and a top coat 304 or diffusion layer 304 also comprising a polymer. The lubricious coating 300 is affixed to the top coat 302 by any suitable means, including but not limited to spraying, brushing, dipping or spin coating of the coating material from a solution or suspension with or without the polymers used to create the top coat, followed by curing or solvent removal step as needed. Vapor deposition polymerization and RF-plasma polymerization may also be used to affix those lubricious coating materials that lend themselves to this deposition method, to the top coating. In an alternate exemplary embodiment, the lubricious coating may be directly incorporated into the polymeric matrix.
[0079] If a self-expanding stent is utilized, the lubricious coating may be affixed to the inner surface of the restraining sheath. FIG. 8 illustrates a self-expanding stent 400 within the lumen of a delivery apparatus sheath 402 . As illustrated, a lubricious coating 404 is affixed to the inner surfaces of the sheath 402 . Accordingly, upon deployment of the stent 400 , the lubricious coating 404 preferably minimizes or substantially eliminates the adhesion between the sheath 402 and the drug, agent or compound coated stent 400 .
[0080] In an alternate approach, physical and/or chemical cross-linking methods may be applied to improve the bond strength between the polymeric coating containing the drugs, agents or compounds and the surface of the medical device or between the polymeric coating containing the drugs, agents or compounds and a primer. Alternately, other primers applied by either traditional coating methods such as dip, spray or spin coating, or by RF-plasma polymerization may also be used to improve bond strength. For example, as shown in FIG. 9, the bond strength can be improved by first depositing a primer layer 500 such as vapor polymerized parylene-C on the device surface, and then placing a second layer 502 which comprises a polymer that is similar in chemical composition to the one or more of the polymers that make up the drug-containing matrix 504 , e.g., polyethylene-co-vinyl acetate or polybutyl methacrylate but has been modified to contain cross-linking moieties. This secondary layer 502 is then cross-linked to the primer after exposure to ultraviolet light. It should be noted that anyone familiar with the art would recognize that a similar outcome could be achieved using cross-linking agents that are activated by heat with or without the presence of an activating agent. The drug-containing matrix 504 is then layered onto the secondary layer 502 using a solvent that swells, in part or wholly, the secondary layer 502 . This promotes the entrainment of polymer chains from the matrix into the secondary layer 502 and conversely from the secondary layer 502 into the drug-containing matrix 504 . Upon removal of the solvent from the coated layers, an interpenetrating or interlocking network of the polymer chains is formed between the layers thereby increasing the adhesion strength between them. A top coat 506 is used as described above.
[0081] A related problem occurs in medical devices such as stents. In the drug-coated stents crimped state, some struts come into contact with each other and when the stent is expanded, the motion causes the polymeric coating comprising the drugs, agents or compounds to stick and stretch. This action may potentially cause the coating to separate from the stent in certain areas. The predominant mechanism of the coating self-adhesion is believed to be due to mechanical forces. When the polymer comes in contact with itself, its chains can tangle causing the mechanical bond, similar to Velcro®. Certain polymers do not bond with each other, for example, fluoropolymers. For other polymers, however, powders may be utilized. In other words, a powder may be applied to the one or more polymers incorporating the drugs, agents or other compounds on the surfaces of the medical device to reduce the mechanical bond. Any suitable biocompatible material which does not interfere with the drugs, agents, compounds or materials utilized to immobilize the drugs, agents or compounds onto the medical device may be utilized. For example, a dusting with a water soluble powder may reduce the tackiness of the coatings surface and this will prevent the polymer from sticking to itself thereby reducing the potential for delamination. The powder should be water-soluble so that it does not present an emboli risk. The powder may comprise an anti-oxidant, such as vitamin C, or it may comprise an anti-coagulant, such as aspirin or heparin. An advantage of utilizing an anti-oxidant may be in the fact that the anti-oxidant may preserve the other drugs, agents or compounds over longer periods of time.
[0082] Although shown and described is what is believed to be the most practical and preferred embodiments, it is apparent that departures from specific designs and methods described and shown will suggest themselves to those skilled in the art and may be used without departing from the spirit and scope of the invention. The present invention is not restricted to the particular constructions described and illustrated, but should be constructed to cohere with all modifications that may fall within the scope of the appended claims.
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Local drug delivery medical devices are utilized to deliver therapeutic dosages of drugs, agents or compounds directly to the site where needed. The local drug delivery medical devices utilize various materials and coating methodologies to maintain the drugs, agents or compounds on the medical device until delivered and positioned.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a national phase filing, under 35 U.S.C. §371(c), of International Application No. PCT/EP2009/061560, filed Sep. 7, 2009, the disclosure of which is incorporated herein by reference in its entirety.
FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
[0002] Not Applicable
BACKGROUND
[0003] The invention relates to an impregnation plant for impregnating a liner.
[0004] Pipelines are commonly used to transport fluids over a long distance. Faulty pipeline systems may be renovated by introducing a lining tube into the pipeline. The lining tube, which further on will be referred to as a liner, may be placed inside the faulty pipeline such that the inner walls of the pipeline are completely covered by the liner. The liner may be used to repair faults such as leakage by sealing the interior of the pipeline to the walls of the pipeline. Leaking pipelines may constitute a hazard for the environment and for personal health, since contaminated and/or dangerous fluids may escape the pipeline into the surrounding outside environment. Alternatively, the liner may be used preventively to repair worn, damaged or badly maintained pipelines to prevent further damage, which may eventually lead to a leakage.
[0005] The lining technology may be used on any pipeline system such as gas pipelines, water pipelines etc. The pipelines may have any orientation, such as e.g. vertical or horizontal. Further, the location of the pipeline may be e.g. either below ground or above ground, indoor or outdoor, in private buildings or in industrial environments. The liner may be installed by simply pulling it into place inside the pipeline, or by using eversion. By eversion is meant the technology of fastening one end of the liner onto a manhole and subsequently inverting the liner into the pipeline by the use of water, steam or pressurized gas.
[0006] The major advantage of the above technology is achieved in connection with underground pipelines, such as sewer pipelines. The renovation may be performed quickly and trenchless with minimum inconvenience to the surroundings and considerably lower costs compared to a complete replacement of the pipeline.
[0007] The liner is preferably made of a soft and flexible material, which is easy to package and transport to the installation site and which may be inserted into the pipeline system from the outside through e.g. a manhole or the like. When the liner is put in place inside the pipeline system it should be hardened for maximum stability. The liner is therefore preferably made from a fibre material. The fibre material may be a woven or non-woven material and may e.g. be of any of the following types: glass, carbon, aramid, polyester, polyacrylonitrile, mineral, viscose, polyamide, polyacrylic or natural fibres or a combination of the above. The fibre material is impregnated with a resin, such as styrene/polyester or styrene-free polyester, styrene/vinylester or styrene-free vinylester, vinylester urethane, furan, phenol, water glass, epoxy, methacrylate, isocyanate or the like. The resin should be curable, e.g. by application of heat or radiation, for an irreversible transition from a soft and flexible state into a hardened state. One example of such a liner may be found in EP 1 920 913, to which reference is made and which is hereby incorporated in the present specification by reference. The fibre material may be e.g. a glass fibre material or felt material, which is flexible and at the same time may hold a large quantity of resin. The material should exhibit affinity to the resin to allow the resin to soak the liner completely.
[0008] The liner is typically impregnated by submerging the liner in a resin bath. When the liner is submerged, the resin will enter into the fibre material structure of the liner, such that the liner is soaked with resin. Thereafter the resin may be partially cured to achieve the soft and flexible state and avoid resin leaking from the liner.
[0009] When impregnating the liner using the above technology, there is a need to ensure that no voids exist inside the liner. Such voids may be gas (air) bubbles trapped inside the fibre material after impregnation. Voids of any kind will constitute weak spots when the liner has been cured and may lead to premature degradation and damage to the liner. Voids may further lead to cracking of the liner and possibly to a leakage.
SUMMARY
[0010] It is therefore an object according to the invention to provide a method and a system for impregnating a liner and at the same time reduce the risk of a void inside the liner after curing.
[0011] The above need and the above object together with numerous other needs and objects which will be evident from the below detailed description are according to a first aspect of the present invention obtained by an impregnation plant for impregnating a liner with a resin, the liner being fibrous and flexible, the impregnation plant comprising:
a vacuum lock comprising a housing having an inlet and an outlet and defining an ambient pressure space near the inlet and a low pressure space near the outlet, the ambient pressure space and the low pressure space being separated by a substantially gas-tight seal comprising a first sealing element and a second sealing element located juxtaposed the first sealing element, the first and second sealing elements being flexible for allowing the fibrous liner to be conveyed through the seal between the first sealing element and the second sealing element in a direction from the inlet towards the outlet, the liner being degassed by compressing the liner into a compressed state between the first and second sealing elements and subsequently relaxing the liner into a substantially uncompressed state inside the low pressure space, a vacuum pump communicating with the low pressure space for reducing the pressure in the low pressure space in relation to the pressure in the ambient pressure space, and an impregnation station being in gas-tight communication with the outlet of said vacuum lock, the impregnation station comprising a resin bath for accommodating the liner, a resin reservoir, a nozzle, a pipe system and a resin pump for propelling the resin from the resin reservoir via the pipe system and the nozzle into the resin bath in a direction towards the liner.
[0015] In the impregnation plant according to the first aspect of the present invention the liner is impregnated while being conveyed through a vacuum lock and a resin bath. The liner is made of a soft and porous fibre material, such as a woven or non-woven material or fabrics or combination comprising glass fibre, polyester or felt or a combination of the above. The material should preferably have a high resin affinity. The porous structure of the fibre material will contain a large volume of air. The air volumes may be encapsulated in resin during impregnation and constitute voids after curing. To avoid the above the liner is first of all compressed between two sealing elements to remove a substantial amount of the air located inside the liner. It must however be ensured that the liner is not crushed or damaged when compressing the liner. Therefore, the pressure applied to the liner by the sealing elements is limited. Consequently, some amount of residual air will remain inside the liner after degassing. The sealing element may comprise sealing lips or rollers or the like. The sealing element should be soft to allow it to deform and correspond to the compressed shape of the liner such that any air leakage is minimized.
[0016] To remove the residual air in the liner it is subsequently allowed to expand inside a low pressure space, which may define a low pressure chamber. The low pressure chamber is connected to a constantly running vacuum pump such that the low pressure chamber may define a partial vacuum. The residual air in the liner will expand in the low pressure chamber and the vacuum pump will suck away any residual air from the low pressure chamber. The liner will thereby become substantially degassed.
[0017] The liner subsequently enters the resin bath. Resin bath should in the present context be understood to mean any volume or body of liquid resin without specifying any particular shape. To ensure that the liner is completely soaked and all cavities in the liner are filled with resin in the resin bath, a resin jet is propelled against the liner. The resin jet will allow resin to penetrate deep into the liner by applying a resin pressure and a velocity at the liner. The flow jet is propelled from a nozzle connected to a pipe system and a pump is used to pump resin from the reservoir towards the liner. The flow jet will allow the resin to penetrate deeper into the liner and fill out the cavities better than by e.g. submerging the liner. The word “nozzle” should be understood to mean any form of fluid outlet having either a constant or a varying shape, e.g. a straight shape, a converging shape or a diverging shape. The ambient pressure space is understood to encompass any space having atmospheric pressure.
[0018] In a further embodiment according to the first aspect of the present invention the resin reservoir may constitute a resin receptacle for receiving excess resin. By excess resin is meant any resin exiting the resin bath while not being accommodated inside the liner. Excess resin is a result of a pressure in the resin bath/nozzle and is preferred since it shows that resin has penetrated the liner and impregnated it sufficiently. The excess resin is collected in the resin receptacle and may be re-used by re-circulating it to the resin bath via the nozzle. A filter may be employed in the resin receptacle to remove any contamination such as fibres from the liner in the excess resin to avoid clogging the nozzle or pipe system.
[0019] In a further embodiment according to the first aspect of the present invention the impregnation station may have a first end being in gas-tight communication with said outlet of said vacuum lock and a second end being in gas-tight communication with a further vacuum lock, said further vacuum lock comprising a further housing having a further inlet and a further outlet and defining a further ambient pressure space near said further outlet and a further low pressure space near said further inlet, said further ambient pressure space and said further low pressure space being separated by a substantially gas-tight further seal comprising a further first sealing element and a further second sealing element located juxtaposed said further first sealing element, said further first and second sealing elements being flexible for allowing said fibrous liner to be conveyed through said further seal between said further first sealing element and said further second sealing element in a direction from said further inlet towards said further outlet. The working principle of the further vacuum lock is reversed compared to the original vacuum lock. The further vacuum lock should apply a very limited force on the liner to avoid pressing out any resin accommodated inside the liner. It should be noted that the two vacuum locks may have different working principles, i.e. one may employ sealing lips while the other may employ rollers.
[0020] In a further embodiment, according to the first aspect of the present invention the impregnation station has a first end being in gas-tight communication with said outlet of said vacuum lock and a second end being open to the outside ambient pressure, said first end and said second end being separated gas-tightly by said resin. The resin will thus act as a further vacuum lock comprising a liquid vacuum lock between the low pressure space and the ambient air pressure. A liquid vacuum lock will have the additional advantage of substantially zero leakage. The ambient air pressure acting on the resin at the second end will act as a pressure force to push the resin towards the first end. This pressure may be balanced by the pressure inside the resin bath generated by the supply of resin from the nozzle and pipe system. Alternatively, the pressure force may be balanced by the gravity force from the resin such that the gravity force of the pile of resin located near the first end and above the resin level of the second end compensates the pressure force of the ambient air pressure. Thus, the resin level at the first end of the receptacle will be higher than the resin level at the second end.
[0021] In a further embodiment according to the first aspect of the present invention the resin bath is formed between said first and second end by the continuous supply of resin by said nozzle. This way, the resin bath must not comprise a reservoir suitable for permanently storing the resin, but may simply comprise a defined space where resin and liner may interact. This means the continuously supplied resin may either be accommodated inside the liner or exit the resin bath as excess resin. The resin bath may thus comprise e.g. a partially enclosed volume or alternatively a single surface or the resin bath may be entirely defined by the continuous supply of resin.
[0022] In a further embodiment according to the first aspect of the invention the impregnation plant may comprise a system for monitoring the level of resin in said resin reservoir. Such system may range from a simple floatation device inside the resin reservoir to more advanced radar detectors for detecting the surface of the resin in the resin reservoir.
[0023] In a further embodiment according to the first aspect of the invention the impregnation plant may comprise a resin supply tank and a resin supply pump for delivering resin from said resin supply tank to said resin reservoir. When the liner is constantly impregnated the resin level in the resin reservoir will sink. To compensate for this and to keep the resin level constant, resin must be injected into the resin reservoir. This may be done by delivering resin to the resin reservoir from a nearby resin supply tank via a pump.
[0024] In a further embodiment according to the first aspect of the invention the impregnation plant may comprise two nozzles mounted in a juxtaposed position for applying the resin on both sides of said liner. The nozzles are preferably mounted such that the resin flow jet is applied perpendicular to the liner surface. Since the resin can penetrate the liner from two opposite directions, the resin needs to penetrate only half the distance compared to when the resin jet is only applied from one direction. This way the resin need not penetrate the entire liner, and the risk of voids will be additionally reduced. The impregnation plant may further comprise a plurality of nozzles, such as 2-1000, preferably 100-800, more preferably 400-600, most preferably 400, or alternatively 200-400, or alternatively 400-600. The nozzles should be equally distributed such that the whole surface of the liner is subjected to the resin flow jet, and preferably equally distributed on each side of the liner. If some areas of the liner are not subjected to the resin jet, they may not be completely impregnated and consequently a void may arise there.
[0025] In a further embodiment according to the first aspect of the invention the impregnation plant may comprise a low pressure space having an absolute pressure lower than 100 kPa, preferably 10−90 kPa, more preferably 50−70 kPa, most preferably 60 kPa, or alternatively 50−60 kPa, or alternatively 60−70 kPa. Lower pressure will reduce the amount of voids in the liner. High vacuum is costly to achieve and maintain and will in most cases not be necessary to achieve the intended void-free result.
[0026] In a further embodiment according to the first aspect of the invention the impregnation plant may comprise a system for monitoring the pressure in said low pressure chamber. Such a system may comprise a pressure sensor in the low pressure space. The pressure in the low pressure space should be controlled since it influences the amount and severity of any voids in the liner and may additionally influence the resin level.
[0027] In a further embodiment according to the first aspect of the invention the sealing element may comprise a roller seal or alternatively a lip seal or yet alternatively a roller and lip seal. A roller has the advantage of being able to provide a gas-tight seal with low wear compared to the alternative lip seals. The roller may in turn preferably be sealed by lip seals in relation to the housing.
[0028] In a further embodiment according to the first aspect of the invention the roller may comprise rubber foam. Rubber foam is a soft and air-tight material which may preferably be used for the rollers. By having soft rollers the airtight properties may be realized without any need of compressing the liner excessively.
[0029] In a further embodiment according to the first aspect of the invention the liner may be guided through said device by one or more guiding rollers. The guiding rollers as well as the rollers in the vacuum lock may be driven by a motor, such as a pneumatic motor or an electric motor. In this way the liner may be conveyed inside the impregnation plant.
[0030] In a further embodiment according to the first aspect of the invention the vacuum lock may be having more than 2 rollers, such as e.g. 3-10 rollers, or preferably 6 rollers. Having a series of rollers will improve the sealing quality by providing additional compartments having a pressure between the pressure of the low pressure compartment and the ambient pressure. In this configuration the pressure difference across a pair of rollers will be lower and consequently the amount of gas leaking through the seal will be lower. The rollers may be configured in juxtaposed pairs in a row, or alternatively form a sequence where each roller, except the first and the last, is juxtaposed to 2 other rollers. The compartments formed between the rollers may optionally be connected to a vacuum pump.
[0031] In a further embodiment according to the first aspect of the invention the impregnation plant may comprise a control unit. A control unit may be used to control the different features of the invention, such as the pressure in the low pressure space, the pressure of the resin jet, the level of resin, the velocity of the liner and many other features, which will be evident from the description.
[0032] In a further embodiment according to the first aspect of the invention the liner may be submerged in the resin reservoir. The submersion of the liner may be used in addition to the flow jet for impregnating the liner. The submersion may be performed either before, during or after applying the flow jet.
[0033] In a further embodiment according to the first aspect of the invention the resin-filled receptacle comprises a first vessel having an elongated and substantially vertical orientation and defining an upper inlet and a lower outlet, a second vessel having an elongated and substantially vertical orientation and defining a lower inlet and an upper outlet, and a third vessel connecting the lower outlet and the lower inlet. Upper and lower should in this context be understood in relation to the earth gravity. The shape described above has been proved to be the most efficient concerning material use. If vacuum is applied to the upper inlet, the resin level will rise in the first vessel and fall in the second vessel if it is assumed that ambient pressure is applied to the second opening. The earth gravity and ambient pressure determine the resin levels as discussed above. Assuming earth conditions, typical vacuum pumps/seals and typical resin density, the resin-filled receptacle and/or said second vessel of said resin-filled receptacle should have/has an elongation of 1-10 meters, preferably 2-6 meters, more preferably 3-5 meters, and most preferably 4 meters, or alternatively 2-4 meters, or alternatively 4-6 meters.
[0034] In a further embodiment according to the first aspect of the invention the impregnation plant may comprise a pre-curing device for applying radiant energy onto said liner after impregnation. Such pre-curing may be achieved by applying radiant energy directly after impregnation of the liner. This way the resin will attach better to the liner.
[0035] The above need and the above object together with numerous other needs and objects which will be evident from the below detailed description are according to a second aspect of the present invention obtained by a vacuum lock comprising a housing having an inlet and an outlet and defining an ambient pressure space near said inlet and a low pressure space near said outlet, said ambient pressure space and said low pressure space being separated by a substantially gas-tight seal comprising a first sealing element and a second sealing element located juxtaposed said first sealing element, said first and second sealing elements being flexible for allowing a fibrous liner to be conveyed through said seal between said first sealing element and said second sealing element in a direction from said inlet towards said outlet, said liner being degassed by compressing said liner into a compressed state between said first and second sealing elements and subsequently relaxing said liner into a substantially uncompressed state inside said low pressure space. From the above it is evident that the vacuum lock from the first aspect of the present invention may be used as a stand-alone unit. The above vacuum lock will allow a liner to enter from an ambient pressure space into a low pressure space with a low leakage. At the same time the liner is compressed and drained from gas located inside the liner. The rollers are preferably connected to a motor such that the liner is driven and guided through the vacuum lock. It is further evident that the vacuum lock may be used in the opposite direction, i.e. for conveying a liner from a low pressure space to an ambient pressure space or alternatively from a high-pressure space to a low pressure space or vice versa.
[0036] From GB 1080562, a labyrinth gland is known, allowing a glass fibre mat to be introduced into a vacuum chamber. The reference, however, fails to describe the essential feature of degassing the mat by compressing the mat in the labyrinth gland.
[0037] From JPA 61051312 a further degassing vacuum chamber is known, in which a labyrinth gland similar to the above described structure known from GB 1080562 is described. Similar to the GB reference, the Japanese reference fails to describe the essential feature of degassing the material by compressing the material in the labyrinth gland.
[0038] From U.S. Pat. No. 3,730,678, a technique of treating textile fibres is known. The reference, however, includes no vacuum lock. On the contrary, the technique involves the pressurizing of the treatment chamber by injection of steam or suitable reaction vapour or air into the reaction chamber.
[0039] The above need and the above object together with numerous other needs and objects which will be evident from the below detailed description are according to a third aspect of the present invention obtained by a impregnation station comprising a resin bath for accommodating said liner, a resin reservoir, a nozzle, a pipe system and a resin pump for propelling said resin from said resin reservoir via said pipe system and said nozzle into said resin bath in a direction towards said liner. From the above it is evident that the impregnation station from the first aspect of the invention may be used as a stand-alone unit. The above impregnation station may preferably be made substantially flat and compact.
[0040] From JPA 04193506, a technique of impregnating fibre bundles by the use of melted resin is known. The reference, however, describes no technique in relation to the impregnation of a fibrous liner, i.e. a structure including fibres orientated in a multiplicity of direction or in any arbitrary direction and constituting a structure similar to a mat. The impregnation of the fibre bundles by use of a melted resin is according to the teachings of the Japanese reference performed under an elevated pressure or high pressure as distinct from the technique according to the present invention, according to which technique the impregnation is performed in a degassed or low pressure chamber.
[0041] The above need and the above object together with numerous other needs and objects which will be evident from the below detailed description are according to a fourth aspect of the present invention obtained by a method of impregnating a liner by providing an impregnation plant, said liner being fibrous and flexible, said impregnation plant comprising:
a vacuum lock comprising a housing having an inlet and an outlet and defining an ambient pressure space near said inlet and a low pressure space near said outlet, said ambient pressure space and said low pressure space being separated by a substantially gas-tight seal comprising a first sealing element and a second sealing element located juxtaposed one another, said first and second sealing element being flexible, a vacuum pump communicating with said low pressure space, and an impregnation station being in gas-tight communication with said outlet of said vacuum lock, said impregnation station comprising a resin bath, a resin reservoir, a nozzle, a pipe system and a resin pump, and by performing the following steps: reducing the pressure in said low pressure space in relation to the pressure in said ambient pressure space, degassing said liner by conveying said liner through said seal between said first sealing element and said second sealing element in a direction from said ambient pressure space to said low pressure space, and impregnating said liner by conveying said liner through said impregnation station and by using said pump propelling said resin from said resin reservoir via said pipe system and said nozzle into said resin bath in a direction towards said liner. It has been shown that by impregnating a liner according to the above method the amount of voids caused by air/gas bubbles inside the liner will be considerably reduced. The method may be applied as a continuous process where a liner of infinite length is impregnated and afterwards cut into suitable lengths. Alternatively, the liner is cut into suitable lengths before entering the impregnation plant. Yet alternatively, the method may be applied in a mobile impregnation plant, e.g. where the impregnation plant is mounted on a truck for on-site impregnation and installation.
[0048] The above need and the above object together with numerous other needs and objects which will be evident from the below detailed description are according to a fifth aspect of the present invention obtained by a method of degassing a liner by providing a vacuum lock comprising a housing having an inlet and an outlet and defining an ambient pressure space near said inlet and a low pressure space near said outlet, said ambient pressure space and said low pressure space being separated by a substantially gas-tight seal comprising a first sealing element and a second sealing element located juxtaposed said first sealing element, said first and second sealing elements being flexible for allowing a fibrous liner to be conveyed through said seal between said first sealing element and said second sealing element in a direction from said inlet towards said outlet, and by performing the following steps:
reducing the pressure in the low pressure space in relation to the pressure in the ambient pressure space, conveying said liner through said seal between said first sealing element and said second sealing element in a direction from said ambient pressure space to said low pressure space, and degassing said liner by compressing said liner into a compressed state between said first and second sealing elements and subsequently relaxing said liner into a substantially uncompressed state inside said low pressure space. The above method may be applied for degassing a liner before further treatment. The method is preferably applied together with the previously described vacuum lock.
[0052] The above need and the above object together with numerous other needs and objects which will be evident from the below detailed description are according to a sixth aspect of the present invention obtained by a method of impregnating a fibrous liner by providing an impregnation station, said impregnation station comprising:
a resin bath, a resin reservoir, a nozzle, a pipe system and a resin pump, and by performing the following steps: impregnating said fibrous liner by accommodating and conveying said liner through said resin bath and propelling said resin from said resin reservoir via said pipe system and said nozzle into said resin bath in a direction towards said liner.
[0055] It is further evident that numerous variations of the systems and methods described above are possible, in particular by combining some of the features of the aspects and embodiments described above. A detailed description of the figures of five specific and currently preferred embodiments of the invention follows below.
BRIEF DESCRIPTION OF THE DRAWINGS
[0056] The invention will now be further described by reference to the drawings, in which
[0057] FIG. 1 shows a side cut-out view of a first and currently preferred embodiment of an impregnation plant;
[0058] FIG. 2 shows a further embodiment of a compact impregnation plant, which may be suitable for a mobile impregnation plant;
[0059] FIGS. 3A and 3B show two different embodiments of a vacuum lock for use with an impregnation plant; and
[0060] FIG. 4 shows an impregnation station for use in an impregnation plant.
DETAILED DESCRIPTION
[0061] FIG. 1 shows an impregnation plant 10 for impregnating a liner 12 with a resin. The resin is indicated in FIG. 1 by hatching. The liner 12 is used for lining and re-lining pipelines such as sewer pipelines. The liner 12 is made of a glass fibre material or alternatively a felt material or a combination. The liner 12 has a flat shape with an indefinite length and a predefined width, which is determined according to the circumference of the pipeline, which is going to be lined. The width of the liner 12 may typically range from a few centimetres up to a few meters. The liner 12 is conveyed in a travelling direction according to the arrow A and enters the impregnation plant 10 at an opening 14 . The liner 12 is transported and directed via a first guiding roller 18 through the opening 14 into an ambient pressure chamber 15 . The ambient pressure chamber 15 and a low pressure space 24 together form parts of a vacuum lock 16 . The vacuum lock 16 is divided into the ambient pressure chamber 15 and the low pressure space 24 by three vacuum seals 20 mounted in a row. Each vacuum seal 20 comprises two juxtaposed mounted sealing rollers 22 , 23 . The sealing roller 22 has a circular shape and has a flexible surface. The sealing roller 22 may preferably be made of a flexible and pressure-tight material such as e.g. rubber to achieve a good sealing effect. The sealing roller 22 is mounted such that it seals the space between the wall of the vacuum lock 16 and the juxtaposed mounted sealing roller 23 substantially gas-tight. The sealing roller 22 is preferably made to apply a force to the wall of the vacuum lock 16 as well as to the juxtaposed mounted sealing roller 23 . The force may deform the sealing rollers 22 , 23 slightly. Optionally, a separate gasket (not shown) may be used to improve the sealing and/or reduce the friction between the wall of the vacuum lock 16 and the sealing roller 22 . Such a gasket should be made of low friction material. The sealing rollers 22 , 23 rotate in opposite rotational directions such that the liner 12 may be transported in the travelling direction between the rollers 22 , 23 .
[0062] The liner 12 is compressed between the sealing rollers 22 , 23 such that no substantial amount of air may leak into the low pressure space 24 between the rollers 22 , 23 . The sealing rollers 22 , 23 should be made significantly less flexible than the liner 12 , such that the liner 12 is compressed to a fully compressed state. The fully compressed state should be understood to mean the state where the liner 12 is compressed by the rollers 22 , 23 to its maximum flexibility, but still may resume an uncompressed state, i.e., substantially the initial state, when relaxed, i.e., when the compression force from the rollers 22 , 23 is removed. During the compression the force from the rollers 22 , 23 must not permanently deform the shape of the liner 12 or substantially damage the material, such that the uncompressed state is not reached when removing the compression force. The sealing rollers 22 , 23 may optionally be spring-loaded in direction towards each other for the rollers 22 , 23 to be able to apply a higher pressure onto the liner and at the same time to be able to adapt to any unevenness of the liner 12 .
[0063] The compartments between the seals 20 may have a pressure between the pressure of the low pressure space 24 and the ambient pressure. This reduces the pressure force and sealing requirement of each separate vacuum seal 20 . Optionally, the compartments between the vacuum seals 20 may be connected to a vacuum pump (not shown) for achieving a lower pressure inside the low pressure space. Alternatively, a pressure regulator may be used to define a specific pressure inside each of the compartments between the vacuum seals 20 .
[0064] After the vacuum seals 20 the liner enters the low pressure space 24 . The rollers will have removed the most of the air inside the liner 12 . Inside the low pressure space 24 the liner 12 will resume an uncompressed state. The low pressure space 24 is connected to a vacuum pump (not shown), which preferably is constantly acting to reduce the pressure inside the low pressure space 24 . The pressure in the low pressure space 24 should be considerably lower than the ambient (atmospheric) pressure. The vacuum pump may e.g. be of the piston type to achieve a suitable pressure in the low pressure space 24 of around 50% to 70% of the atmospheric pressure. The low pressure inside the low pressure space 24 will allow any residual gas bubbles inside the liner 12 to expand and exit the liner 12 . The vacuum pump (not shown) should preferably run continuously to allow a constant low pressure, since a leakage may quickly result in an unsuitably high pressure inside the low pressure space 24 .
[0065] The liner 12 is directed within the low pressure space 24 by a second guiding roller 26 . The vacuum efficiently acts on any gas volumes still present within the liner. Any gas volume inside the liner 12 will expand due to the vacuum and the gas will be sucked away by the vacuum pump (not shown). Consequently, the liner 12 will be degassed of any substantial amount of air left within the liner after the compression by the sealing rollers 22 , 23 . Any air left within the liner 12 will constitute voids after impregnation. Such voids may compromise the material properties of the impregnated liner and may lead to a rupture of the liner 12 .
[0066] The liner subsequently enters a resin bath 28 . The resin bath 28 is filled with a resin. The resin is preferably a polymeric resin and more preferably a light curable polymeric resin. On each side of the walls of the resin bath 28 a set of nozzles 32 is located. The nozzles 32 constitute a reduced flow area for achieving a flow velocity of the resin through the nozzles 32 . The nozzles 32 inject resin into the resin bath 28 towards the liner 12 with a flow velocity such that a jet is formed. The jet is directed towards the liner 12 and interacts with the liner 12 . When the jet is interacting with the liner 12 the flow velocity will be reduced and the pressure will be increased. The locally increased pressure at the point of interaction between the flow jet and the liner 12 will allow the resin to enter further into the liner 12 . The flow velocity additionally will cause the resin to reach even further into the liner 12 . Preferably, a large number of nozzles is used, such as 300 to 500, to ensure that the whole liner 12 is subjected to a flow jet. The nozzles may be placed on both sides of the liner 12 and preferably spread out on the wall of the resin bath 28 .
[0067] The resin is guided through the resin bath 28 via the bottom 34 of the resin bath 28 via a pump 36 and a pipe system 38 into the nozzles 32 , forming a closed circuit. The resin will circulate according to the arrows E indicated in the resin. The liner 12 is further guided by a third guiding roller 40 near the bottom 34 of the resin bath 28 . The liner 12 will then exit the resin bath 28 into an ambient pressure space 42 . The fourth guiding roller 44 directs the liner 12 out of the resin bath 28 to the outside as shown by arrow B. The space may optionally be used for pre-curing the resin-impregnated liner 12 .
[0068] The ambient pressure space 42 may be used for applying pre-curing to the resin. Pre-curing may be applied by a heat or radiation source and has the objective of turning the liquid resin into a semi-solid state. The pre-curing acts to partially cure the resin to achieve a highly viscous liquid for avoiding any resin leaking from the liner 12 and for gaining simplified handling of the liner 12 . In subsequent stages the impregnated liner 12 may be wrapped in one or more layers of plastic foil, cut into suitable lengths, folded into transportable packages and loaded on a truck for transportation to an installation site.
[0069] It should be noted that there is a difference in resin level inside the resin bath. This is due to the different pressures inside the resin bath 28 . The pressure along the direction of the liner from level C to level D will first rise until the lowest point near the bottom 34 is reached. The pressure will fall until the level D is reached. Local pressure deviations may result from the flow jet. In the present embodiment the resin bath 28 constitutes a second vacuum lock. The resin bath takes the shape of a U. The resin level at the end of the resin bath 28 communicating with the low pressure space 24 will be higher than the resin level at the second end communicating with the ambient pressure space, assuming a standard pressure and gravity. The ambient air pressure acting on the resin at the second end will act as a pressure force to push the resin towards the low pressure space. The gravity force from the resin may balance the pressure force such that the gravity force of the pile of resin located near the low pressure space and above the resin level D will compensate the pressure force of the ambient air pressure.
[0070] The pressure force acting on the resin is permitting a higher resin pillar on the vacuum side than on the ambient side. The difference in length is calculated according to the specific density of the resin. An ambient pressure of 100 kPa absolute is assumed. The direction of gravity is assumed to be in the direction towards the lower end of the figure. The value of the gravitational constant is assumed to be 9.81 N/kg. Having a resin density of around 1.1 kg/cm 3 will yield a resin pillar and minimum height of the resin bath 28 of 9 meters when assuming a perfect vacuum. Assuming less than a perfect vacuum will lower the minimum height of the resin bath 28 . Assuming a typical pressure of 60% of the atmospheric pressure inside the low pressure space will yield a minimum height of the resin bath of 4 m. To avoid any leakage of resin due to local pressure fluctuations a safety margin should be applied when dimensioning the resin bath 28 .
[0071] The resin level C and D should be continuously monitored and additional resin should continuously be delivered to the resin bath 28 to keep the resin levels C and D substantially constant within a certain margin. Resin will continuously exit the resin bath by being impregnated into the liner 12 . Preferably, a resin supply tank is connected to the resin bath 28 via a supply pump (not shown), which is controlled by a control system (not shown).
[0072] The pressure in the low pressure space 24 should as well be monitored and controlled, since any pressure fluctuation in the low pressure space 24 results in a deviation in the resin levels C and D. A pressure rise in the low pressure space 24 will make the level C drop. To avoid any leakage of resin if the pressure in the low pressure space 24 rises the ambient pressure space 42 should be properly sealed up to the fourth guiding roller 44 , located at substantially the same elevation as the vacuum lock 16 .
[0073] FIG. 2 shows a compact impregnation plant 10 ′ for impregnating a liner 12 ′. The liner 12 ′ is fed by a first guiding roller 18 ′ from an ambient pressure chamber 15 ′ to a low pressure space 24 ′ via a primary vacuum lock 16 ′ comprising a series of three vacuum seals 20 ′. Each vacuum seal 20 ′ comprises sealing rollers 22 ′ and 23′. The functional principle of the vacuum seal 20 ′ is analogous to the description in FIG. 1 . The liner is then guided by a second guiding roller 26 ′ into a resin bath 28 ′ filled with a resin. The resin is indicated in FIG. 2 by hatching. The resin bath 28 ′ comprises a set of nozzles 32 ′ directing a resin flow jet onto the liner 12 ′.
[0074] The nozzles 32 ′ are fed with pressurized resin from a pipe system 38 ′ connected to a pump 36 ′. The pump 36 ′ sucks resin from the bottom of the resin bath 28 ′ forming a closed circuit. The liner 12 ′ is fed through the resin bath 28 ′ and back into the low pressure space 24 ′ by a third guiding roller 40 ′, which in the present embodiment constitutes a pair of rollers. The liner 12 ′ is subsequently guided in an opposite direction in relation to the primary vacuum seals 20 ′ by a fourth guiding roller 44 ′ and exits the low pressure space via a secondary vacuum lock 16 ″. The functional principle of the secondary vacuum lock 16 ″ is analogous to the primary vacuum lock 16 ′, except for the conveying direction being reversed, i.e from the low pressure space 24 ′ into the ambient pressure space 42 ′.
[0075] The above embodiment has the drawback of needing a secondary vacuum lock 16 ″, in which rollers may cause some resin to leak from the liner 12 ′. This may be partially prevented by a pre-curing before the liner 12 ′ exits the low pressure space 24 ′. The advantage of the above embodiment is the compact shape, making it a preferred alternative for a mobile impregnation plant.
[0076] FIG. 3A shows a close up view of a vacuum lock 16 ′″ having lip seals according to the present invention. The vacuum lock 16 ′″ is located between a low pressure space 24 ′″ and an ambient pressure space 42 ′″. The vacuum lock 16 ′″ comprises 3 vacuum seals 20 ′″, each comprising two juxtaposed lip seals 21 ′. A liner 12 ′″ is propagated through the vacuum seals 20 ′″ between the lip seals 21 ′. The lip seals 21 ′ seal the area between the wall of the vacuum lock 16 ′″ and the liner 12 ′″ pressure-tightly. The lip seals 21 ′ are preferably made of rubber or any similar soft material. The compartments between the vacuum seals 20 ′″ will have reduced pressure as well. They may optionally be connected to a vacuum pump or pressure regulator.
[0077] FIG. 3B shows a close up view of an alternative embodiment of a vacuum lock 16 ″ between a low pressure space 24 ″ and an ambient pressure space 42 ″. In the alternative embodiment the vacuum seals 20 ″ additionally comprise two juxtaposed rollers 22 ″, 23 ″. A liner 12 ″ is propagated through the seal between the rollers 22 ″, 23 ″. The rollers 22 ″, 23 ″ are made of soft material, such as rubber foam, to achieve good sealing properties and at the same time avoid damage to the liner 12 ″. The rollers 22 ″, 23 ″ are sealed towards the wall of the vacuum lock by lip seals 21 ′, preferably made of flexible material such as rubber. Using rollers 22 ″, 23 ″ will reduce the resistance caused by friction when the liner is passing through the vacuum seals 20 ″. High resistance may cause damage to the liner 12 ″ since a high force is then needed to drive the liner 12 ″ through the vacuum seals 20 ″. The rollers 22 ″, 23 ″ may optionally be motorized for additional reduction of the resistance.
[0078] The above embodiments may also be combined as a lip and roller seal. From the above it is evident to any person skilled in the art that the above vacuum locks may be employed to bridge not only a low pressure space and an ambient pressure space, but also a low pressure space and a high pressure space, or an ambient pressure space and a high pressure space. It is further evident to the skilled person that the conveying direction of the liner may be reversed without any further changes to the vacuum lock. The arrow in FIGS. 3A and 3B shows only a preferred conveying direction.
[0079] FIG. 4 shows an alternative embodiment of an impregnation plant 10 ″ according to the present invention. The alternative embodiment 10 ″ features an impregnation station 11 , which may be used in connection with the above vacuum lock 16 . The impregnation station 11 comprises two parallel plates 13 located close to each other and defining a resin bath 28 ″ between them. The plates 13 and thereby the resin bath 28 ″ extend between a low pressure space 24 and an ambient pressure space 42 . The distance between the plates is approximately equal to the thickness of the liner 12 , such that the liner 12 may be accommodated between the plates 13 . The liner 12 is conveyed through the resin bath 28 ″ between the plates 13 from the low pressure space 24 to the ambient pressure space 42 in the direction of the arrow A.
[0080] Each plate 13 comprises a set of nozzles 32 ″ connected to a pipe system 38 ″. A pump 36 ″ propels the resin, which is indicated in FIG. 4 by hatching, from a resin reservoir 29 via the nozzles 32 ″ towards the liner 12 . The liner 12 is thereby subjected to a pressurized resin jet from both sides. The continuous flow of resin will fill the resin bath 28 ″ with resin. Due to the pressure of the resin, a large amount of resin will penetrate deep into the liner and fill all the cavities of the liner with resin. Some resin will, however, not enter the liner 12 , but exit the resin bath 28 ″ outside the liner as excess resin. The excess resin will, due to the pressure, propagate towards the low pressure space 24 , and in the opposite direction towards the ambient pressure space 42 . The viscosity of the resin will cause the excess resin to propagate slowly outside the resin bath 28 ″. A continuous supply of pressurized and viscous resin will completely fill the resin bath 28 ″ and thus act as a liquid pressure seal between the low pressure space 24 and the ambient pressure space 42 . It should be noted the resin bath 28 ″ is not completely encapsulated and a continuous flow of resin is required for impregnation and good sealing quality.
[0081] The excess resin is allowed to slowly drip off the resin bath 28 ″ and may preferably be collected into the resin reservoir 29 outside the resin bath at both sides. The excess resin may thus be re-used by re-circulating it according to the arrows E from the resin bath via the pump 36 ″ and nozzles 32 ″ into the resin bath 28 ″ towards the liner 12 and possibly again into the resin reservoir 29 . A filter or the like may be applied in the resin reservoir 29 to remove any contamination from the used resin. Such contamination may be fibres of fibre particles released from the liner 12 during impregnation. Such contamination may possibly clog the nozzles 32 ″, the pipe system 38 ″ or the pump 36 ″.
LIST OF PARTS
[0000]
10 . Impregnation plant
11 . Impregnation station
12 . Liner
13 . Plate
14 . Opening
15 . Ambient pressure chamber
16 . Vacuum lock
18 . First guiding roller
20 . Vacuum seal
21 . Lip seal
22 . Sealing roller
23 . Sealing roller
24 . Low pressure space
26 . Second guiding roller
28 . Resin bath
29 . Resin reservoir
32 . Nozzle
34 . Bottom
36 . Pump
38 . Pipe system
40 . Third guiding roller
42 . Ambient pressure space
44 . Fourth guiding roller
A & B. Liner-conveying direction
C & D. Resin level
E. Resin circulation direction
[0108] It should be further noted that a prime symbol in the description and in the figures denotes an alternative realization of the same part.
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The object of the invention is to provide a method and system for impregnating a liner, simultaneously reducing the risk of a void inside the liner after curing. This object is achieved by an impregnation plant ( 10 ) comprising a vacuum lock ( 16 ) comprising a housing having an inlet ( 14 ) and an outlet and defining an ambient pressure space ( 15 ) near the inlet and low pressure space ( 24 ) near the outlet. The pressure spaces are separated by a seal ( 20 ) comprising a first and a second sealing element ( 22, 23 ), allowing the fibrous liner ( 12 ) to be conveyed there between from the inlet ( 14 ) towards the outlet. The liner is degassed by compressing it between the first and second sealing elements ( 22, 23 ) and is subsequently relaxed in an uncompressed state inside the low pressure space ( 24 ). The plant further comprises a vacuum pump communicating with the low pressure space, and an impregnation station in gas-tight communication with the outlet or the vacuum lock ( 16 ) and comprising a resin bath ( 28 ) for accommodating the liner, a resin reservoir, a nozzle ( 32 ), a pipe system ( 38 ) and a resin pump ( 36 ) for propelling the resin from the resin reservoir via the pipe system ( 38 ) and the nozzle ( 32 ) into the resin bath ( 28 ) in a direction towards the liner.
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FIELD OF THE INVENTION
The present invention relates to a process for extracting and purifying the recombinant Placental Growth Factor from genetically modified cells.
STATE OF ART
The Placental Growth Factor (PLGF) is a homodimeric glycoprotein with a structure similar to the Vascular Endothelial Growth Factor (VEGF). The complete polynucleotide sequence codifying the PLGF protein was described by Maglione and Persico in patent EP-B-550 519 (WO-A-92/06194) claiming Italian priority of 27.09.1990. Alternative processes of splicing the ARN of PLGF generate three homologue forms of the Placental Growth Factor, precisely PLGF-1, PLGF-2 and PLGF-3, having different polypeptide sequences, and all described in literature.
The above-mentioned patent also describes a method for producing the PLGF factor comprising the use of an inducible prokaryotic expression system characterised by host cells modified with an expression vector, in which the human PLGF gene is integrated under the control of an inducible promoter (directly or indirectly). After inducing the PLGF expression with appropriate activator, the cells are incubated, isolated and submitted to lysis.
The so-obtained raw lysate is a complex mixture of proteins containing low quantities of the expressed PLGF protein and having low specific activity. In fact, in the known process, the protein expression is induced in cultures containing low cellular density, as it is evident from the low optical density at time of induction, that is between 0.2 and 0.6 OD at 600 nm. Furthermore, the process described in the preceding document does not comprise additional purification stages of the expressed protein. For this reason, the lysates obtained according to the application WO-A-92/06194 are inappropriate as such to be used directly in the preparation of medicaments.
A more complex method for purifying the same placental factor is envisaged by Maglione et al. in “Il Farmaco” 55 (2000), pages 165 to 167. Nevertheless, the method disclosure merely gives a simple listing of known applicable techniques, without describing conditions and experimental details thereof, which are essential for obtaining the PLGF protein in the purity and quantity necessary for a pharmaceutical use.
The scope of the present invention is to provide a new method for extracting and purifying the recombinant PLGF expressed in bacterial cells, allowing to obtain PLGF at high level of purity and with yields suitable to be industrially used in the preparation of medicaments.
A further scope of the invention is to obtain the PLGF protein in essentially active form (greater than 98.5%), that is mainly composed by dimeric (not less than 70%) and multimeric forms and containing residues of the monomeric form (little or not active) not greater than 1.5%.
SUMMARY OF THE INVENTION
The invention is based upon the identification of a sequence of purification techniques particularly appropriate for the extraction and purification of human PLGF expressed in bacterial cells. The invention is further based upon the determination of the optimum operative conditions with respect to the single techniques and to the chemical-physical features of the substance to be purified.
Then, object of the present invention is a process for extracting and purifying the recombinant Placental Growth Factor (PLGF) expressed by means of an inducible prokaryotic expression system comprising the steps of: I) fermentation of the bacterial cells, II) extraction and purification of the inclusion bodies, III) renaturation of the expressed protein, IV) ion-exchange chromatography, V) reverse-phase chromatography, and optionally VI) final stages of ultrafiltration, formulation and lyophilization. According to such method, the fermentation (step I) is performed until obtaining a high bacterial density in the medium, as it is shown by the high optical density in the medium, before proceeding with the induction step. The step (II) comprises bacterial lysis, rupture of DNA and isolation of the inclusion bodies. The renaturation of the expressed protein (step III) is obtained by solubilizing the inclusion bodies in denaturant buffer, and by transforming, at least partially, the expressed protein in the dimeric form. At last, in the step (IV) and (V) the dimeric and multimeric forms of the expressed protein are separated from the monomeric form and isolated in pure form, to be subsequently ultrafiltrated and lyophilised in presence of usual lyophilisation and formulation additives.
A specific object of the invention is the above-mentioned process for extracting and purifying the PLGF-1 protein of human origin, but substantially valid also for PLGF-1 of animal origin.
The claimed process advantageously allows the obtaining of production yields of expressed protein from 30 to 50 times higher than the yields obtained according to the method described in the preceding state of art. The claimed process furthermore allows the obtaining of the highly pure protein, with high specific activity and in substantially dimeric form.
Further object of the invention is the active Placental Growth Factor obtainable by means of the process of the invention, free from any residual protein or other bacterial contaminant and containing residues of monomeric form not higher than 1.5%.
DESCRIPTION OF THE FIGURES
FIG. 1 : The figure shows the results obtained by electrophoresis SDS-PAGE under reducing conditions for monitoring step I. Pre1 and Pre2 represent the pre-induction checks, prepared as follows. Soon before the induction, about 0,064 units of optical absorption measured at 600 nm (OD600) are taken and diluted 5 times with water. Of this dilution 20 μl are taken which are added to 20 μl of reducing buffer and submitted to boiling. 20 μl of this last solution are loaded onto the SDS PAGE matrix. Post1 and Post2 represent the post-induction checks prepared as above. M designates the mixture of markers of molecular weight. In the post-induction columns (Post1 and Post2) a band is noted just above the indicator of molecular weight 14.3 substantially absent in the pre-induction columns (Pre1 and Pre2) corresponding to the PLGF-1 protein expressed and segregated within the inclusion bodies.
FIG. 2 : The figure shows the monitoring chromatogram of the anionic-exchange chromatography on Q-Sepharose Fast Flow resin. X-axis shows the elution volume (ML), y-axis shows the optical absorption units (OD). The first elution peak obtained by eluting by 20% with buffer B (NaCl 200 mM) corresponds to the PLGF-1 protein in substantially dimeric form, but it comprises impurities and the monomeric form. The following peak, eluted by 100% with buffer B (NaCl 1M) contains impurities which are eliminated.
FIG. 3 : The figure shows the monitoring chromatogram of the first elution stage in reverse-phase chromatography on RP Source 30 resin. X-axis shows the elution volume (ml), y-axis shows the optical absorption units (OD). The first abundant elution peak corresponds to the various impurities, which do not bond to the resin. The second elution peak corresponds to the PLGF protein in monomeric form eluted under isochratic conditions (experimentally found at about 10%-15% of buffer B).
FIG. 4 : The figure shows the monitoring chromatogram of the second elution stage in reverse-phase chromatography on RP Source 30 resin. X-axis shows the elution volume (ml), y-axis Shows the optical absorption units (OD). The elution peak corresponds to the PLGF protein in dimeric-multimeric form.
FIG. 5 : The figure shows the results obtained in electrophoresis on SDS-PAGE for the final monitoring of the whole process. Prerefol and Postrefol represent the checks preceding and following the renaturation of the expressed protein (step III). QFF represents the peak eluted from the Q Sepharose fast flow resin, containing the protein mainly in dimeric form. Mon represents the peak containing the monomeric form. Dim represents the peak eluted in the second substep of the reverse-phase chromatography on RP Source 30 resin. It is noted that before the renaturation, the expressed protein is mainly in monomeric form. After the renaturation, part of the protein is in dimeric form. The following purification on QFF and RF 30 chromatography allow the obtaining of PLGF-1 protein with high purity degree.
DETAILED DESCRIPTION OF THE INVENTION
The genetic modification of the bacterial host cells is described by Maglione et al. in the preceding patent EP-B-0550519 (WO-A-92/06194). For this purpose, bacterial cells are transformed introducing of an expression vector comprising an insert corresponding to the human gene coding for PLGF-1 factor. The complete gene sequence is known in literature and it is freely accessible. A plasmid containing such sequence was deposited with the ATCC under accession number ATCC No 40892. The expression is performed under the control of the system of RNA polymerase of T7 phage and it is induced with IPTG (isopropyl-β-D-tiogalactopyranoside).
Nevertheless, other inducible prokaryotic expression systems may be utilised. Examples of such systems, obtainable on the market, are represented by:
1) pBAD expression system (In vitrogen BV) wherein the synthesis of a protein is placed under the control of the araBAD promoter and it may be induced in different strains of E. Coli by means of arabinose.
2) T7 Expression System (In vitrogen BV or Promega) wherein the synthesis of a protein is controlled by the promoter of RNA polymerase of T7 phage and it may be induced by means of lactose or the analogues thereof (IPTG). In this case it is required the use of E. Coli derivatives of DE3 (Bl21(DE3) or JM109(DE3)) type containing, namely, a copy of the gene of Rna polymerase of T7 phage placed under the control of a lactose-inducible promoter.
3) Trc expression system (In vitrogen BV) wherein the synthesis of a protein is placed under the control of the trc hybrid promoter. Such promoter has been obtained by melting the trp promoter and the lac promoters and it may be induced in different strains of E. Coli by means of lactose or the analogues thereof (IPTG).
4) Tac expression system (Amerham biosciences) wherein the synthesis of a protein is placed under the control of the tac promoter. In this system the protein synthesis is induced in strains of E. Coli lacIq (type JM105) by means of lactose or the analogues thereof (IPTG).
5) P L expression system wherein the synthesis of a protein is placed under the control of the PL promoter and it may be induced by adding tryptophan. In this case it is required the use of E. Coli derivatives (GI724) containing a copy of the codifying gene for the cI repressor of the Lambda phage placed under the control of a tryptophan-inducible promoter.
Step I: Fermentation and Induction
The first stage of the claimed process consists in the fermentation of a functionally-modified bacterial strain equivalent to the strain described in the preceding European patent (above). In a preferred embodiment the micro-organism is a derivative of Escherichia Coli modified with an expression plasmid comprising the human gene of PLGF. A preferred micro-organism is the one called [B12(DE3)pLysS PLGF-1] obtained by integrating in the commercially available strain [B12(DE3)pLysS] (Promega Corporation USA) the gene of the human PLGF-1. The present invention, nevertheless, is not limited to the human PLGF-1 factor, but it also relates to the one of animal origin (monkey, mouse, rabbit etc.). The present invention is not limited so much the less to the use of a E. Coli derivative, but it includes the use of any prokaryotic micro-organism susceptible to be genetically modified and able to express heterologous proteins under the form of inclusion bodies.
The strains utilised as inoculum in the process of the invention are kept before using them in the lyophilised form to preserve the expression capacity thereof. Upon use, the lyophilised material is brought again in solution by utilising an appropriate buffer.
Although there is a wide range of known culture media available on the market and which may be effectively used, the fermentation step according to the invention is preferably performed in a medium free from any material of animal or human origin in order to avoid any infection risk. Yeast's extracts (Difco) added with one or more suitable antibiotics represent the most suitable means for the process. In the preferred embodiment a medium is used which has been obtained by mixing under sterility conditions a first solution (A) containing yeast's extracts, glycerol and ammonium sulphate with a second solution (B) containing a phosphate buffer. The mixture is then integrated with ampicillin and chloramphenicol or equivalent antibiotics. Appropriate antibiotic concentrations are from 50 to 300 μg/ml of ampicillin, preferably from 100 to 200 μg/ml and from 10 to 100 μg/ml of chloramphenicol, preferably from 30 to 40 μg/ml.
The fermentation step may be preceded by a preinoculum step wherein the lyophilised micro-organism is suspended in the medium and submitted to consecutive incubation and dilution steps aimed at having in culture the optimum quantity of micro-organism cells. Preferably, the micro-organism is incubated for one night at 37° C., then diluted and incubated again for some hours. The chosen pre-inoculum volume is subsequently centrifuged, suspended again in the culture solution enriched with ampicillin and inoculated in the fermentation vessel for the fermentation step.
The fermentation is performed in the above-mentioned medium added with ampicillin and chloramphenicol at the temperature suitable for the micro-organism, usually at about 37° C., in presence of a percentage of dissolved O2, with respect to the saturation with air, from 20% to 40%, preferably 30%. The pH during fermentation is kept at neutral or weakly acid values (6.4 to 7.4). Furthermore, since the fermentation process takes place under stirring, antifoam agents are preferably to be used.
The fermentation progress is accompanied by the increase in the optical density of the medium. For this reason, the optical density is the parameter utilised according to the invention to monitor the progress degree of the fermentation. Readings at 600 nm are particularly appropriate.
Essential feature of the invention is the high cellular density achieved in the culture at time of the expression induction. Optical densities at 600 nm (OD600) from 1 to 50 may be achieved thanks to culture media of the invention. Densities higher than 18, nevertheless, are preferred to obtain the high production levels typical of the claimed method. Densities between 16 and 20 are particularly preferred to induce the producing bacterial strain and gave optimum results. The fermentation, then, is kept at the above-mentioned conditions until achieving such values of optical density, then one proceeds to induce the protein expression.
Any agent or chemical-physical condition able to induce in the cells of the used micro-organism the machinery of expression of the heterologous protein may be advantageously utilised. In the specific case wherein the bacterial strain BL21(DE3)pLysS modified with an expression plasmid containing the promoter of T7 phage is used, the expression is induced with lactose or the derivatives thereof, such as isopropyl-β-tiogalactopyranoside (IPTG) with a proper concentration, namely about 1 mM. The induction duration may vary according to need. Good results are obtained for periods of some hours, preferably from 3 to 4 hours; in the optimum process the induction is kept for 3 hours and 20 minutes by using a percentage of dissolved O2 equal to about 10%.
Cell samples are taken before and after induction and submitted to analytical techniques of control such as electrophoresis on SDS-PAGE, to determine the induction outcome.
When the protein expression reaches the desired levels, the culture is centrifuged and the cells are moved to the following step.
Step II: Extraction and Purification.
The expressed heterologous protein in bacterial strains is segregated inside the cell itself in the form of inclusion bodies. Therefore, the process of the invention provides passages of lysis of the cells, rupture of the extracted nucleic material (DNA) and recovery and washing of the inclusion bodies.
The cells are washed, although not necessarily, and suspended in solutions containing emulsifier agents in appropriate concentration, preferably Triton X100 in concentrations from 0.5% to 1%, then they are submitted to lysis of the cellular membrane. The lysis process may be performed by means of freezing/thawing, French Press, sonication or other similar known techniques. Nevertheless, the preferred method for the bacterial strain BL21(DE3)pLysS is the freezing/thawing method, which in the most preferred embodiment is repeated at least for two consecutive cycles. After the mechanical lysis, the lysis stage is continued for a few minutes in the lysis solution at room temperature under stirring.
The release in the lysis medium of the inclusion bodies is accompanied by the release of micro-organism different components and cellular substances, above all the nucleic materials. These substances could interfere with and jeopardise the following protein purification process. Therefore, the suspension/solution obtained by lysis is submitted to rupture of such nucleic material, specifically DNA, by means of enzymatic agents, such as DNAse (natural or recombinant such as the Benzonase), chemical agents, such as deoxycholic acid, or physical-mechanical agents, such as sonication or high energy stirring by means of blades, for example, in a mixer. The rupture of DNA, carried out for example in a mixer, is performed on lysed cells re-suspended in appropriate volumes of washing solutions containing chelating and deterging agents, for example EDTA and Triton X100. It is preferably repeated for more cycles, preferably 2, alternated with stages of dilution, in washing solution, centrifugation and elimination of the supernatant in order to remove components and cellular substances from the fraction containing the inclusion bodies.
Step III Renaturation (Refolding) of the Protein
The fraction containing the purified inclusion bodies of PLGF-1 is then solubilised in denaturing buffer containing known denaturant agents such as urea, guanidine isothiocyanate, guanidine-hydrochloride. Preferably, the denaturant solution is a urea solution in denaturant concentration, for example 8M. In order to accelerate the solubilisation process, the fraction may advantageous be submitted to homogenisation or sonication. After solubilizing the inclusion bodies, the solution is diluted with the same denaturant buffer until obtaining an optical density measured at 280 nm of about 0.8 (OD280 0.8). Subsequently, the solution is further diluted with a dilution buffer until 0.5 OD280. Suitable dilution solutions contain salts and polyethylene glycol (PEG) and have basic pH (about 8). The renaturation of the PLGF-1 protein in diluted solution is obtained by adding to the solution appropriate concentrations of oxidising/reducing pairs, followed by an incubation of 10 to 30 hours, preferably 18 to 20 at a temperature of 10° C. to 30° C., preferably 20° C., under stirring. Examples of such pairs are: Cystine/Cysteine, Cystamine/Cysteamine, 2-hydroxyethyldisulphide/2-mercapto-ethanol. Preferred example of oxidising/reducing pair is the glutathione in its oxidised and reduced forms, respectively at concentrations between 0.1 mM and 2.5 mM (preferably 0.5 mM) and between 0.25 mM and 6.25 mM (preferably 1.25 mM). By means of renaturation, the PLGF-1 protein expressed essentially in monomeric form is partially brought back to the dimeric form ( FIG. 5 ).
Step IV: Anionic-exchange Chromatography
The solution coming from the preceding step, preferably through centrifugation and/or filtration and containing the protein in mainly monomeric and partially dimeric form, is loaded onto anion-exchange resin in order to enrich the mixture with the dimeric form and to purify it from bacterial contaminants. Any commercially available matrix suitable for anion-exchange chromatography may be likewise used to the extent that its features of capacity, loading and flow speed be similar to those of the Q Sepharose Fast Flow resin (Amersham biosciences), apart from being suitable for an industrial process. In a preferred embodiment a high-flow resin is used, for example Q-sepharose Fast Flow (Amersham biosciences) or equivalent. The resin is washed and equilibrated with solutions having low ionic strength. An example of such solution comprises ethanolamine-HCl pH 8.5 with low or absent salt content. The same solution may be utilised for loading, absorbing and washing the protein mixture to be purified. The used resins allow loading of large volumes of protein solution with ratios Volume loaded/Volume column varying from 1:1 to 10:1. Ratios Vol./Vol. next to 10:1 are preferred since they allow optimising the use of the column. However, ratios higher than 10:1 are to be avoided since, due to the saturation of the adsorbing capacity of the matrix, they lead to high loss in the dimeric form of the protein.
Whereas the PLGF-1 protein in monomeric form already percolates in the stages of washing with low ionic strength, the elution of the dimeric and multimeric forms is obtained by increasing the ionic strength of the starting solution. Such increase is obtained by mixing the equilibration solution with increasing and pre-established percentages of a second solution containing NaCl 1M. In a preferred embodiment, the protein in dimeric form is eluted with solutions containing from 15% to 25% of NaCl 1 M solution, which corresponds to a NaCl concentration from 150 to 250 mM. In the best embodiment, the protein is eluted in isochratic conditions at NaCl concentration of 200 mM. The elution of the various species is automatically monitored by measuring the optical absorption at 280 nm ( FIG. 2 ). The collected fractions containing the PLGF-1 protein in dimeric form are subsequently controlled by electrophoresis SDS-PAGE ( FIG. 5 ). Advantageously, the whole chromatography process is automatically performed by a computerised system operating under the control of a suitable programme, for example the Software FPCL Director system (Amersham biosciences).
Step V: Reverse-phase Chromatography
The fractions coming from the preceding step containing the PLGF-1 protein enriched with the active forms are collected, diluted with appropriate buffer and loaded onto an reverse-phase chromatography column in order to further purify the protein in active form. The quantity of loaded solution corresponds to OD280 between 4.5 and 5.5 per millilitre of chromatographic matrix. Such quantities are to be considered maximum quantities.
Any commercially available chromatographic matrix suitable for the intended use may be utilised to the extent that its features of loading capacity and flow speed are compatible with the process requirements. In a preferred embodiment, a resin is used having such bead-sizes so as to guarantee the best exploitation of the absorbing capability together with the easiness in packing the column itself. Examples of such matrixes are the RP Source 15 or RP Source 30 (Amersham biosciences) resins. All the solutions for equilibration, loading, resin washing and elution are hydro-organic solutions comprising different percentages of organic solvent. Examples of such solutions are solutions comprising ethanol, methanol or acetonitrile. Preferably, hydro-alcoholic solutions comprising increasing percentages of ethanol are utilised. In an embodiment of the invention appropriate quantities of two buffer solutions are mixed, the former comprising buffer A, i.e. ethanol 40% and TFA (trifluoroacetic acid) 0.1%, the latter comprising buffer B, i.e. ethanol 70% and TFA 0.1%.
The protein material loaded onto the resin and properly washed is then eluted through an elution process comprising two subsequent stages wherein elution solutions containing an increasing gradient of organic solvent are utilised. The first stage is performed under conditions of rising gradient of organic solvent until obtaining the elution peak of the monomeric form. Such gradient is obtained by adding the buffer B to the buffer A in percentages from 4% to 40%, with an increasing rate of buffer B of 3% for each eluted column volume. As soon as the elution peak corresponding to the monomeric form of the protein appears, the elution is continued under isochratic conditions until exhaustion of the elution peak of the monomeric form. The so-set isochratic conditions cause the largest possible separation of the chromatographic peaks corresponding to the two monomeric and dimeric forms and, then, the best obtainable resolution for a process of industrial, and not analytical type. The second stage is performed again under condition of increasing gradient of organic solvent until whole elution of the protein mainly in dimeric form is achieved. In this second stage, the gradient is obtained by adding the buffer B to the buffer A in percentages from 10% to 100%, with an increasing rate of buffer B of 40.9% for each eluted column volume. The elution of the various forms of PLGF-1 protein is automatically monitored by measuring the optical absorption at 280 nm ( FIG. 3 and FIG. 4 ). The collected fractions containing the PLGF-1 protein essentially in dimeric form are subsequently controlled by electrophoresis SDS-PAGE ( FIG. 5 ). Advantageously, the whole reverse-phase chromatography process is automatically performed by a computerised system operating under the control of a suitable programme, for example the Software FPCL Director system (Amersham biosciences).
The results of the electrophoresis show that PLGF-1 protein obtained from the second stage of the reverse-phase chromatography is in highly pure active form, namely it comprises the protein in dimeric and partially multimeric form, but it is essentially free from any contamination of the monomeric form. The so-obtained product comprises not less than 98.5% of active form, preferably not less than 99.5%, wherein not less than 70% is in dimeric form. The residual of monomeric form is not higher than 1.5%. The protein in active form is obtained in average amounts of 160 mg per litre of bacterial culture. The pure protein obtained according to the above-described method may be submitted to additional working stages such as ultrafiltration on membrane. In this case the product is filtered on membrane having cut-off limit lower than, or equal to 30 kD and it is submitted to diafiltration against TFA acidulated water until a dilution factor of 1:106. The so-obtained final product may be properly formulated with lyophilisation additives and lyophilised to keep its best biological activity.
The invention is here below described by means of examples having, however, only illustrating and not limiting purposes.
EXAMPLE 1
Fermentation
The following procedure relates to the method of fermentation and induction of the genetically modified micro-organism (MOGM) [Bl21(DE3)pLysS PlGF-1] in a fermentation vessel using 1 mM IPTG.
Materials:
Solution SBM constituted by:
Solution A (per 1 liter)
Bacto yeast extract (Difco)
34
g
Ammonium sulphate
2.5
g
Glycerol
100
ml
H2O q.s. at:
900
ml
Solution B (10 X) (per 100 ml)
KH2PO4
1.7
g
K2HPO4 −3H2O
20
g, or
K2HPO4
15.26
g
H2O q.s. at
100
ml
The solutions A and B are separately autoclaved and mixed upon use under sterile conditions. Alternatively, the solutions A and B are mixed and filtered under sterile conditions.
IPTG 200 mM (200X) is produced by dissolving 5 g of pure substance in 100 ml of distilled water. The solution is filtered by means of 0.22-μm filters, subdivided into aliquots and frozen at −20° C.
The utilised antifoam agent is Antifoam O-10 (not siliconic) Sigma Cat A-8207.
The used bacterial strain is [BL21pLysS PlGF-1 WCB] (working cell bank).
Preinoculum: A tube of lyophilised genetically modified micro-organism (MOGM) WCB is taken and it is suspended in 1 ml of SBM+100 μg/ml Ampicillin+34 μg/ml of chloramphenicol.
The suspension is diluted in 30 ml of SBM+100 μg/ml Ampicillin+34 pg/ml of chloramphenicol.
The suspension is incubated at 37° C. for one night (O/N). The day after the 30 ml of the O/N culture are diluted in 800 ml of SBM+100 pg/ml Ampicillin+34 μg/ml of chloramphenicol and they are subdivided into 4 1-liter Erlenmeyer flasks, each containing 200 ml.
The content of each flask is incubated at 37° C. for 24 hours. The content of the 4 flasks is mixed and the OD600 are read by diluting 1/20 in water (50 μl+950 μl of water).
An established volume of preinoculum is then centrifuged for 10 min. at 7.500×g at 4° C. in sterile tubes.
The bacteria are then re-suspended in 20 ml of SBM+200 μg/ml of Ampicillin+10 μg/ml chloramphenicol per each litre of fermentation by stirring at 420 rpm at R.T. for 20 minutes. At the same time the fermentation vessel is prepared and the oxygen probes are calibrated.
The oxygen probes are calibrated at 37° C. temperature at 0% with nitrogen, then at 100% with air without antifoam under stirring at 600 RPM.
The fermentation is carried out under the following experimental conditions:
Medium: SBM+200 ug/ml of ampicillin and 10 μg/ml of chloramphenicol
Temperature:
37° C.
% dissolved O2:
30% (with respect to saturation
with air)
pH:
from 6.4 to 7.4.
Antifoam: 1:10 is diluted in water; strongly stirring before adding it in quantities of 140 μl per 750 ml of medium.
Induction:
The induction is carried out under the following experimental conditions:
OD600 of induction:
16–20.
Inducing agent:
IPTG 1 mM final.
% dissolved O2:
10% (with respect to saturation
with air).
Induction length:
3 hours and 20 minutes.
Just before the induction 20 μl of bacteria are taken, added to 80 μl of water and kept for the pre-induction check.
At time of induction, IPTG is added to the final concentration of 1 mM.
The percentage of dissolved O2 is brought to 10%.
At the end of the induction the final OD600 are read and the overall volume is measured.
Then, 10 μl of bacteria are taken, added to 90 μl of water and kept for the post-induction check.
The induction is controlled by way of a SDS-PAGE electrophoresis by loading 20 μl of the 2 previously boiled samples.
The medium containing the induced bacteria is then centrifuged at 7.500×g for 10 min. or at 3000×g for 25 min. at 4° C. and the supernatant is eliminated.
Results: The induction results are checked by SDS-PAGE electrophoresis as shown in FIG. 1 .
EXAMPLE 2
Extraction and Purification of the Inclusion Bodies
The following procedure relates to the preparation and refolding of the inclusion bodies of PlGF-1. By means of refolding the PLGF-1 bacterial protein is partially brought back to the dimeric form.
Material:
Mixer with appropriate capacity.
Lysis solution:
1 mM Mg2SO4 + 20 mM Tris-HCl pH8 +
Triton X100 by 1%.
Washing solution:
0.5% triton X100 + 10 mM EDTA pH 8.
BD (denaturing buffer):
8 M urea, 50 mM Tris pH 8,
Ethylenediamine 20 mM.
Dissolving and bringing to volume in H2O.
Oxidised glutathione 200x:
100 mM in H2O;
Reduced glutathione 200x:
250 mM in H2O.
Dilution buffer:
600 μM final PEG 4000 (2.4 g/l),
50 mM Tris-HCl pH 8, 20 mM NaCl.
Antifoam:
Antifoam O-10 (not siliconic) Sigma.
Preparation of the PLGF-1 Inclusion Bodies.
The lysis and washing solutions are equilibrated at room temperature (RT).
Two cycles of freezing/thawing at −80/37° C. are performed.
The bacterial pellet is lysed in 1 ml of lysis solution per each 450 OD600 of bacteria.
It is then incubated at RT 30 min. under stirring (250 RPM).
The solution is poured into a mixer with appropriate capacity and a quantity of washing solution of 3 ml for each 450 OD600 of bacteria is added.
If necessary, 0.4 μl of not-diluted antifoam per each millilitre of sample are added.
The solution is spun at the maximum speed for 1 minute or until the sample is well homogeneous.
The content of the mixer is then transferred into a container with appropriate capacity and,6,5 ml of washing solution per each 450 OD600 of bacteria are added. It is incubated for 45 min. at RT under stirring.
The so-obtained suspension is centrifuged at 13.000×g for 45 min. at 25° C. and the supernatant is discharged.
The settled pellet is re-suspended in 4 ml of washing solution per each 450 OD600 of bacteria and the cycle in the mixer is repeated for the second time.
The suspension is transferred into a container with appropriate capacity, diluted with 6.5 ml of washing solution per each 450 OD600 and incubated for 30 min. at RT under stirring.
The centrifugation under the above seen conditions is then repeated and the supernatant is eliminated.
EXAMPLE 3
Renaturation of the Protein
The inclusion bodies are solubilised in 7 ml of denaturing buffer BD (containing urea 8M) and further diluted in BD until OD280 of 0.8. Subsequently, 0.6 volumes of dilution buffer are added in order to bring the final urea concentration to 5M.
Afterwards 1/200 of reduced glutathione 200× (final concentration of 1,25 mM) and 1/200 of oxidised glutathione 200× (final concentration of 0.5 mM) are added. A 15 μl sample for checking (prerefol) is taken and the solution is then incubated at 20° C. for 18-20 hours under stirring.
At the end of the incubation, the medium is centrifuged for 10 min. at 20° C., 10.000×g, filtered by means of 0.45 or 0.8 μm filters and a 15 μl sample is taken for checking (postrefol).
Results: The 15-μl samples of the pre- and post-refolding solutions are analysed by means of SDS-PAGE electrophoresis ( FIG. 5 ).
EXAMPLE 4
Anion-exchange Chromatography
The following procedure relates to the first step of purification of the PlGF-1 protein after refolding. Upon loading of the sample onto the column, there will be a high loss of not-absorbed PlGF-1 monomer. The loaded quantity must not exceed 10 times the volumes of the column, since this would cause a significant loss in the PLGF-1 dimer.
The elution is performed under isochratic conditions at 20% of buffer B (see below), which corresponds to a NaCl concentration of 200 mM. The eluted peak still contains the glutathiones used for refolding, which contribute by about 50% of OD280.
Material and parameters:
FPLC system:
Amersham-biosciences handled by the
software called FPLC Director.
Monitoring parameters
U.V.:
Wavelength = 280 nm; scale top = 2.
Temperature:
20° C. (minimum 15, maximum 25)
Resin:
Q-sepharose Fast Flow (Amersham-
biosciences)
Column volume/height:
Volume: 1/10 of volume of
the sample to be loaded;
height: between 13 and 16 cm.
Equilibration:
2 Column Volume (CV) of buffer
B, then 1.5 CV of buffer A.
Sample:
Renatured, centrifuged and/or filtrated
P1GF-1. Load no more than 10 CV thereof.
Buffer A:
20 mM Ethanolamine-HCl pH 8.5.
Buffer B:
Buffer A + 1M NaCl.
Injection speed:
1 cm/min (maximum speed tested
on small columns = 1.887 cm/min;
minimum tested speed = 0.5 cm/min.).
Elution speed:
1 cm/min (maximum speed tested on
small columns = 1.887 cm/min;
minimum tested speed = 0.5 cm/min.).
Washings after
1.5 CV with 0% of buffer B.
Injection:
Peak collected:
Peak eluted at isochratic
conditions at 20% of buffer B,
running for about 3 CV.
Final washing:
2 CV at 100% B.
Procedure:
The peak eluted under isochratic conditions at 20% of buffer B is collected, then 0.271 water volumes, 0.0045 TFA volumes and 0.225 ethanol volumes are added thereto. In this way the sample results to be diluted 1.5 times and contains 15% ethanol and 0.3% TFA. The addition of these 2 substances facilitates the bounding of PlGF-1 to the reverse-phase resin (see example 5).
Results: The chromatography step is continuously controlled by monitoring the optical densities at 280 nm as illustrated by FIG. 2 .
The purity of the isolated protein material is analysed by means of SDS-PAGE electrophoresis ( FIG. 5 ).
EXAMPLE 5
Reverse-phase Chromatography
The following procedure may be performed with RP source resin with 15 micron or 30 micron average particle diameter. However, the 30-micron RP source resin, while not involving any alteration in the purification process, allows an economical saving of the resin itself (about 50%), a greater easiness in the packaging procedure of the column and a lower backpressure.
The procedure relates to the second phase of the purification of the PlGF-1 protein after passing on the QFF resin. During the sample injection, a high adsorbance is apparent and corresponds to the not adsorbed peak of the glutathiones which do,not bound to the resin. This procedure consists of 2 sub-stages, the, former called RPCmon, is used to eliminate most of the monomeric component of PlGF-1, whereas the latter is used to elute the essentially dimeric component of the protein and it is called RPCdim.
First Sub-stage (RPCmon)
Material and Parameters:
FPLC system:
Amersham-biosciences handled by the
software called FPLC Director.
Monitoring parameters
U.V.:
Wavelength = 280 nm; full scale = 0.05.
Temperature:
20° C. (minimum 15, maximum 25)
Resin:
Reverse Phase Source 30 (Amersham-
biosciences).
Resin volume/height:
Volume: ⅕-⅙ of the
overall OD280 of the sample to be loaded;
height: between 27 and 33 cm.
Equilibration:
2 Column Volume (CV) of buffer B,
then 2 CV of buffer A.
Sample: PlGF-1 coming from the preceding step (example 4), diluted 1.5 times and containing ethanol 15% and TFA 0.3%. Loading max. 4.5 to 5.5 OD280 per ml of resin.
Buffer A:
Ethanol 40% + TFA 0.1%.
Buffer B:
Ethanol 70% + TFA 0.1%.
Injection speed:
1.887 cm/min.
Elution speed:
1.887 cm/min.
Washings after
1.5 CV with 4% buffer B.
injection:
Monomer peak: Gradient ranging from 4 to 40% of B in 12 CV (3%B/CV). Just after starting the elution of the peak, by OD280 reaching 25% of the full scale, the elution is continued with isochratic conditions with the buffer B concentration reached in that moment until the peak elution is complete (about 2.5 -3.5 CV).
Operations
A suitable quantity of the solution corresponding to the “monomer” peak is taken and it is concentrated for checking (mon in FIG. 5 ).
Second Sub-stage (RPCdim)
Material and Parameters:
Without re-equilibrating the column, but by simply shifting the scale range of the UV monitor to the value 2, a gradient ranging from 10 to 100% of the buffer B is run in 2.2 CV (40.9%B/CV).
Operations:
The fractions corresponding to the “Dimer” peak are taken. FIG. 4 illustrates an example thereof. They are collected and the volume and the optical density at 280 nm are measured.
The overall yield (expressed in mg) obtained before the lyophilisation is calculated by multiplying the OD280 times the volume times the dilution. The average value of such yield is 164 mg of pure PLGF-1 per litre of bacterial culture with a standard deviation of 23.21. It may also be expressed in mg per 1000 OD600 of fermented bacteria, resulting to 5.58 mg of pure PLGF-1 each 1000 OD600 of fermented bacteria with a standard deviation of 0.8.
The so-obtained dimer solution is kept at −20° C. until ultradiafiltration and lyophilisation. A sample of such solution is submitted to SDS-PAGE electrophoresis as illustrated in FIG. 5 .
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Process for extracting and purifying the recombinant Placental Growth Factor (PLGF) expressed in inducible prokaryotic expression systems comprising the following steps: I) fermentation of the bacterial cells, II) extraction and purification of the inclusion bodies, III) renaturation of the expressed protein, IV) ion-exchange chromatography, V) reverse-phase chromatography.
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CROSS REFERENCE TO RELATED APPLICATION
This non-provisional application is a continuation-in-part of, and claims the benefit of, U.S. non-provisional application Ser. No. 12/949,213 that was filed on 18 Nov. 2010 the entire disclosure of which is hereby incorporated by reference (hereafter “213 application). The 213 application is a divisional of, and claims the benefit of, U.S. non-provisional application Ser. No. 12/069,627 that was filed on 12 Feb. 2008 and that is now U.S. Pat. No. 7,868,027 (hereafter “627 application”). The 627 application is a non-provisional application that claims priority from provisional application 60/903,471 filed on Feb. 26, 2007, and hereby incorporates the entire disclosure thereof herein.
BACKGROUND OF THE INVENTION
The present invention concerns a process for preparing certain substituted sulfilimines and sulfoximines.
The substituted sulfilimines are useful intermediates for the preparation of certain new insecticidal sulfoximines; see, for example, U.S. Patent Publication 2005/0228027 in which cyano-substituted sulfilimines are prepared by the reaction of the corresponding sulfide with cyanamide in the presence of iodobenzene diacetate. It would be advantageous to produce the sulfilimines efficiently and in high yield from the corresponding sulfides without having to use iodobenzene diacetate, which, in addition to its expense, presents waste disposal problems.
SUMMARY OF THE INVENTION
In the present invention, iodobenzene diacetate is replaced by hypochlorite. In addition to being low cost, hypochlorite eliminates the severe waste issues associated with iodobenzene diacetate. Thus, the present invention concerns a process for preparing certain substituted sulfilimines, having the general structure of (I),
wherein
Het represents:
X represents halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkenyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, CN, NO 2 , SO m R 6 where m is an integer from 0-2, COOR 4 or CONR 4 R 5 ;
Y represents hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkenyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, CN, NO 2 , SO m R 1 where m is an integer from 0-2, COOR 4 , CONR 4 R 5 , aryl or heteroaryl;
n is an integer from 0-3;
L represents either a single bond, —CH(CH 2 ) p — where R 1 , S and L taken together represent a 4-, 5-, or 6-membered ring and p is an integer from 1-3, —CH(CH 2 OCH 2 )— where R 1 , S and L taken together represent a 6-membered ring, or —CH— where L, R 2 and the common carbon to which they connect taken together represent a 4-, 5-, or 6-membered ring with up to, but no more than, 1 heteroatom;
R 1 represents C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 haloalkenyl, arylalkyl, heteroarylalkyl, or —CH 2 — in cases where R 1 , S and L taken together represent a 4-, 5-, or 6-membered ring;
R 2 and R 3 independently represent hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, C 2 -C 4 haloalkenyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, CN, SO m R 6 where m is an integer from 0-2, COOR 4 , CONR 4 R 5 , arylalkyl, heteroarylalkyl, or R 2 and R 3 and the common carbon to which they attach form a 3-6 membered ring;
R 4 and R 5 independently represent hydrogen, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl; C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 haloalkenyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl; and
R 6 represents C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 6 haloalkenyl, arylalkyl or heteroarylalkyl; which comprises contacting a sulfide of formula (II)
wherein
R 1 , R 2 , R 3 , L, Het and n are as previously defined with cyanamide and hypochlorite solution at a temperature from about −40° C. to about 30° C. in a suitable organic solvent that is essentially inert to the reaction conditions.
The process is well suited to prepare sulfilimines of the following classes:
(1) Compounds of formula (I) wherein Het is (6-substituted)pyridin-3-yl and where X is halogen or C 1 -C 2 haloalkyl and Y is hydrogen.
(2) Compounds of formula (I) wherein R 2 and R 3 are as previously defined, R 1 is methyl, n is 1, and L is a single bond, having the structure:
(3) Compounds of formula (I) wherein n is 1, R 1 , S and L taken together form a standard 4-, 5-, or 6-membered ring such that L is —CH(CH 2 ) p — and p is an integer from 1-3, and R 1 is —CH 2 — having the structure:
(4) Compounds of formula (I) wherein n is 0, R 1 , S and L taken together form a standard 4-, 5-, or 6-membered ring such that L is —CH(CH 2 ) p — and p is an integer from 1-3, and R 1 is —CH 2 — having the structure:
DETAILED DESCRIPTION OF THE INVENTION
Throughout this document, all temperatures are given in degrees Celsius, and all percentages are weight percentages unless otherwise stated.
The terms “alkyl”, “alkenyl” and “alkynyl”, as well as derivative terms such as “alkoxy”, “acyl”, “alkylthio”, “arylalkyl”, “heteroarylalkyl” and “alkylsulfonyl”, as used herein, include within their scope straight chain, branched chain and cyclic moieties. Thus, typical alkyl groups are methyl, ethyl, 1-methylethyl, propyl, 1,1-dimethylethyl, and cyclo-propyl. Unless specifically stated otherwise, each may be unsubstituted or substituted with one or more substituents selected from but not limited to halogen, hydroxy, alkoxy, alkylthio, C 1 -C 6 acyl, formyl, cyano, aryloxy or aryl, provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied. The term “haloalkyl” and “haloalkenyl” includes alkyl and alkenyl groups substituted with from one to the maximum possible number of halogen atoms, all combinations of halogens included. The term “halogen” or “halo” includes fluorine, chlorine, bromine and iodine, with fluorine being preferred. The terms “alkenyl” and “alkynyl” are intended to include one or more unsaturated bonds.
The term “aryl” refers to a phenyl, indanyl or naphthyl group. The term “heteroaryl” refers to a 5- or 6-membered aromatic ring containing one or more heteroatoms, viz., N, O or S; these heteroaromatic rings may be fused to other aromatic systems. The aryl or heteroaryl substituents may be unsubstituted or substituted with one or more substituents selected from halogen, hydroxy, nitro, cyano, aryloxy, formyl, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 1 -C 6 alkoxy, halogenated C 1 -C 6 alkyl, halogenated C 1 -C 6 alkoxy, C 1 -C 6 acyl, C 1 -C 6 alkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 alkylsulfonyl, aryl, C 1 -C 6 OC(O)alkyl, C 1 -C 6 NHC(O)alkyl, C(O)OH, C 1 -C 6 C(O)Oalkyl, C(O)NH 2 , C 1 -C 6 C(O)NHalkyl, or C 1 -C 6 C(O)N(alkyl) 2 , provided that the substituents are sterically compatible and the rules of chemical bonding and strain energy are satisfied.
The sulfide starting materials of Formula II or a process for their preparation have been disclosed in U.S. Patent Publication 2005/0228027. The sulfides (II) can be prepared in different ways as illustrated in Schemes A, B, C, D, E, F and G.
In Scheme A, the sulfide of formula (A 1 ), wherein L is a single bond, n is 1, R 3 ═H, and R 1 , R 2 and Het are as previously defined can be prepared from halides of formula (D) by nucleophilic substitution with the sodium salt of an alkyl thiol.
In Scheme B, the sulfide of formula (A 2 ), wherein L is a single bond, n is 3, R 3 ═H, and R 1 , R 2 and Het are as previously defined, can be prepared from the chloride of formula (E) by reacting with a 2-mono substituted methyl malonate in the presence of base such as potassium tert-butoxide to provide 2,2-disubstitued malonate, hydrolysis under basic conditions to form a diacid, decarboxylation of the diacid by heating to give a monoacid, reduction of the monoacid with borane-tetrahyrofuran complex to provide an alcohol, tosylation of the alcohol with toluenesulfonyl chloride (tosyl chloride) in the presence of a base like pyridine to give a tosylate and replacement of the tosylate with the sodium salt of the desired thiol.
In Scheme C, the sulfide of formula (A 3 ), wherein L is a single bond, n is 2, R 3 ═H, and R 1 , R 2 and Het are as previously defined, can be prepared from the nitrile of formula (F) by deprotonation with a strong base and alkylation with an alkyl iodide to give α-alkylated nitrile, hydrolysis of the α-alkylated nitrile in the presence of a strong acid like HCl to give an acid, reduction of the acid with borane-tetrahyrofuran complex to provide an alcohol, tosylation of the alcohol with tosyl chloride in the presence of a base like pyridine to give a tosylate and replacement of the tosylate with the sodium salt of the desired thiol.
In Scheme D, the sulfide of formula (A 4 ), wherein n is 0, R 1 is —CH 2 —, L is —CH(CH 2 ) p — where p is either 2 or 3 and, taken together with R 1 , S and L form a 5- or 6-membered ring, and Het is as previously described can be prepared from tetrahydrothiophene (p=2) or pentamethylene sulfide (p=3) (G). Chlorination of the cyclic sulfide starting material with N-chlorosuccinimide in benzene followed by alkylation with certain lithiated heterocycles or Grignard reagents can lead to the desired sulfides (A 4 ) in satisfactory yield.
A more efficient protocol to access cyclic sulfides of formula (A 4 ) is illustrated in Scheme E where Het is a 6-substituted pyridin-3-yl and Z is previously defined. Accordingly, thiourea is added to a substituted chloromethylpyridine, which, after hydrolysis, and alkylation with the appropriate bromo chloroalkane (p=1, 2, or 3) under aqueous base conditions, yields sulfide (H). Subsequent cyclization of (H) in the presence of a base like potassium-t-butoxide in a polar aprotic solvent such as THF provides cyclic sulfide (A 4 ).
Certain sulfides of formula (A 1 ) wherein Het is a substituted pyridin-3-yl, Z is as previously defined, and R 1 , R 2 ═CH 3 can be prepared alternatively via methods illustrated in Scheme F. Accordingly, the appropriate enone is coupled with dimethylaminoacrylonitrile and cyclized with ammonium acetate in DMF to yield the corresponding 6-substituted nicotinonitrile. Treatment with methyl-magnesium bromide, reduction with sodium borohydride, chlorination with thionyl chloride, and nucleophilic substitution with the sodium salt of an alkyl thiol provides desired sulfides (A 1 ).
A variation of Scheme F is illustrated in Scheme G, wherein enamines, formed from the addition of an amine, e.g., pyrrolidine, with the Michael adduct of certain sulfides with appropriately substituted α,β-unsaturated aldehydes, are coupled with substituted enones and cyclized with ammonium acetate in CH 3 CN to yield the desired sulfides (A 1 ) wherein R 1 , R 2 , R 3 , and Z are previously defined.
Cyanamide can be used as a solid or as an aqueous solution. The use of a 50 weight percent solution of cyanamide in water is often preferred. A stoichiometric amount of cyanamide is required, but it is often convenient to employ from about 0.9 to about 1.1 molar equivalents based on the amount of sulfide.
By hypochlorite solution is meant an aqueous solution of a metallic salt of hypochlorous acid. The metallic salt can be a Group I alkali metal salt or a Group II alkaline earth metal salt. The preferred hypochlorite salts are sodium hypochlorite or calcium hypochlorite. The aqueous hypochlorite solution usually contains from about 2 percent to about 12 percent hypochlorite salt, most preferably from about 5 percent to about 6 percent hypochlorite salt. It is often most convenient to use commercial Clorox™ bleach which contains about 5 to about 6 weight percent sodium hypochlorite in water. A stoichiometric amount of hypochlorite is required but it is often convenient to employ from about 0.95 to about 1.2 molar equivalents based on the amount of sulfide.
Salts of meta-bisulfite (such as sodium or potassium) can be used to quench any excess hypochlorite. The preferred salt of choice is sodium. The number of equivalents of meta-bisulfite can range from about 1.0 to about 5.0 relative to the hypochorite stoichiometry. The preferred range of equivalents is from about 2.0 to about 4.0 equivalents of meta-bisulfite per equivalent of hypochlorite remaining
The process of the present invention is conducted in a suitable organic solvent that is essentially inert to the strong oxidizing conditions of the reaction. Particularly suitable organic solvents are aliphatic hydrocarbons like petroleum ether, aliphatic alcohols resistant to oxidation like t-butyl alcohol, halogenated aliphatic and halogenated aromatic hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and dichlorobenzene, and aliphatic and aromatic nitriles such as acetonitrile and benzonitrile. Halogenated aliphatic hydrocarbons and aliphatic nitriles are preferred. It is often convenient to perform the oxidation in a biphasic solvent system comprising a mixture of, for example, a halogenated aliphatic hydrocarbon such as dichloromethane and water. An organic solvent that can facilitate partitioning of the desired sulfilimine is also desirable, with acetonitrile being especially preferred.
The reaction temperature can range from about −40° C. to about 30° C. The preferred range is about −10° C. to about 10° C., with about −5° C. to about 0° C. being most preferred.
The reaction is conveniently carried out in a two step sequence. For example, hypochlorite can be added to a cold solution of cyanamide in an essentially inert solvent, followed by a second later addition of the sulfide. Alternatively, the cyanamide and sulfide can be mixed together in an essentially inert solvent, and the hypochlorite can added to this cold mixture directly. After addition of the hypochlorite, the reaction mixture is allowed to stir anywhere from 15 min to 2 hr, typically 30 min at 0° C. A small amount of aqueous metabisulfite solution is typically added to destroy excess oxidant, as determined via testing with starch-I 2 paper. At this point, the aqueous phase is separated from the organic sulfilimine phase. The organic solution of the sulfilimine can be used directly in a subsequent oxidation to an insecticidal sulfoximine or the sulfilimine can be isolated and purified by conventional techniques.
In Scheme H,
X is a C 1 -C 4 haloalkyl;
R1, R2, and R3, are each independently a C 1 -C 4 alkyl.
In the oxidation of the sulfilimine to the sulfoximine with sodium permanganate in a mixture of acetonitrile and water as the reaction medium, the sulfilimine and permanganate are mixed in such a way as to control any adverse affects from the heat of the reaction. The addition of about 0.3 molar equivalents of a pH modifier to about 1 molar equivalent of a pH modifier (molar equivalents based on the moles of sulfilimine starting material) can increase the yield of the sulfoximine and reduce the amount of undesirable pyridine by-products being formed. Suitable pH modifiers are acetic acid, propionic acid, benzoic acid, potassium hydrogen sulfate, and phosphoric acid. The pH modifiers should have a pKa value in the range of about 2 to about 6, preferably about 2 to about 5. Specifically, when the sulfilimine is N-Cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfilimine and it is being oxidized to N-Cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfoximine, using a pH modifier can increase the yield of the sulfoxime by about 10% and reduce the yield loss to 5-acetyl-2-(trifluoromethyl)pyridine to less than 2%.
The following examples are presented to illustrate the invention.
EXAMPLES
Comparative Example with Iodobenzene Diacetate
Preparation of (1-{6-[trifluoromethyl]pyridin-3-yl}ethyl)(methyl)-λ 4 -sulfanylidenecyanamide
A mixture of 221 g (1.0 mol) of 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine and 42 g (1.0 mol) of cyanamide in 1200 mL of acetonitrile was cooled below 10° C. To this solution was added 322 g (1.0 mol) of iodobenzene diacetate all at once. The reaction mixture was allowed to stir below 10° C. for 10 min and then the ice-bath was removed. The reaction mixture slowly warmed to room temperature over 1.5 hr, and then slowly exothermed from 22°-30° C. over the next 0.5 hr. The reaction mixture was allowed to return to room temperature, and 800 mL of water was added. Excess oxidant was destroyed by adding ˜20 mL of an aqueous solution of sodium meta-bisulfite. To the mixture was added 800 mL of hexanes, the mixture stirred 5 min, and separated. The bottom aqueous layer was returned to the flask, 400 mL of water was added followed by 400 mL of hexanes. The mixture was stirred 5 min and separated. The aqueous layer was again returned to the round-bottom flask and extracted a third time with 400 mL of hexanes. The aqueous layer was concentrated in vacuo until a cloudy two-phase mixture was obtained. This mixture was extracted two times (700 mL, 300 mL) with dichloromethane, the organics combined and dried overnight over MgSO 4 . After filtration, LC analysis indicated the dichloromethane solution (1560 g) contained a 28:64 (area) ratio of two sulfilimine isomers.
Isomer A:
A portion of sulfilimine solution from above (40 mL) was concentrated in vacuo and exposed to high vacuum to give a thick, orange/amber oil. This oil was dissolved in 10 mL of EtOAc, and 10 mL of hexanes was added. To the cloudy mixture was added 1 mL of EtOAc to give back a clear solution. The flask was scratched with a glass rod to induce crystallization. The mixture was cooled in a refrigerator for 1 hr, filtered and exposed to high vacuum drying to give 1.2 g of a white powder, mp 115°-117° C., >99% (area) LC of the first eluting isomer; 1 H nmr (CDCl 3 ): δ 8.72 (d, J=2 Hz, 1H), 8.04 (dd, J=2 Hz, 8 Hz, 1H), 7.81 (d, J=8 Hz, 1H), 4.41 (q, J=7 Hz, 1H), 2.62 (s, 3H), 1.90 (d, J=7 Hz, 3H).
Isomer B:
The filtrate from above was concentrated in vacuo to give a thick amber oil (15:67 area ratio of two isomers by LC). This oil was flash chromatographed on silica, eluting with 5% EtOH in CHCl 3 . Some minor colored material was discarded first. The major sulfilimine isomer (second eluting isomer by LC) was collected next, concentrated in vacuo and exposed to high vacuum drying to give 3.2 g of a thick amber oil. This oil was slurried and scratched with 20 mL of Et 2 O, cooled in a refrigerator, filtered and exposed to high vacuum drying to give 2.48 g of a white powder, mp 78°-80° C., >99% (area) LC of the second eluting isomer; 1 H nmr (CDCl 3 ): δ 8.74 (d, J=2 Hz, 1H), 7.95 (dd, J=2 Hz, 8 Hz, 1H), 7.81 (d, J=8 Hz, 1H), 4.45 (q, J=7 Hz, 1H), 2.65 (s, 3H), 1.92 (d, J=7 Hz, 3H).
Example 1
Preparation of (1-{6-[trifluoromethyl]pyridin-3-yl}ethyl)(methyl)-λ 4 -sulfanylidenecyanamide
A solution of 22.1 g (0.1 mol) of 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine and 5.04 g (0.12 mol) of cyanamide in 150 mL of acetonitrile was cooled to −5° C. To this solution was added 150 g (0.115 mol, Clorox™ 5.7% wt) of aqueous NaOCl dropwise over 15 min. The reaction mixture was allowed to stir at −5° C. for 45 min, and then allowed to warm to 5° C. To the mixture was added 5 mL of 25% aq sodium metabisulfite and the two phase mixture was allowed to settle. To the organic phase was added 5.7 mL (0.1 mol) of glacial acetic acid, and the solution concentrated in vacuo to an oil. This oil was dissolved in 70 mL of CH 2 Cl 2 and washed with 50 mL of water. The aqueous layer was re-extracted with 30 mL of CH 2 Cl 2 . The organics were combined and dried over MgSO 4 . After filtration, the dichloromethane solution was analyzed by LC and contained 42:52 (area) ratio of isomers A and B above.
Example 2
Preparation of (1-{6-[trifluoromethyl]pyridin-3-yl}ethyl)(methyl)-λ 4 -sulfanylidenecyanamide
solution of 110.6 g (0.475 mol, 95% assay) of 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine and 25.2 g (0.6 mol) of cyanamide in 600 mL of acetonitrile was cooled to −5° C. To this solution was added 750 g (0.575 mol, Clorox™ 5.7% wt) of aqueous NaOCl dropwise over 45 min with the temperature kept below 0° C. The reaction mixture was allowed to stir at −1° C. for 30 min To the mixture was added 9.5 g (0.05 mol) of sodium metabisulfite in 25 mL of water and the two phase mixture was allowed to settle. The aqueous phase was re-extracted 2×'s with 50 mL of acetonitrile. The organics were combined and this acetonitrile/sulfilimine solution was used directly in the following oxidation. LC analysis indicated a 40:54 (area) ratio of two isomers.
Example 3
Preparation of [1-(6-trifluoromethylpyridin-3-yBethyl](methyl)-oxido-λ 4 -sulfanylidenecyanamide
mixture of 100 mL of acetonitrile, 200 mL of water, and 160 g (0.45 mol) of a 40% aq solution of NaMnO 4 (Aldrich) was cooled to 15° C. To a solution of sulfilimine (0.475 mol from Example 2) in ˜700 mL of acetonitrile was added 26 mL (0.45 mol) of glacial acetic acid. This sulfilimine solution was added over 50 min with rapid stirring to the permanganate mixture. During this time the ice-bath was lowered or raised to maintain a reaction temperature near 19° C. The reaction was allowed to post-react for 45 min The mixture was cooled to 12° C., and a solution of 171 g (0.9 mol) of sodium metabisulfite in 300 mL of water was added with rapid stiffing over 15 min The mixture was stirred at room temperature for 30 min, and then filtered. The off-white solid was rinsed with 50 mL of acetonitrile. The two phase mixture was transferred to a 2 L separatory funnel, and the aqueous layer discarded. The organic layer was concentrated in vacuo to ˜50% wt product. This mixture was poured onto 300 mL of rapidly stirred water in an ice-bath. The mixture was stirred cold for 1 h and filtered to give 147.6 g of a white solid. The product was air-dried in a hood to give 116.5 g of product, and further dried in a vacuum oven at 35° C. to give 116.5 g (88% wt) of a white powder. LC analysis indicated a 43:52 (area) ratio of two isomers and a 95% area purity.
Example 4
Preparation of N-Cyano-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]-S-methylsulfilimine
Acetonitrile (50 mL), cyanamide (1.14 grams, 27.1 mmoles) and 3-[1-(methylthio)ethyl]-6-(trifluoromethyl)pyridine (5.00 grams, 22.6 mmoles, 99+% assay) were combined in a 100 mL, 3-necked round bottom flask equipped with a thermowell/K-thermocouple, stopper, nitrogen oil bubbler and magnetic stir bar. The stirred solution was cooled to about −5° C. with an acetone/ice bath. To this solution was added 55.96 grams of an aqueous 6.0 wt % calcium hypochlorite solution (3.36 grams of calcium hypochlorite, 23.5 mmoles, 65% available chlorine) dropwise over 44 minutes. Some undissolved solids were present in the calcium hypochlorite solution and were added as well. The temperature was kept below 0° C. during the addition. The pale yellow reaction mixture was allowed to stir at about 0° C. for 65 minutes. To the yellow reaction mixture was added 0.53 g (2.8 mmoles) of sodium metabisulfite, in portions as a solid to destroy any remaining oxidant. A white flocculant was present in the reaction mixture. It was removed by vacuum filtration of the entire reaction mixture through a medium sintered glass filter funnel. The filtrate was transferred to a separatory funnel and the phases were allowed to settle. The phases were separated and the aqueous phase re-extracted with acetonitrile (10 mL) and (15 mL). Sodium chloride (10.01 grams) was added to the aqueous phase during the second extraction to facilitate a phase break. The organics were combined and this acetonitrile/sulfilimine solution was used directly in the following oxidation. LC analysis indicated a 1.00:1.08 area ratio of the two sulfilimine isomers and showed sulfilimine at 80 area % and sulfoxide (two isomers) at 13 area %.
Example 5
Preparation of N-Cyano-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]-S-methylsulfoximine
Acetonitrile (5 mL), water (10 mL) and 7.63 grams (21.5 mmoles) of a 40% aqueous solution of NaMnO4 (Aldrich) were combined in a 100 mL three necked, round bottom flask equipped with a magnetic stir bar, pressure equalizing addition funnel, thermowell/K-thermocouple, nitrogen oil bubbler and stopper. A solution of (˜22.6 mmoles) sulfilimine in about 70 mL of acetonitrile was filtered through a cone of Whatman filter paper to remove a small amount of white flocculant. To the filtrate was added 1.23 mL (21.5 mmoles) of glacial acetic acid. The resulting solution was loaded to the addition funnel. The sodium permanganate solution was cooled to about 13° C. The sulfilimine solution was added over 60 min with rapid stiffing to the permanganate mixture. The temperature ranged from 13 to 18° C. during the addition. The reaction was allowed to post-react for 45 minutes. The dark mixture was cooled to about 12° C., and a solution of 7.75 grams (40.8 mmoles) of sodium metabisulfite in 12 mL of water was added with rapid stirring over 7 minutes. A maximum reaction temperature of about 16° C. occurred during the addition. The reaction mixture was still dark at the end of the addition but gradually lightened to afford an off-white flocculent. A small dark rind remained on the flask sides at this point, but dissipated on continued stiffing. The mixture was allowed to warm to room temperature with stiffing over 105 minutes. The entire mixture was vacuum filtered through a course sintered glass filter funnel. The tan wet cake was rinsed with acetonitrile (10 mL). The combined filtrate was transferred to a separatory funnel and the phases were allowed to settle. The clear, colorless lower phase (43.0 grams) was removed. The upper organic phase (56.1 grams) was concentrated to a mass of 22.0 grams at a pressure of 70 to 80 mm Hg and a temperature of 20 to 25° C. The resulting two phase mixture was poured into 44.5 grams of well stiffed, chilled (<5° C.) water. A white slurry developed and was stirred at <5° C. for about one hour. The solids were collected by vacuum filtration on a course sintered glass filter funnel and the white solid was rinsed with 10 mL of cold water. The product wet cake 5.24 grams was air-dried in a hood overnight to give 4.01 grams (65%) of the desired sulfoximine. LC analysis indicated a 1.04:1.00 (area) ratio of the two isomers and a 94% area purity, with the major impurity being the sulfone (3.5% area).
Example 6
Preparation of N-cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfoximine employing acetic acid
The reaction was run in a 500 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 99.76 g of sulfilimine solution (20.9% sulfilimine, 0.080 moles), 45 g of acetonitrile, and 1.48 g (0.025 moles) of acetic acid. The mixture was cooled to <15° C. A solution of 40% NaMnO 4 shot added (19×1.65 g shots, 4 minutes apart). Total addition was 31.4 g (0.088 moles) over 74 minutes while holding the temperature at 10-15° C. This was followed by a 45 minute post reaction at 15° C. It was sampled at 25 minutes into the post reaction and analyzed by area % HPLC to verify the conversion was >98%. Analysis showed the reaction yield to be 97%, with less than 1% lost to 5-acetyl-2-trifluoromethylpyridine.
Example 7
Preparation of N-cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfoximine employing propionic acid
The reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.9 g of sulfilimine solution (20.5% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 0.85 g (0.011 moles) of propionic acid. The mixture was cooled to <15° C. A solution of 40% NaMnO 4 shot added (19×0.84 g shots, 4 minutes apart). Total addition was 16.0 g (0.045 moles) over 74 minutes while holding the temperature at 10-15° C. This was followed by an 86 minute post reaction at 15° C. It was sampled at 33 minutes into the post reaction and analyzed by area % HPLC to verify the conversion was >98%. Analysis showed the reaction yield to be 96%, with less than 1% lost to 5-acetyl-2-trifluoromethylpyridine.
Example 8
Preparation of N-cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfoximine employing phosphoric acid
The reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.8 g of sulfilimine solution (20.6% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 1.44 g (0.013 moles) of 85% phosphoric acid. The mixture was cooled to <15° C. A solution of 40% NaMnO 4 shot added (19×0.84 g shots, 4 minutes apart). Total addition was 16 g (0.045 moles) over 75 minutes while holding the temperature at 10-15° C. This was followed by a 61 minute post reaction at 15° C. It was sampled at 25 minutes into the post reaction and analyzed by area % HPLC to verify the conversion was >98%. Analysis showed the reaction yield to be 95.2%, with less than 1.2% lost to 5-acetyl-2-trifluoromethylpyridine.
Comparative Example with Sodium Bicarbonate
Preparation of N-cyano-S-methyl-S-[1-(6-trifluoromethyl-3-pyridinyl)ethyl]sulfoximine employing sodium bicarbonate
The reaction was run in a 250 ml round bottom flask equipped with an air-driven stirrer (half moon agitator), thermowell, addition port and nitrogen pad. It was cooled with a water/salt/dry-ice bath. The flask was loaded with 50.8 g of sulfilimine solution (20.6% sulfilimine, 0.040 moles), 23 g of acetonitrile, and 1.0 g (0.012 moles) of sodium bicarbonate. The mixture was cooled to <15° C. A solution of 40% NaMnO 4 shot added (19×0.84 g shots, 4 minutes apart). Total addition was 16 g (0.045 moles) over 75 minutes while holding the temperature at 10-15° C. This was followed by a 75 minute post reaction at 15° C. It was sampled at 60 minutes into the post reaction and analyzed by area % HPLC to verify the conversion was >98%. Analysis showed the reaction yield to be 89.3%, with 7.1% lost to 5-acetyl-2-trifluoromethylpyridine.
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Cyano-substituted sulfilimines and sulfoximines are produced efficiently and in high yield from the corresponding sulfides by reaction with cyanamide and hypochlorite.
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BACKGROUND OF THE INVENTION
Originally, the milky liquid obtained from rubber trees was called "latex"; now this term refers to an aqueous dispersion of polymeric substances whether they are natural or synthetic. Latexes can be made by emulsion polymerization from the monomer or by emulsification of resins.
Due to environmental and energy problems, water-based systems are becoming more and more desirable. Nowadays, latexes are widely used in adhesives, textiles, inks, plastics, coatings, photographic applications, pharmaceuticals, and paper industries. In addition, monodisperse latexes also have important applications in the fields of medical, biological, and fundamental research studies. Latexes are required to be stable during preparation, storage, formulation, and applications. The stability of latexes is dependent on the total interaction energies between the particles. This has been described by the DLVO theory.
Polystyrene latexes have been used as pigment particles in paper coating, and the coating prepared from monodisperse polystyrene latex particles of different sizes has been tested for light scattering efficiency.
It has been found that a plastic pigment of polystyrene latex can meet most of the criteria for an ideal pigment. The criteria are: (1) low specific gravity, (2) high brightness, (3) high refractive index, (4) controlled particle size, (5) easily dispersible, (6) chemically inert, (7) compatible with other pigments, (8) nonabrasive, (9) low adhesive demand, (10) high price/performance efficiency. Usually plastic pigments are white in color, and the opacity can be changed by the variation of the particle size, but no satisfactory colored plastic pigments have yet been made.
Colored latexes have been made from polymerizable dyestuffs. Colored copolymers have been suggested in latex form for coating of leather. It has also been reported that colored latexes can be made by the reaction of an aqueous dispersion of microgel with hydrogen bromide through the unsaturated double bond and then followed by a nucleophilic substitution reaction with dye-molecules (Kolthoff et al, J. Polymer Sci. 15 459 (1955)).
The chemical modifications of reactive microgels cannot be carried out in aqueous solution, but involve the use of organic solvent systems. Besides, the particle sizes of microgels are usually between 5 nm and 50 nm which are too small to be used as pigments in coating applications. One of the major problems in the preparation of highly crosslinked reactive microgels is the occurrence of agglomeration phenomena, which leads to total coagulation. For polymerizable dyestuffs, the copolymerization reactivity ratios must be considered in copolymerization with styrene in addition to the solubility problem.
Generally there are three methods described in the prior art for the incorporation of dyes into a polymer latex. In "The Applications of Synthetic Resin Emulsions" by H. Warson, Ernest Benn Ltd., London, 1974 beginning on Page 848 it is stated:
"It is possible to obtain colored copolymers, even in emulsion by copolymerizing dye-stuffs including unsaturated groups, azo dyes and anthraquinone dyes being particularly suitable. These groups may be a vinyl group on an ester, an acrylate on a base, a vinylsulfonamide derivative and so on. A range of colors are available. Various specifications quote the method of preparing the colored copolymers (G. Krehbiel (to BASF), Brit. No. 877,402 (1961); H. Wilhelm (to BASF), Brit. No. 914,354 (1961); K. H. Beyer et al (2 BASF), Brit. No. 964,757 (1964)). Graft copolymers including polymerizable dyestuffs are also known (BASF, Brit. No. 965,627 (1964)).
These colored copolymers may be used directly in emulsion form for the coating of leather, thereby avoiding the numerous difficulties which have to be overcome when the leather is dyed independently. The dyestuff monomer is present at 1-15 percent by weight of the solids content of the emulsion, and a crosslinking agent such as N-methylolmethacrylamide is preferably present. This will have the effect of chemically combining the colored copolymer with the leather during the curing process on drying at the normal elevated temperature (F. Ebel et al. (to BASF), Brit. No. 998,550 (1965); H. Wilhelm et al. (to BASF), Brit. No. 1,063,219 (1967)).
Since this type of polymerization is novel some examples will be quoted here . . . " Warson then goes on to describe in a table "emulsion polymerization with colored monomers (F. Ebel et al. (to BASF), Brit. No. 998,550 (1965))." The table lists the following polymerizable dyestuffs.
2,4,5-trichloro-4'-(N-ethyl-N-acryloylhydroxyethyl)-aminoazobenzene
2,4-dichloro-4'-(N-ethyl-N-acryloylhydroxyethyl)-aminoazobenzene
2-methoxy-4-nitro-4'-(N-ethyl-N-acryloyhydroxyethyl)-aminoazobenzene
2-cyano-4-nitro-4'-(N-ethyl-N-acryloylhydroxyethyl)-aminoazobenzene
In the polymerization, 20 parts ethyl acrylate are emulsified in 50 parts water containing 0.3 parts potassium persulfate initiator, as well as emulsifier comprising 2.0 parts 20% aqueous sodium salt of a sulfonated iso-octylphenol-polyoxyethylene adduct with 25 moles ethylene oxide and 0.24 parts 50% aqueous sodium salt of sulfonated castor oil. Another emulsion is prepared comprising 7 parts polymerizable dyestuff, 40 parts ethyl acrylate, 23 parts isobutyl acrylate, 7.5 parts acrylic acid, and 5.5 parts 45% aqueous N-methylolacrylamide in 68.5 parts water containing 8.0 parts of the same sulfonated iso-octylphenol-polyoxyethylene adduct and 0.6 parts of the same sulfonated castor oil emulsifiers. The first emulsion is heated with stirring to 80° and the second emulsion is added continuously over a one-hour period; at the same time, 1.2 parts potassium persulfate initiator in 20 parts of water are added continuously in a second stream. The polymerization is continued at the same temperature for a total time of 4 hours.
Other references from the same text include page 179, "The addition of dyestuffs (in the compounding of the emulsion) as distinct from pigments is sometimes desired. If water soluble, direct addition of a concentrate is possible, but the dyestuff ion must have the same charge as the dispersant, e.g., the cationic methyl violet types should not be used with anionic surfactants. An oil soluble dye should be dissolved in a small quantity of solvent or plasticizer before addition to the emulsion."
Also, page 888 states that, "There seems to be no reason why dyestuffs should not be added to emulsion polish compositions based on polymers, just as they are added to solvent-based products, and to direct wax polish emulsions. Compatibility, especially with the emulsifier system, as well as with the organic components, would have to be studied. An oil-soluble dye, probably in the wax component of the polyethylene would seem to be the most probable method of incorporation. The plasticizer could possible be used. A water-based dye, even if acid is likely to cause difficulty, due to bleeding, when any water is poured on to the polish, although it is possible that some types might be strongly absorbed onto the alkali-soluble resin, and thus be reasonably permanent."
Finally, page 857 describes the use of the red dyestuff, Waxolin OS, an azo dye, in the polymerization mixture, where it functions as a chain transfer agent, thus incorporating dyestuff endgroups into the polymer chain.
Another reference work, "Chemical Reactions of Polymers," E. M. Fettes, editor, Interscience, New York, 1964, describes on page 284 the nitration of polystyrene and its subsequent reduction (W. E. Hanford (to E. I. du Pont de Nemours), U.S. Pat. No. 2,396,786, Mar. 19, 1946; G. B. Bachman, H. Hellman, K. R. Robinson, R. W. Finholt, E. J. Kahler, L. J. Filar, L. V. Heisey, L. L. Lewis, and D. D. Micucci, J. Org. Chem. 12, 108 (1947)) to give polyaminostyrene, which is then diazotized and coupled with phenols and amines to give dyes which are insoluble in all solvents. Similar reactions with styrene-maleic anhydride copolymers are also reported (W. O. Kenyon, L. M. Minsk, and G. P. Waugh (to Eastman Kodak), U.S. Pat. No. 2,274,551, Feb. 24, 1942)). These reactions, however, were carried out on polymers dissolved in solvents rather than on emulsion polymers. The high electrolyte concentrations needed for the nitration and reduction reactions would almost certainly either dissolve the latex copolymer or flocculate the latex.
In the same book, D. Taber, E. E. Renfrew, and H. E. Tiefenthal, Chapter XV "Fiber-Reactive Dyes", pages 1113-64, describe the dyeing of textile fibers in some detail and review (pages 1143-7) the evidence for the formation of covalent bonds between reactive dyes and fibers.
As set out above the three general methods described in the prior art for coloring latexes are:
1. simple addition of water-soluble or oil-soluble dyes;
2. use of copolymerizable dyes; and
3. use of dyes that act as chain transfer agents.
This invention provides a different, improved method for coloring latexes.
SUMMARY OF THE INVENTION
It is accordingly an object of this invention to provide new stable, colored latexes, methods of preparing such latexes as well as the colored latex in finely divided solid form.
It is another object of this invention to provide stable, colored synthetic latexes which may be used to provide a compatible color base for other latexes (colored or uncolored).
It is still another object of this invention to provide colored latexes which may be employed to prepare colored films and coatings.
It is a further object of this invention to provide colored latexes which serve as a source of solid colored latex particles, e.g. pigments.
It is a still further object of this invention to provide a stable latex which has chemically bonded thereto a color moiety.
It is yet another object of this invention to provide a stable latex which has chemically bonded thereto an azo moiety providing thereby a colored latex.
It is yet a further object of this invention to provide a stable latex which has a protein moiety linked to the latex material by means of an azo linkage.
Another object of the present invention is to provide processes for making the foregoing products.
Still another object is to provide an azo color producing linkage in polymeric products in finely divided form.
Other objects will appear hereinafter as the description proceeds.
The foregoing and other objects are accomplished by providing a latex containing a reactive grouping which can be further reacted to produce a structure which is capable of coupling with an aromatic diazonium compound to produce an azo linkage whereby a colored latex is effected. The reactive grouping is present in a polymerizable compound (hereinafter also referred to as RGC monomer) which is, preferably an α,β monoethylenically unsaturated compound. The preferred reactive grouping is halomethyl. The base latex is prepared so that it is derived from at least one monomer which contains a reactive grouping. This monomer may constitute the entire latex particles or the monomer may be a minor component of the latex particles and thus be one of at least two copolymerizable monomers. A most preferred embodiment involves the preparation of provision of a "seed" latex which may be a poly- or mono-disperse system wherein Dw/Dn=1.001 to 1.1 for a monodisperse system and Dw/Dn=1.5 to about 5.0 for a polydisperse system and most preferably a monodisperse system of Dw/Dn smaller than 1.05, and wherein
Dw=weight average particle diameter
Dn=number average particle diameter
The "seed" latex (or core) may be any polymerizable monomer or mixture of monomers. Styrene is a most preferred "seed" monomer. In the seed latex environment there is then conducted the "shell" polymerization including in the monomer(s) being polymerized the reactive group-containing (RGC) monomer. In this most preferred embodiment the polymerized RGC monomer is produced as a shell on the surface of the latex seed particles. This technique is highly advantageous. Firstly one can obtain a final colored latex of monodispersivity in a simple manner. Secondly the RGC monomer is utilized to its maximum capability since it is not "buried" in the latex particle; this, obviously, maximizes the economics of the procedure as well.
The general procedure for the preparation of the colored polymers involves chemically reacting the necessary components in an aqueous environment to produce a colored latex, and then, if it is desired to obtain the polymer in dry, particulate (i.e. solid) form, to isolate the polymer from the latex.
The general chemical reactions may be divided into two paths. On the one hand the reactive-group (e.g. CH 2 Cl) containing monomer (RGC) may be emulsion polymerized and the resultant latex then treated with a compound (A) which will make the so modified latex particles couplable to a diazonium salt to produce a colored azo compound (latex). Preferred compounds (A) are aromatic amines capable of coupling. With aromatic amines, for example, the amination of the latex polymer particles proceeds with facility at room temperature. To the aminated latex there is then added a selected diazonium salt whereafter coupling to the latex and, if desired, isolation of the resultant colored latex particles, is accomplished in known manner. It is, of course, obvious that in addition to the RGC monomer(s) other monomers may be co-polymerized therewith. In general, it is preferred that the RGC monomer(s) comprise(s) at least about 5 or more mole % of the total monomers to be polymerized and may indeed comprise all of the polymer product (i.e. homopolymerization with 100 mole % of RGC monomer).
It is also possible to utilize an already prepared polymer containing an RGC monomer in polymerized form and produce a fine aqueous suspension thereof. This suspension can then be aminated and coupled similarly to the emulsion polymerizate. Where the final desired product is latex, it is preferred to employ the first mentioned technique. Where the colored polymer particles are to be recovered as a fine powder, both techniques are suitable.
In a particularly preferred embodiment, a second path of operation is provided. In this technique the RGC monomer(s) with or without additional copolymerizable monomer(s) is polymerized in an existing polymer latex or aqueous polymer dispersion environment whereby a "shell" or surface coating of the RGC monomer(s) in polymerized form is obtained, with the environmental latex polymer particle as the "core". This is referred to as a "structured-particle". The shell polymer may be merely physically bonded to the core or chemically grafted thereon, the latter obtaining depending on polymerization conditions as well as particularly where a cross linking (e.g. difunctional) agent or monomer is used.
In addition to the use of conventional diazotizable aromatic amines as precursors for the diazonium salt one may also use protein material containing diazotizable primary amine groups to azo-link proteins to the latex particle.
DETAILED DESCRIPTION OF THE INVENTION
The essential feature of one aspect of the present invention involves the provision of reactive sites on a polymer particle which are readily reactable with a reagent to produce a modified polymer capable of coupling after such reaction to an aromatic diazonium salt, whereby the azo chromophore is chemically introduced into the modified polymer and a colored polymer results.
The reactive site in the polymer is preferably provided by a reactive halogen atom which may be haloalkyl and may be designated as ##STR1## wherein n is 1 to 10; R 1 and R 2 are independently hydrogen, alkyl, halo, cyano, hydroxy, alkoxy or the like; X is halo; m is an integer from 1 to 2n; and at least one of R 1 and R 2 on a carbon vicinal to a halogen is hydrogen. However lower haloalkyl is preferred especially halomethyl and haloethyl. The reactive halogen may be any of fluorine, chlorine, bromine and iodine, with fluorine least desirable due to its minimal reactivity, and chlorine the most preferred because of acceptable reactivity, availability in monomers, and economic feasibility.
Suitable but merely representative reactive group-containing (RGC) monomers include p-vinyl benzyl chloride, p-vinyl benzyl bromide, bromomethyl acrylate, bromethylacrylate, chloromethyl acrylate, chloromethyl methacrylate, chlorethyl acrylate, chloroethyl methacrylate, chloroethyl chloroacrylate, bromoethyl α-chloroacrylate, iodoethyl acrylate, p-vinyl benzyl iodide, 2-chloroalkyl acetate, 2-chloroalkyl alcohol, 2-chloroalkyl chloride, 2-chlorobenzal acetophenone, 1-chloro-1-bromoethylene, 2-chloro-1, 3-butadiene, beta-chloroethyl itaconate, 2-chloroethylitaconate, 1-chloro-1-propene, 2-chloro-1-propene and α-chlorovinyltriethoxy silane. Mixtures of any of the foregoing may also be used.
As optional comonomers for cojoint polymerization with one or more of the foregoing RGC monomers one may use any of the well known classes of α,β-ethylenically unsaturated compounds. Mention may be made of the vinyl benzenes such as styrene, vinyl toluene, tert-butyl styrene, α-methyl styrene, and divinyl benzene; vinyl halides such as vinyl chloride, vinyl bromide and vinyl fluoride; vinyl esters such as vinyl acetate, vinyl propionate and vinyl butyrate; vinyl pyridine; vinyl lactams, e.g. N-vinyl-2-pyrrolidone; vinyl ethers such as methyl vinyl ether, ethyl vinyl ether, tert-butyl vinyl ether, iso-octyl vinyl ether; acrylonitrile, acrylamide, ethylene, propylene, vinylidene halides (e.g. vinylidene chloride), acrylic acid, methacrylic acid; acrylate, methacrylate and chloracrylate esters, butadiene, isoprene, chloroprene and the like. Mixtures of any of these monomeric substances can also be used. Of preferred status are the vinyl benzenes, the vinyl esters of C 1 to C 8 aliphatic acids, the C 1 to C 8 alkyl acrylates, methacrylates and α-chloracrylates, acrylonitrile, acrylamide, ethylene and propylene. The choice of monomers will be largely dependent upon the desired physical properties of the colored particles. For the production of coatings and films one would prefer polymers which are film-formers whereas for use as pigment particles and for other uses such as for immunological tests (e.g. using a proteinated polymer particle), hard non-film-forming particles are preferred.
Any amount of these additional monomers may be used, from a trace, if desired, to 99+ mole % based on total monomer present. It is preferred when used to employ from about 5 to 95 mole % of these other monomers. This group of monomers will hereinafter be referred to as N.R.G. (non-reactive group) monomers.
Where a "structured particle" is to be prepared utilizing a first "seed" latex, the monomers for the "seed" polymer can be any of the RGC monomers as well as the NRG monomers mentioned above. In addition the "seed" polymer can be any combination of the NRG monomers to produce copolymers (including interpolymers of a multitude of monomers) or any combination of RGC monomers and finally any combination of both NRG and RGC monomers. As previously mentioned, in preparing "seed" latex for "structured particles" the preferred latex is based on styrene monomers.
It is, of course, understood and well-known in the polymerization art that not all monomers copolymerize well with each other and consequently the selection will obviously be based on such considerations particularly where economic feasibility is a major factor.
The reagents useful to modify the polymer so that it is capable of coupling to an aromatic diazonium salt are generally the couplable moieties well known in the azo dye art. These fall into 6 classes which are (1) phenols and napthols; (2) aromatic amines; (3) naphthol-, naphthylamine-, and aminonaphthol-sulfonic acids; (4) substances containing reactive methylene groups; and under exceptional conditions or with specific diazo compounds one can add (5) phenol ethers and (6) hydrocarbons. The preferred group of couplers are the aromatic amines. As a general guide it is well to bear in mind that the coupling reaction is fairly pH sensitive. Thus for amines the coupling reaction is best conducted at about pH 3.5 to pH 7.0, due ostensibly to the need for the diazonium salt to hydrolyze to the diazohydroxide which is believed to be the active coupling form. On the other hand as the pH rises the stability of the diazo-compound falls. Consequently, coupling must be viewed and considered as a race between azo-compound formation and decomposition of the diazo-compound.
Another factor to consider is that as negative substituents increase in the diazo-compound so is it able to couple in increasingly acid solution.
All couplers will per se vary as to their power to couple depending on the presence and position of negative and positive substituents. In the case of amines, coupling generally takes place in the aromatic ring para to the amine group provided there is a free replaceable (labile) hydrogen in the para position. Also, generally, substitution of primary aminohydrogen atoms by alkyl or aryl groups enhances coupling.
The preferred polymer-modifying agents to effect or insert a coupling moiety are the mono- and bicyclic aromatic primary and secondary amines which may have the variety of substituents found in such amines conventionally used as couplers in the azo dye field. Generally such other substituents are preferably hydroxyl and amino, although in many couplers chlore and nitro groups, if not promoting coupling, do not adversely affect it.
Particularly effective amine polymer-modifying reagents capable of coupling (nucleophiles) are aniline, N-methyl aniline, m-toluidine, N-methyl m-toluidine, N-methyl-o-toluidine, N-ethyl aniline, N-allyl aniline, p-hydroxyaniline, p-methoxyaniline, N-phenylenediamine, p-acetamido aniline, p-xylidene, B-naphthylamine, α-naphthylamine, Gamma-acid, J-acid and H-acid.
The preferred mono- and bicyclic amines may be depicted by the following general formulae ##STR2## wherein R is hydrogen or C 1 to C 6 alkyl and Y is hydroxyl, amino or C 1 to C 6 alkyl; ##STR3## R is hydrogen, C 1 to C 6 alkyl or SO 3 Na, and Z 1 and Z 2 are --SO 3 H, OH or NR 1 R 2 where R 1 and R 2 are hydrogen or C 1 to C 6 alkyl.
As will be apparent from the above, these coupling moieties or compounds contain an N-bonded H atom reactive with the reactive halogen atom in the modified polymer particle, and a labile H atom in position for coupling with the subsequently applied color-producing diazonium salt. Naturally, when the reactive group in the polymerized RGC monomer is other than halogen, the coupling moiety must contain a group or atom reactive with such other reactive group.
The diazotizable primary aromatic amines useful herein include substantially all those well known in the dye art. Of particular value are those of the following formulae: ##STR4## wherein X, Y and Z are independently hydroxyl, sulfo, nitro, H, chloro, bromo, --COONa, C 1 to C 6 alkoxy, C 1 to C 6 alkyl, acylamido (e.g. --NHCOCH 3 ), --SO 2 CH 2 CH 2 OSO 3 Na, --SO 2 CH 2 CH 2 CH 2 Cl, etc.
Examples of compounds of Formulae IV, V and VI include aniline, p-nitroaniline, p-aminobenzoic acid, sulfanilic acid, 2-hydroxy sulfanilic acid, 2,5-dimethylaniline, p-aminoacetanilide, anisidine, 2,5-dichloro-4-nitroaniline, 5-hydroxy-7-sulfo-B-naphthylamine, 4,8-disulfo-B-naphthylamine, etc.
In addition to the foregoing preferred color-producing diazotizable amines, another preferred class includes proteins which contain diazotizable primary amine groups.
The general procedures for preparing the colored products of this invention have been described earlier herein. In more specific terms, where the product is of the "structured particle" type one may utilize any previously prepared latex, especially a latex prepared by an emulsion polymerization method following general procedures well known in the art. The main chemical reaction is the known free radical polymerization. The polymerization is preferably initiated by the decomposition of nonionic type initiators (without release of polar groups) or cationic types, such as peroxides, hydroperoxides, or azo compounds, as well as by use of the redox mechanism or by irradiation. There are three stages for free radical polymerization: initiation, propagation and termination. The number of particles initiated depends inter alia on the type and concentration of emulsifiers, type and concentration of electrolyte, the rate of free radical generation, temperature, and type and intensity of agitation.
When using an emulsifier the main site of polymerization initiation is the monomer-swollen micelles; without the emulsifier, the polymerization usually starts in the aqueous phase and as the radicals grow in size, they may become surface-active and combine to form the polymer particles. If a monodisperse latex is to be prepared the surfactant concentration must be below the critical micelle concentration (CMC). Examples of preferred surfactants include hexadecyl trimethyl ammonium bromide (HDTMAB) and other conventional cationic, generally quaternary ammonium, surfactants, the nonionic and anionic surfactants being progressively less preferred especially when an amine coupler reactant is to be employed which optimally calls for a cationic surface charge on the polymer particle.
Suitable cationic surfactants preferred herein for use as emulsifiers in the polymerization steps and as post-stabilizers of the aqueous media resulting from the reaction of the modified polymer particles (i.e. the polymerized RGC monomer) with the primary or secondary amine capable of coupling (e.g. N-methylaniline) include generally the quaternary ammonium compounds which may be described as containing, in addition to the usual halide (chloride, bromide, iodide, etc.) sulfate, phosphate or other anion, aliphatic and/or alicyclic radicals, preferably alkyl and/or aralkyl, bonded through carbon atoms therein to the remaining 4 available positions of the N atom, 2 or 3 of which radicals may be joined to form a heterocycle with the N atom, at least one of such radicals being aliphatic of at least 10 up to 22 or more carbon atoms. As illustrative of such cationic surfactants there may be mentioned the above HDTMAB, distearyldimethyl ammonium chloride, stearyl dimethyl benzyl ammonium chloride, coconut alkyl dimethyl benzyl ammonium chloride, dicoconut alkyl dimethyl ammonium bromide, cetyl pyridinium iodide, cetyl trimethyl ammonium bromide and the like. Other cationic emulsifiers include laurylamine hydrochloride, diethylaminoethyloleylamide HCl, the diethylcyclohexylamine salt of cetyl sulfuric ester, and the like.
Suitable "modifiers" or chain transfer agents include the primary, secondary and tertiary aliphatic mercaptans, e.g. n-dodecylmercaptan and similar alkyl mercaptans, thiophenol, alpha and beta thionaphthol and the like.
Examples of azo initiators include 2,2' azobisisobutyronitrile (AIBN) and 2,2' azobis (2-amido) propane hydrochloride (AAP). Other initiators include hydrogen peroxide, t-butyl hydroperoxide, p-menthane hydroperoxide, and redox systems such as ethylene diamine and sodium formaldehyde sulfoxylate, augmented optionally by heavy metal ions such as ferrous in small amounts.
The amounts of surfactant, catalysts and chain transfer agent will generally vary between about 0.5% to about 10%, preferably from about 0.1% to about 5% and most preferably from about 0.1% to about 2% based on monomer(s) weight.
The various reaction temperatures will range as follows. For the emulsion polymerization it is customary to carry out the polymerizations at from about room temperature to about 100° C. A preferred range is from about 25° C. to about 85° C., and usually about 70° C. For the polymer-modification procedure (e.g. amination), reaction temperatures may vary from about room temperature (e.g. 20° C.) to about 100° C. with 20° C. to about 70° C. being preferred.
This reaction at about room temperature may take up to 1 to 35 days for completion, at elevated temperatures less than a day, and in hours with the further assistance of catalysts such as pyridine, tertiary amines, etc.
In the reactions involving the RGC monomer (polymerization) and between the polymerized RGC monomer and the reactive coupler (e.g. amination), the latex polymer solids concentration is preferably below 5 or 10%, usually about 2%, at which concentrations cleanup by serum replacement (see Example 1C below) is most efficient. Higher concentrations of 10-50% could be employed using other less efficient cleanup procedures such as centrifugation, decantation, etc. The latex polymer average particle size during and resulting from the process of this invention is generally about 0.03 to 3, preferably about 0.1 to 0.3, microns (μm). Extremely small particle size requires unduly high amounts of emulsifier surfactant for stabilization. On the other hand, this invention is operative with larger particle sizes even up to beads and other polymer substrates.
In the reaction between the polymerized RGC monomer particles and the reactive coupler (e.g. amination with N-methylaniline), it will be understood that at least a stoichiometric amount of said coupler, based on the reactive groups in the said polymerized RGC monomer particles, should be employed up to a relatively small excess thereover since unreacted coupler must be thereafter removed, e.g. by serum replacement.
Similar considerations as to stoichiometric amounts and excess amounts thereover apply with respect to the coupling reaction with the diazonium salt. The diazotization of the diazotizable aromatic primary amine with sodium nitrite, and the coupling thereof with the coupler-surfaced polymer particles is conducted by procedures conventional in the azo dye art, generally at low temperatures of 5° to 0° C. or less, the coupling reaction generally being completed in from about 1 to 48 hours. The surface charge on the final azo-colored polymer latex particles will depend on the type of diazonium compound employed, e.g. anionic with a sulfonic diazonium compound, cationic with a quaternary ammonium or aminodiazonium compound.
If desired, the colored polymer particles may be isolated from the final latex as a pigment suitable for many uses as in latex paints, colored films, etc. The optimum particle size for any desired use and color intensity is readily determinable by routine trial of a suitable range of particle sizes in such use. For example, an average particle size of about 0.25 μm is considered effective for hiding a TiO 2 pigmented polymer.
In addition to the many uses of colored latexes described above, films produced with the products of this invention may, with proper selection of coupler and diazonium salt, be employed as pH indicators.
The following examples are only illustrative and not limitative. All amounts and proportions referred to herein and in the appended claims are by weight, and temperatures in °C., unless otherwise indicated.
EXAMPLE I
This example illustrates the preparation of a yellow colored latex of the formula shown in FIG. 1. ##STR5## A. Seed latex preparation.
The seed latex is prepared by bottle polymerization. The bottle is charged with 0.1 g of hexadecyltrimethylammonium bromide (HDTMAB), 200 g of water, 40 g of styrene, 0.2 g of 2,2'-azobisisobutyronitrile (AIBN), 0.004 g of dodecyl mercaptan, and 0.012 g of sodium chloride with grade 5 nitrogen bubbled through the gasket for 20 minutes. The capped bottle with its contents is then rotated end-over-end at 30 r.p.m. in a thermostated water bath for 24 hours at 70° C. The latex is filtered to remove all coagulum formed during polymerization. The conversion is 66%.
B. Structured-particle latex preparation.
The shell-layer polymerization is carried out in a 3 neck 1000 ml flask. 300 g of 6.67% solids content of the above seed latex and 0.26 g of HDTMAB are added to the flask. Nitrogen is bubbled through the latex in the flask. A mixture of 2 g of styrene monomer, 6 g of vinylbenzyl chloride (VBC), and 0.32 g of AIBN solution is added to the flask drop by drop over a two hour period. The mixture is agitated at a moderate rate throughout the polymerization, which is carried out for 7 hours. Unreacted monomer is removed by steam distillation under vacuum. The conversion is found to be over 96% with a particle size of 160 nm (nanometers). At this state, the polymer particles would look like FIG. II. ##STR6## C. Amination
355 g of 2% solids content of the above structured-particle latex is then reacted with 4.2 g of the N-methylaniline nucleophile for 10 days at room temperature. Most of the unreacted N-methylaniline is removed by "serum replacement" using a pH 2.3 hydrochloric acid solution first and then followed by distilled deionized water. After serum replacement, 0.2 g of HDTMAB is added as a post-stabilizer. Serum replacement in this case means agitating the latex in a cell above a filter disc that would allow an aqueous phase to pass but not the latex particles. After this step the modified latex particles are as depicted in FIG. III. ##STR7## D. Colorant production
1.73 g of sulfanilic acid is dissolved in a 5% sodium carbonate solution. A solution of 0.69 g of sodium nitrite in about 2 ml of water is added to the solution of sodium sulfanilate. The mixture is cooled to almost 0° C. and dropped with stirring into an ice-cold solution of 0.98 g of concentrated sulfuric acid in water. The white diazonium salt separates instantaneously. The precipitate is filtered by suction. The diazonium salt is then added to 300 g of 2% solid content aminated latex from C above in a 500 ml round-bottom flask which is kept between 0° to 5° C. A yellow color forms gradually, and the reaction temperature is kept 0° to 5° C. for 48 hours. The decomposed diazonium salt and the absorbed dye-stuff can be removed by distilled deionized water and 95% alcohol. After the coupling reaction, the modified latex has the structure depicted in FIG. I.
The cleaned yellow latex has a zeta potential of 54 mV in distilled deionized water and a maximum absorption at wavelength of 440 mμ measured by a KCS-40 spectrophotometer. A pure white acrylic latex paint can be tinted with the yellow latex very easily. The yellow latex can also be blended with 60:40 poly(styrene-butadiene) (Dow LS-1176-B) to make a particle volume concentration 40% including 0.5% of methyl cellulose as the thickener.
A K303 coater is used to drawdown the uniform film thickness of the paint. Good yellow dry films are obtained. The yellow films can be changed to red color in strong acid solution and change back to yellow color in basic solution. Thus, the colored latex can be a pigment and a pH indicator.
EXAMPLE 2
This example illustrates the preparation of the red-orange latex with the formula depicted in FIG. IV. ##STR8## A. Seed latex preparation
Same as Example 1-A.
B. Structured-particle preparation
The shell-layer polymerization is carried out in the 3 neck 1000 ml flask. 300 g of 6.67% solids content seed latex, 0.26 g of HDTMAB, and 0.32 g of 2,2'-azobis(2-amido) propane hydrochloride (AAP), are added to the flask and allowed to come to a reaction temperature of 70° C. Nitrogen is bubbled through the latex in the flask. A mixture of 2 g of styrene monomer, and 6 g of VBC is added to the flask drop by drop over a two hour period. The mixture is agitated at a moderate rate throughout the polymerization which is carried out for 7 hours. Unreacted monomer is removed by steam distillation under vacuum. The conversion is found to be over 99% with a particle size of 160 nm. The structure is the same as previously depicted in FIG. II.
c. Amination
Same as Example 1-C.
D. Colorant production
0.69 g of p-nitroaniline is added to a mixture of concentrated hydrochloric acid and water. 0.35 g sodium nitrite is added with stirring. The diazonium salt solution thus formed is added to 300 g of 2% solid content aminated latex from C in a 500 ml round-bottom flask which is kept between 0° to 5° C. The red-orange color appears gradually. The latex has a maximum absorption at wavelength of 480 mμ measured by KCS-40 spectrophotometer. After the coupling reaction, the modified latex has the structure depicted in FIG. IV.
EXAMPLE 3
This example illustrates the preparation of a yellow latex, but cationic initiator AAP is used (see Example 2B)
A. Seed latex preparation
The seed latex is prepared by bottle polymerization. The bottle is charged with 0.4 g of HDTMAB, 156 g of water, 40 g of styrene, 0.04 g dodecyl mercaptan, and 0.01 g of sodium chloride with grade 5 nitrogen bubbled through the gasket for 5 minutes. 4 ml of 0.2 g of AAP aqueous solution is injected through the cap by a syringe. The capped bottle with the above contents is then rotated end-over-end at 30 r.p.m. in a thermostated water bath for 24 hours at 70° C. The latex is filtered to remove all coagulum formed during polymerization. The conversion is 97%.
B. Structured-particle latex preparation
The shell-layer polymerization is also carried out by bottle polymerization. 200 g of 5% solids content seed polystyrene latex is swollen with a mixture of 1 g of styrene and 3 g of VBC for 30 minutes. 0.16 g of AAP aqueous solution is injected through the cap. The capped bottle is rotated end-over-end at 30 r.p.m. in a thermostated water bath for 24 hours at 70° C. The conversion is over 99% with particle size 62 nm. Unreacted monomer is removed by steam distillation under vacuum.
C. Amination
300 g of 2% solids content of structured-particle latex is then reacted with 2 g of N-methylaniline for 4 days at room temperature. Most of the unreacted N-methylaniline is removed by serum replacement with a hydrochloric acid solution in deionized water of pH 2.3. 0.2 g of HDTMAB is added as a post-stabilizer.
D. Colorant production
Same as Example 1D.
EXAMPLE 4
This example illustrates the preparation of a yellow colored latex with the formula shown in FIG. I.
A. Seed latex preparation
The bottle is charged with 0.8 g of HDTMAB, 160 g of water, 80 g of styrene, 1.6 g of AIBN, and 0.06 g of dodecyl mercaptan with grade 5 nitrogen bubbled through the gasket for 20 minutes. The capped bottle with its contents, is then rotated end-over-end at 30 r.p.m. in a thermostated water bath for 24 hours at 70° C. The latex is diluted and filtered to remove all coagulum formed during polymerization. The particle size is 94 nm.
B. Structured-particle latex preparation
The shell-layer polymerization is also carried out by bottle polymerization. 150 g of 6.67% solids content seed polystyrene latex and 0.13 g of HDTMAB is added to a mixture of 2 g of styrene, 3 g of VBC, and 0.16 g of AIBN. Grade 5 nitrogen is bubbled through the gasket for 5 minutes. The capped bottle is rotated end-over-end at 30 r.p.m. in thermostated water bath for 24 hours at 70° C. Unreacted monomer is removed by steam distillation under vacuum. The particle size is 108 nm.
C. Amination
300 g of 2% solids content of structured-particle latex is then reacted with 2.6 g of N-methylaniline for 6 days at room temperature. Most of the unreacted N-methylaniline is removed by "serum replacement" using a pH 2.3 hydrochloric acid solution first then followed by distilled deionized water. 0.2 g of HDTMAB is added as a post-stabilizer.
D. Colorant production
A yellow latex is prepared substantially as described in Example 1-D.
EXAMPLE 5
A yellow latex is prepared substantially as described in Example 1 except that the time for amination is 60 hours instead of 10 days, and the temperature for the reaction is 70° C. rather than 25° C.
EXAMPLE 6
This example illustrates the preparation of a yellow colored latex with the formula shown in FIG. 1.
A. Seed latex preparation
Same as Example 1-A.
B. Structured-particle latex preparation
Structured-particle latex is prepared substantially as described in Example 4-B except that 0.5g of styrene and 3.5 g of VBC are used instead of 2 g of styrene and 3 g of VBC.
C. Amination
Same as Example 1-C except that reaction time is 14 days instead of 10 days.
D. Colorant production
Same as Example 1-D.
EXAMPLE 7
This example illustrates the preparation of a yellow colored latex with the formula shown in FIG. I.
A. Seed latex preparation
Seed latex is prepared substantially as described in Example 1-A except that 0.05 g of HDTMAB is used instead of 0.1 g of HDTMAB. The particle size is 198 nm.
B. Structured-particle latex preparation
Same as Example 6-B.
C. Amination
Same as Example 1-C.
D. Colorant production
Same as Example 1-D.
EXAMPLE 8
This example illustrates the preparation of a yellow colored latex with the formula shown in FIG. I.
A. Seed latex preparation
Same as Example 7-A.
B. Structured-particle latex is prepared substantially as described in Example 1-B except that 6 g of styrene and 2 g of VBC are used instead of 2 g of styrene and 6 g of VBC.
C. Amination
Same as Example 1-C except that 1.4 g of N-methylaniline is used instead of 4.2 g of N-methylaniline.
D. Colorant production
Same as Example 1-D.
EXAMPLE 9
This example illustrates the preparation of a yellow colored latex with the formula shown in FIG. I.
A. Seed latex preparation
Same as Example 7-A. The particle size is 198 nm.
B. Structure-particle latex preparation
Same as Example 1-B. The particle size is 240 nm.
C. Amination
Same as Example 1-C.
D. Colorant production
Same as Example 1-D.
EXAMPLE 10
A yellow latex is prepared substantially as described in Example 9 except that the time for amination is 35 days instead of 10 days.
EXAMPLES 11-20
Examples 1-10 are each separately repeated except that the seed latex preparation (Step A) is omitted and colored polymer is formed from the Step B latex alone (i.e. particles of styrene-p-vinylbenzyl chloride polymer). Colored latexes are obtained in each instance excellently.
EXAMPLES 21 and 22
Examples 1 and 11 are repeated except that the monomer in Step B is all (5 gm) p-vinylbenzyl chloride.
EXAMPLES 23-26
Examples 1, 11, 21 and 22 are each repeated separately utilizing 2 chloroethyl acrylate monomer in place of p-vinylbenzyl chloride.
EXAMPLE 27-30
Examples 1, 11, 21 and 22 are each again repeated utilizing the following monomers in place of p-vinylbenzyl chloride:
(a) 2-chlorallyl acetate
(b) 2-chloroethyl itaconate
(c) 2-chloromethyl methacrylate
(d) 2-chlorobenzal acetophenone
The latexes produced in the foregoing examples not only have excellent color but in addition, they are extremely stable products. The modified polymer latexes, as well, (i.g. Step C in the foregoing examples) also have enhanced stability.
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The present invention relates to colored latex products, and especially to colored synthetic polymer emulsions, the finely divided colored polymers obtainable therefrom, and methods for making the colored polymer emulsions as well as the polymers as colored, finely divided solids.
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BACKGROUND
[0001] The present invention relates to a container, and more particular to a container that allows for the separation of the compositions while in storage and the mixing of the compositions at a desired time.
[0002] Most multiple compartment containers have a side by side division or have a compartment with a common closure. None of these have a smaller compartment fully enclosed by a larger compartment with each compartment remaining separate until a desired time and a desired action is performed to the container. The advantage of the latter is its compactness, the ease of accessibility with one closure not getting into the way of the other and the ability of placing different types of items in each compartment that would normally react when mixed.
[0003] Within the pharmaceutical and dietary supplement products and the delivery system of these products there is a problem when storing and delivering products. Many of the elements of these products are reactive to one another when mixed. Thus, it is necessary to store the elements separately until the product is being consumed or applied. Various attempts have been made to keep the elements separate until the desired time, but these attempts require multiple packaging, various coatings or sealants.
[0004] Thus, it is desired to have a delivery system that has multiple compartments and the contents of these compartments are not mixed until the desired time and that is commercially accessible to make, fill, and store.
SUMMARY
[0005] According to one aspect of the present invention a multi container assembly comprising a first container having a first end and a second end, wherein the first end has an opening with a first securing means distal to the opening and integrated within an internal cavity of the first container and a protrusion extends upwards towards the opening and a second securing means is disposed on the protrusion, a second container sized to fit within the opening of the first container having a first end and a second end, wherein the first end has an opening and a first securing means distal to the opening and a second securing means distal to the second end, wherein the second securing means mates with the second securing means of the first container, and a cap having an internal cavity with a first securing means disposed on surface of the internal cavity designed to mate with the first securing means of the first container and a protrusion extending downward from the internal cavity, wherein the protrusion has a second securing means designed to mate with the first securing means of the second container, wherein when the cap is secured to the first container and the second container a substantially impervious seal is formed.
[0006] According to another aspect of the present invention a multi container assembly comprising a container having a first end and a second end, wherein the first end has an opening with a first securing means distal to the opening and a hollow protrusion extending upwards a predetermined distance and having a second end with an opening and a securing means distal to the opening at the second end, a cap having an internal cavity with a first securing means designed to mate with the first securing means of the container and a protrusion extending downward from an internal cavity, wherein the first protrusion has a second securing means designed to mate with the second securing means of the container, wherein when the cap is secured to the container and a substantially impervious seal is formed.
[0007] According to another aspect of the present invention a multi container assembly comprising a container having a first end and a second end, wherein the first end has an opening with a first securing means distal to the opening and integrated within an internal cavity of the first container and a protrusion extends upwards towards the opening and a second securing means is disposed on the protrusion, a cap having an internal cavity with a first securing means disposed on surface of the internal cavity designed to mate with the first securing means of the container and a hollow protrusion extending downward from the internal cavity and the hollow protrusion has an opening and a second securing means distal to the opening designed to mate with the second securing means of the container, wherein when the cap is secured to the first container and the second container a substantially impervious seal is formed.
[0008] Further areas of applicability will become apparent from the description provided herein. It should be understood that the description and specific examples are intended for purposes of illustration only and are not intended to limit the scope of the claims.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0009] FIG. 1 depicts an exploded isometric view of a container, in accordance with one embodiment of the present invention.
[0010] FIG. 2 depicts a side view of the container, in accordance with an embodiment of the present invention.
[0011] FIG. 3 depicts a cross section view of the container, in accordance with an embodiment of the present invention.
[0012] FIG. 4 depicts a cross section view of the container, in accordance with another embodiment of the present invention.
[0013] FIG. 5 depicts a cross section view of the container, in accordance with another embodiment of the present invention.
DETAILED DESCRIPTION
[0014] The present invention can be described as a delivery platform that is capable of delivering multiple product formulas as a single product in a single dose. The formulations are stored separated but are delivered in unison as the multiple formulas are mixed at the point of delivery which reduces the risk of ingredients interacting before consumed by the end user. This unique delivery gives birth to a brand-new breed of products that offers a multitude of applications and functionality.
[0015] The invention solves many aspects of product development. Compatibility, solubility, and stability between active and inactive ingredients. The formulation stage of product development usually introduces any issues between raw materials which leads to many products never getting launched. This enables new formulations that could not be delivered currently and offers products that have never been seen before. In addition, this delivery platform has also proven to increase taste masking aspects of many compositions that contain ingredients that are bitter and of bad taste. excipients in order to produce products that remain shelf stable and contain the same purity throughout the life of the product. For example, preservatives, solvents, stabilizers, and many other excipients are being used in almost all the formulations currently on the market today. The invention can offer a reduction or complete illumination of such excipients which creates cleaner products for consumers.
[0016] This delivery platform creates products that offer the ability to deliver multiple applications in a wide range of industries. This delivery system offers applications that are single dose and disposable or multi-dose and modular. The modular type offers attachments that are interchangeable and in many different designs specific to the type of product application such as liquid/liquid, liquid/powder, and liquid/pill formulations. In addition, the secondary vessels can offer pre-dosed formula's that can be attached and delivered with the main vessel then detached and repeated which offers a new safe dosing application for children and adults.
[0017] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. It is to be understood that this invention is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.
[0018] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention, the preferred methods and materials are now described.
[0019] It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.
[0020] FIG. 1 depicts an exploded isometric view of the container assembly 100 , in accordance with one embodiment of the present invention. The container is comprised of a first container 200 , a second container 300 , and a cap 400 .
[0021] The first container 200 , the second container 300 , and/or the cap 400 may be made from, but not limited to, polyolefins, styrenics, polypropylene, copolymer polypropylene, polystyrene, thermoplastic elastomers, thermoplastic elastomers, polyethylene, polypropylene, polystyrene, copolymer polypropylene, metals, or various other materials thereof known in the art. Additionally almost all resins used for preparing thermosetting plastic bottles can be used such as Acrylonitrile Butadiene Styrene (ABS), Polyethylene Terephthalate (PET), Polyamide, Polycarbonate, Polyvinylchloride (PVC), Low-density polyethylene (LDPE), High-density polyethylene (HDPE), Ultra high molecular weight (UHMW-PE), Polypropylene, Ionomar, and Poly-4-methyl-1-pantene (TPX). The parts may be made from various other materials such as wood, metal, or a combination of woods, metals, or plastics.
[0022] In some embodiments, the first container 200 , the second container 300 , and the cap 400 may be made from, but not limited to, injection, blow, compression, 3-D, thermoforming, foam molding, and the like. In some embodiments, the first container 200 , the second container 300 , and the cap 400 may be made from various other manufacturing techniques depending upon the material the parts are made out of and the machine process.
[0023] In the depicted embodiment, a threaded style locking mechanism is seen on the first container 200 and the second container 300 . In additional embodiments, various detachable locking mechanism may be used, such as, but not limited to, threaded locks, snap lock, pressure fit lock, sliding lock or the like.
[0024] FIG. 2 depicts a cross section view of the container assembly 100 dissembled, in accordance with one embodiment of the present invention.
[0025] The first container 200 is designed to house the first product and also the second container 300 . In the depicted embodiment, the first container 200 has a main compartment 205 , a neck 206 with an opening 202 at a top end 201 . The first container 200 has a predetermined shape, size, and volume based on the intended quantity or volume of the contents that are placed inside. In various embodiments, the first container 200 may have various shapes and sizes. The first container 200 has the opening 202 that is sized to receive the second container 300 . The first container 200 is sealed, expect for the opening 202 to allow the first container 200 to hold a liquid, solid, or gas material. In the depicted embodiment, approximate to the opening 202 is a first securing means 204 exposed on the exterior surface of the first container 200 on the neck 206 which is designed to mate with the cap 400 to create a seal between the cap 400 and the first container 200 . The seal created between the cap 400 and the first container 200 is a substantially air tight, water tight, and/or hermetic seal. Various types of seals may be employed, such as but not limited to mechanical sealing mechanisms, adhesives, welding techniques, induction seals, heat seals, or the like.
[0026] The first container 200 may have various volumes depending upon the intended purpose and quantities to be mixed. In some embodiment, the first container 200 ranges from 1 oz to 16 oz, and the second container 300 ranges from 5 ml to 100 ml dose sizes. In some embodiments, the container assembly 100 is a one-time use design. In some embodiments, the containers may be washed, cleaned, and reused.
[0027] In the depicted embodiment, the first container 200 has an extension 209 extending towards the top end 201 from a bottom surface 203 . The extension 209 has a hollow design with a second securing means 207 integrated into the surface of the extension 209 . The second securing means 207 is positioned so that the second container 300 when inserted into the first container 200 through the opening 202 can mate with the second securing means 207 . In additional embodiments, the second securing means 207 may be integrated into the bottom surface 203 of the first container 200 depending on the thickness of the first container 200 .
[0028] In various embodiments, more than one securing means may be implemented within the interior cavity of the first container 200 so that more than one containers may be attached if the desired mixture requires more than two parts. The opening 202 is sized to accommodate the multiple containers. The second securing means 207 is designed to secure the second container 300 in place so that the second container 300 is not damaged, broken, or opened, thereby releasing the contents of the second container 300 before the desired time.
[0029] The second container 300 is designed to contain a product that is desired to remain separate from the contents of the first container 200 until a predetermined time. In the depicted embodiment, the second container 300 is a substantially cylindrical container a compartment 306 , a first securing means 302 located at a first end 301 and a second securing means 304 located at a second end 303 . The first end 301 has an opening 305 and the second end 303 has an opening 307 . The first securing means 302 is designed to mate with the reciprocal mating feature of the cap 400 and form a substantially air tight, water tight, and/or hermetic seal. The second securing means 304 is designed to mate with the second securing means 207 of the first container 200 and form a substantially air tight, water tight, and/or hermetic seal. When properly secured to the cap 400 and the first container 200 , the content of the first container 200 and the second container 300 are separated. In the depicted embodiment, the first and second securing means 302 and 304 are substantially similar securing means. In additional embodiments, the first and second securing means 302 and 304 are different methods of accomplishing the desired seal. Various types of securing means may be employed by the first and second securing means 302 and 304 . For example, a screw style lock, a snap lock, a pressure lock, a sliding lock or the like.
[0030] In some embodiments, the first end 301 , the second end 303 , or both ends are open with a seal (such as heat seal or induction seal) that provides the air tight, water tight, and/or hermetic seal over opens 305 and 307 . This seal may be used to provide additional security so that the contents do not mix prematurely. In some of these embodiments, the first container 200 or the cap 400 may have a protrusion that is designed to puncture one or both of these seals so that either there is an elongated release period of the contents of the containers, or so that when the cap is removed (either with the second container 300 attached, or alone) the contents of the second container 300 are automatically introduced into the contents of the first container 200 .
[0031] The cap 400 is designed to seal the contents of the first container 200 and the second container 300 and prevent the contents of the containers from mixing. The cap 400 also provides the desired security means to keep children or other individuals from gaining access to the contents. The cap 400 may be various types of caps with child-resistant, senior-friendly designs. In the depicted embodiment cap 400 has a first securing means 402 and a second securing means 404 . The first securing means 402 is designed to mate with the first securing means 204 of the first container 200 . The second securing means 404 is designed to mate with the first securing means 302 of the second container 300 . In the depicted embodiment, the first securing means 402 and the second securing means 404 are integrated into the cap 400 . In additional embodiments, an extension of the cap 400 may extend downwards and have the second securing means 404 integrated into the extension. The length at which the second securing means 404 extends from the interior surface 403 of the cap 400 is determined by the length of the second container 300 . The cap 400 may have various designs and sizes to allow for easier gripping, security for children, or the like know to those of ordinary skill in the art. The cap 400 may be a single element with all necessary features integrated into the unitary design. In additional embodiments, the cap 400 may be constructed out of numerous parts to create the desired functionality.
[0032] FIG. 3 depicts a section view of the container assembly 100 , in accordance with an embodiment of the present invention. The second container 300 is secured to the first container 200 and the cap 400 to keep the contents of the second container 300 separate from the first container 200 and also to secure the second container 300 so that the second container 300 is not damaged during transportation or storage. In the depicted embodiment, the first securing means 302 and the second securing means 304 of the second container 200 is a threaded style lock with the respective securing means of the cap 400 and the first container 200 . It is shown that the second container 300 is a length that allows the cap 400 to have a hollow portion where the securing means 404 inserted. In additional embodiments, the securing means 404 of the cap 400 may extend a predetermined distance into the first container 200 to reach the second container 300 . In the depicted embodiment, the
[0033] FIG. 4 depicts a cross section view of the container assembly 100 , in accordance with an embodiment of the present invention. In the depicted embodiment, the first container 200 has a main compartment 205 and the compartment 306 in a unitary design, wherein the second container 300 is integrated into the bottom surface 203 of the main compartment 205 of the first container 200 . A seal 500 is secured to the top surface 301 of the second container 300 . The cap 400 has a protrusion 405 extending downward from an internal surface 406 . The protrusion 405 is used to break the seal that is separating the compartment 306 from the main compartment 205 . Due to the seal between the cap 400 , the first container 200 and the second container 300 , the contents of the compartment 306 cannot mix with the contents of the main compartment 205 until the cap 400 is removed. The protrusion 405 is shown puncturing the seal 500 , so that when the cap 400 is removed, the contents of the compartments 205 and 306 can be mixed together at the time of removal from the container assembly 100 .
[0034] The cap 400 is secured to the first container 200 via a threaded style lock and the second container 300 is secured to the cap 400 via a pressure fit style lock. When the cap 400 is removed, the second container 300 will be removed with the cap 400 thereby releasing the contents into the first container 200 .
[0035] FIG. 5 depicts a cross section view of the container, in accordance with another embodiment of the present invention. In the depicted embodiment, the cap 400 has a compartment 407 integrated into the cap 400 , and the cap 400 is secured to the first container 200 . The cap 400 has an extended portion 408 with a securing means 409 located at an open end 410 . The compartment 407 is sealed from the main compartment 205 by a seal 500 . The first container 200 has a protrusion 210 within the internal compartment of the extension 209 , so that when the cap 400 is secured to the first container 200 and the securing means 409 is substantially secured to the first container 200 , the protrusion punctures the seal 500 . Thus because of the securing means 409 mating with the first container 200 and forming an air tight and water tight seal, the contents of the compartment 407 and the main compartment 205 will remain separate until the cap 400 is removed from the first container 200 and the contents will then mix.
[0036] In some embodiments, within the second securing means 204 is a protrusion that is designed to puncture the second container 300 or a seal that is used to cap the second container 300 . Thus, because of the seal between the first container 200 and the second container 300 the contents of the second container 300 will not be released until the cap 400 is removed with the second container 300 attached to the cap 400 .
[0037] The invention is inclusive of combinations of the embodiments or embodiments described herein. References to “a particular embodiment” or “embodiment” and the like refer to features that are present in at least one embodiment of the invention. Separate references to “an embodiment” or “particular embodiments” or “embodiments” or the like do not necessarily refer to the same embodiment or embodiments; however, such embodiments are not mutually exclusive, unless so indicated or as are readily apparent to one of skill in the art. The use of singular or plural in referring to “method” or “methods” and the like is not limiting. The word “or” is used in this disclosure in a non-exclusive sense, unless otherwise explicitly noted.
[0038] While this invention has been described in conjunction with the specific embodiments outlined above, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, the preferred embodiments of the invention, as set forth above, are intended to be illustrative, not limiting. Various changes may be made without departing from the spirit and scope of this invention. The present invention shall be easily carried out by an ordinary skilled person in the art, and any modifications and changes are deemed to be within the scope of the present invention.
[0039] This written description uses examples to disclose the invention, including the best mode, and also to enable any person skilled in the art to practice embodiments of the invention, including making and using any devices or systems and performing any incorporated methods. The patentable scope of the invention is defined by the claims, and may include other examples that occur to those skilled in the art. Such other examples are intended to be within the scope of the claims if they have structural elements that do not differ from the literal language of the claims, or if they include equivalent structural elements with insubstantial differences from the literal language of the claims.
[0040] All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.
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A multi container assembly comprising, a first container having an opening with a first securing means distal to the opening and integrated within an internal cavity of the first container and a protrusion extends upwards towards the opening and a second securing means is disposed on the protrusion, a second container wherein the first end has an opening and a first securing means distal to the opening and a second securing means distal to the second end, and a cap having a first securing means designed to mate with the first securing means of the first container and a protrusion extending downward from the internal cavity, wherein the protrusion has a second securing means designed to mate with the first securing means of the second container, wherein when the cap is secured to the first container and the second container a substantially impervious seal is formed.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention is directed to an arrangement for determining the oxygen saturation in human blood vessels and organs with a measurement sensor with at least two light sources of different wavelengths--preferably wavelengths of 660 nm and 940 nm--and with at least one receiver which receives the light transmitted and reflected from the oxygen particles which are bonded with the hemoglobin in the irradiated vessel or organ and transmits it as an electrical signal to a pulsoximeter for evaluation of the measurement results and display on a display device.
2. Description of the Related Art
It is known to determine the oxygen content of blood in human blood vessels by means of pulse oximetry. Generally, two light sources and a receiver are used for this purpose. The light sources, e.g., diodes, preferably emit light with a wavelength of 660 nm (red region) and 940 nm (infrared region). The receiver receives the emitted light waves which are reflected or transmitted from the tissue. The light received by the receiver, e.g., a photodetector, is transmitted as an electrical signal to a pulsoximeter. The pulsoximeter evaluates these signals and displays a measurement value proportional to the existing oxygen content on a display device connected with the pulsoximeter.
Catheters are introduced at the measurement site via punctures and natural body orifices in order to access the measurement point. Light guides for the light sources and the receiver are provided in the catheter and terminate at the distal end of the catheter.
Problems are known to occur when using such catheters, e.g., in right heart catheter measurement. In order to stabilize a life-threatening condition, e.g., after a heart attack, the heart function must occasionally be monitored invasively. For this purpose, due to the large diameter of the catheter, one of the large veins (subclavian or jugular vein) must be punctured by the Seldinger technique. A balloon catheter (Swan Ganz catheter) is then floated into the blood stream through this puncture. In so doing, known techniques are employed when working in the direction of the flow of blood. Puncture and the subsequent feeding of the catheter into the blood vessel may lead to damage to the vessel wall with the possibility of ongoing dissection, perforation, thrombosis, triggering of emboli, and sometimes to formation of pseudoaneurysms or arteriovenous fistulae at the puncture site itself. It is often necessary to operate in order to correct these complications.
There is a high risk of complications in both methods. Puncture and the subsequent feeding of the catheter into the blood vessel may lead to damage or perforation of the vessel wall, especially along branches and curvatures of the vessel and potentially along the vessel wall. Further, there is a risk that movement of the catheter will cause mechanical dislodging of deposits at the vessel walls which can result in thromboses and emboli.
In addition, heart irritation occurs, which can trigger cardiac arrhythmia and fibrillation when the catheter contacts the heart muscles. This fibrillation can sometimes not be brought under control therapeutically even when exercising great care. In order to avert heart failure, which is consequently at risk, electric shocks are administered to the patient in this critical state by the use of a defibrillator which cause severe physical stress aside from the disadvantageous autonomic effects.
The measurement itself requires that the catheter position not be disturbed by movement during measurement so as to rule out falsified measurement results and to ensure reproducible measurement. However, undesirable falsification of readings occurs in this method precisely in the vicinity of the beating heart, since the strong pressure fluctuations in the catheter resulting from heart activity cannot be curbed during measurement. Therefore, it is also difficult to achieve reproducibility for comparison measurements.
Although the catheter with the measuring sensor could also be introduced into the vicinity of the pulmonary artery through the esophagus, it is practically impossible to locate the pulmonary artery with the required accuracy, since the physician performing the procedure has no indication as to which of the numerous arteries containing oxygen-rich blood is to be used for the actual measurement of the oxygen content. Accordingly, it is not guaranteed that the measurement will actually be carried out at the pulmonary artery. Such measurement results do not allow the treating physician to arrive at a diagnosis with certainty and to implement appropriately informed therapy. For this reason, it is also not possible to make comparisons with other measurement results based on values drawn from medical experience.
The oxygen content of deeper vessels and organs cannot be measured externally with the known measurement sensors.
There is a substantial need for an arrangement which allows the oxygen content of blood vessels, particularly the pulmonary artery and deeper vessels or organs, to be identified with certainty and the oxygen content of the selected vessel to be measured without resorting to high-risk arterial or venous access, since this was previously done invasively.
OBJECT AND SUMMARY OF THE INVENTION
It is the primary object of the present invention to remedy this situation by providing an arrangement which makes it possible to measure the oxygen content in blood vessels without having to perform invasive procedures (puncture) on the patient and in which the region of the measurement location of the blood vessel selected for measurement can be reliably located with the entire arrangement without risk and in a reproducible manner and the measurement locations can be displayed on a display device.
This object is met according to the invention in that an additional measurement sensor is associated with the measurement sensor for locating a vessel or organ to be selected and the two measurement sensors are designed to be handled together as a constructional unit.
According to a first embodiment example of the invention, a sonography transmitter-receiver which emits ultrasonic waves is associated with the measurement sensor for locating, the emitted ultrasonic waves and the light waves from the light sources travel in substantially the same direction, and the measurement sensor and sonography transmitter-receiver are combined in a catheter forming a sensor unit.
In the invention, the measurement sensor according to the first embodiment example is combined with a sonography transmitter-receiver emitting ultrasonic waves so as to enable a precise positioning after introducing the measurement arrangement through the mouth and the pharynx into the alimentary canal.
A further advantage of the measurement sensor which is outfitted with the sonography transmitter-receiver emitting ultrasonic waves consists in the unadulterated reproducibility of the measurement results, since the measurement site can be located with certainty by means of the probe emitting ultrasonic waves and all measurements accordingly depend exclusively on the actual oxygen content of the blood in the irradiated blood vessel or organ of the patient and the measurement results are not affected by the selection of incorrect measurement sites. In addition, the arrangement according to the invention also ensures that the measurement site is monitored during the measurement.
Disadvantageous interference in the measurement of the oxygen content in the selected vessel or organ due to the beating of the heart or due to blood flow is extensively eliminated. When the arrangement is located in the esophagus, for example, during measurement, falsification of the measurement results will not occur because so-called movement artifacts are reduced.
According to another embodiment form of the invention, the light sources and the receiver are detachably connected with the sonography transmitter-receiver or the sonography transmitter-receiver is rigidly connected with the light sources and the receiver and is integrated at the distal end of the catheter carrying the pulse oximetry sensor.
According to a second embodiment example, deeper vessels can also be specifically selected and their oxygen content can be measured in that the measurement sensor has two beam paths of two light-generating and light-transmitting systems, which beam paths are swivelable at an angle to a vertical axis, and the systems intersect at a point on the vertical axis and at least one shared receiver is associated with these two systems.
For this purpose, each light-generating and light-conducting system advantageously comprises, within a tube, an objective lens, collimating objective lenses, and light sources which can be adjusted and fixed relative to one another. The tube has a hinge joint in the region of the objective lens and the receivers are arranged parallel to the vertical axis in a receiver housing having hinge joints which are arranged symmetrically with respect to the vertical axis. A system generating and conducting red light and a system generating and conducting infrared light are supported in the respective hinge joint of the receiver housing so as to be swivelable relative to the vertical axis and can be adjusted at an angle to the vertical axis by adjusting means and fixed by clamping means. Finally, a flexible cover for screening out extraneous light is associated with the light-generating and light-conducting systems and with the receivers.
When measuring the oxygen saturation with this embodiment form of the invention, which can be done from any point on the body, invasive procedures are avoided so that physical and psychic side-effects on the patient are substantially reduced. Other risk factors such as heart irritation or perforations are avoided by the arrangement according to the invention.
Additional features of the invention are indicated in the subclaims.
The invention is described in the following with reference to three embodiment examples which are shown more or less schematically in the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the arrangement according to the invention with a measurement sensor for intraesophageal application;
FIG. 2 shows a section through a second embodiment example of the invention, according to FIG. 1, with two light-emitting diodes, a receiver, and a sonography transmitter-receiver placed thereon which are associated with the common distal end of a catheter;
FIG. 3 shows a section through a third embodiment example of the invention, according to FIG. 1, with the same component parts as in FIG. 1, but with an integral construction comprising the measurement sensor and the sonography transmitter-receiver at the distal end of the catheter; and
FIG. 4 shows the arrangement according to the invention with a measurement sensor for external application.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
FIG. 1 shows a flexible catheter 5, known per se in medical science, which is provided with a measurement sensor MS, to be described hereinafter, and which is shown introduced into the human alimentary canal 20. The measurement sensor MS is only shown schematically and is located in the illustrated position at an intraesophageal measurement site 21.
Arranged in the catheter 5 are means, known per se and not shown in the drawing, by which the distal end of the catheter 5 can be guided and positioned when the treating physician introduces the catheter into the alimentary canal 20 of a patient externally, e.g., in order to determine the oxygen content in the pulmonary artery.
As is shown in FIG. 3, the catheter 5 has at the distal end 6 at least two photodiodes 9 and 10 emitting different wavelengths. Photodiode 9 preferably radiates light with a wavelength of 660 nm (red region) and photodiode 10 preferably emits light with a wavelength of 940 nm (infrared region). These different light sources are activated simultaneously or alternately at predetermined time intervals by switching means, not shown, which are arranged in a pulsoximeter 15.
At least one receiver 11, which is likewise arranged at the distal end 6 of the catheter 5, receives the light reflected from the irradiated blood vessel or organ and transmits the light signal outward as a corresponding electrical signal to the pulsoximeter 15 via lines which are accommodated in the catheter 5. Measurement values which are proportional to the oxygen content present at the measurement location in the blood vessel are then calculated from these signals in a known manner in the pulsoximeter 15 and are displayed on a display device 19.
As is well-known, the emitted light is absorbed to varying degrees depending on the oxygen content in the hemoglobin particles contained in the blood flowing through the blood vessel. Hemoglobin particles are either oxygenated or low in oxygen.
Thus, if the hemoglobin particles occurring in the blood are irradiated by two or more different frequencies emitted alternately or simultaneously, the hemoglobin particles absorb the different light wavelengths differently depending on the oxygen content present and a measurable absorption difference will occur, from which the oxygen saturation of the blood at the measurement site can be calculated.
A sonography transmitter-receiver DS is associated with the distal end 6 of the catheter 5 as is shown in FIG. 3. The sonography transmitter-receiver DS is detachably connected as a removable unit 14 with the distal end 6 of the catheter 5 which is formed of a suitable carrier material The connection between the removable unit 14 and the distal end 6 of the catheter 5 is effected by means of springing clamping plates 16 which are arranged at the catheter or unit 14 and which hold the unit 14 and ensure a secure but detachable connection when connected. The sonography transmitter-receiver DS is so arranged in the region of the distal end of the catheter that the radiation is emitted radially.
When introduced into a natural body orifice, e.g., into the esophagus 20, the positioning of the pulse oximetry sensor MS is effected via the sonography transmitter-receiver DS. The measurement site at which the measurement is carried out is selected by means of the sonography transmitter-receiver DS and the oxygen saturation is then recorded by the pulsoximeter sensor MS in the region of the measurement site and displayed on the display device. The measurement site can be a blood vessel or an organ.
Due to the radial alignment, the ultrasonic waves emitted by the sonography transmitter-receiver DS travel in the same direction toward the axes of the emission maxima of the photodiodes 9 and 10.
The reflection signals of the sonography transmitter-receiver DS are transmitted in a known manner through the catheter 5 to a sonography device 17 so that the ultrasonic waves also send a signal which is displayable on the monitor (not shown) of the sonography device during the actual measurement of the oxygen content in a blood vessel or organ. The treating physician can ensure at all times that the measurement position is maintained during measurement by observing the externally displayed measurement signal.
The embodiment example according to FIGS. 2 and 3 likewise shows a measurement sensor MS and a sonography transmitter-receiver DS at the distal end 6 of a catheter 5. In contrast to the embodiment example according to FIG. 3, the sonography transmitter-receiver DS is integrated in the distal end 6 of the catheter 5, that is, it is connected with the catheter 5 in a stationary manner.
A measurement site can also be located by means of differential pressure spectra of a pressure measurement probe which is connected with the measurement sensor of the sensor unit in place of a sonography transmitter-receiver.
Another embodiment form of the measurement sensor MS for external, noninvasive measurement of the oxygen content of deeper measurement locations is shown in FIG. 4. A receiver housing 32 has hinge joints 33 and 33' which are arranged at a distance from one another eccentrically and symmetrically with respect to the vertical axis y and in which a tube 31 and 31' is supported so as to be swivelable with respect to the vertical axis.
Brackets 34 and 34' in which threaded nuts 35 and 36 are supported in an articulated manner are provided at every tube at the ends located opposite to the hinge joints 33 and 33'. The threaded nuts 35 and 36 have left-handed and right-handed threads, respectively, in which the threaded spindles 37 and 38 of an adjusting screw 39 engage for the purpose of changing the angular position of the tubes relative to one another.
The tube 31 which is shown in section in FIG. 4 has, in the region of the hinge joint 33, an objective lens 50 formed of a plano-concave lens 51 arranged at the outlet ends of the tube 31 and a piano-convex lens 52 of greater diameter situated deeper inside the tube 31. The plano-sides of the plano-concave lens 51 and the plano-convex lens 52 face one another and are arranged in an adjustable mounting in the tube 31. On the convex side of the plano-convex lens 52, at least two collimating objective lenses 60 and 61 are held, likewise in an adjustable mounting, in an eccentric arrangement with respect to the optical axis of the objective lens 50. A red light source 70 is associated with the optical axis of the collimating objective lens 60 and a second red light source 71 is associated with the optical axis of the collimating objective lens 61 such that there is a telecentric beam path between the collimating objective lenses 60 and 61 and the imaging objective lens 50. The objective lens unites the beam paths of the collimator objective lenses 60 and 61 and images these beam paths collinearly to infinity. The tube 31' contains the same optical arrangement as the tube 31 described above, but infrared light sources are provided as light sources. Each tube 31 and 31' forms a light-generating and light-transmitting system for red light or infrared light.
A flexible cover 30 of opaque material is associated with the exit openings of the light-generating and light-conducting systems and the entrance opening of the receiver housing in order to screen out extraneous light.
Receivers 80 of suitable spectral sensitivity whose sensitive maxima are aligned approximately parallel to the vertical axis y are provided in the receiver housing 32 eccentrically with respect to the vertical axis y.
The beam bundles which are emitted by the light sources 70 and 71 and projected by the collimators 60 and 61 and the objective lens 50 of each tube 31 and 31', which is swiveled at the same angle alpha to the vertical axis, intersect the downward lengthening of vertical axis y at intersection point SP. By adjusting the adjusting screw 39, the angle of the beam paths of the two light-generating and light-transmitting systems can be adjusted in such a way that the intersection point of the two beam paths is adjustable along the vertical axis y.
In order to measure the oxygen content of a blood vessel situated deeper in the tissue or an organ, the arrangement is placed with the long side of the cover flat against the skin so that the intersection point SP lies in the tissue.
The receivers 80 detect the reflected component of light from the two light-generating and light-transmitting systems and transmit this component as an electrical signal to the pulsoximeter.
By turning the adjusting screw, the intersection point SP along the vertical axis y can be localized on a blood vessel B or organ lying in this region and the oxygen saturation can be measured. The threaded spindles can also be driven by a motor-operated actuating element, e.g., a program-controlled stepper motor, which can be actuated or controlled from a control panel in order to automate the process of locating a measurement site. In a miniaturized version, a piezoelectric actuator can also produce the swiveling movement of the light-generating and light-conducting system.
The tubes 31 and 31' of the light-generating and light-conducting systems can be fixed in the adjusted position by a fastening device 40. The fastening device 40 is formed of two clips 41 and 41', one end of each clip 41 and 41' being connected with the tubes 31 and 31', respectively, in an articulated manner. The clips 41 and 41' are provided with graduated scales and have slots 42 and 42' in which a clamping screw 43 with a corresponding lock nut is arranged.
A sonography transmitter-receiver DS, which is not shown in FIG. 4 for the sake of clarity, can be associated with the measurement sensor MS in accordance with the embodiment examples shown in FIGS. 1, 2 and 3, its radiation direction being arranged with reference to the vertical axis.
While the foregoing description and drawings represent the present invention, it will be obvious to those skilled in the art that various changes may be made therein without departing from the true spirit and scope of the present invention.
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Arrangement for determining the oxygen saturation in human blood vessels and organs with a measurement sensor with at least two light sources of different wavelengths--preferably wavelengths of 660 nm and 940 nm--and with at least one receiver which receives the light transmitted and reflected from the oxygen particles which are bonded with the hemoglobin in the irradiated vessel or organ and transmits it as an electrical signal to a pulsoximeter for evaluation of the measurement results and readout on a display device. An additional measurement sensor is associated with the measurement sensor for locating a blood vessel or organ to be selected and the two measurement sensors are designed such that they can be handled together as a constructional unit.
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CROSS-REFERENCE TO A RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional Patent Application No. 61/388,400 filed on Sep. 30, 2010, the entire contents of which is hereby incorporated herein by this reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to garments and more particularly to hair covers used to protect a wearer's hair while sleeping.
BACKGROUND
[0003] The fundamental purpose underlying existing hair covers or sleeping caps is to protect a wearer's hair while the wearer is sleeping. Hair covers can be found in various shapes, sizes, and materials to provide such protection. Unfortunately, existing hair covers lack other important features because those features are at odds with the fundamental purpose of protecting a wearer's hair. One such feature is environmental friendliness. Consumers are increasingly looking for green products. Existing hair covers, particularly those manufactured from highly regarded silk or satin materials, are not biodegradable and thus are considered harmful to the environment after they are no longer usable and they are thrown away. Compounding this problem is the fact that many hair covers lack durability. For example, many silk hair covers cannot be washed, and hair covers manufactured from other materials known to provide a high level of protection to the wearer's hair can lose their integrity if washed too often or incorrectly. Therefore, dirt, grime, oils, and greases can accumulate on the hair cover and require replacement before the hair cover otherwise loses its ability to protect.
[0004] Moreover, existing hair covers are not well adapted to deal with the growing trend of wearers having long braided hair, natural and synthetic, with a V-shaped body. Many existing hair covers, such as one disclosed in U.S. Pat. No. 6,948,190, have a straight edged bottom and thus offer little or no support for the edges along the V-shape. Therefore, a durable hair cover that protects a wearer's hair and the environment and meets the growing trend of long, braided hair having a V-shaped body is desirable.
SUMMARY
[0005] Certain aspects and embodiments of a hair cover for protecting a wearer's hair while sleeping are described. In one aspect, an upper fabric chamber having a generally domed shape is positioned on a wearer's head. A lower fabric chamber depends from the upper fabric chamber and includes a generally V-shaped pocket for receiving and protecting a generally V-shaped body of hair. The upper fabric chamber has an elastic band secured to the periphery of an opening in the upper fabric chamber with a fastener such that the fastener does not contact the hair.
[0006] In another aspect, a method for making a hair cover is described. A fabric used to make a hair cover includes an upper fabric portion used to form the upper fabric chamber and a lower fabric portion used to form the lower fabric chamber. The lower fabric portion depends from the upper fabric portion. The lower fabric portion includes a left portion, a right portion that mirrors the left portion, and a flap located centric to the left portion and the right portion formed by cutting away a section of the lower fabric portion. An opening in the upper fabric chamber is formed by securing a first straight edge of the left portion to a second straight edge of the right portion. A pocket in the lower fabric chamber is formed by securing a first curved edge of the left portion to a first side of the flap and by securing a second curved edge of the right portion to a second side of the flap. An elastic band is secured along the outer surface of the periphery of the opening in the upper fabric chamber with a fastener.
[0007] These illustrative aspects and embodiments are mentioned not to limit or define the invention, but to provide examples to aid understanding of the inventive concepts disclosed in this application. Other aspects, advantages, and features of the present invention will become apparent after review of the entire application.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a profile view of a hair cover depicting an opening in the upper fabric chamber.
[0009] FIG. 2 is a profile view of the hair cover shown at a different angle than that shown in FIG. 1 .
[0010] FIG. 3 is a top view of the hair cover depicting the upper fabric chamber.
[0011] FIG. 4 is a bottom view of the hair cover depicting the opening in the upper fabric chamber.
[0012] FIG. 5 is a front view of the hair cover depicting the opening in the upper fabric chamber.
[0013] FIG. 6 is a rear view of the hair cover.
[0014] FIG. 7 is an illustration of a fabric used to make the hair cover.
[0015] FIG. 8 is an illustration of a band that attaches to the periphery of the opening in the upper fabric chamber.
DETAILED DESCRIPTION
[0016] An exemplary hair cover 10 has an upper fabric chamber 20 , a lower fabric chamber 30 , and an elastic band 12 , as shown in FIG. 1 . The lower fabric chamber 30 can depend from the upper fabric chamber 20 to form one contiguous hair cover 10 . Dotted line 24 represents a virtual separation of the upper fabric chamber 20 and the lower fabric chamber 30 . The lower fabric chamber 30 is comprised of a left portion 715 , a right portion 720 , and a flap 725 , as shown in FIG. 7 .
[0017] The portions of the hair cover 10 can cooperate with one another such that they can be secured together using a fastener. “Secured,” “secured to,” or generally the act of securing can mean attaching, joining, coupling, or binding portions of the hair cover 10 to one another. Examples of various fasteners that can be used to secure the portions are stitches, staples, glue, and tape.
[0018] FIGS. 1-4 depict an upper fabric chamber 20 having a generally domed shape for securing a wearer's hair. The upper fabric chamber 20 can adjust according to the shape and size of a wearer's head and the amount of hair thereon. The upper fabric chamber 20 can include an opening 25 for receiving the wearer's head and hair. The opening 25 can have a diameter of approximately 15.75 inches according to an exemplary embodiment.
[0019] The elastic band 12 can be secured to a periphery along the opening 25 to expand and contract the opening 25 to receive and secure heads of various sizes. In an exemplary embodiment, the wearer's hair can be tucked into the lower fabric chamber 30 by the wearer pulling at least a portion of the band 12 away from the wearer's head to create a gap, while at least another portion of the band 12 is secured to the wearer's head. In another embodiment, the opening 25 can be pulled apart with the wearer's hands first to receive the wearer's hair and thereafter to receive the wearer's head. An exemplary configuration has an elastic band 12 with a length of about 25.5 inches and a width of about 2.5 inches to provide such flexibility and interaction with the opening 25 .
[0020] In one embodiment, the elastic band 12 can be manufactured by folding the band 80 shown in FIG. 8 along a longitudinal center line of the band to create a left side and a right side of the band. An elastic material can be inserted between the left side and the right side of the band. The edges of the band can be secured by a fastener to enclose the elastic material within the band. As shown in FIGS. 1 and 2 , the elastic band 12 can have a stitched line 16 that spans the length of the elastic band 12 to create ruffles in the band. An upper ruffled portion 14 and a lower ruffled portion 18 can be used to grip the wearer's head. According to one embodiment, the elastic material can be inserted into the upper ruffled portion 14 and/or the lower ruffled portion 18 . Similarly, in another embodiment, a drawstring can be inserted into the upper ruffled portion 14 and/or the lower ruffled portion 18 to tighten or loosen the band 12 around the wearer's head. Still in another embodiment, a drawstring can be used in conjunction with an elastic material. Under such a configuration, the elastic material can be inserted into either the upper or lower ruffled portion while the drawstring can be inserted into the opposite portion to provide, for example, additional security, adjustability, and comfort along the wearer's head. In embodiments in which a drawstring is used, the band 80 can comprise one or more openings through which ends of the drawstring can extend to be adjusted by a wearer's hands.
[0021] The elastic band 12 can be secured to the periphery of the opening 25 with a fastener such that the fastener does not come in contact with the hair, thereby preventing hair breakage, or the separation of the hair from the head, where the elastic band 12 contacts the wearer's head. In one embodiment, the fastener is secured to the outer surface 32 instead of the inner surface 31 (as shown in FIG. 1 ) so that the fastener does not contact the wearer's head. In an exemplary embodiment, stitches are used to secure the band 12 to the periphery of the opening 25 .
[0022] FIGS. 1 , 2 , 5 and 6 depict a lower fabric chamber 30 . In one embodiment, the lower fabric chamber 30 is elongated, or extends downward or otherwise outward to a distance away from the upper fabric chamber 20 . Such a distance is represented by the length 50 in the figures. A longer or shorter version of the hair cover 10 may be created by increasing or decreasing the length 50 of the lower fabric chamber 30 . Such a modification can enable the lower fabric chamber 30 to receive and protect hair of varying lengths.
[0023] The lower fabric chamber 30 can include a pocket 55 . Horizontal line 34 , as shown in FIGS. 5 and 6 , represents a virtual demarcation of an edge of the pocket 55 within the lower fabric chamber 30 . In one embodiment, the pocket 55 has a generally V-shape for receiving a generally V-shaped body of hair. The V-shape of the pocket 55 can be a shape where the length of a cross section of the pocket 55 decreases while traversing in a direction away from the upper fabric portion 705 . The length of the cross section can decrease by a greater amount when measured closer to the bottom of the pocket 55 such that the pocket 55 can have a rounded edge at point 742 where a first side 740 meets a second side 744 , as shown in FIG. 7 . The first side 740 and the second side 744 of the flap 725 can have a flatter or steeper angle to compress or expand the general V-shape of the pocket 55 .
[0024] The V-shaped pocket 55 can be especially suitable for relatively long hair that is braided so that the edges of the hair form a V-shape. Other braided hair styles such as synthetic hair extensions can have a V-shape by design. The pocket 55 can also receive and protect hair of various other types, shapes, and sizes, or can itself have various shapes and sizes for receiving and protecting the wearer's hair.
[0025] As shown in FIG. 7 , the fabric 700 can be used to make the hair cover 10 of FIGS. 5 and 6 . The upper fabric portion 705 can meet the lower fabric portion 710 at point 730 along the left side of the fabric 700 and at point 732 along the right side of the fabric 700 . Horizontal line 704 represents a virtual separation of the upper fabric portion 705 and the lower fabric portion 710 . The upper fabric portion 705 can include a central arc 750 that is connected to a lower left arc 754 by a left straight edge 753 along the left side of the fabric 700 . Along the right side of the fabric 700 , the central arc 750 can be connected to a lower right arc 756 by a right straight edge 755 . The arcs and straight edges can form the periphery of the opening 25 in the upper fabric chamber 20 ( FIG. 5 ).
[0026] The lower fabric portion 710 can include a left portion 715 , a right portion 720 , and a flap 725 . A section of the lower fabric portion 710 can be cut away or removed to form a generally V-shaped flap 725 located centric to the left portion 715 and the right portion 720 . The right portion 720 can mirror the left portion 715 . The left portion 715 can have a first curved edge 738 for cooperating with a first side 740 of the flap 725 . The right portion 720 can have a second curved edge 746 for cooperating with a second side 744 of the flap. Cutting away the section of the fabric can leave a gap between the left portion 715 and the flap 725 whereby the gap increases while traversing along the first curved edge 715 in a direction away from the upper fabric portion 705 . A similar gap can exist between the right portion 720 and the flap 725 . The left portion 715 can have a first straight edge 736 joined at an angle to the curved edge 738 . Similarly, the right portion 720 can have a second straight edge 748 joined at an angle to the second curved edge 746 .
[0027] In an exemplary embodiment, the fabric 700 can be approximately 30.75 inches long along a longitudinal center line of the fabric 700 and at least 15 inches wide across the broadest portion of the fabric portion 710 . The flap 725 can have a length of approximately 7.5 inches along a longitudinal center line, while the left portion 715 and the right portion 720 can have a length of approximately 13.25 inches across its longest cross section. Such a design requires relatively few stitches, which can reduce the amount of time required to manufacture the hair cover 10 .
[0028] The fabric 700 can be used to manufacture the hair cover 10 . According to one embodiment, the pocket 55 in the lower fabric chamber 30 ( FIGS. 5 and 6 ) can be formed by securing the first curved edge 738 of the left portion 715 to the first side 740 of the flap 725 , and by securing the second curved portion 746 of the right portion 720 to the second side 744 of the flap 725 . The opening in the upper fabric chamber 20 can be formed by securing the first straight edge 736 of the left portion 715 to the second straight edge 748 of the right portion 720 .
[0029] An exemplary embodiment of the hair cover 10 can protect a wearer's hair while being both durable and environmentally friendly. For example, the hair cover 10 can be manufactured from a biodegradable, cotton sateen fabric. Furthermore, cotton sateen can be gentle enough to protect a wearer's hair while being durable enough to endure regular washings by hand, washing machine, or other cleaning apparatuses without losing its integrity. Other types of biodegradable materials that are washable by hand or machine can be used in other embodiments.
[0030] It should be understood that the foregoing relates only to certain embodiments of the invention, which are presented by way of example rather than limitation. Numerous changes may be made to the embodiments described herein without departing from the spirit and scope of the invention. Many other modifications, features, and embodiments of the present invention will become evident to those of skill in the art. For example, the hair cover 10 , and the portions used to manufacture it, can comprise various shapes, sizes, and materials. The hair cover 10 can also receive various amounts, shapes, and types of hair. Various sizes and shapes of the fabric 700 and its portions can be used to manufacture the hair cover 10 . For example, the left portion 715 and the right portion 720 can have fewer or more curved or straight edges. Additionally, the flap 725 can have a different size, shape, and orientation with the left portion 715 and the right portion 720 .
[0031] Furthermore, various embodiments described herein use terms such as “left,” “right,” “upper,” and “lower.” These terms are used merely for convenience and should not limit the orientation of any portion forming or within the hair cover 10 . For example, a “right” portion can be located on the “left” side of the fabric 700 , depending on the orientation of the fabric 700 .
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A hair cover for protecting a wearer's v-shaped hairdo while sleeping having two fabric chambers, one dome-shaped and the other v-shaped.
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GOVERNMENT INTEREST
[0001] The invention described herein may be manufactured, used, and/or licensed by or for the United States Government.
FIELD OF THE INVENTION
[0002] This invention relates generally to desulfurization and more specifically, the invention relates to the removal of hydrogen sulfide at high temperatures.
BACKGROUND OF THE INVENTION
[0003] The military in the 21 st Century needs a more responsive, more versatile, more lethal, more survivable, and more sustainable force. This modern military force will require more electric power that is available in theater any where any time. At the same time, it is beneficial to use materials which reduce the load (by weight) that needs to be carried into the battlefield for ease of mobility and to reduce transportation requirements.
[0004] Currently the military depends on its logistics fuel, JP-8, a kerosene based jet fuel which has the highest energy density as energy source, to meet most of the power needs in battlefield. Since the fuel consumption has been increased more than ten fold over the last half century by the Army during war time, the reduction of logistics burden is in urgent need and development of advance energy conversion technology is highly desirable to meet the great power demand in today's battlefield.
[0005] Fossil fuels, such as petroleum based logistics fuel and abundant coal, usually contain sulfur impurities. Power generation processes from fossil fuels in most cases will produce some form of sulfur compounds as by-product(s). This sulfur containing by-product(s) is not only detrimental to the function of electrochemical device such as fuel cell, but is also environmentally unfriendly. Effective and efficient removal of sulfur by-product(s) from fuel stream is an essential step for any type of fossil fuel based power generation system that requires zero or near zero level of sulfur compound(s) in the consumed fuel.
[0006] One way to achieve the goal is to develop a capability to effectively and efficiently convert JP-8 to electricity so that overall fuel consumption can be reduced. Fuel cell generation of electricity in battlefield directly by JP-8 through fuel reformation is a promising technology currently under intense development. As mentioned above, sulfur impurities must be removed from the fuel stream before feeding to fuel cells and desulfurization is one of the crucial steps that may enable the advanced technology for electricity generation by hydrocarbon fuel in battlefield. Materials used in the desulfurization component require (a) a high capacity to adsorb as much as possible of hydrogen sulfide molecule per unit weight; and (b) stable and functioning at temperature as close as to the operating temperature of both the fuel reformer and the fuel cells, that is, 600 to 800° C. Zinc oxide based sorbent materials are widely used for desulfurization including hydrogen sulfide removal. Unfortunately, they are only suitable for applications at below 600° C. in reducing atmosphere such as hydrogen rich reformate and in presence of water vapor that is one of the products in the hydrocarbon fuel reformate.
[0007] JP-8 is merely an example of a type of fuel for which the present invention may be utilized. Other examples include types of fossil fuels such as diesel fuel and gasified coal.
SUMMARY OF THE INVENTION
[0008] The present invention is directed to utilizing metal oxides in a more efficient manner for the purification of gases. For example, lanthanum oxide and calcium oxide have different chemical properties with respect to the reaction with hydrogen sulfide to form lanthanum sulfide and calcium sulfide, respectively. Lanthanum metal reacts with sulfur more favorably (−141 kcal/mol for lanthanum) than calcium metal (−79.2 kcal/mol for calcium). On the other hand, lanthanum oxide has less capacity (98 mg S/g) than calcium oxide (571 mg S/g) to adsorb sulfur. An embodiment of the present invention takes advantage of the higher desulfurization capacity of calcium oxide and the more favorable sulfide formation reaction of lanthanum oxide in such a way that the overall desulfurization performance has been significantly improved than using any one of them alone, on the same weight basis. Particularly, in accordance with the principles of this invention, calcium oxide was placed to be contacted with incoming reformate gases first and in relatively large quantity for its high capacity; and lanthanum oxide was placed second in a separate, individual filtration stage so that it was contacted with the reformate gases that were already largely desulfurized by calcium oxide. The favorable sulfide formation between lanthanum oxide and hydrogen sulfide will then allow all the remaining hydrogen sulfide in the gas stream with lower level of sulfur content after calcium oxide to be reduced to basically zero level. Although in the exemplary embodiment, each of the calcium oxide and lanthanum oxide layers are separated by that enclosure 11 , one of ordinary skill in the art would appreciate that the material used as the separation/support layer 13 between the bi-layers could be eliminated without departing from the principles of the present invention. Also, the space between elements 13 and 14 could be eliminated without departing from the principles of the present invention.
[0009] An exemplary use of a preferred embodiment is the generation of electricity by fuel cells with JP-8 fuel, where the hydrocarbon molecules in the fuel have to be first converted to hydrogen gas and carbon monoxide gas in a device that called fuel reformer which operates at 800° C. to 1000° C. The operating temperature of the fuel cells is optimally in a range of 600 to 800° C. for the so-called fuel reformate (a gas mixture rich in hydrogen with some amount of carbon monoxide). A desulfurization component may need be placed in between the fuel reformer and the fuel cell to clean the fuel reformate to remove sulfur impurities, specifically, hydrogen sulfide molecule.
[0010] Materials used in the desulfurization component, require (a) a high capacity to adsorb as much as possible of hydrogen sulfide molecule per unit weight; and (b) stable and functioning at temperature as close as to the operating temperature of both the fuel reformer and the fuel cells, that is, 600 to 800° C. Lanthanum oxide and calcium oxide are two high temperature hydrogen sulfide sorbents that are both stable and functioning at 600 to 800° C. In a preferred embodiment resembling that depicted in FIG. 1A , the experimental results of a bi-layer assembly of calcium oxide and lanthanum oxide was about 4 times better than lanthanum oxide or calcium oxide individually; the performance being measured by the duration time of complete removal of hydrogen sulfide from the fuel stream by the sorbent materials based on the per unit weight.
[0011] A preferred embodiment effectively adsorbs hydrogen sulfide from hydrogen rich stream in presence of water and at temperature range of 600° C. to 800° C.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] The present invention can best be understood when reading the following specification with reference to the accompanying drawings, which are incorporated in and form a part of the specification, illustrate alternate embodiments of the present invention, and together with the description, serve to explain the principles of the invention. In the drawings:
[0013] FIG. 1A is a schematic illustration of an exemplary bi-layer sorbent assembly 10 .
[0014] FIG. 1B is a schematic illustrating the top view of assembly 10 .
[0015] FIG. 2 graphically illustrates experimentally derived desulfurization results of CaO, La 2 O 3 , and a preferred embodiment sorbent assembly combination where incoming H 2 S is 420 ppm and the total amount of the sorbent material in each case is 0.3 g.
[0016] FIG. 3 graphically illustrates experimentally derived desulfurization results of the same amount of CaO (0.2 g) and La 2 O 3 (0.2 g) combined or positioned in different ways in the assembly 10 at 600° C. where the incoming H 2 S was 420 ppm.
[0017] FIG. 4 graphically illustrates experimentally derived desulfurization results of CaO (first layer) and La 2 O 3 (second layer) in the assembly 10 with different ratio of CaO to La 2 O 3 at 600° C. Graphical line A correlating to 0.35 g CaO and 0.05 g La 2 O 3 . Graphical line B correlating to 0.3 g CaO and 0.1 g La 2 O 3 . Graphical line C correlating to 0.2 g CaO and 0.2 g La 2 O 3 .
[0018] FIG. 5 illustrates experimentally derived desulfurization results at 500° C., with graphical line A correlating to the results from using 0.3 g La 2 O 3 only, and graphical line B correlating to the results from using 0.2 g CaO (first layer) and 0.1 g La 2 O 3 (second layer).
[0019] FIG. 6 graphically illustrates experimentally derived desulfurization results at 700° C. using 0.3 g La 2 O 3 only (line A) and 0.1 g CaO (first layer) and 0.2 g La 2 O 3 (second layer) (line B).
[0020] FIG. 7 graphically illustrates the experimentally derived desulfurization results at 800° C. A: 0.3 g La 2 O 3 only; B: 0.1 g CaO (first layer) and 0.2 g La 2 O 3 (second layer).
[0021] FIG. 8 is a graphical illustration depicting the experimental results obtained by varying the weight ratio of CaO to La 2 O 3 (using a total of 0.2 gram) with incoming H 2 S concentration of 820 ppm at 600° C.
[0022] FIG. 9 is a graphical illustration depicting the experimental results obtained by varying the weight ratio of CaO to La 2 O 3 from 1:0 to 0:1 (using a total of 0.2 gram) with incoming H 2 S concentration of 820 ppm at 600° C.
[0023] A more complete appreciation of the invention will be readily obtained by reference to the following Description of the Preferred Embodiments and the accompanying drawings in which like numerals in different figures represent the same structures or elements. The representations in each of the figures are diagrammatic and no attempt is made to indicate actual scales or precise ratios. Proportional relationships are shown as approximates.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0024] The present invention now will be described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. However, this invention should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. In the drawings, the thickness of layers and regions may be exaggerated for clarity. Like numbers refer to like elements throughout. As used herein the term “and/or” includes any and all combinations of one or more of the associated listed items.
[0025] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the full scope of the invention. As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms “comprises” and/or “comprising,” when used in this specification, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof.
[0026] It will be understood that, although the terms first, second, etc. may be used herein to describe various elements, components, regions, layers and/or sections, these elements, components, regions, layers and/or sections should not be limited by these terms. These terms are only used to distinguish one element, component, region, layer or section from another region, layer or section. Thus, a first element, component, region, layer or section discussed below could be termed a second element, component, region, layer or section without departing from the teachings of the present invention.
[0027] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein.
[0028] A preferred embodiment of the present invention comprises apparatus and methodology directed to the making a combination of lanthanum oxide and calcium oxide as desulfurization sorbent assembly that results in significant increase of effective removal of hydrogen sulfide, that is, the increased duration time of complete removal of hydrogen sulfide from the fuel gas stream by the sorbent materials based on the per unit weight. In this case, hydrogen sulfide in the treated fuel gas stream remained virtually at zero parts per million (ppm) level with several hundred ppm in the incoming untreated fuel gas stream, in comparison to the case that either lanthanum oxide is used alone, or calcium oxide used alone, on the basis of the same weight of the sorbent materials applied.
[0029] As an exemplary use, a desulfurization assembly constructed in accordance with the principles of the present invention may be used in a power generation system employing fuel reformer and fuel cell to produce electricity with fossil fuels such as JP-8. The assembly serves the purpose of removing hydrogen sulfide molecule in the reformate before it is sent to the fuel cell. Two layers of sorbent materials, each of which consists of a particular metal oxide, calcium oxide and lanthanum oxide, are used in the assembly in particular order and in particular amount with each other. The desulfurization assembly may operate at 600° C. to 800° C. Because the fuel cell may be carried by a person or weight-sensitive vehicle over miles of terrain, the weight of the desulfurization assembly is optimally reduced by using a combination of calcium oxide and lanthanum oxide in predetermined ratios (by weight) in order that the overall weight is reduced while maintained an output that is substantially free of hydrogen sulfide.
[0030] FIG. 1A is a schematic illustration of an exemplary bi-layer sorbent assembly. Assembly 10 comprises an enclosure 11 having two layers 12 , 14 of sorbent materials in the assembly and the gas flow direction, may for example, flow from the top of the assembly 10 to the bottom as shown in FIG. 1A . As used herein the terminology “enclosure” includes a partial enclosure having an inlet 16 and an outlet 17 , and includes configurations such as a cylinder, vessel, chamber, container, receptacle, or pipe. The enclosure 11 may be in the form of a cylinder in which a continuous wall is formed on both the right and left sides as seen in FIG. 1B . Alternately, the enclosure may comprise first and second walls 18 A and 18 B. A variety of cross-sectional forms can be used to form the passage for the flow of gas, including rectangular, oval, square, triangular, etc. The first layer 12 is calcium oxide and the second layer 14 is lanthanum oxide. The first and the second may be separated by inert porous material layers 13 and 15 . The calcium oxide and lanthanum oxide were positioned as shown in FIG. 1A along a common axis with the reformate gases fed successively through calcium oxide first and then lanthanum oxide next in an axial direction through the sorbent assembly vertically from the top to the bottom of the assembly, as shown in FIG. 1A . It can be readily appreciated by those of ordinary skill in the art that other filter configurations may be utilized such as a cylindrical arrangement of two layers of the oxides where the first layer 12 is used as the inner layer and the second layer 14 is as the outer layer with the gas coming into the inner cylinder and passing radially through the first inner cylindrical layer followed by passing through the second outer cylindrical layer.
[0031] The working principle is described as follows based on the fundamental properties of the two metal oxides. As used herein, the stoichiometrical capacity is the theoretical value of the amount of sulfur molecule in milligram (mg) that can be adsorbed on one gram sorbent oxide. The ΔH(298) correlates to the enthalpy value at 298K (25° C.) of a chemical reaction measured in heat released in kilo-calorie per mole of reacted molecule.
[0000] CaO+H 2 S---->CaS+H 2 O [Equation 1]
[0032] Stoichiometrical Capacity: 571 mg S/g
[0000] Ca (g)+S (g)---->CaS (g) [Equation 1A]
[0033] ΔH(298): −79.2 kcal/mol
[0000] La 2 O 3 +H 2 S---->La2O2S+H2O [Equation 2]
[0034] Stoichiometrical Capacity: 98 mg S/g
[0000] La (g)+S (g)---->LaS (g) [Equation 2A]
[0035] ΔH(298): −141 kcal/mol
[0036] As seen from the above, lanthanum and calcium should have different chemical properties with respect to the reaction to form lanthanum sulfide and calcium sulfide, respectively. Based on the above known data, we expect that lanthanum oxide reacts with sulfur more favorably (−141 kcal/mol for lanthanum metal) than calcium oxide (−79.2 kcal/mol for calcium metal). On the other hand, lanthanum oxide has less capacity (98 mg S/g) than calcium oxide (571 mg S/g) to adsorb sulfur. An embodiment of the present invention takes advantage of the higher desulfurization capacity of calcium oxide and the more favorable sulfide formation reaction of lanthanum oxide in such a way that the overall desulfurization performance has been significantly improved than using any one of them alone, on the same weight basis. Particularly, in accordance with the principles of this invention, calcium oxide was placed to be contacted with reformate gases first and in relatively large quantity for its high capacity; and lanthanum oxide was placed second in a separate, individual filtration stage so that it was contacted with the reformate gases that were already largely desulfurized by calcium oxide. The favorable sulfide formation between lanthanum oxide and hydrogen sulfide will then allow all the remaining hydrogen sulfide in the gas stream with lower level of sulfur content after calcium oxide to be reduced to basically zero level. Although in the exemplary embodiment, each of the calcium oxide and lanthanum oxide layers are separated by the wall 11 , one of ordinary skill in the art would appreciate that the material used as the separation/support layer 13 between the bi-layers could be eliminated without departing from the principles of the present invention. Also, the space between elements 13 and 14 could be eliminated without departing from the principles of the present invention.
[0037] FIG. 2 graphically illustrates desulfurization results of CaO, La 2 O 3 , and a preferred embodiment sorbent assembly combination at 600° C. The line graph A corresponds to the results obtained using only 0.3 g CaO. The graphical line B corresponds to the results obtained using only 0.3 g La 2 O 3 . The graphical line C corresponds to the results obtained using 0.2 g CaO (first layer) and 0.2 g La 2 O 3 (second layer) in the preferred embodiment assembly 10 . Incoming gases contained approximately 420 ppm hydrogen sulfide H 2 S and the total amount of the sorbent material in each experiment was 0.3 g.
[0038] As shown in the FIG. 2 , calcium oxide alone did not reduce hydrogen sulfide from 400 ppm to near zero ppm (graphical line A), while lanthanum oxide alone only reduced hydrogen sulfide from 400 ppm to near zero ppm for the duration of about 250 minute (graphical line B). However, in the invented assembly, the duration was increased to over 1000 minute with the same total weight of 0.3 g sorbents combined (graphical line C).
[0039] FIG. 3 graphically illustrates desulfurization results of the same amount of CaO (0.2 g) and La 2 O 3 (0.2 g) combined and/or positioned in different ways in the assembly 10 at 600° C. Graphical line A correlates to the result of physically mixing CaO and La 2 O 3 . Graphical line B correlates to the result of positioning the CaO in the second layer and La 2 O 3 in the first layer. Graphical line C correlates to the result of positioning CaO in the first layer and La 2 O 3 in the second layer. Incoming gases contained 420 ppm hydrogen sulfide. The total amount of the sorbent materials in each experiment was 0.4 g.
[0040] The duration of time when the desulfurization (removal of H 2 S) is effectively achieved correlates to zero on the y-axis as shown in FIGS. 2 and 3 . When the two metal oxides (CaO and La 2 O 3 ) with 0.2 g each were mechanically mixed together, the effective desulfurization duration was found to be less than 200 min, as shown by the graphical line A in FIG. 3 . Without any mixing, but when lanthanum oxide (0.2 g) was in contact with the incoming gas stream first and calcium oxide (0.2 g) next in the assembly, the result was still less than 200 minutes, as shown by the graphical line B in FIG. 3 . When the two metal oxides (CaO and La 2 O 3 ) were placed in the assembly 10 in the manner shown in FIG. 1A , with calcium oxide as the first layer and lanthanum oxide as the second layer, the duration of effective desulfurization (where approximately zero H 2 S/ppm remained) extended more than 1000 minutes, correlating to the graphical line C in FIG. 3 .
[0041] FIG. 4 graphically illustrates the effect of changing the ratio of CaO (first layer) and La 2 O 3 (second layer) in the assembly 10 . Incoming H 2 S is 420 ppm. and the total amount of the sorbent materials in each case is 0.4 g.
[0042] The particular individual lanthanum oxide and calcium oxide layers provide a significantly improved desulfurization performance over either lanthanum oxide or calcium oxide used individually on the same weight basis. FIG. 4 showed the result of variation of the amount of calcium oxide and lanthanum oxide in the invented assembly. Graphical line A represents a ratio of 0.35 g. CaO in a first layer and 0.05 g La 2 O 3 (second layer) in the assembly 10 . Graphical line B represents a ratio of 0.3 g. CaO in a first layer and 0.1 g La 2 O 3 (second layer) in the assembly 10 . Graphical line C represents a ratio of 0.2 g. CaO in a first layer and 0.2 g La 2 O 3 (second layer) in the assembly 10 . The experiment demonstrated the optimal ratio is roughly around 3:1 as indicated by graphical line B.
[0043] FIG. 5 graphically illustrates the experimental desulfurization results at 500° C., with graphical line A correlating to the results from using 0.3 g La 2 O 3 only, and graphical line B correlating to the results from using 0.2 g CaO (first layer) and 0.1 g La 2 O 3 (second layer) in the assembly 10 depicted in FIG. 1A . Incoming gases contained 420 ppm hydrogen sulfide. The total amount of the sorbent materials in each experiment was 0.3 g.
[0044] FIG. 6 graphically illustrates experimental desulfurization results at 700° C., utilizing 0.3 g La 2 O 3 only (shown by graphical line A) and 0.1 g CaO (first layer) and 0.2 g La 2 O 3 (second layer) (shown by graphical line B) in the assembly 10 depicted in FIG. 1A . Incoming gases contained 420 ppm hydrogen sulfide and the total amount of the sorbent materials in each experiment was 0.3 g.
[0045] FIG. 7 graphically illustrates experimental desulfurization results at 800° C. using 0.3 g La 2 O 3 only, as represented by graphical line A. The second experimental result, graphical line B, resulted from utilizing a first layer of 0.1 g CaO and a second layer of 0.2 g of La 2 O 3 (also at 800° C.) in the assembly 10 depicted in FIG. 1A . Incoming gases contained 420 ppm hydrogen sulfide. The total amount of the sorbent materials in each experiment was 0.3 g.
[0046] FIG. 8 is a graphical illustration depicting the experimental results obtained by varying the weight ratio of CaO to La 2 O 3 at 600° C. with incoming H 2 S concentration of 820 ppm. In FIG. 8 , the yellow line represents the experimental results using a weight ratio of 0.3 to 1 of calcium oxide to lanthanum oxide. The dark red line depicts the experimental results using a weight ratio of 1 to 1. The black line depicts the experimental results using a weight ratio of 2 to 1. The red line depicts the experimental results using a weight ratio of 3 to 1. The blue line depicts the experimental results using a weight ratio of 4 to 1. In view of the removal of substantially all of the H 2 S for the longest duration, the results indicate that weight ratios of 2:1 (black) and 3:1 (red) are the best, 0.3:1 (yellow) and 1:1 (brown) are next, followed by 4:1 (blue).
[0047] FIG. 9 is a graphical illustration depicting the experimental results obtained by varying the weight ratio of CaO to La 2 O 3 from 1:0 to 0:1 at 600° C. with incoming H 2 S concentration of 820 ppm. In FIG. 9 , the light blue line represents the experimental results using all lanthanum oxide. The yellow line represents the experimental results using a weight ratio of 0.3 to 1 of calcium oxide to lanthanum oxide. The dark red line depicts the experimental results using a weight ratio of 1 to 1. The black line depicts the experimental results using a weight ratio of 2 to 1. The red line depicts the experimental results using a weight ratio of 3 to 1. The blue line depicts the experimental results using a weight ratio of 4 to 1. The violet line depicts the experimental results using a weight ratio of 7 to 1. The green line depicts the experimental results using only calcium oxide. In view of the removal of substantially all of the H 2 S for the longest duration, 3:1 is the preferred weight ratio.
[0048] Unlike desulfurization process currently employed in industry, which generally removes majority of the sulfur in the fuel stream and leaves some small amount of remaining sulfur behind in the desulfurized product, the desulfurization of reformate stream for fuel cells requires that the remaining sulfur level be substantially zero or near zero (e.g. 0.0 ppm for hydrogen fuel cells and 0.1˜2 ppm for solid oxide fuel cells at the present technological development stage). An additional requirement is that the desulfurization process should be carried out at temperature that is close to solid oxide fuel cells' operation temperature which is expected to be between 600-800° C. for the benefit of relatively easier component integration and thermal management. To meet the above two basic requirements, high temperature stable metal oxides with high desulfurization capacity and highly effective sulfur adsorption property are desired. As discussed in the foregoing, no single metal oxide can meet all the requirements for an extended period of time, and a combination of two metal oxides, such as calcium and lanthanum in this case, offers one solution to solve the problem. Prior art of using zinc oxide as effective sorbent works only below 500° C. under fuel reformate conditions with reducing atmosphere and in presence of water vapor.
[0049] By utilizing two metal oxides (calcium oxide and lanthanum oxide) in a desulfurization sorbent assembly in which calcium oxide is first in contact with reformate gases and subsequently in contact with lanthanum oxide (for example, along a common axis) to effectively and efficiently remove hydrogen sulfide for fuel reformation and fuel cell applications at 600-800° C., significant performance improvement is gained over using either calcium oxide or lanthanum oxide alone on the same weight basis.
[0050] The present invention of hydrogen sulfide sorbent assembly can be used in power generation by fuel cell to remove hydrogen sulfide in hydrocarbon based fuel stream. It can also be used as a hydrogen sulfide scrubber/scavenger in wide range of emission control systems.
Example
[0051] Experiments were carried out at specified temperatures as shown in FIGS. 2 to 9 with total amount of sorbent oxide from 0.2 g to 0.4 g. The incoming fuel gas stream contained 49% H2, 29% He, 10% water, and 8% H 2 S containing gas cylinder (a mixture of 0.05% H 2 S and 99.5% Helium). The exit gases from the assembly were sent to sulfur analyzer in real time to determine the H 2 S level continuously. Water in the gas mixture was removed before the analyzer. The obtained desulfurization capacity of the oxides in the assembly was determined by the point where the H 2 S in the exit gas mixture reached to above 2 ppm, and is listed in Tables 1 and 2.
[0000]
TABLE 1
Desulfurization Capacity (mg S/g) at 600° C.
0.3 g CaO
0.3 g La 2 O 3
0.2 g CaO
(first layer)
0.1 g La 2 O 3
(second layer)
4.13 mg S/g
41.3 mg S/g
175 mg S/g
0.3 g CaO
0.35 g CaO
0.2 g CaO
(first layer)
(first layer)
(first layer)
0.1 g La 2 O 3
0.05 g La 2 O 3
0.2 g La 2 O 3
(second layer)
(second layer)
(second layer)
185 mg S/g
64.5 mg S/g
129 mg S/g
[0000]
TABLE 2
Desulfurization Capacity (mg S/g) at 600, 700, and 800° C.
600° C.
0.3 g La 2 O 3
0.2 g CaO
(first layer)
41.3 mg S/g
0.1 g La 2 O 3
(second layer)
175 mg S/g
700° C.
0.3 g La 2 O 3
0.1 g CaO
(first layer)
0.2 g La 2 O 3
(second layer)
46.4 mg S/g
86.0 mg S/g
800° C.
0.3 g La 2 O 3
0.1 g CaO
(first layer)
0.2 g La 2 O 3
(second layer)
51.6 mg S/g
105 mg S/g
[0052] As used herein, the terminology “stoichiometry” is the calculation of quantitative relationships of the reactants and products in a balanced chemical reaction.
[0053] As used herein the terminology “stoichiometric capacity” relates to the quantities (for example, the amount of products) produced from the given reactants and percent yield.
[0054] As used herein the terminology “enclosure” includes a partial enclosure and includes configurations such as a cylinder, vessel, chamber, container, receptacle, or pipe.
[0055] In view of the foregoing, it is understood that numerous modifications and variations of this invention will be readily apparent to those of skill in the art. The foregoing drawings, discussion and description are illustrative of specific embodiments; but are not meant to be limitations upon the practice of this invention. It is the following claims, including equivalents, which define the scope of the invention.
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A method and system for desulfurization comprising first and second metal oxides; a walled enclosure having an inlet and an exhaust for the passage of gas to be treated; the first and second metal oxide being combinable with hydrogen sulfide to produce a reaction comprising a sulfide and water; the first metal oxide forming a first layer and the second metal oxide forming a second layer within the walled surroundings; the first and second layers being positioned so the first layer removes the bulk amount of the hydrogen sulfide from the treated gas prior to passage through the second layer, and the second layer removes substantially all of the remaining hydrogen sulfide from the treated gas; the first metal oxide producing a stoichiometrical capacity in excess of 500 mg sulfur/gram; the second metal oxide reacts with the hydrogen sulfide more favorably but has a stoichiometrical capacity which is less than the first reactant; whereby the optimal amount by weight of the first and second metal oxides is achieved by utilizing two to three units by weight of the first metal oxide for every unit of the second metal oxide.
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BACKGROUND OF THE INVENTION
1. Field of the invention
This invention relates to a pharmaceutical composition for antifungal use, especially anti-Candida use (for treatment of the infection known as candidiasis).
2. Description of prior art
The antibiotics most commonly used for treatment of candidiasis, especially vaginal candidiasis are polyenes, especially nystatin. Such polyenes are not always effective if applied topically and their systemic administration is suspected of giving rise to kidney failure in some patients.
An antifungal cream and dusting powder based on miconazole is available under the Trade Mark "Daktarin" from Janssen Pharmaceutical Ltd. Since occasional irritation has been reported when using this product, it would be advantageous to have an alternative product for topical application.
Another imidazole, ketoconazole, has been used as a systemic fungicide, but recently there have been reports of hepatitis or liver damage occurring in some patients treated with ketoconazole, see Committee for Safety of Medicines Data Sheet, April 1983, and the article "New antifungal and antiviral chemotherapy" by J. C. M. Stewart et al., British Medical Journal, 286, 1802-1804 (1983).
There has therefore been a need to develop new antibiotics for the treatment of candidiasis.
Additional prior art is described below after the "Summary of the invention", without which its context would not be clear.
SUMMARY OF THE INVENTION
It has now been found, very surprisingly, that bile acids and their simple derivatives have anti-Candida activity.
An important feature of the invention consists in a pharmaceutical composition in a form suitable for topical application, comprising (1) a bile acid component in the form of at least one bile acid or a derivative thereof which is a conjugate thereof formed between the carboxylic acid of the bile acid and the NH 2 group of an amino acid having 3 to 6 chain atoms, inclusive of the amino and acid groups, or a salt of such an acid or conjugate, and (2) a pharmaceutically acceptable excipient for topical application.
The above feature of the invention can be formulated as the use of the bile acid component for the manufacture of a medicament for the therapeutic application of treating topical fungal infections, preferably candidiasis, and especially vaginal candidiasis.
The bile acid component is also useful for protecting any pharmaceutical composition against fungal growth. According to a second feature of the invention, therefore, there is provided a pharmaceutical composition in a solid or semi-solid form comprising at least the following three components: (1) an active ingredient in association with (2) a pharmaceutically acceptable excipient and (3) a bile acid component defined as above (compatible with the required purpose of the pharmaceutical composition, whether it is for topical application or some other route of administration). In this aspect of the invention the active ingredient is self-evidently not itself a bile acid component. That is, the bile acid component is additional to the active ingredient which can in principle be any conventional pharmaceutical material susceptible to fungal attack.
The bile acids referred to above are compounds of the general formula ##STR1## where Me represents a methyl group, X represents a hydrogen atom or a hydroxyl group (in the 7α-position), Y represents a hydrogen atom or hydroxyl group (in the 12α-position) and Z represents a hydrogen atom or hydroxyl group (in the 6α-position). These compounds are:
Cholic acid: 3α, 7α, 12α-trihydroxy-5β-cholan-24-oic acid
Deoxycholic acid: 3α, 12α-dihydroxy-5β-cholan-24-oic acid
Lithocholic acid: 3α-hydroxy-5β-cholan-24-oic acid
Chenodeoxycholic acid: 3α, 7α-dihydroxy-5β-cholan-24-oic acid
Hyodecholic acid 6α, 7α-dihydroxy-5β-cholan-24-oic acid
Hyodeoxycholic acid 6α-hydroxy-5β-cholan-24-oic acid
The bile acid salts can be any of those which are pharmaceutically acceptable, especially sodium, as the compound permits. The conjugates include those with glycine (NH 2 CH 2 COOH) and taurine (NH 2 CH 2 CH 2 SO 3 H) for example, and are amides formed between NH 2 group of the amino acid and the carboxylic acid group of the bile acid. Preferably the amino acid has 3 or 4 chain atoms.
Additional description of prior art
The bile acids are produced in various mammals, including man, and are excreted in large quantities. This origin is a prima facie indication that they are unlikely to be toxic to man.
Various bile acid derivatives have been administered intravenously or orally to increase the flow of bile, i.e. as choleretics. Dehydrocholic acid (3,7,12-trioxo-5β-cholan-24-oic acid) is the most active. Others are ox bile extract, cholic acid, sodium glycocholate and sodium taurocholate. See "The Pharmaceutical Basis of Therapeutics" by L. S. Goodman and A. Gilman, 3rd edition., The MacMillan Company, New York 1965 pages 1003 to 1007 and The Merck Index, 10th edition, 1983, entries 2183 and 8951.
Chenodeoxycholic and ursodeoxycholic acids have been administered orally for the prevention and dissolution of gallstones, see Oxford Textbook of Medicine, Ed. D. J. Weatherall, J. G. G. Ledlingham and D. A. Warrell, Oxford University Press, Vol. 1, Section 12-171 (1983), G. D. Bell et al., The Lancet Dec. 9, 1972, pages 1213-1217 and R. G. Danzinger et al., The New England Journal of Medicine, 286, 1-8, (1972).
It is known that amino acid-conjugated cholic acid has an inhibitory effect on the growth of the bacteria Bacillus subtilis and Saccharomyces cerevisiae and carlsbergensis, see S. Aonuma et al., Yakugaku Kenkyu 38, 381-392 (1967). The compounds tested were however ineffective against Escherichia coli bacteria and against the fungus Asperillus niger.
The anti-Candida preparation Fungizone is administered intravenously and is sold in the form of 20 ml vials each containing amphotericin B together with 41 mg of sodium deoxycholate as a dispersant to "solubilize" the amphotericin and sodium phosphate buffer. Toxicity tests were carried out on Fungizone and separately on sodium deoxycholate by K. Saito, Odontology (Journal of Nippon Dental University) 6 (5), 650-671 (1979). The paper nowhere suggests that sodium deoxycholate has any fungicidal activity. Other papers relating to "Fungizone" are H. H. Gadebusth et al., The Journal of Infectious Diseases 134, 423-427 (1976) and Paul B. Fisher et al., In vitro, 12, 133-139 (1976).
M. E. Macintosh and R. H. Pritchard, Genet, Res. Camb. 4, 320-322 (1963) investigated the effect of the surface active agents sodium dodecyl sulphate and sodium deoxycholate on growth of Aspergillus nidulans, in the hope that they might promote growth. It was concluded that sodium deoxycholate had a growth-enhancing effect and the authors mention that after making this finding they learned that sodium deoxycholate was known to promote the growth of Neurospora and Syncephalastrum.
In the light of these prior disclosures, it was surprising to find by the present invention, that a bile acid or derivative thereof such as sodium deoxycholate, sodium cholate, or the like has at least a fungistatic effect on strains of Candida.
BRIEF DESCRIPTION OF THE DRAWINGS
In the Examples hereinafter reference is made to the accompanying drawings, in which:
FIG. 1 is a plot showing growth of Candida albicans in the presence of various amounts of sodium cholate;
FIG. 2 is a photograph of untreated cells of Candida albicans; and
FIGS. 3 to 6 are photographs of cells of Candida albicans treated with various amounts of various bile acid components, namely sodium salts of cholic, chenodeoxycholic, lithocholic or deoxycholic acids.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The bile acid component can be formulated in any conventional way suitable for topical application, for example as a capsule, suppository or pessary for intracavital application (to the vagina, urethra or rectum) or a gel, ointment, cream or the like, dusting powder or aerosol spray. A suppository or pessary may contain theobroma oil, glycerinated gelatin or polyethylene glycol, for example, as a carrier which melts at body temperature or dissolves in body fluids. The bile acid component can be formulated as an ointment or cream with an oleaginous or waxy binder. An aqueous phase may be present, to provide a cream. Other forms of formulation include gelatin capsules containing the ingredient in a liquid diluent, mixtures with talc or the like to provide dusting powder and aerosol bombs which comprise the ingredient and an inert propellant.
A preferred formulation is an ointment or cream containing say, from 1 to 5 percent by weight of the bile acid component depending on its effectiveness.
Tablets for oral administration of cholic acid, containing merely a choleretic or gallstone-dissolving amount of a bile acid component for such a use, are not within the scope of the invention. Other tablets and pills, for intravaginal use for example, are within the scope of the invention. They may contain conventional inert excipients for the intended purpose. Such pessaries can be formulated as controlled release compositions using as excipient a polymeric carrier comprising residues which are cross-linked through urethane groups and which comprise polyethylene oxide, as described in UK Patent Specification No. 2047093A (National Research Development Corporation).
A particularly preferred aspect of the invention comprises the bile acid component in association with an anti-inflammatory agent, especially of the steroidal type, most especially a corticosteroid, e.g. betamethasone, fluocinolone acetonide, beclomethasone dipropionate, hydrocortisone, cortisone or cortisol. These compositions are useful for the treatment of fungal infections of the skin.
A reasonable prediction from the information available is that the invention would be useful in treating the same kinds of topical fungal infections as miconazole.
It is contemplated that the bile acids and derivatives could also be formulated as an aerosol for application to the orapharynx or upper respiratory tract, orally or intranasally.
Referring now to the second feature of the invention, namely the use of the bile acids and derivatives to inhibit fungal attack on pharmaceutical preparations such as tablets, capsules, creams, ointments pessaries and suppositories, tablets can be coated with the bile acid component or any of the preparations can contain a small proportion of bile acid component effective to confer on it resistance to fungal attack. This would ordinarily be a subtherapeutic amount, especially a sub-choleretic amount. In general the amount of bile acid or derivative per dosage unit should be from 1-10 mg, especially about 5 mg. In this way it would be possible in particular to protect tablets made by wet granulation processes where fungal attack is particularly serious.
The following Examples illustrate the invention. Proportions expressed as weight/volume are metric, i.e. g/100 ml.
EXAMPLE 1
The strains of Candida albicans used were A39 (a clinical isolate provided by Boots PLC, Nottingham, England) and CMI 45348 (available as an ordinary scientific deposit from the Commonwealth Mycological Institute, Ferry Lane, Kew, Surrey TW9 3AF, England).
Starter cultures were made by growing the Candida albicans in an aqueous medium in shake culture at 140 rpm in an orbital incubator for 18 hours at 30° C. The medium used consisted of Tris, 1.2 g; NaCl, 0.1 g; Ammonium tartrate, 5.0 g; Ammonium nitrate, 1.0 g; KH 2 PO 4 , 1.0 g; MgSO 4 .7H 2 O, 0.5 g; CaCl 2 , 0.1 g; glucose, 100 g; and biotin 1×10 -5 g, all per liter, to which was added 1.0 ml per liter of a mineral salts solution which contained H 3 BO 3 , 6 mg; (NH 4 ) 6 MoO 24 .4H 2 O, 26 mg; FeCl 3 .6H 2 O, 100 mg; CuSO 4 5H 2 O, 40 mg; MnCl 2 .4H 2 O, 8 mg; and ZnCl 2 , 200 mg, all per 100 ml of mineral salts solution. 5 ml aliquots of this starter culture were then transferred to 100 ml volumes of fresh medium of the same composition, to which aqueous sodium cholate solution has been added to give the required test concentration. In a control experiment, no sodium cholate was added. These cultures were incubated at 140 rpm at 30° C. and the optical density measured at 420 nm at definite time intervals.
The concentrations of the sodium salt of cholic acid (reckoned as the salt) used and the responses were as follows:
______________________________________Control no response0.001% w/v no response0.01% w/v no response0.1% w/v no significant response0.2% w/v0.3% w/v response as shown in FIG. 1 of the drawings.0.4% w/v0.5% w/v no growth after 3 hours1.0% w/v no growth after 3 hours______________________________________
FIG. 2 of the drawings shows normal control cells of Candida albicans (A39 strain) and FIG. 3 cells of the same strain grown in the presence of 0.4% w/v sodium cholate for 6 hours at 30° C. The principal differences between the cells of FIG. 3 and normal cells of Candida albicans are (a) that in FIG. 3 the lemon-shaped yeast-form cells are not dividing properly but are joined together by a relatively thick "neck" portion and (b) that in FIG. 3 the cell walls are cracked (whereas in normal Candida cells they are not). The FIG. 3 cellular morphology is similar to that observed by S. De Nollin and M. Borgers, Antimicrobial Agents and Chemotherapy, 7, 704-711 (1975), in Candida albicans treated with the antifungal agent miconazole, see especially FIG. 2 thereof.
EXAMPLE 2
The procedure of Example 1 was repeated using sodium salts of chenodeoxycholic acid, lithocholic acid and deoxycholic acid. All these salts are less soluble in water than sodium cholate. Because of the solubility problem, meaningful quantitative data at different concentrations of additive could not be obtained. Nevertheless, the experiments showed that each of these salts affected the cellular structure of the organism in a broadly similar way to the necking effect seen in FIG. 3. Since this effect was also observed in miconazole treatment, it can reasonably be concluded that these other bile acid salts also have an anti-Candida effect.
In more detail, the chenodeoxycholate treatment (1% w/v, sodium salt) caused the yeast cells to become incompletely separated after 6 hours growth at 30° C. and the amount of the elongated mycelial structure to increase, see FIG. 4. The necking effect is clearly visible. A lithocholate treatment (1% w/v, sodium salt) after 6 hours growth at 30° C. (FIG. 5) showed similar effects. When deoxycholate 0.05% w/v, sodium salt) was used instead, cell elongation, "necking", and incomplete separation were again observed (FIG. 6).
EXAMPLE 3
The effectiveness of various bile acids and derivatives of the invention to inhibit Candida albicans A39 on agar was demonstrated in spread and seeded plate tests. The plates had a diameter of 9 cm. In both tests a culture of 10 7 -10 8 cells/ml of the Candida organism was used. In the seeded plate test 1 ml of the culture was dispersed in agar to a total volume of 20 ml and the agar allowed to solidify. In the spread plate test 0.1 ml of the culture was spread on the surface of the solidified agar. 1% w/v solutions of the bile acids and derivatives were made in distilled water of if necessary in ethanol and sterilised by membrane filtration. Sterile 5 mm discs (Whatman AA) were dipped in these solutions and allowed to dry in sterile petri dishes. They were then placed on the surfaces of the plates to provide approximately 0.2 mg of bile acid or derivative per disc. The plates were then incubated for 24 hours at 30° C. The zones of inhibition, represented by cleared areas were then recorded. In nearly all cases they extended beyond the area of the disc, the Candida albicans having grown outwardly from the original 5 mm diameter area during the incubation and the bile acid or derivative being sufficiently potent an agent to inhibit it.
The results are shown in the Table below. It will be seen that most of the bile acids or derivatives gave good inhibition in both tests. Although two of them were effective only in the seeded plate test their performance in that test does indicate some anti-Candida activity.
TABLE______________________________________Zones of inhibition of growth of Candida albicans by bile acid Zone of inhibition (cm)Compound Seedednumber Compound Spread plate plate______________________________________19 Sodium cholate 0.51 1.220 Sodium deoxycholate 0.73 0.8121 Chenodeoxycholic acid 0.63 1.3822 Hyocholic acid 0.69 0.5523 Hyodeoxycholic acid 0.66 0.8524 Sodium lithocholate 0 0.5525 Sodium glycocholate 0 0.6426 Sodium glycodeoxycholate 0.62 1.16______________________________________
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A valuable alternative antifungal antibiotic, for treatment especially of candidiasis, particularly vaginal candidiasis, is proposed. The antibiotic is a bile acid or simple derivative (salt or conjugate) thereof. Cholic, deoxycholic, chenodeoxycholic and lithocholic acid are preferred bile acids. The antibiotic is formulated for topical application. It can be used in association with an anti-inflammatory steroid for the treatment of fungal infections of the skin. It is also proposed to inhibit fungal growth in a variety of pharmaceutical compositions (containing some other active ingredient) by including in the composition, or coating a tablet, pill or capsule with, the bile acid component.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a closure used in conjunction with containers such as bottles, vials and bags containing pharmaceutical products for parenteral administration. More particularly, the invention relates to an elastomeric stopper for hermetically sealing a parenteral container, bottle, vial or bag the contents of which is accessed by the use of a spike integral with the stopper.
2. Reported Developments
Stopper systems for vials, bottles and the like are made of materials that are resistant to chemicals and pharmaceuticals such as corrosive materials, reagents, parenteral solutions and solid formulations reconstitutable with a solvent prior to use. The most commonly used stopper/vial system for such products has been glass or plastic bottles and vials equipped with rubber stoppers made of elastomeric materials. The system provides for good hermetical seal, safe storage and easy access to the content through the elastomeric stopper via the use of an infusion spike or a syringe when withdrawal of the content is desired. The elastomeric stopper used generally comprises an elastomeric base, such as natural or synthetic rubber and an inert coating covering at least some portions of the stopper. The coating used includes chlorobutyl rubber, polymeric fluorocarbon resins such as polytetrafluoroethylene and various thermoplastic films. The coating is intended to insulate the elastomeric stopper base from the contents of the container in order to prevent contact and possible chemical reactions therebetween.
Generally, the elastomeric stopper is of cylindrical shape and has a flange head portion overlying the open top end of the container. Integral with the head portion is a body portion which extends into the open end and seated in the neck portion of the container, the diameter of the body portion being somewhat larger than the inside diameter of the container so that a tight seal is created between the body portion and the wall of the container. The lower end of the body portion is beveled towards the central, longitudinal axis of the body portion to facilitate the insertion of the body portion into the container. The circular bottom surface that faces the contents of the container is substantially planar and is imperforate, having no recess therein. The head portion of the stopper is provided with a central recess extending downwardly from the top thereof a substantial distance into the body portion so that the central recess and the circular bottom surface define a diaphragm. The walls forming the recess are generally cylindrical but may be provided with one or more circular protuberances extending inwardly to terminate just short of the center line of the stopper. The circular protuberances serve to press against, seal and hold the needle of a syringe when the needle is inserted through the recess to penetrate the diaphragm for removal of the contents of the container. The elastomeric stopper is held in position by a metal ring or cap usually constructed of aluminum. The metal ring or cap has a removable center opening for allowing insertion of the syringe needle into the container.
Another type of the prior art stoppers has the needle penetrable diaphragm on the top portion of the stopper.
Various stopper and access systems exist in the prior art to hold and remove the contents of containers which are illustrated hereunder.
U.S. Pat Nos. 2,289,677 and 2,326,490 disclose a rubber stopper for use in vials comprising: an outer wall which serves a seal between the vial and the stopper; and an inner wall forming a chamber in the center of the stopper, the bottom portion of the inner wall serving as a diaphragm. A hollow needle, having a sharp end for piercing the diaphragm, and an outer end exposed for connection with a syringe, is carried by the outer wall. A syringe connected to the outer end of the needle and pushed inwardly effects piercing of the diaphragm thereby permitting aspiration of the contents of the vial.
U.S. Pat. No. 2,342,215 discloses a dispensing and sealing stopper for a vial comprising: a stopper body having a hollow needle therein, one end of said hollow needle is in constant communication with the contents of the vial, and the other end is sealed by a penetrable, thin membrane. When withdrawal of the contents of the vial is desired, a syringe is inserted into the stopper to penetrate the thin membrane and to engage the other end of the hollow needle. When the syringe is removed, the thin membrane self-closes to maintain the hollow needle and the contents of the vial sterile.
U.S. Pat. No. 5,232,109 discloses an elastomeric stopper for a bottle, said bottle includes an annular protuberance which forms a second seal with the shaft of a spike inserted in the stopper to prevent leakage, blow-out and introduction of particulate matter into the fluid-containing bottle.
U.S. Pat. No. 5,364,386 relates to an infusion unit which comprises: a flexible, large container, a small medicine vial and a pipe which serves to communicate between the large, flexible container and the small medicine vial.
The large container is adapted to hold a solvent or diluent, while the medicine vial contains a powdery medicine which is to be mixed and dissolved in the solvent or diluent contained in the large, flexible container. Upon dissolution, the mixed medicine is discharge through an outlet at the lower end of the large container for infusion into a patient.
U.S. Pat. No. 5,429,256 pertains to a drug withdrawal system for a vial. The withdrawal system comprises: a vial containing a medicament therein and closed with a rubber gasket; and an apparatus which snap fits on top of the vial. The apparatus comprises: a chassis and a cap which is attached to the cap by a living hinge.
The chassis is cylindrical and has vertical grooves on the external sides to facilitate handling. The top of the chassis has a central opening. The chassis includes a male luer lock adapter having external threads thereon, and a ferrule structure the lower end of which has a hollow sharpened lance. The apparatus is used with a syringe having a female luer lock connector which snap fits with the male luer lock adapter.
In use, a tamper evident tear seal on the cap cover is opened, and the outer cap is pressed toward the bottle contents. The lance penetrates the gasket on the vial thereby establishing flow communication with the contents in the vial. A syringe is then screwed onto the outer end of the adapter and then tightened on the adapter. The contents of the vial is withdrawn by pulling back on the plunger of the syringe. The syringe is then removed with the content therein ready to receive a needle assembly for injecting the contents into a patient.
U.S. Pat. No. 5,433,330 relates to a needleless access stopper used on containers with a cannula having a blunt stopper penetrating tip.
The present invention provides tamper evident sealing and access means for containers, such as bottles or vials made of glass or plastic, and bottles and bags made of plastic containing medical fluids, such as x-ray contrast media and parenteral liquids. For convenience the invention will be described in combination with containers. It is to be understood that the invention includes tamper evident sealing and access means for containers in general which comprise rigid or semi rigid access ports and capable of receiving such sealing and access means.
SUMMARY OF THE INVENTION
In accordance with the present invention, a closure assembly is provided for a container having a medical fluid therein, said closure assembly comprising:
an elastomeric stopper for hermetically sealing the container at its open end;
a spike access means to withdraw the contents of the container; and
a tamper evident cover member for enclosing and sealing the spike access means onto the open end of the container and to maintain the spike access means and the elastomeric stopper free from contamination.
The elastomeric stopper is piercable and hermetically seals the medical fluid contained in the container. The elastomeric stopper has a head portion and a skirt portion integral with the head portion which comprises:
a) a flange extending laterally outwardly from the skirt portion and is designed to cover the transverse end surface of the neck of the container; and
b) a target area at the center of the head portion designed to be pierced by the spike access means.
The elastomeric stopper used in the closure assembly of the present invention should be a fluid impervious, resilient, and inert without leachable additives therein in order to prevent any alteration of the product contained in the container. It may be of a single component or a blend of components. Examples of materials include synthetic or natural rubber, such as butyl rubber, isoprene rubber, silicone rubber, halogenated rubber, ethylene propylene therpolymer and the like. Specific examples of a synthetic elastomeric rubber include the CH 2 CF 2 --C 3 F 6 (C 3 F 5 H) and the C 2 F 4 --C 2 F 3 OCF 3 series of elastomers made by DuPont under the trade names of VITON® and CARLEZ®; the fluoro-silicone rubbers, such as those made by Dow Corning under the trade name of SILASTIC®; and polyisobutylenes, such as VISTANEX MML-100 and MML-140; and halogenated butyl rubber, such as CHLOROBUTYL 1066, made by Exxon Chemical Company.
These or other suitable elastomers may be made into the desired stopper configuration by known methods. Such methods conventionally include the use of a curing agent, a stabilizer and a filler and comprise a primary and a secondary curing step at elevated temperatures.
The container used in conjunction with the present invention may be of glass or polymeric material, i.e., plastic, which are well known in the pharmaceutical industry. When the container is made of glass, it is in the shape of a vial or bottle. Polymeric materials are preferred for reasons of economy and safety. The plastic containers may be in the shape of a vial, bottle or bag. The vial or bottle is of rigid or semi-flexible polymeric material, while the bag is of a pliable polymeric material. In all shapes the container is provided with a neck portion which is rigid and retains its configuration so that it is capable of being hermetically sealed by the closure assembly of the present invention. The container comprises a neck portion having an interior surface, an interior radial surface, and a transverse end surface. The interior radial surface and the transverse end surface form the opening or mouth of the container. The neck portion further comprises an exterior surface which, being adjacent to the transverse end surface, forms an exterior radial ring. The exterior radial ring facilitates the holding of the closure assembly of the present invention. The container may have a volume capacity of from 5 ml to 5000 ml or more.
The mouth of the container is to receive the elastomeric stopper. The external diameter of the stopper is slightly larger than the internal diameter of the neck of the container so that on insertion of the stopper into the mouth of the container, a tight, hermetic seal is achieved.
After insertion of the stopper into the mouth of the container a cylindrical collar is positioned over the radial ring of the container and the stopper to securely hold the stopper in place. The cylindrical collar comprises: a flat top portion having a central opening therein so that the target, pierceable area of the stopper head remains exposed; a bottom portion; and a cylindrical side portion having an inner wall and an outer wall. The inner wall incorporates an inwardly projecting ring which, upon assembly, is positioned below the exterior radial ring of the neck portion of the container so as to securely hold the elastomeric stopper in the container. The outer wall of the cylindrical side portion of the cylindrical collar incorporates an annular groove and, spaced from the annular groove, an annular protuberance at the bottom portion of the cylindrical collar projecting outwardly. The annular groove is to receive the spike access means when the spike access means is in its stationary or inactivated position, and the annular protuberance serves as a stop means to the spike access means after its activation. The cylindrical collar may be made of rigid polymeric material so that it retains its configuration or metal such as aluminum.
The spike access means has an inverted, essentially U-shape configuration having a top portion, side portion and a bottom portion. The top portion at its center incorporates a spike which comprises: a cylindrical shaft having a channel therein terminating in a sharp tip at one end thereof; and a male or female luer connector at the other end thereof to engage a corresponding female or male luer lock at the end of an IV tubing which delivers the medical fluid into a patient. The bottom portion of the spike access means incorporates an annular protuberance projecting inwardly towards the container, which fits into the annular groove of the cylindrical collar. The spike access means is positioned over the annular cylindrical collar by fitting the annular protuberance into the annular groove. In this initial position, the spike access means is in an inactivated stage because the sharp tip of the spike is just very slightly above the center, pierceable target area of the elastomeric stopper.
The spike access means is made of a rigid but slightly flexible polymeric material so that, when activation of the same is desired, the sides of the annular collar flex outwardly as a result of manual force exerted on the top portion of the spike access means. The exerted manual force will dislodge the annular protuberance from the annular groove and slides the spike access means downward so that the sharp tip of the spike penetrates the center target area of the elastomeric stopper thereby providing access to the medical fluid contained in the container. The spike access means, in its sliding downward motion, will be stopped when the annular protuberance of the spike access means reaches the annular protuberance on the bottom of the cylindrical collar.
A removable cover member completely encloses the spike access means along with the elastomeric stopper and the neck portion of the container. The removable cover is made of plastic, or metal such as aluminum. The removable cover at its bottom portion is sealed to the neck of the container by a tear strip. At the point of use, the tear strip is removed. This allows the removable cover member to be pushed axially toward the container. During the axial movement the spike penetrates the target area thereby establishing fluid communication with the contents of the container. Upon activation the removable cover member is removed revealing the female luer connector with locking threads thereon. A male luer connector is then attached and the contents is either delivered to the patient via a tubing and catheter, direct injection for therapeutic drugs, or transferred to another container for subsequent administration to the patient.
BRIEF DESCRIPTION OF THE DRAWINGS
With reference to the annexed drawings, illustrating the invention:
FIG. 1 is a perspective view of a container, a stopper with spike access means, and removable cover member;
FIG. 2 is a top plan view thereof;
FIG. 3 is a top plan view thereof without the removable cover member;
FIG. 4 is a bottom plan view thereof;
FIG. 5 is a section al view of the container, the stopper with the spike access means and the removable cover member taken along the line 4--4 of FIG. 1;
FIG. 6 is a sectional view of the neck portion of the container, the stopper with the spike access means and the removable cover member shown in FIG. 1;
FIG. 7 is a sectional view of the removable cover member removed form the container shown in FIG. 1; and
FIG. 8 is a sectional view of the neck portion of the container, and the stopper with the spike access means having penetrated the target area in the stopper.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIGS. 1, 2, 4, 5 and 7, the container 10 having an open end in which the closure assembly of the present invention is used comprises a neck portion 12, a side portion 14, and a bottom portion 16. The closure assembly is covered with a cylindrical removable cover member 18 having a flat top portion 20, a bottom portion 22 which is sealed to the neck portion 12 of the container 10 by a tear strip 25 and side portion 24.
Located on the underside of the removable cover member 18 are two or more equally spaced ribs 19 which are provided to allow the removable cover member to withstand the forces associated with capping and stacking during sterilization. The ribs serve to transfer any external force directly to the spike access means without coming in contact with the luer connector 118.
Referring to FIGS. 5, 6 and 8, the container 10 comprises a neck portion 12 having an interior surface 44, and interior radial end surface 46 on the top end portion of the interior surface 44, and transverse end surface 48. The interior radial surface and the transverse end surface form the mouth of container 10. The neck portion 12 further comprises an exterior surface which, adjacent to the transverse end surface 48, evolves into an exterior radial ring 50. The exterior radial ring is adapted to facilitate the holding of the closure assembly, described later.
The mouth of the container is to receive an elastomeric stopper 60, as shown in FIGS. 5, 6 and 8. The elastomeric stopper 60 comprises a head 62 and integral therewith a skirt 64. The head 62 comprises: a flange 66 extending laterally outwardly from skirt 64 and is adapted to cover transverse end surface 48 of container 10; and a target area 68 which is adapted to be pierced by a spike access means.
As best seen in FIGS. 6 and 8 the container 10, after being filled with the desired amount of medical fluid, is sealed with the elastomeric stopper 60. To hold the elastomeric stopper securely in place and to serve as a receiving means for the spike access means, a cylindrical collar 70 is fastened over a portion of the elastomeric stopper 60 and the neck 12 of the container 10. The cylindrical collar 70 comprises:
a flat top portion 72 having a central opening therein 74 so that the target area 68 in the elastomeric stopper 60 remains exposed;
a circular bottom portion 76; and a cylindrical side portion 78 having an inner wall 80 and an outer wall 82.
The inner wall 80 incorporates an inwardly projecting ring 84 which is positioned below the exterior radial ring 50 of the neck portion 12 of container in order to securely hold the elastomeric stopper 60 in container 10.
The outer wall 82 of cylindrical side portion 78 of cylindrical collar 70 incorporates: an annular groove 86; and an annular protuberance 88 projecting outwardly at the bottom portion of the cylindrical collar 70. The annular groove 86 is to receive the spike access means when the spike access means is in its stationary or inactivated position, while the annular protuberance 88 serves as a stop means after the activation of the spike access means.
The spike access means 100 has an inverted U-shaped configuration in sectional view having: a top portion 102; a side portion 104; and a bottom portion 106. The top portion 102 at its center incorporates a spike 110 which comprises: a cylindrical shaft 112, having a channel therein 114, terminating in a sharp tip 116 at the lower end thereof; and a female Luer connector 118 at the other end thereof to engage a corresponding male Luer connector at the end of an IV tubing (not shown)which delivers the medical fluid contained in the container into a patient.
The bottom portion 106 of spike access means 100 incorporates an annular protuberance 120 projecting inwardly towards the container and engages the annular groove 86 of cylindrical collar 70. During assembly the spike access means 100 is positioned over the annular cylindrical collar 70 by fitting the annular protuberance 120 of the spike access means 100 into the annular groove of the cylindrical collar 86. As shown in FIG. 6, in this initial position the spike access means is in an inactivated stage because the sharp tip of the spike does not penetrate the target area of the elastomeric stopper. However, it may be preferred to allow the spike to contact, but not penetrate, the stopper to minimize the required stroke/range of axial movement to accomplish reliable penetration of the stopper. The container 10, having the medical fluid therein, is capped with removable cover member 18 and the removable cover member is sealed to the neck of the container with a tear strip 25. The container is then sterilized, shipped and stored ready to be used.
The removable cover member 18 as shown in FIG. 7 completely encloses the spike access means 100 and the neck portion 12 of the container 10 as shown in FIGS. 1, 5 and 6.
When it is desired to deliver medical fluid to a patient, the tear strip 25 is removed and manual force is exerted onto the removavle cover member 18. The force so exerted dislodges annular protuberance 120 on spike access means 100 from annular groove 86 of cylindrical collar 70. As the exertion of force continues, the side portion 104 of spike access means 100 flexes outwardly from the container. At the same time the sharp tip 116 of shaft 112 of spike 110 penetrates the target area 68 of the elastomeric stopper 60. Spike access means 100 ti-avels downward into the container until annular protuberance 120 on the spike access means reaches protuberance 88 of the cylindrical collar 70. At this point, the top portion 102 of the spike access means 100 also reaches the flat top portion 72 of the cylindrical collar 70. The removable cover member 18 is then removed exposing the underlying female luer connector 118 to which an IV line, having a male luer connector, is attached. The medical fluid in the container is ready for delivery to the patients by turning the container upside-down.
The present invention has been described in connection with the preferred embodiment shown in the drawings, however, various changes and modifications will be apparent to those skilled in the art.
______________________________________PARTS LIST______________________________________Container 10Neck portion of container 12Side portion of container 14Bottom portion of container 16Cylindrical removable cover member (of closure assembly) 18Ribs on cylindrical removable cover member 19Flat top portion of removable cover member 20Bottom rim portion of removable cover member 22Cylindrical side portion of removable cover member 24Tear strip on the base of the removable cover member 25Interior surface of the neck portion of container 44Interior radical end surface of the neck portion of container 46Transverse end surface of container 48Exterior radial ring of neck portion of container 50Elastomeric stopper 60Head of elastomeric stopper 62Skirt of elastomeric stopper 64Flange of head of elastomeric stopper 66Target area of elastomeric stopper 68Cylindrical collar 70Flattop portion of cylindrical collar 72Central opening in the flat top portion of the cylindrical 74llarCircular bottom portion of cylindrical collar 76Cylindrical side portion of cylindrical collar 78Inner wall of cylindrical side portion 80Outer wall of cylindrical side portion 82Inwardly projecting ring of inner wall 84Annular groove of cylindrical collar 86Annular protuberance of cylindrical collar 88Spike access means 100Top portion of spike access means 102Side portion of spike access means 104Bottom portion of spike access means 106Spike 110Cylindrical shaft of spike 112Channel in shaft 114Sharp tip of shaft 116luer Connector 118Annular protuberance on spike access means 120______________________________________
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A disposable closure assembly/container combination for delivering medial fluid to a patient by needleless access means. The closure assembly comprises an elastomeric stopper for sealing the container at its open end and a spike access means equipped with a luer lock.
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BACKGROUND
This invention relates to a method of preparing a phosphorus fertilizer in a form which will absorb quickly into plant systems and thereafter be oxidized into a form more readily useable by a plant system.
Fertilizers have long been used to supply needed nutrition to plants. The principle components of plant fertilizers have centered on three elements: nitrogen, phosphorus and potassium.
Phosphorus is not found in nature in its elemental form. The principal source of phosphorus for the fertilizer industry, however, is obtained from the ores of phosphorus containing minerals. The usual practice in the fertilizer industry is to convert phosphorus ores into a phosphorus product containing the phosphoric radical (PO 4 -3 ) which can be absorbed, although rather inefficiently, into plants and thereafter used as nutrition. It is well known in the prior art that phosphorus is biologically active and nutritionally useful to plants only in the phosphoric form (PO 4 -3 ). A common source of the phosphoric radical (PO 4 -3 ) for fertilizers is phosphoric acid.
Many of the phosphorus fertilizers currently used have a number of undesired qualities. First, if not used rather quickly, they tend to form precipitates if prepared in concentrated solutions. Further, they must be maintained within a narrow pH range to prevent precipitation, which results in fertilizers with limited application. Only soluble materials can be utilized by plants.
Still another problem with phosphorus containing fertilizers, particularly phosphoric fertilizers, is that they are not readily absorbed by foliage and must be applied to the soil and thereafter absorbed by the plant root system. Since only a small portion of the phosphoric fertilizer applied to the soil is actually absorbed by a root system, frequent reapplication usually occurs. This is undesirable because it can lead to leaching of phosphate into the groundwater which may cause eutrophication of lakes, ponds and streams.
Prior art formulas of phosphorus fertilizers have identified these problems. U.S. Pat. No. 5,514,200, issued to Lovatt, describes a formula utilizing the more readily absorbed phosphorous form (PO 3 -3 ) in a composition buffered with an organic acid. However, as is discussed below, the present invention represents an improved and more effective composition for providing phosphorus to plants.
SUMMARY
The present invention is directed to a process for preparing a stable and highly concentrated phosphorus fertilizer which is stable when stored for long periods of time and, when subsequently diluted and thereafter applied to plants and/or soil, can be easily absorbed through the foliage or the root system of a plant. The absorbed phosphorus is then used by plants to perform or accelerate biological functions. Further, the present invention is directed to phosphorous acid or its salts dissolved in water and stabilized with an inorganic complexing agent such as polyphosphoric acid to prevent phosphorus or calcium phosphate precipitation. Although the present invention can function properly and remain dissolved in solution in the range of pH between 0.5 and 10.0, it is preferably maintained in a pH range between 5.0 and 7.5 for ideal absorption into plants.
DESCRIPTION
To prepare the more readily assimilated phosphorus, phosphorous acid or its salts are dissolved in water. The solution is then stabilized by adding polyphosphoric acid (superphosphoric acid) or its salts, added in intervals, until the polyphosphoric acid constitutes 1-30% by weight of the solution. Addition of the polyphosphoric acid or its salts prevents the precipitation of by-products such as calcium phosphate and increases the uptake of phosphorus by plants. The novel composition can be delivered to plants by foliar or soil applications such as through an irrigation system. The phosphorus fertilizers so prepared are taken up by plants in the phosphorous form and are gradually converted by enzymes in the plants to phosphoric form to perform or accelerate biological functions in the plant.
Phosphoric acid exists in the meta (HPO 3 ) n , pyro (H 4 P 2 O 7 ) and ortho (H 3 PO 4 ) form. Polyphosphoric acid or its salts function as complexing agents for minerals in water and prevent precipitation of phosphorus from phosphorous acid. Salts of polyphosphoric acid include but are not limited to potassium polyphosphate, ammonium polyphosphate, sodium polyphosphate, zinc polyphosphate, magnesium polyphosphate and iron polyphosphate. Polyphosphoric acid is a genus which includes the following species: polyphosphoric acid, dipolyphosphoric acid, tripolyphosphoric acid, tetra polyphosphoric acid, penta polyphosphoric acid, hexapolyphosphoric acid or the combinations.
The desired pH range is between 5.0 and 7.5. However, the pH can be from 0.5 to 10.0.
In order to more clearly define the invention, the following examples of methods of preparation are set forth. These examples are illustrative only and are not limiting as to the scope of the invention. Examples I and VII are typical fertilizer found in the prior art. Examples II and VIII embody the present invention with regards to phosphorous acid and an inorganic buffering agent. Examples III and IX are also prior art formulations embodying formulations of the Lovatt U.S. Pat. No. 5,514,200 which utilize phosphorous acid buffered with an organic acid. Examples IV, V and VI set forth alternative compositions of matter embodying the concept of the present invention.
EXAMPLE I (PRIOR ART)
A 0-28-25 fertilizer was prepared by mixing the following:
(1) 376 grams water
(2) 299 grams potassium hydroxide
(3) 325 grams phosphorous acid
The fertilizer had a pH of approximately 6.2 with a resulting appearance that was cloudy. The solution was analyzed to contain 25.9% P 2 O 5 and 25.2% K 2 O.
EXAMPLE II
A 0-28-25 fertilizer was prepared by mixing the following:
(1) 366 grams water
(2) 299 grams potassium hydroxide
(3) 315 grams phosphorous acid
(4) 10 grams polyphosphoric acid
The fertilizer had a pH of approximately 6.2 with a resulting appearance that was clear and was analyzed to contain 28.1% P 2 O 5 and 24.9% K 2 O.
EXAMPLE III (U.S. PAT. NO. 5,514,200)
A 0-28-25 fertilizer was prepared by mixing the following:
(1) 356 grams water
(2) 299 grams potassium hydroxide
(3) 325 grams phosphorous acid
(4) 20 grams citric acid
The resulting appearance was clear with some precipitation. The solution was analyzed to contain 26.2% P 2 O 5 and 24.7% K 2 O.
In comparing Examples I, II, and III, the results indicate that the composition embodying the invention, Example II, results in over 10% additional P 2 O 5 in solution than either the prior art or the recent patented formulation according to Lovatt.
EXAMPLE IV
A 4-25-15 fertilizer was prepared by mixing the following:
(1) 438 grams water
(2) 180 grams potassium hydroxide
(3) 285 grams phosphorous acid
(4) 87 grams urea
(5) After all the materials were dissolved, 10 grams of ammonium polyphosphate was added.
The resulting fertilizer had a pH of 5.9 and analyzed to obtain 4.1%N, 25.2% P 2 O 5 and 14.9% K 2 O.
EXAMPLE V
A 0-40-0 fertilizer was prepared by mixing the following:
(1) 534 grams water
(2) 463 grams phosphorous acid
(3) 3 grams sodium tripolyphosphate
The fertilizer had a pH of 0.5 and was clear in appearance. This fertilizer can be further diluted with water at ratios of concentrate to water up to 1:10,000 and used as soil application or with irrigation water.
EXAMPLE VI
A 0-27-25 fertilizer was prepared by mixing the following:
(1) 308 grams water
(2) 307 grams phosphorous acid
(3) 365 potassium carbonate
(4) 20 grams potassium polyphosphate
The pH was approximately 6.2 and the fertilizer was observed to remain in solution for 30 days without formation of precipitate.
EXAMPLE VII (PRIOR ART)
A 4-25-15 fertilizer was prepared by mixing the following:
(1) 448 grams water
(2) 180 grams potassium hydroxide
(3) 285 grams phosphorous acid
(4) 87 grams urea
The fertilizer had a pH of approximately 5.8 and was analyzed to contain 4.1% N, 24.8% P 2 O 5 and 15.3% K 2 O.
EXAMPLE VIII
A 4-25-15 fertilizer was prepared by mixing the following:
(1) 448 grams water
(2) 180 grams potassium hydroxide
(3) 275 grams phosphorous acid
(4) 87 grams urea
(5) 10 grams polyphosphoric acid
The fertilizer had a pH of approximately 5.9 and was analyzed to contain 4.1% N, 25.2% P 2 O 5 and 15.1% K 2 O.
EXAMPLE IX (U.S. PAT. NO. 5,514,200)
A 4-25-15 fertilizer was prepared by mixing the following:
(1) 428 grams water
(2) 180 grams potassium hydroxide
(3) 285 grams phosphorous acid
(4) 87 grams urea
(5) 20 grams citric acid
The fertilizer had a pH of approximately 5.1 and was analyzed to contain 4.1% N, 24.6% P 2 O 5 and 15.0% K 2 O.
EXPERIMENTS
Experiment 1
The 3 fertilizer samples prepared as Examples I, II, and III were diluted with water at a ratio of concentrate to water of 1:250. The solutions were then sprayed on tomato plants at 5 mililiters per each plant. Four different plants were sprayed with each solution. One week after the application of the solution, the twelve plants were cut at soil level, washed with dilute acid and water and then dried in an oven at 75° C. for 24 hours. The dried plants were then analyzed for total phosphorus and potassium. The analysis results are as follows:
______________________________________DRIED PLANT ANALYSIS Example I Example II Example III Prior art Invention Lovatt patent______________________________________Total P (%) 0.69 0.82 0.69Total K (%) 1.90 1.91 1.79______________________________________
The results of Experiment 1 indicate that the composition of Example II provides an improved rate of absorption of phosphorus into a plant 18.18% better when compared with the prior art or a comparable formula as taught by Lovatt without affecting the potassium uptake.
Experiment 2
Experiment 1 was repeated upon bush bean plants rather than tomato plants. The analysis results are as follows:
______________________________________DRIED PLANT ANALYSIS Example I Example II Example III Prior art Invention Lovatt patent______________________________________Total P (%) 0.26 0.31 0.27Total K (%) 1.73 1.80 1.78______________________________________
The results indicate that the novel composition of Example II provides an improved rate of absorption of phosphorus (19.2% improvement) into a bush bean plant when compared to the prior art or a comparable formula according to Lovatt (4% improvement).
Experiment 3
Samples from Examples VII, VIII, and IX were diluted 250 to 1 with water and then sprayed on tomato plants at 5 mililiters per plant. Four different plants were sprayed with each solution. One week after the application of the solution, the twelve plants were cut at soil level, washed with dilute acid and water and then dried in an oven at 75 degrees C. for 24 hours. The dried plants were then analyzed for nitrogen, phosphorus and potassium. The analysis results are as follows:
______________________________________DRIED PLANT ANALYSIS Example VII Example VIII Example IX Prior art Invention Lovatt patent______________________________________Total N (%) 3.9 3.9 3.6Total P (%) 0.41 0.49 0.40Total K (%) 2.82 2.95 2.93______________________________________
As in Experiments 1 and 2, the fertilizer embodying the invention increased the plant's phosphorus intake by about 20% when compared to examples of the prior art.
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Concentrated phosphorus fertilizers of the phosphorous variety are described which are absorbed quickly into plant systems and improve plant growth. When diluted with water, there is formed a substantially fully soluble fertilizer having a foilage-acceptable pH.
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[0001] This application is a continuation-in-part of U.S. provisional patent application Serial No. 60/072,574, filed Jan. 26, 1998.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to determining the prognosis of a patient with breast cancer by determining whether the HER-2/neu gene is amplified in tumor cells.
[0004] 2. Description of Related Art
[0005] Breast cancer remains a major cause of illness and death among women in the United States, with over 180,000 new cases and 44,000 deaths per year (American Cancer Society, 1997). Possibly the most important predictor of clinical course in breast cancer is the presence or absence of lymph node metastases. Many prognostic indicators aid in evaluation of invasive cancers in addition to the presence or absence of lymph node metastasis, including tumor size, histologic type, tumor grade (differentiation reflected in extent of gland formation), nuclear grade (extent of nuclear alteration and frequency of mitosis), DNA content (ploidy), and hormone receptor status. A reasonable and desirable approach would be the use of prognostic factors to risk-stratify invasive breast cancer patients into low-risk and high-risk groups in terms of the probability of recurrence (McGuire, et al., 1990).
[0006] The HER-2/neu (ERBB2) gene is an oncogene which shares significant homology to the epidermal growth factor receptor (EGFR) gene (Yamamoto, et al, 1986) and the retroviral gene v-erbB. It was first detected as a mutated transforming gene in chemically induced rat neuronal tumors. It has been isolated from diverse sources, including: rat neuroblastoma (Schechter et al, 1985); human tumor lines from gastric cancer (Fukushige et al, 1986); salivary adenocarcinoma (Semba et al, 1985); and a human breast cancer cell line where HER-2/neu was identified in an amplified form (King et al, 1985). The gene has been localized to 17q11.2q12 (Human Gene Mapping 11, 1991), in a region where several genes relevant to breast cancer are located, including BRCA1 estradiol-17β dehydrogenase, NM23 and RARA.
[0007] Current evidence indicates that HER-2/neu protein over expression and gene amplification are indicative of poor patient prognosis at all stages of breast tumor development. Amplification appears early in tumor progression (Iglehart et al 1990 and Van de Vijver et al 1988), and when present is homogeneously distributed throughout the tumor (Press et al, 1994). Thus, it is a logical choice as a prognostic marker when used as an adjunct with other accepted prognostic indicators.
[0008] While such immunoassays for HER-2/neu protein have been commercially available, interpreting results is somewhat difficult. Protein denaturation or degradation during handling, staining, embedding in paraffin and sectioning gives variable results, including both false negatives and false positives. Additionally, slightly different conditions during antibody-antigen binding results in false positives and false negatives. Unacceptable results have been reported for immunohistochemical detection of HER-2/neu amplification. See Thor et al 1989; Richner et al, 1990; O'Reilly et al, 1991; and Lovekin et al, 1991. By contrast, counting the number of copies of the HER-2/neu gene in a cell represents a more objective determination and involves DNA markers which are less susceptible to degradation and provide less variable results.
[0009] HER-2/neu gene amplification status is useful as an adjunct in the evaluation of the prognosis of node negative breast cancer patients and is also an independent marker of high risk in node-negative patients. Amplification of HER-2/neu is indicative of poor patient prognosis at all stages of breast cancer development and correlates with relatively shorter disease-free and overall survival.
[0010] Studies have shown positive correlation between HER-2/neu gene amplification and other common indicators of poor prognosis in breast cancer (Tsuda, et al., 1989 and Seshadri, et al., 1993 and Slamon et al, U.S. Pat. No. 4,968,603). However, even strong breast cancer prognostic factors, such as number of positive lymph nodes, tumor size and histograde do not predict patient outcome unfalteringly (Wright, et al, 1989 and Ro, et al., 1989). Current evidence indicates that HER-2/neu protein over expression and gene amplification are indicative of poor patient prognosis at all stages of breast cancer development (Seshadri, et al., 1993, Wright, et al., 1989 and Niehans et al., 1993). Because HER-2/neu amplification appears early in breast cancer progression (Iglehart, et al., 1990 and van de Vijver, et al, 1988) and, when present is homogeneously distributed throughout the cancer (Inglehart, et al., 1990 and Press, et al., 1994), it can serve as a prognostic marker for this disease (when used as an adjunct with other accepted prognostic indicators).
[0011] The use of Fluorescent In-Situ Hybridization (FISH) targeted to the HER-2/neu gene, has successfully demonstrated gene amplification in breast cancer cell lines and primary tumors, and has shown that FISH results are concordant with other measures of amplification (Kallioniemi, et al., 1992). [The gene has been localized to 17q11.2-q12 (Human Gene Mapping 11, 1991), in a region where several genes relevant to breast cancer are located, including BRCA1, estradiol-17 dehydrogenase, NM23, and RARA.] FISH technology combines the advantages of direct gene amplification assessment with direct localization in morphologically identified tumor cells. FISH is applicable to tumors of all sizes because studies can be performed on sections from the original specimen blocks used for diagnosis. In many samples, direct comparison can be made with FISH assays on normal cells from the same preparation. Further, if amplification were localized rather than diffusely distributed within a tumor, it would be detectable by FISH but could be diluted below detectable limits in extracted tumor DNA required for other procedures.
[0012] When performing an assay of such importance to the patient, it is critical to have appropriate controls. Sections of previously tested tissue are somewhat undesirable as controls due to cell variability, unclear boarders, necrotic tissue in the center of the tumor, variable responses to protease digestions and finite source material. Therefore, there is a need for quality control materials which can be run with every test which lack the above mentioned problems.
[0013] There is also a need for a set of statistical benchmarks to allow the medical practicioner to stratify the patient according to likelihood of cancer recurrence. This will aid the practioner and patient in deciding whether agressive treatments (e.g. chemotherapy, radiation and anti-HER-2/neu therapy) should be empoloyed in lieu of a passive “watchful waiting” approach.
SUMMARY OF THE INVENTION
[0014] The present invention is directed to methods and reagents which determine the number of copies of the HER-2/neu gene in a breast cancer specimen. This method uses a FISH assay for HER-2/neu in surgically removed breast cancer tissue. Determination of an abnormally high copy number of the gene correlates with poor prognosis and such patients should be treated aggressively.
[0015] The present invention is also directed to a set of control slides, one of which has a normal copy number of the HER-2/neu gene, one has a high copy number of the HER-2/neu gene and one has a slightly elevated copy number of the HER-2/neu gene.
[0016] The present invention further includes the preparation of control slides using cell lines instead of primary tumor tissue. The preferred cell lines used for controls are one with high amplification of the HER-2/neu gene, one with non-amplification and one with low amplification.
[0017] The HER-2/neu gene detection system of the present invention is a kit consisting of DNA probe and detection reagents that yields a green fluorescent signal at the site of each HER-2/neu gene, on a blue fluorescent background of stained nuclear DNA. The kit is intended to be used with sections (4 μm) of formalin-fixed, paraffin-embedded human breast cancer tissue. The kit is untended to include or recommend the use of another kit which includes the control lines.
[0018] The HER-2/neu gene detection system of the present invention is preferably a fluorescence In situ hybridization (FISH) DNA probe assay that determines the qualitative presence of HER-2/neu gene amplification on formalin-fixed, paraffin-embedded human breast tissue as an aid to stratify breast cancer patients according to risk for recurrence or disease-related death. It is indicated for use as an adjunct to existing clinical and pathologic information currently used as prognostic indicators in the risk stratification of breast cancer in patients who have had a primary, invasive, localized breast carcinoma and who are lymph node-negative.
[0019] A recent review and comparison is Ross et al, The Oncologist 3: 237-252 (1998).
BRIEF DESCRIPTION OF FIGURES
[0020] [0020]FIG. 1 is a survival curve of HER-2/neu Amplification Status with the cumulative probability of early recurrence.
[0021] [0021]FIG. 2 is a survival curve of HER-2/neu Amplification Status with the cumulative probability of disease-free survival.
[0022] [0022]FIG. 3 is a tumor size cumulative probability-1 cm overall survival
[0023] [0023]FIG. 4 is a an interaction, without error bars, of HER-2/neu amplification and tumor size cumulative probability of overall survival HER-2/neu Amplification Status (amp+/amp−) and tumor size (>1 cm/<1 cm)
DETAILED DESCRIPTION OF THE INVENTION
[0024] The HER-2/neu gene amplification detection system according to the present invention is a fluorescence in situ hybridization (FISH) DNA probe assay intended for formalin fixed, paraffin-embedded human breast tissue as an aid in predicting risk of breast cancer recurrence so that patient management decisions can be improved. Post surgery lymph node negative patients with no amplification may receive little or no further treatment whereas patients with tumors having the HER-2/neu gene amplified may receive more aggressive monitoring, chemotherapy and/or radiation. Clearly, the appropriate use of the drug HERCEPTIN®(Genentech, South San Frisco, Calif.), humanized monoclonal antibody to HER-2/neu, is determinable by measuring HER-2/neu gene amplification. In the few months since release of the commercial assay it has become accepted standard practice to include the HER-2/neu gene amplification detection system routinely on breast cancer patients and particularly before the particular therapy noted above.
[0025] The relationship between HER-2/neu gene amplification and probability of remaining disease free and surviving is demonstrated in the Figures. These clinical studies are based on breast cancer patients who had excision of a primary, invasive, localized breast tumor, who were node negative and who did not receive any adjuvant therapy except in cases of disease recurrence. While remaining disease-free is somewhat different from survival, both measures are important even when the data does not exactly parallel.
[0026] While this specification is described with respect to breast cancer, one skilled in the art will readily appreciate the application of the techniques herein described of use with other cancers where the HER-2/neu gene is amplified, such as ovarian, prostate, endometrial and certain colon cancers. In such situations, different control cell lines and different amplification cut off numbers may be required but the need for appropriate quality controls remains.
[0027] Briefly, the methodology is as follows. Sections of formalin-fixed, paraffin-embedded breast cancer tissue mounted on microscope slides are pretreated chemically (Pretreatment Step, reduction of peptide disulfide bonds) and enzymatically (Protein Digestion Step, digestion of proteins) to remove proteins that block DNA access. The DNA in the sections is converted from double- to single-strand by solution denaturation at 75° C. using a mixture of 20× SSC (saline sodium citrate) and formamide. A hybridization solution, containing labeled DNA probe which is complementary to the HER-2/neu gene sequence, is applied to the tissue section, which is then incubated under conditions favorable for annealing of probe DNA and genomic DNA sequences. Unannealed probe is washed off using a mixture of 20× SSC and formamide. The hybridized probe is detected using a fluorescently-tagged ligand (fluorescein-labeled avidin) which binds to the label on the DNA probe, thereby immobilizing the fluorescein at the site of the HER-2/neu gene. The remainder of the DNA is then stained with an intercalating fluorescent counterstain (DAPI in Antifade). Excitement of fluorescein and DAPI by light from a mercury arc lamp with appropriate filters in an epifluorescence microscope results in the emission of green and blue light, respectively. The observer selects for these two colors by using a microscope filter set designed for simultaneous viewing of DAPI and fluorescein, and scores nuclei in the tissue section for the number of green signals on a blue background.
[0028] When performing such an assay of great importance to the patient, it is always necessary to use the best available controls. Tissue sections from an excised tumor are somewhat variable by being a mixed population of cells, sometimes having unclear boarders. Tissue sections can only be as good at the tumor itself which may have a necrotic center, have blood vessels through it, and contain a number of inflammatory response cells. The density of cells in a primary tissue section (tumor or normal) may be high with a 4 μm thick section having only a small part of a cell. In FISH assays, a protein digestion step is performed. The digestion conditions differ between different tumors and normal cell types. All of this requires skilled individuals to determine which cells are appropriate tumor cells to be considered on the slide. Additionally, tumor and normal sections represent a finite source of controls as each new tissue block will require restandardization before it can become a control standard.
[0029] By comparison, cell lines have the advantage of uniformity in cell type with no chance of misidentifying the cells. The cell concentration is regulatable so that the control slide will have cells evenly distributed and clearly separated. Since the cell line is uniform, the protein digestion conditions may be perfected, not merely optimized. Uniformity also reduces interpretation mistakes and permits use of less skilled, and less expensive, personnel. Because cell lines are used, the exact cell type may be used indefinitely as an permanent source of control cells without further need to restandardize the cell line. Should doubt remain as to the advantages of standardized controls over previously tested samples, several subclasses of U.S. patents are devoted to analytical clinical controls, their preparation and use.
[0030] In the present invention, the control slides include a slide with a normal copy number of the HER-2/neu gene, a slide with a highly amplified copy number of the HER-2/neu gene, and a slide with a lowly amplified copy number of the HER-2/neu gene. Representative examples are:
Level 1 Control ATCC HTB 132 (MDA-MB-468) non-amplification, ≦3 copies per cell Level 2 Control ATCC HTB 133 (T-47D) low amplification, 3-10 copies per cell Level 3 Control ATCC HTB 30 (SK-BR-3) high amplification, ≧10 copies per cell
[0031] The use of a control with a low level of amplification is preferred as clinical samples with low levels of gene amplification are the mostly likely to be miss detected. Such primary cancers may be difficult to find and standardize, thus the use of such a cell line has considerable benefits.
[0032] It will be appreciated that numerous other cell lines may be used as controls provided that the number of copies of HER-2/neu gene is adequately quantified and it is uniform in the cell line. Cell line controls should fall into one of the three level control ranges recited above. Once another cell line has been so standardized, it may be used in lieu of the specific cell lines recited above. It is preferred to use tumor cell lines originating from the same tissue as being tested from the patient For example, the three cell lines above originated from breast cancers.
[0033] Briefly, control slides are prepared by culturing the cell lines, suspending a predetermined concentration of cells in plasma, clotting the plasma, formalin fixing, embedding in paraffin, sectioning and mounting on a slide. It should be noted that additional and alternative steps of preparing the slide for FISH may also be performed with a goal of preparing the control cell line to resemble breast tumor tissue for comparative parallel testing. Such sample preparation techniques are described for example, in Diagnostic Molecular Pathology , Vol. 1, IRL Press, NY.
[0034] While these steps are individually well known in the art, numerous variations on the above procedure may be used. For example, other solidifying materials may be used in the place of plasma provided that they do not alter the cellular DNA. Examples include agarose, gelatin, pectin, alginate, carrageenan, monomers, polymers etc. where the gel is formed by cooling, adding ions (calcium, potassium) adding a polymerizing or a cross linking agent, etc. Other fixatives are known and may be used if any is desired at all. Paraffin embedding may be standard but other similar materials may be used and may even be optional. Likewise, the thickness of the section cut from a block is variable and is optimized depending on the microscope and assay conditions.
[0035] The relative sensitivity and specificity of the HER-2/neu gene amplification detection system for measuring HER-2/neu gene copy numbers was accessed. Breast cancer specimens with a known HER-2/neu gene copy and expression levels were selected as archival tissue specimens. Amplification was previously determined by Southern Blot hybridization or dot blot using extracted DNA. Expression had been determined by Northern hybridization, Western immunoblotting and/or immunohistochemistry using total RNA, total protein or histologic sections from tumor tissue. Slamon et al, 1989 and Press et al, 1993. Gene amplification levels correlated with gene expression levels in approximately 90% of the breast cancers under research conditions. In a less standardized clinical setting, the divergence may be higher. The comparison with FISH was performed by the HER-2/neu gene amplification gene detection system on 140 breast cancer specimens. Forty-nine were considered true positive, 90 true negative, 0 false positive and 1 false negative. This is a the relative sensitivity value of 98% and the relatively specificity value of 100%.
[0036] The expected HER-2/neu gene detection system assay result in normal breast tissue (non-cancerous) was estimated in a population of 20 breast tissue samples from reduction mammoplasties. The overall observed mean was 2.2 signals per nucleus with a range of 1.8-2.6 signals per nucleus. The target population for analysis using the HER-2/neu gene detection system was patients with primary node-negative, invasive breast carcinoma. The expected prevalence of early recurrence within 2 years is 4 to 6%. The expected prevalence of recurrence within 3 years is 2 to 10%. The expected prevalence of disease-related death (within 3 years) is 10 to 15% (Clinical Oncology, 1993, page 207).
[0037] A clinical study evaluated HER-2/neu gene amplification status in 220 women with node negative invasive breast cancer whose only course of treatment was surgery, unless diagnosed with disease recurrence. For this study population HER-2/neu amplification was shown to have predictive power independent of the other prognostic markers evaluated (patient age at diagnosis, tumor size, tumor grade, and estrogen receptor). HER-2/neu was shown to be the strongest predictor for early recurrence (within 24 months), recurrence and disease-related death.
[0038] The negative predictive value, probability of no disease being present in women with HER-2/neu non amplified tumors, was found to be high three years after diagnosis (93.3% based on a prevalence of 10.4%). The probability of being alive three years after diagnosis was 99.4%, based on a prevalence of 2.4%.
[0039] HER-2/neu was analyzed along with and controlling for the above listed prognostic factors. The combined effect (interaction) of tumor size and HER-2/neu amplification status is presented in FIG. 4. One analysis used tumor size at 1 cm (FIG. 3) and additional analysis looked at tumor size at 2 cm. In both sets of analyses, tumor size is not significant (p>0.05) for predicting recurrence and disease-related death when the tumor is HER-2/neu amplified.
[0040] When the tumor is not amplified for the HER-2/neu gene, tumor size is also an insignificant predictor of recurrence and disease-related death within 3 years. With longer follow-up, disease-related death was significantly predicted in a comparison of tumors>1 cm. In this particular data set, there were no disease-related deaths for HER-2/neu non-amplified tumors.
[0041] These data show that for this study tumor size failed to be a good predictor of recurrence and disease-related death within 3 years. Tumor size is of little consequence in HER-2/neu positive tumors and only becomes of value when evaluating disease-related death, in HER-2/neu negative tumors . HER-2/neu amplification was shown to have predictive power independent of all other prognostic markers evaluated and to be the strongest predictor for recurrence and disease-related death.
[0042] The following Examples utilized the commercially available Oncor INFORM HER-2/neu Gene Detection System (Ventana Medical Systems, Gaithersburg, Md., USA), Cat. No: S8000-KIT. The Procedure and Interpretation Guide enclosed with the kit is expressly incorporated by reference. This kit was the subject of a FDA PMA No. P9400004, the public contents of which are expressly incorporated by reference.
EXAMPLE I
Preparation of HER-2/neu Probes
[0043] Partial restriction enzyme digests of human Chromosome 17 DNA were prepared to create a library. Fragments were cloned into BAM H1 restriction sites on a cosmid vector and grown in E. Coli HB 101. Positive clones were selected with Kanamycin containing medium. The cosmid probe set represent overlapping segments with a four member contig. A probe used to detect the cDNA is preparable using primers 5′-CGGCCAAGATCCGGGAGTTGGT-3′ and 5′-TCTTGATGCCAGCAGAAGTCAGGC-3′. Numerous publications exist regarding the HER-2/neu gene and other probes may be prepared and used.
[0044] Biotintylated HER-2/neu DNA probe was prepared containing a biotin-labeled single-stranded DNA fragment derived from human genomic DNA sequences, suspended in a solution of formamide, SSC and blocking DNA. The probe DNA sequences are complementary to the sample HER-2/neu (erb-b2) gene sequence and specifically bind to them upon hybridization. The probe used below is the commercially available HER-2/neu probe (Ventana Medical Systems, Gaithersburg, Md.)
EXAMPLE II
Sample Preparation for Fish Assay for HER-2/neu
[0045] Slides were prepared by cutting paraffin embedded tissue samples into 4 μm thin sections and applying them to silanized or positively charged slides. The slides were air dried and baked at 65° C.±5° C. overnight. The slides were deparaffinized in fresh xylene that has not been used for more than one week and repeated through three changes of xylene for five minutes each. The slides were then washed in fresh 100% ethanol that has not been used for more than one week for two minutes. The ethanol washing was repeated and the slides allowed to air dry.
[0046] The slides were pretreated by immersing slides in a coplin jar containing 40 ml of pre-warmed 30% w/v sodium bisulfite Pretreatment Solution in a 43° C.±2° C. water bath for 15 minutes. This solution is designed to reduce disulfide bonds, aid in protein digestion and improve probe penetration to target DNA sequences. The slides were then washed in 40 ml of 2× SSC at room temperature for 1 minute and then washed twice using fresh 2× SSC. The slides were then dehydrated through a room-temperature graded series of ethanol solutions for 2 minutes in each of 70%, 80%, 90% and 100% ethanol and allowed to air dry inclined with label end down.
[0047] 40 ml of Protein Digesting Enzyme Working Solution was freshly prepared by mixing 25 mg of proteinase K in 37° C.±2° C. of prewarmed 2× SSC. Slides were immersed in a coplin jar of prewarmed Protein Digesting Enzyme Working Solution and incubated at 37° C.±2° C. for 40 minutes. This solution is needed to digest protein and improve probe penetration. The slides were washed three times in 40 ml of fresh 2× SSC at room temperature for 1 minute. The slides were dehydrated through the room-temperature graded series of ethanol solutions for 2 minutes in each grade of ethanol: 70%, 80%, 90% and 100% and allowed to air dry inclined with label end down.
[0048] The slides were denatured by immersing them in a coplin jar containing 40 ml of prewarmed Denaturation Solution (70% formamide/2× SSC, pH 7.0) in a 75° C. water bath for 8 minutes. The slides were immediately transferred to the pre-chilled (−20° C.±5° C.) 70% ethanol and rinsed for 2 minutes. The rinse was repeated in pre-chilled (−20° C.±5° C.) 80%, 90%, and 100% ethanol solutions, successively and allowed to air dry inclined with label end down.
[0049] The HER-2/neu DNA probe was prewarmed at 37° C.±2° C. for 5 minutes, vortexed for 1 minute and centrifuged for 2 to 3 seconds to collect contents in the bottom of the tube. 10 μl of probe solution was pipetted onto the denatured tissue section and covered gently with a 25 mm×25 mm glass coverslip. Larger tissue sections may require up to 20 μl of probe and larger glass coverslips. The slides were incubated at 37° C.±2° C. for 12 to 16 hours in a humidified chamber.
[0050] The coverslips were then removed by sliding it to the side and lifting the overhanging edge with forceps. The slides were washed in a coplin jar containing 40 ml of pre-warmed Post-Hybridization Wash Solution (50% Formamide/2× SSC, pH 7.0) in the 43° C.±°C. water bath for 15 minutes. The slides were then rinsed in a coplin jar containing 40 ml of pre-warmed 2× SSC in the 37° C. water bath with frequent agitation for 10 minutes and repeated with fresh 2× SSC and placed in a coplin jar containing 40 ml of 1× PBD (phosphate buffered detergent) at 18° C. to 25° C.
[0051] 60 μl of Blocking Reagent One (0.05 g nonfat dry milk, Nonidet P40, phosphate buffer and sodium azide) was added to each slide, a plastic coverslip placed over the solution and incubated 5 minutes in a humidified chamber at room temperature. The plastic coverslip was pealed off and blotted dry for re-use. The slide was tilted to allow fluid to drain briefly. This reagent contains salts, detergent, proteins and sodium azide (preservative) which aid in reducing non-specific binding of fluorescein-labeled avidin to the hybridized and washed tissue section.
[0052] 60 μl of Detection Reagent (fluorescein labeled avidin in sodium azide preservative) was added to each slide and the plastic coverslip replaced over the solution. The slide was incubated 20 minutes in a humidified chamber at room temperature. After 10 minutes of the 20 minute incubation, one lifts and replaces the plastic coverslip to ensure even fluid distribution. This reagent detects hybridized probe DNA by binding to the biotin conjugated to the probe.
[0053] The plastic coverslip was then pealed off and discarded. The slides were washed in a coplin jar containing 40 ml of 1× PBD at room temperature for 2 minutes and the wash repeated 2 times using fresh 1 × PBD.
[0054] The slides were removed from 1× PBD, tilted to allow fluid to drain briefly, then excess fluid was briefly blotted from the edge.
[0055] 60 μl of Blocking Reagent Two (0.05 ml goat serum, Nonidet P40, phosphate buffer and sodium azide) was added to each slide and a fresh plastic coverslip placed over the solution. The slides were incubated 5 minutes in a humidified chamber at room temperature, the plastic coverslip pealed off and blotted dry for reuse and the slide tilted to allow fluid to drain briefly. This reagent is a mixture of salts, detergent and proteins in a sodium azide preservative which reduce non-specific binding of the Anti-Avidin Antibody to the hybridized ans washed tissue section during the signal amplification phase of detection.
[0056] 60 μl of Biotin-labeled Anti-Avidin Antibody was added to each slide and the plastic coverslip replaced over the solution. Incubation was for 20 minutes in a humidified chamber at room temperature. At 10 minutes of incubation, the plastic coverslip was lifted and replaced to ensure even fluid distribution. This reagent binds to fluorescein-labeled avidin what has previously bound to the hybridized probe and allows amplification of the fluorescent signal by providing multiple additional biotin moieties for binding by fluorescein-labeled avidin for each one originally bound with probe. The reagent contains sodium azide as a preservative.
[0057] The plastic coverslip was removed and discarded. Slides were washed in a coplin jar containing 40 μl of 1× PBD at room temperature for 2 minutes. This wash was repeated 2 times using fresh 1× PBD.
[0058] 60 μl of Blocking Reagent One was applied to each slide and a fresh plastic coverslip placed over the solution. Incubation was for 5 minutes in a humidified chamber at room temperature. After that the plastic coverslip was pealed and blotted dry for reuse while the slide was tilted to allow fluid to drain briefly.
[0059] 60 μl of Detection Reagent was applied to each slide and the plastic coverslip replaced over the solution. Incubation was for 20 minutes in a humidified chamber at room temperature. After 10 minutes of incubation, the plastic coverslip was lifted and replaced to ensure even fluid distribution.
[0060] The plastic coverslip was pealed and discarded and the slides washed in a coplin jar containing 40 ml of 1× PBD at room temperature for 2 minutes. The wash was repeated 2 times using fresh 1× PBD.
[0061] The cell nuclei were counterstained by adding 20 μl of DAPI/Antifade (DAPI, glycerol, P-phenylene diamine dihydrochloride, sodium bicarbonate, sodium hydroxide in phosphate buffered saline) to each slide and covered with a 24×50 mm glass coverslip. Stained slides may be stored in the dark at −15° C. to −25° C. for up to five days before analysis. This reagent is a mixture of a blue-fluorescing DNA-intercalating dye and a chemical which reduces photo bleaching. This is used to counterstain nuclear DNA blue to prolong probe signal fluorescence.
[0062] If the tissue section was insufficiently digested under the designated digestion conditions and is determined to interfere with interpretation of assay results, an extended protein digestion may be used as follows. The coverslip was removed by gently wiping off the immersion oil with tissue paper and soaking the slide in 40 ml 2× SSC, pH 7.0 in a coplin jar at room temperature until the coverslip falls off. The slide was placed in a coplin jar containing fresh 2× SSC, pH 7.0 for several minutes to clean off any residual DAPI/Antifade.
[0063] The slides were placed in prewarmed Protein Digestion Enzyme Working Solution at 37° C.±2° C. The effect of this protein digestion and the initial digestion is cumulative. Twenty (20) additional minutes of digestion might be an appropriate starting time for tissue that seems very undigested after the initial 40 minute digestion.
[0064] The slides were washed in 40 ml 2× SSC, pH 7.0 room temperature with agitation for 10 seconds, then dehydrated in 70%, 80%, 90%, and 100% ethanol at room temperature for 1 minute each and allowed to air dry. The process above is then repeated.
Example III
Preparation of Control Slides
[0065] The control slides are prepared using the following cell lines:
[0066] Level 1 Control ATCC HTB 132 (MDA-MB-468) cell line
[0067] Level 2 Control ATCC HTB 133 (T-47D) cell line
[0068] Level 3 Control ATCC HTB 30 (SK-BR-3) cell line
[0069] Each cell line is available from the American Type Culture Collection, Manassas, Va., USA and grown using standard media and techniques to produce approximately 1.5×10 8 cells. The cell growth is divided into approximately 30 5×10 6 cells. Pellets of the cultured cells were suspended in a plasma/thrombin matrix and clotted. Fibrin clotted blocks were then formalin fixed. Each block is paraflin embedded, cut into 4 μm sections and mounted on a silanized glass slide. The HER-2/neu Control Slides were stored at 18° C. to 25° C. prior to processing and at −15° C. to −25° C. after processing
EXAMPLE IV
Scoring of Control Slides
[0070] A non-amplified sample has a mean HER-2/neu signal per nucleus less than or equal to (≦) 4. Specimens with a mean signal per nucleus greater than (>) 4 are amplified for the HER-2/neu gene. Control Slides are divided into three (3) categories. These are listed below and should not be confused with the amplification cut-off value of 4.
[0071] Level 1 (0 to 3 Signals/Nucleus) Control Slides
[0072] A Level 1 control has a mean signal per nucleus value of less than or equal to 3. This range of assay scores (0 to 3) is defined as non-amplified for the HER-2/neu gene. In most patient specimens, an internal non-amplified control is present in the form of cells that are identifiably non-cancerous by the criteria of histopathologic morphology.
[0073] Level 1 control slides are 4μm sections of a formalin-fixed, paraffin-embedded human breast cancer tissue culture cell line on silanized slides. The preferred cell line is MDA-MB-468 (ATCC # HTB 132).
[0074] Level 2 (>3 to <10 Signals/Nucleus) Control Slides
[0075] A Level 2 control has a mean signal per nucleus value of greater than 3 to less than 10. This range of assay scores (>3 to <10) is defined as low amplified HER-2/neu gene amplification. Level 2 control slides are 4μm sections of a formalin-fixed, paraffin-embedded human breast cancer tissue culture cell line on silanized slides. The preferred cell line is T-47D (ATCC # HTB 133).
[0076] Level 3 (Symbol≧10 Signals/Nucleus) Control Slides
[0077] Level 3 control specimens represent a highly amplified specimen. A Level 3 control has a mean signal per nucleus value equal to or greater than 10. This range of assay scores (≧10) is well above the cutoff of >4 signals per nucleus. Level 3 control slides are 4 μm sections of a formalin-fixed, paraffin-embedded human breast cancer tissue culture cell line on silanized slides. The preferred cell line is SK-BR-3 (ATCC # HTB 30).
[0078] Level 1, Level 2 and Level 3 controls should be run and evaluated with each run of the HBER-2/neu gene detection system assay. Paraffin-embedded human breast cancer cell lines are run simultaneously with each run of samples. The control slides are read by scoring 20 cells from each of two (2) randomly selected areas of the slide (total of 40 nuclei) and the results interpreted as described below. Scoring criteria for invasive cancer do not apply to the paraffin-embedded cell line controls.
[0079] Because breast cancer cell nuclei are often considerably thicker than the 4 μm sections of tissue required to perform the assay, the control tissue nuclei are frequently not intact. This effect of sectioning will result in the observation of fewer HER-2/neu signals than are actually contained in an intact nucleus.
[0080] The mean signal per nucleus of a Level 1 control must be less than the mean signal per nucleus of a Level 2 control for a processing run to be considered valid. For cell line controls acceptance ranges see the list below:
[0081] Based on 393 observations (40 nuclei scored per observation) of 4 μm sections of the Level I control cell line a mean of 2.4 (standard deviation=0.25) HER-2/neu signals per nucleus was determined.
[0082] Based on 102 observations (40 nuclei scored per observation) of 4 μm sections of the Level 2 control cell line, a mean of 3.5 (standard deviation=0.71) HER-2/neu signals per nucleus was determined.
[0083] Based on 338 observations (40 nuclei scored per observation) of 4 μm sections of the recommended Level 3 control cell line, an acceptance range of 15.8 to 20.0 HER-2/neu signals per nucleus was determined (determined by non-parametric analysis).
[0084] In addition to these HER-2/neu Control Slides, controls may also take the form of 4 μm tissue sections from invasive breast cancers that have been previously identified to have specific levels of HER-2/neu gene amplification by fluorescence in situ hybridization (FISH). Use of breast cancer tissue as control material requires qualification and validation by the user laboratory according to the laboratory's established procedures. While these controls may be useful to classify or group tissues according to HER-2/neu amplification status such controls are time consuming to prepare and generally considered inferior to standardized controls. Additionally, controls from cell lines are homogeneous and reproducible, neither quality can be attributed to surgically removed tumors and their sections
[0085] For determination of HER-2/neu gene amplification level in tissue specimens, 40 nuclei were scored from specimens processed with two (2) lots of the control cell lines. Multiple observers were used (3 or 4) to achieve accurate estimates of the mean and standard deviation (SD). Acceptance ranges were calculated from the mean plus and minus three (3) standard deviations. The results of six (6) Level 1 tissue specimens are summarized below.
TABLE 1 Examples of Level 1 Tissue Specimen Means and Acceptance Ranges Specimen Mean ± SD, ( no. of observations) Acceptance Range 1. 1.96 ± 0.37, (N = 42) 0.85-3.07 2 2.14 ± 0.79, (N = 42) 0-4.51 3 2.01 ± 0.41, (N = 42) 0.78-3.24 4 2.08 ± 0.64, (N = 42) 0.16-4.00 5 1.70 ± 0.31, (N = 36) 0.77-2.63 6 2.01 ± 0.29, (N = 36) 1.14-2.88
[0086] In general, a 4 μm section of a Level 2 control tissue will exhibit a mean of greater than 3 to less than 10 (>3 to <10) HER-2/neu signals per nucleus (40 nuclei scored) when assayed with the HER-2/neu gene detection system of the present invention.
[0087] For determination of HER-2/neu gene amplification level in tissue specimens, 40 nuclei were scored from specimens processed with two (2) lots of the control slides. Multiple observers were used (3 or 4) to achieve accurate estimates of the mean and standard deviation (SD). Acceptance ranges were calculated from the mean plus and minus two (2) standard deviations. The results of ten (10) Level 2 tissue specimens are summarized below.
TABLE 2 Examples of Level 2 Tissue Specimen Means and Acceptance Ranges Specimen Mean ± SD, ( no. of observations) Acceptance Range 1 3.93 ± 0.74, (N = 36) 2.46-5.41 2 5.69 ± 1.31, (N = 36) 3.07-8.31 3 3.97 ± 1.65, (N = 36) 0.67-7.27 4 3.56 ± 0.47, (N = 36) 2.62-4.50 5 3.05 ± 0.41, (N = 36) 2.23-3.87 6 6.35 ± 1.06, (N = 51) 4.23-8.47 7 8.07 ± 2.08, (N = 53) 3.91-12.23 8 6.17 ± 2.19, (N = 36) 1.79-10.55 9 5.52 ± 1.6, (N = 36) 2.32-5.52 10 8.21 ± 2.47, (N = 30) 3.27-13.51
[0088] In general, a 4 μm section of a Level 3 control tissue will exhibit a mean of greater than or equal to 10 HER-2/neu signals per nucleus (40 nuclei scored) when assayed with the HER-2/neu gene detection system.
[0089] In a study for determination of HER-2/neu gene amplification level in tissue specimens, 40 nuclei were scored from specimens processed with two (2) lots of the control slides. Multiple observers were used (3 or 4) to achieve accurate estimates of the mean. Acceptance ranges were calculated from the mean plus and minus two (2) standard deviations with the upper limit truncated at 20. The results of eight (8) Level 3 tissue specimens are summarized below.
TABLE 3 Examples of Level 3 Tissue Specimen Means and Acceptance Ranges Specimen Mean ( no. of observations) Acceptance Range 1 17.72 (N = 36) 12.34-17.72 2 17.46 (N = 36) 11.66-20.00* 3 15.95 (N = 36) 11.15-20.00 4 10.85 (N = 44) 6.25-15.45 5 14.54 (N = 42) 8.84-20.00 6 10.73 (N = 42) 6.16-15.31 7 15.09 (N = 36) 6.19-20.00 8 12.20 (N = 36) 4.46-19.94
EXAMPLE V
Fish Assay for HER-2/neu Amplification on Clinical Samples
[0090] Slides were viewed with an epifluorescence microscope equipped with a DAPI filter set and a DAPI/FITC/Texas Red triple band pass filter set (a filter set capable of simultaneously passing FITC and DAPI fluorescence). A FITC/Texas Red dual band pass filter set (a filter set that allows visualization of the FITC signal but not the DAPI counterstain) is helpful in resolving background from true signal. The microscope may be equipped with 10×, 40× (optional for viewing hematoxylin and eosin stained sections) and 100× objectives and a 100 watt mercury arc light source. Scoring should be performed in a darkened room with excessive light leaking from microscopes minimized.
[0091] Using the DAPI filter set and the same low power objective used to view hematoxylin and eosin stained sections, it was confirmed that the tissue section contains areas of invasion as previously identified in hematoxylin and eosin stained sections. Areas of invasion are scored; carcinoma in situ should not be scored.
[0092] Using the DAPI/FITC/Texas Red triple band pass filter set and a 100× oil objective, the FITC signal was present in approximately ¾ or more of the cancer cell nuclei in the area to be scored.
[0093] It should be noted that non-cancerous cell nuclei (e.g. from normal epithelium) may be more resistant to protein digestion and may show lower levels of hybridization than tumor cell nuclei; therefore, these non-cancerous cell nuclei are not a reliable gauge of hybridization efficiency for the cancerous cell nuclei. The hybridization signals to be scored within a cancer cell nucleus will be of similar size and intensity, whether separated or clustered.
[0094] With the DAPI filter set and a 100× oil objective, individual cancer nuclei were selected for scoring. Only cancer nuclei that are non-overlapping are selected. Severely truncated cancer nuclei were excluded. Cancer nuclei that are less than ⅓ the diameter of the average cancer cell nucleus are not selected. Overdigested and mechanically damaged cancer cell nuclei are not selected. Only cancer cell nuclei that have relatively well-defined borders are selected to be scored.
[0095] Using the DAPI/FITC/Texas Red triple band pass filter set and a 100× oil objective, probe signals were differentiated from background if present. FITC stain appearing over cytoplasm or in the extra-cellular matrix is considered background. Background confined to the cancer nucleus is more difficult to interpret and could interfere with counting, but the background is generally much smaller and more diffuse than true probe signal.
[0096] Using the DAPI/FITC/Texas Red triple band pass filter set and a 100× oil objective, the number of FITC signals present in each of 20 randomly-selected cancer nuclei that meet all the above mentioned criteria were counted. In FISH analysis, signals are often in different planes of focus within the tumor cell nucleus. Focusing up and down through the section to find all of the signals present in the cancer cell nucleus was used. If the signal count is greater than 20 per cancer cell nucleus, it was recorded as 20+ and not grouped with any other counts.
[0097] Scoring in a second area of invasive breast cancer was repeated following all steps above. The two areas examined were separate, distinct microscopic areas within a single section. The total number of cancer nuclei scored was 40 from 2 distinct areas of the same lesion in one section the mean number of HER-2/neu signals per nucleus was determined.
[0098] If more than 5% of the fluorescein signals (those of similar size and intensity to true signal within invasive tumor nuclei) are located over the cytoplasmic compartment or extra cellular matrix and all troubleshooting methods have been exhausted, the background is excessive and the assay repeated.
[0099] When the positive or negative control results fall outside the expected values, then the specimen results are unreliable and the assay repeated.
[0100] When 40 non-overlapping nuclei cannot be identified, then the sample is inadequate and the assay repeated on a new slide.
[0101] When signal intensity varies widely after all troubleshooting methods have been exhausted, then the specimen results is unreliable and the assay repeated.
[0102] Values at or near the cut-off (3.5 to 4.5 mean signals/nucleus) are expected to occur in approximately 3.6% of the patient population. Scoring of borderline specimens should be repeated by another qualified user or the test should be repeated using a new tissue section. If the value of 3.5 to 4.5 persists, then the borderline results should be interpreted with caution and increased emphasis should be given to the other clinical and prognostic information available to the practitioner.
[0103] A retrospective study of 220 node-negative breast cancer patient specimens were collected from multiple sources and analyzed at two clinical sites in the United States. This combined data set was used to determine the association of HER-2/neu gene amplification, using the HER-2/neu gene detection system of the present invention, to the clinical outcomes; early recurrence (within 24 month of diagnosis), recurrences, and death, due to breast cancer.
[0104] The clinical performance characteristics of the HER-2/neu gene detection system are described with amplification defined as >4 signals per nucleus and non-amplification defined as <4 signals per nucleus.
[0105] The HER-2/neu gene detection system was used to retrospectively identify the risk of recurrence and death for node-negative breast cancer patients meeting the following criteria:
[0106] 1) Diagnosis of invasive breast cancer;
[0107] 2) Available formalin-fixed, paraffin-embedded tissue for HER-2/neu analysis;
[0108] 3) Primary treatment surgery only;
[0109] 4) Clinical follow up for at least 2 years for early recurrence, 3 years for recurrence and death.
[0110] The safety and effectiveness of the HER-2/neu Gene Detection System was evaluated in a population of 220 node-negative, invasive breast cancer patients for early recurrence within two years. Two hundred twelve (212) of the 220 specimens were eligible for evaluation of recurrence at anytime and 210 of the 220 specimens were eligible for evaluation of disease-related death. Eight (8) subjects did not recur and were lost to follow-up before 36 months; ten (10) subjects did not die of their disease and were lost to follow-up before 36 months.) The relationship of the HER-2/neu gene detection system assay result to the probability of remaining recurrence-free (disease-free survival) in lymph node negative breast cancer is presented in Table 4. The relationship of the assay results to the probability of surviving (overall survival) is shown in Table 5.
[0111] The survival curves presented in the figures are graphical representations of the probability of early recurrence-free survival (no recurrence within 24 months) (FIG. 1), recurrence-free survival (no recurrence at anytime) (FIG. 2), and overall survival for subjects with and without HER-2/neu amplification. Error bars show the standard error around the values.
TABLE 4 Probability of disease-free survival of breast cancer patients with non-amplified and amplified lesions. Time from Probability of Remaining Disease-Free* Surgery Non-Amplified Amplified (in Years) (95% CI)† N** (95% CI)† N** 0.5 100% (100.0% to 100.0%) 179 93.8% (85.7% to 100.0%) 31 1.0 98.3% (96.4% to 100.0%) 176 81.8% (68.7% to 95.0%) 27 1.5 96.7% (94.1% to 99.2%) 173 75.8% (61.1% to 90.5%) 25 2.0 94.4% (91.1% to 97.7%) 169 75.8% (61.1% to 90.5%) 25 2.5 93.9% (90.3% to 97.4%) 168 72.7% (57.4% to 88.0%) 24 3.0 93.3% (89.6% to 97.0%) 167 69.7% (54.0% to 85.4%) 23 5.0 85.9% (80.6% to 91.2%) 121 66.7% (50.6% to 82.7%) 19 10.0 70.5% (60.3% to 80.7%) 23 61.9% (44.5% to 79.3%) 4 Non-Amplified Amplified Time from Cumulative Probability of Cumulative Probability of Surgery Cumulative No. Cases Remaining Cumulative No. Cases Remaining (in years) N** No. Events Censored Disease Free N** No. Events Censored Disease Free 0.5 179 0 0 100.0% 31 2 0 93.9% 1.0 176 3 0 98.3% 27 6 0 81.8% 1.5 173 6 0 96.7% 25 8 0 75.8% 2.0 169 10 0 94.4% 25 8 0 75.8% 2.5 168 11 0 93.9% 24 9 0 72.7% 3.0 167 12 0 93.3% 23 10 0 69.7% 5.0 121 24 34 85.9% 19 11 3 66.7% 10.0 23 35 121 70.5% 4 12 17 61.9%
[0112] [0112] TABLE 5 Probability of Overall Survival Tumor Size large (>1 cm) / small (<1 cm) and HER-2/neu Amplification Status Probability of overall survival of breast cancer patients with large/small and non- amplified/amplified tumors. Probability of Survival* Small (≦1 cm); Small (≦1 cm); Time from Surgery Non-Amplified (≦4) Amplified (>4) (in Years) (95% CI)† N** (95% CI)† N** 0.5 100% (100.0% to 100.0%) 39 100% (100.0% to 100.0%) 5 1.0 100% (100.0% to 100.0%) 39 100% (100.0% to 100.0%) 5 1.5 100% (100.0% to 100.0%) 39 100% (100.0% to 100.0%) 5 2.0 100% (100.0% to 100.0%) 39 80.0% (44.9% to 100.0%) 4 2.5 100% (100.0% to 100.0%) 39 80.0% (44.9% to 100.0%) 4 3.0 100% (100.0% to 100.0%) 39 80.0% (44.9% to 100.0%) 4 5.0 100% (100.0% to 100.0%) 29 60.0% (17.1% to 100.0%) 2 10.0 100% (100.0% to 100.0%) 6 60.0% (17.1% to 100.0%) 1 Probability of Survival* Large (>1 cm;) Large (>1 cm); Time from Surgery Non-Amplified (≦4) Amplified (>4) (in Years) (95% CI)† N** (95% CI)† N** 0.5 100% (100.0% to 100.0%) 117 100% (100.0% to 100.0%) 25 1.0 100% (100.0% to 100.0%) 117 100% (100.0% to 100.0%) 25 1.5 100% (100.0% to 100.0%) 117 96.0% (88.4% to 100.0%) 24 2.0 100% (100.0% to 100.0%) 117 96.0% (88.4% to 100.0%) 24 2.5 99.2% (97.4% to 100.0%) 116 96.0% (88.4% to 100.0%) 24 3.0 99.2% (97.4% to 100.0%) 116 88.0% (75.3% to 100.0%) 22 5.0 96.4% (92.9% to 99.9%) 89 68.0% (49.8% to 86.2%) 15 10.0 83.4% (74.2% to 92.6%) 21 51.0% (19.1% to 82.9%) 3 # (death or recurrence) or being lost to follow-up.
EXAMPLE VI
Multi-Tiered Cutoffs for HER-2/Neu Gene Copy
[0113] The data from the above testing was analyzed to determine the effect for using a ≦3 cutoff and a ≦10 cutoff on early recurrence (within 24 months), recurrence anytime and disease related death at any time. The relative hazard for each was calculated buth unadjusted and adjusted for estrogen receptor, tumor size, patient age, study site and tumor grade. The results are in Tables 6.
TABLE 6 Relative Risk Unadjusted Adjusted ≦3 cutoff ≦10 cutoff ≧10 ≦3 cutoff ≦10 cutoff ≧10 Early Recurrence 4.8 6.6 7.8 4.3 5.5 8.3 Recurrence 2.0 3.4 3.4 2.0 3.8 4.3 Death 4.7 5.8 6.9 4.5 7.3 11.0
[0114] As can be seen from this data, the higher the average HER-2/neu gene copy number per cell, the greater the risk to the patient.
[0115] Although preferred embodiments are specifically described herein, it will be appreciated that many modifications and variations of the present invention are possible in light of the above teachings and within the purview of the appended claims without departing from the spirit and intended scope of the invention. Other and further embodiments will be apparent to those in the art from the preceding description and examples. No unreasonable limitations or the like are to be drawn therefrom in interpreting the following claims.
[0116] References cited in text and related to the invention.
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[0136] Other References Related to Subject Matter
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[0217] All references mentioned above are herein incorporated by reference.
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This invention relates to a method, kit and controls for detecting HER-2/neu gene amplification as a predictor of breast cancer reoccurrence and patient survival. The method is a fluorescent in-situ hybridization (FISH) assay using a labeled DNA probe. By determining the genetic nature of the cancer cells, appropriate treatment may be utilized. Control tumor cell lines with predefined amounts of HER-2/neu gene amplification are also disclosed.
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[0001] This application claims the benefit of U.S. application Ser. No. 60/232,093, filed Sep. 12, 2000.
FIELD OF THE INVENTION
[0002] The invention relates to compounds protective against ischemia and reperfusion injury, particularly in the myocardium, and their use.
BACKGROUND
[0003] Tissues deprived of blood and oxygen undergo ischemic necrosis or infarction with possible irreversible organ damage. In some circumstances, however, such as during cardiac surgery, it is desirable to interrupt the normal myocardial contractions (cardioplegia) and actually induce ischemia. Such elective or obligatory ischemia occurs in the presence of safeguards such as cardioplegia-induced cardiac arrest and hypothermia. While these safeguards provide considerable myocardial protection, alteration of myocardial energetics (stunning) and poor postoperative ventricular function still remain significant problems.
[0004] Once the flow of blood and oxygen is restored to the organ or tissue (reperfusion), the organ does not immediately return to the normal preischemic state. Reperfused postischemic non-necrotic myocardium is poorly contractile and has reduced concentrations of high energy nucleotides, depressed subcellular organelle function and membrane damage that resolves only slowly. Although reperfusion restores oxygen and reverses ischemia, repletion of high energy nucleotides such as adenosine triphosphate (ATP) and reversal of ischemic membrane damage is slow, and contractile function may be profoundly depressed for a long period. Just minutes of ischemia causes loss of myocardial systolic wall thickening for hours. Longer periods of reversible ischemia may depress contractility for days. Studies confirm that, despite restoration of myocardial flow and a quick recovery of myocardial oxygen consumption (MVO 2 ) following ischemia, there is only very slow recovery of myocardial contractile function. The problems are exacerbated in high risk patients, such as those with poor preoperative ventricular function, recent myocardial infarction or left ventricular hypertrophy. These same problems also occur during organ storage for cardiac transplant, under which there are time constraints due to the limits of myocardial preservation.
[0005] Postischemic dysfunction may be due to a variety of factors. Oxygen free radicals may play a role, as generation of free radicals in stunned myocardium has been demonstrated and free radical scavengers have been shown to attenuate contractile dysfunction. Impaired intracellular calcium handling and calcium overload during early reperfusion may contribute to postischemic dysfunction; while calcium infusions enhance contractility in both normal and postischemic myocardium, ischemia as short as a few minutes produces an impairment in sarcoplasmic reticulum calcium transport and a shift of the calcium ATPase activity. Postischemic myocardium is also associated with reduced concentrations of myocardial high-energy phosphates and adenine nucleotides, as obligatory reduction in myocardial ATP content during ischemia occurs as myocytes utilize ATP for maintenance of cellular integrity. Since ATP is essential for myocardial contraction and relaxation, ATP depletion may have detrimental effects upon postischemic myocardial functional recovery.
[0006] The high volume of cardiac-related surgeries, both elective and emergency procedures and including cardiac transplants, lead to the above-described problems. Thus, methods and agents to provide protection against myocardial ischemia and to avoid post ischemic dysfunction are needed.
SUMMARY OF THE INVENTION
[0007] The invention is directed to agents and a method of using the agents to reduce the injury associated with ischemia and reperfusion of organs such as the heart. The compounds are Tyr-D-Met-Phe-His-Leu-Met-Asp-NH 2 SEQ ID NO:1, hereinafter referred to as Deltorphin A, and Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-Gly-Glu-Ala-Lys-Lys-Ile SEQ ID NO:2, hereinafter referred to as Dermorphin H. Administration of Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2, particularly prior to an ischemic event, reduces tissue necrosis and preserves organ function.
[0008] In one embodiment, a method of protecting against ischemia and reperfusion injury in a mammal is disclosed. An effective concentration of Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2 is administered to the mammal in a pharmaceutically acceptable formulation prior to the onset of ischemia, for example, 24 hours prior to ischemia. In other embodiments, Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2 is administered substantially concurrently with the onset of ischemia, during an ischemic episode, or post-ischemia. The formulation may be administered parenterally at a concentration in the range of about 1-20 mg/kg of body weight.
[0009] The invention is also directed to a method to prevent damage to an isolated organ, for example, a heart for transplant. The isolated organ is exposed to a preservative solution containing an effective amount of Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2. The concentration of Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2 in the preservative solution for a heart is about 100 μM.
[0010] The invention is additionally directed to a method for reducing effects of an ischemic episode in a mammal by administering an effective concentration of Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2 in a pharmaceutically acceptable carrier. Administration is prior to or substantially concurrently with the onset of ischemia, or one hour post cerebral ischemia.
[0011] The invention is further directed to a composition that protects a mammalian organ from injury. The composition contains Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2, in either a naturally occurring form or a synthesized form.
[0012] The invention is also directed to an organ preservative solution that contains Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2 at a concentration effective to protect the organ, such as a heart, from ischemic injury.
[0013] These and other advantages of the invention will be apparent in light of the following drawings and detailed description.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] [0014]FIG. 1 is a histogram showing myocardial infarction size in control and treated animals.
[0015] [0015]FIG. 2 is a histogram showing post-ischemic release of troponin I in control and treated animals.
[0016] [0016]FIG. 3 is a graph showing end diastolic pressure in the left ventricle of control and treated animals.
[0017] [0017]FIG. 4 is a graph showing functional recovery in control and treated animals.
DETAILED DESCRIPTION
[0018] The invention is directed to compounds that have a salutary effect on cardiac function following ischemia, and methods of using the compounds. The compounds may be administered directly to an individual, and are particularly effective when administered 24 h prior to the onset of ischemia. This may occur, for example, prior to scheduled cardiac surgery. The compounds may also be included in a preservative solution for an isolated organ, such as a heart or liver being maintained viable for transplant.
[0019] One of the compounds is a heptapeptide having the sequence Tyr-D-Met-Phe-His-Leu-Met-Asp-NH 2 SEQ ID NO:1, hereinafter referred to as deltorphin A. Another of the compounds is an eleven amino acid sequence Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-Gly-Glu-Ala-Lys-Lys-Ile SEQ ID NO:2. The peptides may be produced by a number of methods, such as using an automated peptide synthesizer, through recombinant molecular techniques, or isolated from a naturally occurring source, as is known to one skilled in the art. Deltorphin A SEQ ID NO:1 has a molecular weight of 955.1 daltons, and Dermorphin H SEQ ID NO:2 has a molecular weight of about 1430.64 daltons. Both Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 are insoluble in water or saline, but may be solubilized by adding 100 μM of a solution comprised of ethanol, propylene glycol, and 1 N NaOH in a 1:1:1 ratio, with sterile physiological saline then used to obtain the appropriate concentration. The initial alkaline pH is adjusted to 7.4 with 1 N HCl.
[0020] Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 that have been solubilized may be administered by parenteral means, for example, intravenous injection. In one embodiment, administration of Deltorphin A SEQ ID NO:1 is at the time of induced ischemia, but may also be added during or even after an ischemic event. For administration into a mammal, a dose of about 1-20 milligrams per kilogram (mg/kg) is useful. For administration into a tissue or organ preservation solution, a concentration of about 100 μM is useful.
[0021] Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 may be administered directly into a mammal, either alone or in combination with other substances. Alternatively, it may be added as a component of a solution used to maintain the viability of isolated organs, such as an additive to cardioplegia and other organ preservation solutions. In one embodiment, Deltorphin A SEQ ID NO:1 and/or Dermorphin H SEQ ID NO:2 is coadministered as an adjuvant with other compounds or strategies that are designed to protect organs from ischemia. As an example, Deltorphin A SEQ ID NO:1 and/or Dermorphin H SEQ ID NO:2 may be administered with agents that affect nitric oxide (NO) synthase, such as arginine hydrochloride. Arginine hydrochloride is known to prevent the decline in cardiac function following an ischemic episode.
[0022] The following description demonstrates use and efficacy of Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 in a variety of systems.
[0023] Perfused Heart
[0024] Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2, at a dose of 2 mg/kg and solubilized as described above, was administered by tail vein injection into rats weighing between about 350-400 g (number of animals (n)=6). Control rats (n=6) were injected in the same manner with an equal volume of 0.9% NaCl. After 24 h, the hearts from both treated and control animals were excised and perfused in a modified Langendorff perfusion apparatus at 37° C. using oxygenated Krebs-Henseleit buffer as the perfusate, as known to one skilled in the art. Coronary perfusion pressure was maintained at 700 mm Hg by regulating coronary flow. All hearts were paced at 5.5 Hz (300 beats per minute, bpm) except during ischemia. A saline-filled balloon was inserted in the left ventricle to measure developed pressure (DP) and end-diastolic pressure (EDP) in mm Hg. After 15 min equilibration, both groups were subjected to 20 min zero-flow global ischemia, and then were reperfused for 120 min.
[0025] Left ventricles were isolated and divided into three segments along their short axis, stained with triphenyltetrazolium chloride, and stored in formalin. Infarct size was measured on digitized images and expressed as a percentage of myocardium. Data were expressed as mean plus or minus standard error of the mean (±SEM) and were analyzed using a paired Student's t-Test. Confidence limits were established at 95%.
[0026] The results are shown in FIG. 1, which is a histogram of the infarct size in hearts from animals receiving only saline (control, solid bar), in animals treated with Deltorphin A SEQ ID NO:1 at 2.0 mg/kg (treated, open bar) 24 h prior to 20 min ischemia and 120 min reperfusion, and animals treated with Dermorphin H SEQ ID NO:2 at 2.0 mg/kg (treated, hatched bar) 24 h prior to 20 min ischemia and 120 min reperfusion. Pretreatment of animals with Deltorphin A SEQ ID NO:1 or Dermorphin H SEQ ID NO:2 decreased the percent of infarct size. Control rats had a mean infarct size of 27±5%, while rats pretreated with Deltorphin A SEQ ID NO:1 had a reduced mean infarct size of 12.95±3.3%, and rats pretreated with Dermorphin H SEQ ID NO:2 had a reduced mean infarct size of 13.5±3.5%.
[0027] Specific infarct volumes in four separate cross sectional areas of brains isolated from animals treated post-ischemia with Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 are shown in Tables 1-3. In each case, six male mice (strain C57) were subjected to ischemia for one hour and then received an injection of either 100 μl normal saline (vehicle), 100 μl of 4.0 mg/kg Deltorphin A SEQ ID NO:1 (Table 2), or 100 μl of 4.0 mg/kg Dermorphin H SEQ ID NO:2 (Table 3). The dose of Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 may be in the range of 1 mg/kg to 4 mg/kg. Reperfusion followed for 24 hours, then animals were sacrificed and 2 mm brain sections from each of four areas were evaluated. The total cross section area is the sum of the four cross section areas; likewise, the total damaged cross section areas is the sum of the four damaged cross section areas for each animal.
TABLE 1 Saline (Vehicle) Treated Cross 14.81 14.65 12.55 13.18 15.35 15.9 Section Area 1 Cross 22.52 22.39 19.52 20.68 22.08 20.22 Section Area 2 Cross 25.24 25.45 21.84 23.51 24.77 22.69 Section Area 3 Cross 24.51 24.05 21.54 24.98 23.81 22.73 Section Area 4 Total 87.08 86.54 75.45 82.35 86.01 81.54 Cross Section Area Damaged 6.58 4.49 5.77 5.02 4.83 5.86 Cross Section Area 1 Damaged 9.7 6.86 7.42 8.21 8.81 6.57 Cross Section Area 2 Damaged 11.86 10.7 10.65 11.79 9.52 8.24 Cross Section Area 3 Damaged 10.02 12.22 11.03 11.21 10.26 10.76 Cross Section Area 4 Total 38.16 34.27 34.87 36.23 33.42 31.43 Damaged Cross Section Area Damaged 43.82 39.60 46.22 44.00 38.86 38.55 % Corrected 87.644 68.54 69.74 72.46 66.84 62.86 Volume
[0028] For animals receiving only saline after one hour of ischemia, the infarct volume was about 42% (total damaged cross section area of 208.38, total cross section area of 498.97, 208.38/498.97=0.417). The corrected volume was obtained by multiplying the damaged cross section area by 2, since 2 mm sections were assessed. In all six control animal this was 428.08, yielding an average infarct volume of 71.35 mm 3 (428.08/6), with a standard deviation of ±8.598.
TABLE 2 Deltorphin A Treated Cross 16.42 15 13.89 14.67 15.23 14.56 Section Area 1 Cross 22.07 22.81 20.06 21.23 20.78 21.34 Section Area 2 Cross 24.17 25.51 23.52 23.79 24.14 24.56 Section Area 3 Cross 20.77 23.49 23.24 21.55 22.34 20.98 Section Area 4 Total 83.43 86.81 80.71 81.24 82.49 81.44 Cross Section Area Damaged 5.16 4.14 5.09 4.98 5.32 4.76 Cross Section Area 1 Damaged 7.48 5.86 7.7 6.97 7.36 6.83 Cross Section Area 2 Damaged 3.69 3.26 9.49 8.59 9.23 8.75 Cross Section Area 3 Damaged 3.77 3.4 7.36 6.74 6.94 7.11 Cross Section Area 4 Total 20.1 16.66 29.64 27.28 28.85 27.45 Damaged Cross Section Area Damaged 24.09 19.19 36.72 33.58 34.97 33.71 Corrected 40.2 33.32 59.28 54.56 57.7 54.9 Volume
[0029] For animals receiving Deltorphin A after one hour of ischemia, the infarct volume was reduced to about 30% (total damaged cross section area of 149.98, total cross section are of 496.12, 149.98/496.12=0.302). In all six Deltorphin A treated animals, the corrected volume was 299.96, yielding an infarct volume of 49.99 mm 3 (299.96/6), with a standard deviation of ±10.63.
TABLE 3 Dermorphin H Treated Cross 14.92 13.87 14.94 14.65 13.69 14.27 Section Area 1 Cross 22.62 21.52 21.48 22.33 21.66 21.36 Section Area 2 Cross 23.5 23.8 23.69 23.98 23.71 22.35 Section Area 3 Cross 23.8 21.24 21.59 21.87 22.43 23.39 Section Area 4 Total 84.84 80.43 81.7 82.83 81.49 81.37 Cross Section Area Damaged 4.5 5.24 3.76 4.25 3.99 3.47 Gross Section Area 1 Damaged 5.41 6.75 5.2 7.13 5.87 5.13 Cross Section Area 2 Damaged 6.43 7.34 4.82 6.77 6.22 5.36 Cross Section Area 3 Damaged 3.45 3.23 3.37 4.62 4.15 3.89 Cross Section Area 4 Total 19.79 22.56 17.15 22.77 20.23 17.85 Damaged Cross Section Area Damaged 23.33 28.05 20.99 27.49 24.83 21.94 Corrected 39.58 45.12 34.3 45.54 4046 35.7 Volume
[0030] For animals receiving Dermorphin H after one hour of ischemia, the infarct volume was reduced to about 24% (total damaged cross section area of 120.35, total cross section are of 492.66, 120.35/492.66=0.244. In all six Dermorphin H treated animals, the corrected volume was 240.7, yielding an infarct volume of 40.12 mm 3 (240.7/6), with a standard deviation of 4.652.
[0031] These results are summarized as follows.
Average Infarct Standard Treatment Volume (mm 3 ) Deviation Infarct Volume Control 71.35 8.598 42% Deltorphin A 49.99 10.63 30% Dermorphin H 40.12 4.652 24%
[0032] The data demonstrate the efficacy of Deltorphin A and Dermorphin H treatment post cerebral ischemia.
[0033] Pretreatment with Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 also significantly decreased the cardiac form of troponin I (cTn-1) values following 20 min ischemia, as shown in FIG. 2. An increase in cTn-1, a protein associated specifically with the cardiac muscle, indicates myocardial damage, likewise, a decrease in cTn-1 indicates less cardiac damage.
[0034] [0034]FIG. 3 is a histogram showing cTn-I released during reperfusion of isolated hearts after 20 min ischemia in rats treated 24 h prior to ischemia with 0.5 ml saline (control), 2.0 mg/kg Deltorphin A SEQ ID NO:1, and 2.0 ml/kg Dermorphin H SEQ ID NO:2. The solid bars represent control animals (n=6), the open bars represent Deltorphin A SEQ ID NO:1 treated animals (n=6), and the hatched bars represent Dermorphin H SEQ ID NO:2 treated animals (n=6). At time point sduring reperfusion where samples were collected for cTn-1 analysis (1, 60, and 120 min reperfusion), Tn-1 levels in control rats were significantly higher than Tn-1 levels in Deltorphin A SEQ ID NO:1 treated rats at 1 min and 60 minutes following reperfusion, and were also higher at 120 min following reperfusion. Tn-1 levels in control rats were higher than Tn-1 levels in Dermorphin H SEQ ID NO:2 treated rats at 1 minute and 120 minutes following reperfusion. This data indicated that pretreatment with Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 decreased the damage to the myocardium, as compared to untreated animals.
[0035] Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 pretreatment also resulted in improved postischemic ventricular function. FIG. 3 is a graph of end diastolic pressure in mm/Hg in the left ventricle (LVEDP) during reperfusion of isolated rat hearts after 20 min ischemia in rats pretreated 24 h prior to ischemia with 2.0 mg/kg Deltorphin A SEQ ID NO:1 or 2.0 mg/kg Dermorphin H SEQ ID NO:2. Open squares are from treated animals, and solid circles are from animals treated with 0.5 ml saline (control). FIG. 4 is a graph showing percent of functional recovery during reperfusion of isolated rat hearts after 20 min ischemia in rats treated 24 h prior to ischemia with 2.0 mg/kg Deltorphin A SEQ ID NO:1 or 2.0 mg/kg Dermorphin H SEQ ID NO:2. Open squares are from treated animals, and solid circles are from control animals. Differences in recovery of developed pressure (DP) in hearts from Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 treated animals remained lower following the initiation of reperfusion, as shown in FIG. 3. As shown in FIG. 4, left ventricular functional recovery (% recovery of baseline preischemic developed pressure during reperfusion) for animals treated with 2 mg/kg Deltorphin A SEQ ID NO:1 was significantly increased over control animals up to 120 min following reperfusion (p=0.01). Left ventricular functional recovery for animals treated with Dermorphin-H SEQ ID NO:2 (2.0 mg/kg) was also increased over control animals up to 120 min post reperfusion, but the increase was not statistically significant.
[0036] As shown in FIG. 5, left ventricular functional recovery was significantly improved in Deltorphin A SEQ ID NO:1 treated animals (about 85%) (open bar) compared to control animals (about 51%) (solid bar) at 5 min of reperfusion, while left ventricular functional recovery in Dermorphin H SEQ ID NO:2 treated animals and control animals was about the same (about 51%).
[0037] These results show that in a normoxic, isolated perfused rat heart preparation, administration of Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 confers cardioprotection when administered either prior to planned ischemia or post ischemia. The salutary effects on the post-ischemic myocardium include reduced infarct size, reduced infarct volume, decreased release of cardiospecific troponin I, and improved ventricular performance.
[0038] As another benefit, Deltorphin A SEQ ID NO:1 and Dermorphin H SEQ ID NO:2 may provide a benefit in protecting against arrhythmias, similar to the effect of the δ-opioid receptor agonist TAN-67, as reported by Fryer et al. in 274 J. Biol. Chem. 451-457, 2000, which is expressly incorporated by reference herein in its entirety.
[0039] The invention in its broader aspects is therefore not limited to the specific details, representative apparatus and method, and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the spirit or scope of applicant's general inventive concept.
1
2
1
7
PRT
Artificial Sequence
MOD_RES
(1)...(7)
Xaa = D-Met; artificial sequence is completely
synthesized
1
Tyr Xaa Phe His Leu Met Asp
1 5
2
13
PRT
Artificial Sequence
MOD_RES
(1)...(13)
Xaa = D-Ala; artificial sequence is completely
synthesized
2
Tyr Xaa Phe Gly Tyr Pro Ser Gly Glu Ala Lys Lys Ile
1 5 10
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A compound and method for using the compound to reduce injury associated with ischemia and reperfusion of mammalian organs such as the heart. The compound, either Deltorphin A and/or Dermorphin H, may be administered as part of a preconditioning strategy which reduces the extent of injury and improves organ function following cessation and restoration of blood flow. The compound may be used in preparation for planned ischemia or in a prophylactic manner in anticipation of further ischemic events.
| 0 |
BACKGROUND
[0001] This invention relates to marking substrates.
[0002] One technique for marking substrates is known as laser marking. In laser marking, radiation is directed onto a substrate to modify the substrate, or a coating on the substrate, in a way that induces a change in the substrate or coating that can be detected optically. For example, the substrate may be aluminum beverage cans that are oriented such that the radiation can be directed to the bottom of the can for marking indicia. The radiation can be directed, or addressed, in a pattern over the substrate such that a desired image is rendered.
SUMMARY
[0003] The invention relates to marking substrates. For example, the substrate can be a coating, such as a laser sensitive coating, that can be applied on a beverage can, such as on the bottom or the neck of the can, for marking indicia such as date codes, lot numbers, promotional indicia, graphics, and sell by dates. In addition, the substrate can also be used for identification of parts, such as automotive parts, e.g., oil filters, two-piece cans, three-piece cans, aerospace parts, and saw blades.
[0004] In one aspect, the invention features a marking composition including a polymerizable first material that comprises silicon, and a second material capable of extending polymeric chains of the first material, wherein the marking composition is capable of undergoing a change that can be detected optically when the composition is contacted with energy.
[0005] Embodiments include one or more of the following features. The second material is capable of crosslinking with the first material. The second material includes a polyol, e.g., a diol and/or a triol. The first material includes a silicone resin, e.g., one that includes a combined aromatic and aliphatic substituted silicone resin. The first material includes a phenyl methyl silicone resin. The ratio of phenyl to methyl groups is between about 0.4:1 and 2.1:1. The composition further includes a crosslinking agent, e.g., a silane. The composition further includes a blocked crosslinking agent, e.g., a carbamate. The composition further includes a catalyst, e.g., a platinum-based catalyst, a zinc-based catalyst, and/or a Lewis acid. The composition further includes an optical tag.
[0006] In another aspect, the invention features a marking composition, including a polymerizable silicone resin, a crosslinking agent capable of crosslinking with the resin, and a polyol capable of extending polymeric chains of the silicone resin, wherein the marking composition is capable of undergoing a change that can be detected optically when the composition is contacted with energy.
[0007] In some embodiments, the composition includes about 10 to about 90 percent of the resin, about 0.1 to about 9 percent of the crosslinking agent, and about 1 to about 10 percent of the polyol.
[0008] In another aspect, the invention features a method of marking a substrate. The method includes contacting the substrate with a composition having a polymerizable first material that comprises silicon, and a second material capable of extending chains of the first material, and contacting the composition with energy to produce a change in the composition that can be detected optically.
[0009] Embodiments include one or more of the following features. The first material comprises a silicone resin and the second material comprises a polyol. The method further includes curing the composition. The method further includes contacting the substrate with a second composition comprising a crosslinking agent. The crosslinking agent includes a silane. The substrate can be a beverage can. Contacting the composition with energy includes forming a marking indicative of a date. The energy is delivered from a laser.
[0010] In another aspect, the invention features an article including a substrate and a marking composition, as described herein, on the substrate.
[0011] In another aspect, the invention features a method of marking a substrate. The method includes applying to the substrate a coating as described herein and irradiating the coated substrate in a desired pattern with select radiation effective to induce a color change or contrast. In other embodiments, the coating is applied to a metal substrate, such as a beverage can. The coating is irradiated in a pattern indicating indicia.
[0012] Embodiments may have one or more of the following advantages. The coating may be colorless, clear, and/or transparent prior to irradiation. As a result, the underlying substrate, and any markings directly on the coated substrate, will be visible in areas not exposed to radiation.
[0013] The coatings may also be strongly adherent to a wide variety of substrate materials, for example, metals, such as aluminum, tin, or stainless steel, as well as glass, paper, and packaging film. For example, the composition provides good adhesion of lased coatings to the bottom of cans, as measured by a “dome inversion” test sometimes used by beverage can printers. In this test, fluid inside the can may freeze, which causes the can to expand and to push the bottom of the can outwardly. In some circumstances, in order for a coating formed on the bottom of the can to be acceptable to industry standards, the coating preferably does not fracture or flake off the bottom surface. The coating is resistant to thermal shock degradation, e.g., when cans are at room temperature and receive a beverage at about 43-47° F.
[0014] In some applications, by applying a coating composition to a substrate, e.g., a beverage can, the substrate may be marked in a production environment, e.g., one having relatively high line speed, e.g., about 1250 cans/min, and a relatively fast rate of imaging, e.g., about 250 microsecond pulse for each pixel of marking.
[0015] The coating is stable until imaged, i.e., there is a relatively long shelf life without substantial contrast development or discoloration until a laser addresses the coating. The coating is also stable at relatively high temperatures, e.g., 200° C. minimum without substantial discoloration or visual degradation, e.g., a color shift. The coating can be delivered from an environmentally friendly solvent, followed by evaporation of the solvent. The coating can be delivered as a 100% reactive fluid. By adjusting the rheological properties of the coating fluid, various application methods can be used. Such methods include, for example, spraying, lithographic pressing, and reciprocal pad printing. The applied coating can be cured by thermal treatment, e.g., at 200° C. in less than 2 minutes or less than 1 minute.
[0016] All composition percentages given are weight percent.
[0017] Other features and advantages of the invention will be apparent from the description and drawings, and from the claims.
DESCRIPTION OF DRAWINGS
[0018] [0018]FIG. 1 is a Fourier transform infrared (FTIR) spectrum of an embodiment of an uncured coating composition;
[0019] [0019]FIG. 2 is a FTIR spectrum of an embodiment of a cured coating composition;
[0020] [0020]FIG. 3 is a FTIR spectrum of an embodiment of a cured coating composition that has been pyrolyzed with a propane torch;
[0021] [0021]FIG. 4 are FTIR spectra of an embodiment of a cured coating that has been pyrolyzed and an embodiment of a cured coating that has been addressed with a laser;
[0022] [0022]FIG. 5 is a plot of energy (mJ) vs. average diameter (mil); and
[0023] [0023]FIG. 6 is a plot of dot diameter (mil) vs. pulse width (microseconds).
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0024] Prior to marking a substrate, such as an aluminum can, with a laser, the substrate is treated with a laser marking coating, such as a polymeric coating.
[0025] The coating fluid generally includes a solvent having dissolved therein a resin, a crosslinking agent, and a catalyst. Reaction 1 shows an illustrative composition having an α, ω-siloxanediol (I) as the resin, a γ-aminopropyltriethoxysilane (II) as the crosslinking agent, and a metal octanoate (III) as the catalyst.
[0026] Referring to Reactions 2 and 3, through a condensation reaction catalyzed by the metal octanoate, the α, ω-siloxanediol (I) polymerizes via linear chain extension.
[0027] Other mechanisms are possible.
[0028] The γ-aminopropyltriethoxysilane (II) crosslinking agent can undergo base-catalyzed hydrolysis to form a γ-aminopropylhydroxysilane (Reaction 4).
[0029] Through polycondensation, the γ-aminopropylhydroxysilane reacts with the catalyzed siloxanediol to provide crosslinking (Reaction 5) of the linear chains. For example,
[0030] The amine can also act as a catalyst for further polycondensation reactions, for example,
[0031] The combined condensation reactions 3 and 5 provide a crosslinked polymer having a network structure and suitable for substrate marking.
[0032] In a preferred embodiment, the above coating fluid composition further includes additives that enhance the properties, e.g., physical and/or mechanical, of the cured, polymerized coating such as flexibility and resistance to delamination and cracking. A preferred additive is a polyol, e.g., 1,4 butanediol (V), that can crosslink with the resin during the polycondensation reaction, thereby enhancing the flexibility of the polymer coating (VI).
[0033] A more detailed description of polysiloxane chemistry can be found, for example, in John C. Bevington and Sir Geoffrey Allen, “Comprehensive Polymer Science: The Synthesis, Characterization, Reactions and Applications of Polymers,” Oxford, N.Y., Pergamon Press 1989 (1 st ed.); “Silicon, Germanium, & Tin Compounds Metal Alkoxides Diketonates and Carboxylates: A Survey of Properties and Chemistry” Gelest, Inc., Tullytown, Pa. 1998 (2 nd ed.); and references cited therein, all hereby incorporated by reference in their entirety.
[0034] The coating fluid may be applied from solvent or as a 100 percent reactive solution. The coating is typically about 4-13 microns thick wet and can be applied by several methods including, industrial spraying techniques, lithography, and reciprocal pad printing. Typically, the coating fluid is then dried, e.g., by removing solvent, and cured, e.g., by heating. The substrate may be cleaned prior to application of the coating fluid by, for example, a solvent treatment or hydrogen flame treatment.
[0035] Irradiating the dried coating with a laser produces a black marking or image on the coating. Accordingly, the coating is preferably sufficiently absorbent at a select wavelength such that the coating can be heated to a desired temperature that can induce a color change (Example 1).
[0036] Without wishing to be bound to theory, it is believed that the black mark formed is “black glass”, a form of SiO 2 . Black glass can form when pyrolysis of a polysiloxane takes place in an oxygen-containing environment such as air, forming SiO 2 . If enough carbon is present on the polysiloxane chain (in the form of hydrocarbons), free carbon can get trapped into the matrix to form SiO x C y , which is black (Example 2). More information on the pyrolysis of polysiloxanes can be found in the paper Soraru, G. D. “Polysiloxanes as Ceramic Precursors” J. Sol - Gel Sci. and Technol., 1994, 2, 843, and references cited therein, all hereby incorporated by reference in their entirety.
[0037] The preferred materials for the coating fluid will now be described in more detail.
[0038] Solvent: Generally, the solvent can be any material that can dissolve the resin and other materials in the coating fluid (described below), preferably providing a clear and colorless solution. The solvent is preferably non-toxic, environmentally friendly, e.g., is EPA-approved and does not produce hazardous pollutants, stable with respect to the materials in the coating, and/or cost effective for relatively large scale manufacturing. Preferred solvents include, for example, aromatic solvents such as toluene, halogenated aromatic solvents such as benzene, 1-chloro-4-[trifluoromethyl] (CAS #98-56-6, available as Oxsol 100 from Oxidental Chemical Co.), and aliphatic solvents such as one containing n-butylpropionate.
[0039] Resin: The resin is selected such that the coating can form a mark of a select color, e.g., black, when the coating is addressed with a laser. Selection of the resin can also be based on the coating application method, adhesion and environmental durability requirements, and minimizing formation of unwanted color (e.g., bleeding or feathering) in areas adjacent to the laser address site. Preferably, the resin is essentially colorless in the visible range but absorbs in the wavelengths produced by a laser, e.g., infrared. When heated and/or with the addition of an active crosslinking agent or catalyst, as described below, the resin preferably polymerizes, e.g., via a condensation mechanism, at reaction rates required for some laser marking applications, such as 200° C. in a force air oven with a dwell time of 2 minutes or greater. In some embodiments, the resin can polymerize in less than about 1 minute, e.g., about 40 seconds or less.
[0040] The resin can be any silicon-containing material with one or more pendent carbon group, e.g., a silicone resin. For example, the silicon can be disubstituted with aromatic groups and/or aliphatic groups, or the silicon can be monosubstituted with the other group being hydrogen. Generally, the pendent group(s) can be all aromatic, all aliphatic, or a mixture of aromatic and aliphatic groups. A preferred resin is a combined aromatic and aliphatic substituted silicone resin that can absorb light energy at wavelengths produced by a laser, e.g., a carbon dioxide laser. Preferably, the resin is a hydroxyl terminated silicone resin that can undergo condensation as described above. The resin is preferably substituted with pendent groups covalently bound to the silicon atoms along the backbone.
[0041] Generally, since the black mark formed by the laser is presumably free carbon in an SiO 2 matrix, the resin includes a material, such as a polysiloxane, having relatively high carbon content. For example, a color change can be observed in crosslinked polysiloxanes that contain only methyl groups, but the markings created from these polysiloxanes have relatively low optical density, e.g., not sufficient for marking. Markings produced from a phenyl methyl substituted polysiloxane, however, can have relative high optical density, e.g., blacker in color. Thus, the amount of carbon present in the resin tends to determine how black a mark is (Example 3). Preferably, the pendent groups include substituents having high carbon content, such as phenyl, octyl, and propyl groups.
[0042] For phenyl methyl silicone resins, the ratio of phenyl to methyl (Ø:Me) groups is typically between about 0.4:1 and 2.1:1. As the ratio of phenyl to methyl increases, the thickness of a coating that provides good opacity, and therefore a readable image, generally decreases. For example, a resin having a 0.4:1 phenyl:methyl ratio can provide a good image with a 12 micron thick wet film (about 5 micron thick dry), while a resin having a 1.3:1 phenyl:methyl ratio can provide a good image with a ˜6 micron thick wet film (about 2.5 micron thick dry).
[0043] Examples of resins include resins with silanol functionality such as phenyl, propyl silicone (propyl substituted) resin (68037-90-1, 2.3:1 Ø:Me, 6.4 wt. % hydroxyl); diphenyl, methyl, phenyl, phenylmethyl silicone resin (68037-81-0, 1.3:1 Ø:Me, 6 wt. % hydroxyl); dimethyl, methyl, phenyl silicone resin (25766-16-9, 0.6:1 Ø:Me, 6 wt. % hydroxyl); dimethyl, diphenyl, methyl, phenyl silicone resin (28630-33-3, 2:1 Ø:Me, 6 wt. % hydroxyl); dimethyl, diphenyl, methyl, phenyl silicone resin (28630-33-3, 0.7:1 Ø:Me); dimethyl, methyl, phenyl silicone resin (25766-16-9, 0.4:1 Ø:Me); and resins with methoxy functionality such as a water borne intermediate/liquid phenyl, phenylmethyl, methoxy functional resin (QP8-5314, 3:1 Ø:Me), all available from Dow Corning.
[0044] Other resins include dimethyl polymers with phenyl silsesquioxanes (73138-88-2); and dimethyl diphenyl polymers with methyl phenyl silsesquioxanes, hydroxy terminated (28630-33-3) (e.g., with 50%, 60%, 80%, or 86% solids), both available from General Electric. Still other resins are available from Wacker Chemie under the trademarks Silres REN 100 (silsesquioxanes, phenyl propyl (68037-90-1); and Silres 602 (silsesquioxanes, phenyl, propyl silicone resin, 68037-90-1, 2.3:1 Ø:Me).
[0045] Still other silicones that may be used are described in B. J. Kollmeier, Th. Goldschmidt A G, “Organo-modified silicones: Their properties and applications” Specialty Chemicals, Mar. 26-31, 1986, hereby incorporated by reference in its entirety.
[0046] In some embodiments, the resin can be a water-borne resin, and the solvent can be water.
[0047] The coating fluid typically includes about 10 to about 90 percent, preferably about 40 to about 60 percent, and more preferably, about 45 to about 55 percent, of the resin.
[0048] Crosslinking agent: In some embodiments, the crosslinking agent can act as a crosslinking agent and as a catalyst, e.g., by an amine functionality (Example 5). The crosslinking agent can increase the reaction kinetics of resin polymerization, thereby reducing the time required to reach a minimum degree of polymerization required for producing a resilient, markable coating, e.g., a coating that does not easily rubs off (Example 6).
[0049] Generally, the crosslinking agent includes any mono-functional or multi-functional material that will undergo condensation-type reactions with the hydroxyl groups on the silicone resin resulting in covalent bridging of the silicone resin through the crosslinking agent. Some preferred cross-linking agents include, for example, hydroxy-terminated silicone resins, alkoxy functional silanes, such as a gamma-aminopropyltriethoxysilane (available under the tradename Silquest A-1100 from OSI Specialties (Danbury, Conn.), although there was little observable difference in print durability with changes in ethoxy functionality (see Example 4). In addition, the preferred silane contains functionality that can catalyze hydrolysis reactions, such as an amino functionality on the preferred silane. In some circumstances, a significant increase in the rate of polymerization was observed with amine functional silanes compared to, for example, glycidyl ether modified silanes. In some circumstances, an epoxy terminated silane can stay fluid for about 7 days.
[0050] Other examples of crosslinking agents include Triethoxysilyl Modified Poly-1,2-Butadiene, 50% in Toluene (72905-90-9); N-(Triethoxysilylpropyl)-O-Polyethylene Oxide Urethane (37251-86-8); 3-(Triethoxysilylpropyl)-p-Nitrobenzamide (60871-86-5); N-(3-Triethoxysilylpropyl) 4,5-Dihydroimidazole (58068-97-6); N-(Triethoxysilylpropyl)Dansylamide (70880-05-6); N-[3-(Triethoxysilyl)Propyl-2-Carbomethoxyaziridine (193417-26-4); 3-Thiocyanotopropyltriethoxysilane (34708-08-2); N-(3-Methacryloxy-2-Hydroxypropyl)-3-Aminopropyltriethoxysilane; 3-Mercaptopropyltriethoxysilane (14814-09-6); 3-Isocyanotopropyltriethoxysilane (24801-88-5); 3-(2,4-Dinitrophenylamino)Propyltriethoxysilane (71783-41-0); 3-Cyanopropyltriethoxysilane (1067-47-6); Bis(Pentanedionato)Titanium-O,O′-Bis(Oxyethyl)Aminopropyltriethoxysilane; Bis(2-Hydroxyethyl)-3-Aminopropyltriethoxysilane (7583-44-5); 3-Aminopropyltriethoxysilane (919-30-2); 4-Aminobutyltriethoxysilane (3069-30-5); and N-(3-Acryloxy-2-Hydroxypropyl)-3-Aminopropyltriethoxysilane (123198-57-2).
[0051] While the silane described above can effectively crosslink the resin, under some circumstances, the coating fluid can have limited stability, e.g., for about 3-4 hours, before the coating fluid becomes undesirably viscous and difficult to process, e.g. to spread. In some embodiments, the silane is a blocked silane that can lose its blocking group(s) at elevated temperatures to act as an in situ crosslinking agent (Example 7). The blocked silane can delay extensive crosslinking of the coating fluid until initiated, e.g., by heat, which can provide easier handling and/or processing of the coating fluid, allow the coating fluid to be sprayed onto a substrate, and increase stability of the coating fluid.
[0052] Examples of blocked silanes include (3-triethoxysilylpropyl)-t-butylcarbamate; Bis[3-(Triethoxyslyl)Propyl]Urea; O-(Vinyloxyethyl)-N-(Triethoxysilylpropyl)Urethane; N-Triethoxysilylpropylquinineurethan; (S)-N-Triethoxysilylpropyl-O-Menthocarbamate (68479-61-8); N-(3-Triethoxysilylpropyl)-4-Hydroxybutyramide (186543-03-3); N-(3-Triethoxysilylpropyl)Gluconamide (104275-58-3); Triethoxysilylpropylethylcarbamate (17945-05-0); O-(Propargyloxy)-N-(Triethoxysilylpropyl)Urethane; (S)-N-1-Phenylethyl-N′-Triethoxysilylpropylurea (68959-21-7); (R)-N-1-Phenylethyl-N′-Triethoxysilylpropylurea (68959-21-7); O-(Methacryloxyethyl)-N-(Triethoxysilylpropyl)Urethane; and (S)-N-Triethoxysilylpropyl-O-Menthocarbamate (68479-61-8).
[0053] The coating fluid typically includes about 0.1 to 9 percent, preferably about 1 to about 6 percent, and more preferably, about 2 to about 4 percent, e.g., about 2.9 percent, of the crosslinking agent.
[0054] The chemistry of silanes, including, for example, their packaging and mixing sequences, are described in Sin Siew Weng et al., Silane Coupling Agents, (November 2000), available from http://www.sinrubtech.com/short%20notes/Short%20Notes%205.1.htm, cited with this application and hereby incorporated by reference. For example, the storage stability of many silanes can be relatively poor such that once an air-tight seal is broken, the silane is preferably used as soon as possible; silanes are preferably mixed first with certain materials before mixing with other materials, such as mixing silanes with silica before adding competing chemicals like glycols, amines, zinc oxide and some antidegradants; and liquid silanes can be prone to hydrolysis so the silanes can be provided in, for example, heat-sealed silane +N330 in ethylene vinyl acetate bags, wax bound silane in pellet form, and thermoplastic resin bound silanes in pellet form.
[0055] Additive: An additive to the coating fluid composition can be any material that enhances the properties, e.g., physical and/or mechanical, of the coating. Preferably, the additive is a material that increases chain extension and/or that can cross link with the resin. For example, the additive can provide a cured or polymerized coating with improved resistance to tearing, cracking, e.g., upon curing, and/or delamination from a substrate. Preferably, the additive has a stability and solubility in the solvent comparable to other materials (e.g., the resin) in the coating. Preferably, the additive does not discolor or cloud the coating composition.
[0056] A preferred additive is a polyol, e.g., a diol and/or a triol. A polyol can crosslink with the resin and/or the crosslinking agent, thereby increasing the flexibility of the cured resin. A cured resin that is flexible can resist mechanical deformation, such as delamination and cracking, when the resin is applied to a substrate, e.g., a curved or dome surface of a beverage can (Examples 8 and 9). The polyol may also help increase the opacity of the lased image by increasing carbon content within the cured coating. Generally, the polyol can enhance the properties of the coating compared to a substantially identical coating without the polyol (Example 10).
[0057] Examples of polyols include materials having long carbon chains with hydroxyl termination and/or hydroxyl groups along the backbone, such as 1,2,6-hexanetriol (CAS #106-69-4); materials with long linear or non-linear, e.g., cyclic, carbon backbones with hydroxyl termination (e.g., diols) such as 1,6 hexanediol (CAS #629-11-8) and 1,10-decanediol (CAS #112-47-0); and triols such as Tone 0305 (Union Carbide) (which is <4.8% soluble in Oxsol 100, if at all, and hazy even at 4.8%.; Tone 0301 (CAS #37625-56-2, Union Carbide) (which is <4.8% soluble in Oxsol 100, if at all, and hazy even at 4.8%), and glycerol (CAS #56-81-5, Aldrich) (which is <1.0% soluble in Oxsol 100, if at all). Preferably, the polyol includes 1,4 pentanediol (CAS #626-95-9, Aldrich) (which is ≧6.9% soluble in Oxsol 100), 1,4 butanediol (CAS #110-63-4, Aldrich) (which is about 4.8% soluble in Oxsol 100 but not soluble at 6.9%). More preferably, the polyol includes caprolactone polyol materials from Union Carbide referred to as the Tone series of polyols, such as, for example, Tone 1270 (CAS #31831-53-5) (which is about 42.8% soluble in Oxsol 100) (which is solid after cooling and needs heating to be soluble), and Tone 0201 (CAS #36890-68-3) (which is 42.8% soluble in Oxsol 100, with no separation seen after a number of days).
[0058] The coating fluid typically includes about 1 to about 10 percent, preferably about 3 to about 7 percent, and more preferably, about 5 to about 6 percent, e.g., about 5.5 percent, of the additive.
[0059] Catalyst: A catalyst may be added to the coating fluid to increase the rate of polymerization. Increases in polymerization kinetics can be accomplished by adding, for example, platinum-based catalysts, zinc-based catalyst, and Lewis acids. These catalysts include, for example, acids, bases, and salts of metals, such as, for example, chromium, lead, tin, platinum complexes such as a platinum cyclovinyl siloxane complex (available as in 2-3% platinum concentration in cyclic vinylmethylsiloxanes as PC085 from UCT), and zinc, e.g., zinc octanoate. A preferred catalyst is zinc octanoate (16% Zn), which can increase the polymer molecular weight and decrease cyclic content (CAS #136-53-8; 111-90-9; 8052-41-3, available from Shepherd Chemical, Cincinnati, Ohio).
[0060] The coating fluid typically includes about 0.5 to about 5 percent, preferably, about 1 to about 4 percent, and more preferably, about 2 to about 3 percent, of the catalyst.
[0061] For coating fluid with the platinum cyclovinyl siloxane complex as a catalyst, the coating fluid typically includes about 0.01 percent to about 1.0 percent, preferably, about 0.1 percent to about 0.5 percent, and more preferably, about 0.2 percent to about 0.4 percent, of the catalyst.
[0062] Laser irradiation of the coating may be performed using 20 Watt carbon dioxide laser at 10.6 microns with a 300 microsecond pulse width. (Examples 11 and 12) Other laser conditions are possible.
[0063] In other embodiments, the resin can include organo-hydro silane polymers and copolymer, e.g., those that contain a hydro functionality, such as the methyl hydro, phenylmethyl dimethyl siloxy terminated siloxane copolymer (V) shown below (available as PS129.5 from United Chemical Technologies (UCT), Bristol, Pa.).
[0064] Some reactions associated with this type of resin are shown in Reactions 6 and 7 below:
[0065] In reaction 6, the organo-hydrosiloxane can condense with itself or with any hydroxyl containing species. In reaction 7, where CH 2 ═CHR can be a silicone resin containing a vinyl group, the Si—H bond is added across the olefin. The catalyst can be, for example, tin salts, zinc salts, and platinum complexes, as described above.
[0066] In other embodiments, heat may be provided by radiation with non-laser sources or by application of heat directly to the coating, e.g., with a resistive thermal element positioned closely adjacent to the coating.
[0067] The coating fluid can further include an optical brightener or tag that can be detected by a photodetector, which can confirm that the coating has been applied to a substrate. Preferably, the brightener is soluble in the solvent. Preferably, the brightener has a high extinction coefficient so that it can be easily detected and less material can be used. The coating with a brightener is preferably compatible for overprinting with an ink jet coder and/or with ink jet print, in addition to being laser addressable. An example includes 2,2′-(2,5-thiophenediyl)bis[5-tert-butylbenzoxazole (CAS # 7128-64-5, available as Uvitex OB from Ciba Geigy, Hawthorne, N.Y.)
[0068] The coating may also include a pigment so that, rather than a clear and colorless coating, the coating has a desired background color to enhance contrast of the image. The pigment is preferably an inert material. For example, for a white coating, titanium dioxide may be added. Other suitable pigments include barium sulfate, and Rhoplex beads, (e.g., Rhoplex ac 1024, available from Rohm and Haas, Philadelphia, Pa.).
[0069] In other embodiments, the coating can be applied to the substrate premixed or as two separate solutions, e.g., by a spray gun. The coating can be formed as a free standing film by casting it onto a piece of Teflon®, curing at 200° C., and addressing the film with a laser.
[0070] In some embodiments, the coating fluid contains no cross-linking agent, such as a silane, for example, if polymerization kinetics can be relatively slow, e.g., greater than about two minutes.
[0071] The following examples are illustrative and not intended to be limiting.
[0072] For the following examples, Sample I refers to a solution containing 5.079 grams (50.79%) Oxsol 100 (CAS #98-56-6), 4.169 grams (41.69%) diphenyl, methyl, phenyl, phenylmethyl silicone resin (Dow Corning Binder Resin 4-3136, CAS # 68037-81-0), 0.500 gram (5%) Union Carbide Tone Polyol 0201 (CAS # 36890-68-3), 0.250 gram (2.50%) Shepherd Chemical zinc octanoate (16% Zn) (CAS #s136-53-8, 111-90-0, 8052-41-3), 0.002 gram (0.02%) 2,2′-(2,5-thiophenediyl)bis[5-tert-butylbenzoxazole (Uvitex OB, CAS# 7128-64-5).
[0073] Sample II refers to a solution containing 75 grams Dow Corning Binder Resin 4-3136 (45.86%), 75 grams Oxsol 100 (45.86%), 9 grams Tone Polyol 0201 (5.5%), 4.5 grams zinc octanoate, 16% Zn (2.75%), and 0.035 gram Uvitex OB (0.02%).
[0074] Sample III refers to a solution containing 50% Dow Corning 4-3136 Binder resin and 50% Oxsol 100.
EXAMPLE 1
[0075] When lasing a coating, heat is created near the laser beam, sometimes raising the temperature to >600° C. To determine whether the heat created by the laser and/or another effect of the laser is creating the black marking, the following experiments were performed.
[0076] Sample II was coated on an aluminum plate with a 0.5 mil drawdown bar and cured at 200° C. for 10 minutes. The plate was then heated with a propane torch. At the softening point of the aluminum, the coating turned a gray/black color. This result, however, may be inconclusive because the aluminum plate melted.
[0077] The same composition as above was coated and cured on a ceramic tile. The coating was heated directly with a propane torch. As the coating was heated, it turned a brown color in the entire area of the flame. With further heating, the coating appeared to glow red-hot in isolated areas. The longer the flame was left in one place the more of the coating started to glow. When the flame was removed, the areas that were glowing had turned black. It appears that heat alone can create a color change, which is consistent with pyrolysis.
[0078] Thermogravimetric analysis (TGA) experiments were performed on cured Sample II in air under isothermal conditions at 400° C., 500° C., and 700° C. At 400° C., an amber color was observed; at 500° C., a brown color was observed; and at 700° C., a dark brown color was observed. Cured Sample II was also pyrolyzed under a nitrogen atmosphere at 1000° C. The sample turned into a shiny black glass. FTIR analysis indicates that the glass is the same material that is formed with the propane torch and laser.
EXAMPLE 2
[0079] Fourier transform infrared (FTIR) spectra were obtained for a dried and uncured (i.e., not crosslinked) coating (Sample II), a cured (crosslinked) coating (Sample II cured at 200° C. for 10 minutes), and a charred material obtained from heating the cured coating with a propane torch. Spectra were interpreted using “Silanes, Silicones, and Metal-Organics,” a catalog available from Gelest, Inc., as a guide.
[0080] The FTIR spectrum for the uncured coating is shown in FIG. 1. Table 2A shows the peak assignment for FIG. 1:
TABLE 2A Functional Group Wavenumber (cm −1 ) 1429, 772 1270 Si—O—Si 1130 Si—O—C 2 H 5 998, and peaks hidden under broad peak at 1130 750-699
[0081] The peaks at 1959 cm −1 , 1889 cm −1 , and 1822 cm −1 are assigned to phenyl substitution overtones. The peak at 1324 cm −1 is assigned to the residual Oxsol 100 solvent. According to the Gelest reference, as the molecular weight of a polysiloxane increases, the broad Si—O—Si peak around 1150-1000 cm −1 splits and/or becomes more complex. This is observed in the spectrum obtained for the crosslinked coating.
[0082] Referring to FIG. 2, the spectrum for the cured coating contains the same peaks as in the spectrum for the uncured coating. Furthermore, and the broad Si—O—Si peak has split to include 1132 and 1014 cm −1 .
[0083] Referring to FIG. 3, the spectrum for the charred material contains no organic peaks. The spectrum includes a strong Si—O—Si peak at 1073 cm −1 . The broad peak at 792 cm −1 can be assigned to Si—C (silicon carbide) or amorphous silica, both of which show characteristic absorption at about 800 cm −1 . The peak at about 1633 cm −1 may be due to a carbonyl attached to Si in the β-position, example structure below:
[0084] A FTIR spectrum of a black dust formed by lasing an uncured coating was compared to the FTIR spectrum of the black charred material above (FIG. 4). The Si—O—Si peak is shifted to 1070 cm −1 , and the peak assigned to silicon carbide or amorphous silica is shifted to 806 cm −1 . According to the Gelest reference, these shifts are acceptable, and the exact peak location is dependent on the environment of the functional group.
EXAMPLE 3
[0085] To determine the effect of changing substituent groups on a silicon atom on a lased image, a dimethyl, methyl hydro siloxane copolymer was tested. The copolymer (PS122.5, available from UCT) contains no phenyl groups and can be crosslinked through a self-condensation reaction catalyzed by a platinum complex (e.g., PC085, also available from UCT).
[0086] Ten grams of PS122.5 was mixed with 0.03 g of PC085 in a scintillation vial, and the mixture was shaken well. Using a 0.5 mil drawdown bar, thin films were formed on aluminum substrates. The films were crosslinked at 200° C. for 10 minutes. The cross linked films were passed under a laser (Domino DDC-2) at pulse widths from 50 μs to 800 μs in 50 μs intervals.
[0087] At 50 μs, no color change was observed. At 100-400 μs, a faint black color was observed. Starting at 450 μs, a more noticeable color change was observed, and the amount color observed increased up to 600 μs. At pulse widths above 600 μs, no increase in color was observed. Because the copolymer was able to form an observable marking, it appears that color formation can be achieved without phenyl groups in the resin.
[0088] Additional samples were prepared with a methyl hydro, phenylmethyl copolymer with ˜50% phenylmethyl content (PS129.5); a methyl hydro, octylmethyl siloxane copolymer with ˜50% octylmethyl content (PS125); and a methyl hydro, octylmethyl siloxane copolymer with ˜70% octylmethyl content (PS125.5). Each sample was cured at 200° C. for 10 min and imaged with the laser at a 300 μs pulse width.
[0089] The markings are darker as more carbon is added to the Si—O backbone. PS129.5 produces dots that are larger in size than the others, which gives the appearance of a darker print overall, but PS125 and PS25.5 produce markings that were blacker. This data, which suggest that increasing carbon content in the resin tends to increase color formation, supports the black glass hypothesis.
[0090] TGA isothermal runs at 700° C. were performed on cured samples of PS122.5, PS125.5, and PS129.5. PS122.5 (dimethyl substituted) turned a deep amber color. PS125.5 (methyl octyl substituted) and PS129.5 (methyl phenyl substituted) turned black. Also, PS122.5 showed much lower weight loss compared to PS129.5. The data: is consistent with the black glass theory. Lower carbon content shows lower weight loss, and as carbon content increases, the color change is more noticeable because, it is believed, there is more free carbon available to be trapped in an SiO 2 matrix.
EXAMPLE 4
[0091] To determine the effect of crosslinking density on the durability of coatings and lased images, silanes with varying degrees of ethoxy functionality were tested. The following samples were prepared:
TABLE 4A A B C D Sample I 10.0 10.0 10.0 10.0 3-aminopropyltriethoxysilane 0.3 (Witco Silquest A-1100) 3-aminopropyldimethylethoxysilane 0.3 (UCT A0735, CAS# 18306-79-1) 3-aminopropylmethyldiethoxysilane 0.3 (UCT 0742, CAS# 3179-76-8)
[0092] The above samples were prepared by weighing the materials into scintillation vials and shaking the vials by hand to provide mixing. The samples were then poured into aluminum pans and allowed to air dry to remove some of the solvent. Samples were then placed into an oven at ˜200 C. for 10 minutes.
[0093] To evaluate the susceptibilities of the cured materials to being re-dissolved by a solvent, the above samples were placed into Oxsol 100 and pentane and observed for dissolution. For the samples in Oxsol 100, no visible dissolution was observed, i.e., no Schlerier lines were observed. The films were submerged overnight in Oxsol 100, and there was no change. For the samples in pentane, the samples were mixed using a stir bar inside the scintillation vial for ½ hour. No visible change was observed. Thus, neither Oxsol 100 nor pentane dissolves the tested cured coatings. In Sample D (the control), the large chunk broke up into smaller particles in both Oxsol 100 and in pentane.
[0094] To test coating durability, drawdowns of clear samples were made with a bar onto pre-cleaned aluminum coupons (6061-T6) (1″W×3″L×0.032″T). Coupons were placed into a ˜200 C. oven for 2, 5, and 10 minutes. Coupons were then cooled to room temperature and given 10 double rubs with an Oxsol 100 soaked applicator (Puritan 6 inch Cotton Tipped Applicators) (“Oxsol wipe test”). This test is used to evaluate crosslinking of monomers, for example, a highly crosslinked monomer typically shows no dissolution when immersed in the solvent in which the monomer was dissolved. Films were evaluated for the amount of film deterioration observed. None of the films at any of the times showed deterioration. In Sample D (control), the film was completely removed down to the aluminum substrate for 2 and 5 minutes; and at 10 minutes, there was visual degradation but not complete removal as at 2 and 5 minutes. From this qualitative test, the amount of ethoxy functionality has a minimal effect on coating dissolution, but is desirable to prevent complete removal of the film.
[0095] Print durability was evaluated using a Crock test.
[0096] Aluminum coupons were coated with the above samples. Images were created using a Domino DDC-2 laser using CO 2 wavelength tubes (10.6 μ) at a pulse width of 300 μsec. A typical image was: 12345ABC. After imaging, the coupons were placed onto a crockmeter (A.A.T.C.C. Crockmeter, Model CM 1, available from Atlas Electric Devices Co.) using double backed tape. A white cotton test cloth (A.A.T.C.C. Test Fabrics, Crockmeter Squares) was held in place by a clamp.
[0097] A “finger” having the cloth attached thereto was carefully placed onto the coupon to provide a stroke length that covers the entire image area. The image was crocked for 2×10 strokes and evaluated for legibility and wear.
[0098] The durability of the samples was very similar, if not the same. Results were similar for all cure times. The main observable difference is that the crosslinking agent with three ethoxy functionalities produces better definition of the lased dot. Generally, however, qualitative testing suggests that there is little difference in print durability with changes in ethoxy functionality. In Sample D (control), generally more material was removed with decreasing cure time (i.e., 2 min>5 min>10 min). The print, however, was legible at all tested times.
EXAMPLE 5
[0099] The effect of a primary amine, 2-ethylhexylamine (98% Aldrich), on print durability, was evaluated. Four samples were made: each had 10.0 grams of Sample I and varying amounts of the amine (0.3, 0.5, 0.7, 1.0 gram).
[0100] Solutions were drawn down onto aluminum and cured at ˜200° C. for 2 and 5 minutes. Films were then tested for crosslinking by the Oxsol wipe test described in Example 4.
TABLE 5A Time in Oven Sample 2 minutes 5 minutes 0.3 g amine Material is almost No material is removed completely removed. 0.5 g amine Matenal is almost No material is removed completely removed, slightly better than A 0.7 g amine No material is removed No material is removed 1.0 g amine Very slight removal of No material is removed material
[0101] From Table 5A, it appears that the primary amine is not as resistant to dissolution as the amino functional silanes, as evaluated by the Oxsol wipe test.
[0102] However, the above samples were also evaluated for rub resistance by using the Crock meter test described in Example 4. Here, in terms of assessing how dark the prints remain, the amine appears to be qualitatively comparable with the silanes.
EXAMPLE 6
[0103] To determine any effect on print quality and durability of a coating having a 1°, 2°, or 3° amine, the following samples were prepared:
TABLE 6A A B C Sample 1 10.0 10.0 10.0 2-ethylhexylamine (1° amine) 0.30 Dioctylamine (2° amine) 0.30 Trioctylamine (3° amine) 0.30
[0104] The above samples were weighed into a scintillation vial and hand shaken to provide mixing. ½ mil wet drawdowns were made onto aluminum coupons. The coated coupons were placed into an oven at ˜200 C. for the following times: 2, 5, and 10 minutes. Coatings were then imaged using the Domino DDC-2 laser at ˜3 meters/minute and a pulse width of 300 μs.
[0105] Microphotographs reveal poor print quality for all amines cured for 2 minutes, and the 3 amine sample also shows poor print quality for the 5 minute cure time. The remaining samples were all legible.
[0106] Print durability was evaluated using the Crock meter test described in Example 4. The results are shown in Table 6B:
TABLE 6B Time in Oven (Mins) A (1°) B (2°) C (3°) 2 Completely removed, Completely removed, Completely removed, 1 stroke 1 stroke 2 strokes 5 Completely removed, Completely removed, Completely removed, 10 strokes 10 strokes 3 strokes 10 Almost completely Almost completely Completely removed, removed after 10 removed after 10 10 strokes strokes, print strokes, print somewhat legible somewhat legible, although less than 1
EXAMPLE 7
[0107] An example of a blocked silane is a silane having a secondary amine, (3-triethoxysilylpropyl)-t-butylcarbamate (available as SIT8186.5 from Gelest, “SIT”), which undergoes the following reaction:
[0108] The following samples were prepared:
TABLE 7A Sample A B C D E Sample II 10.0 10.0 10.0 10.0 10.0 SIT 0.1 0.3 0.5 1.0 Silquest A-1100 /15 0.3 Totals 10.1 10.3 10.5 11.0 10.3
[0109] Samples were prepared in scintillation vials and hand shaken to provide mixing. For the initial trial, the samples were left to sit overnight and observed for changes in viscosity or gelling. Of the four samples above, samples A & B showed a cloudy appearance overnight and samples C & D were both clear. To provide a comparison between a SIT sample and a Silquest A-1100 sample, sample B was prepared with the SIT, sample E was prepared with the A-1100, and both samples were placed into a viscometer. The change in viscosity was recorded as a function of time. The results are listed below, with the A-1100 as a reference point.
TABLE 7B A-1100 Sample SIT Sample Change in Change in Hours:Minutes Viscosity Viscosity 0 0 0 0:10 2.6 −0.2 0:20 6.0 −0.2 0:30 9.8 −0.2 0:40 13.8 −0.2 0:50 17.7 −0.1 1:00 22.6 0.0 1:10 27.8 0.0 1:20 33.0 0.1 1:30 38.6 0.1 1:40 44.6 0.1 1:50 51.4 0.1 2:00 58.9 0.2 2:10 67.3 0.3 2:20 76.8 0.4 2:30 86.0 0.5 2:40 95.8 0.6
[0110] The starting viscosities for the above were 34.4 cPs for the A-1100 sample and 28.0 cPs for the SIT sample. The SIT (blocked silane) sample showed good stability.
[0111] Tests were then performed to determine whether the above deblocking reaction would occur to provide crosslinking. ¼ mil wet drawdowns of the A-1100 and SIT were made onto pre-cleaned aluminum coupons, which were then placed into a ˜200 C. oven for 10 minutes. After the coupons cooled, the coating samples were subjected to the Oxsol wipe test described in Example 4. Under this test, neither coating showed any deterioration.
[0112] Samples B and E, with SIT and A-1100, respectively, were also subjected to the Oxsol wipe test over shorter cure times. The results are shown in Table 7C:
TABLE 7C Time (Min) Silane Results 1 A-1100 Slight film deterioration 1 SIT Majority of film removed 2 A-1100 No film removed 2 SIT Majority of the film removed, although better than at 1 minute 3 A-1100 No film removed 3 SIT Slight film deterioration 5 A-1100 No film removed 5 SIT Slight film deterioration 7 A-1100 No film removed 7 SIT No film removed
[0113] Table 7C indicates that the SIT (blocked silane) does not crosslink the resin at 200 C. as quickly as the A-1100 (unblocked silane).
[0114] To identify how durable, e.g., not removable with rubbing, the image is with the SIT, coatings were made at the 3% (w/w) level (Sample B) and cured at 200 C. for 2, 5, and 10 minutes. Durability of the coating was determined by the amount of black marks seen on a cotton square designed to be used with the crock meter. All samples were subjected to 10 2× rubs. Results are shown in Table 7D.
TABLE 7D Time (Min) Results 2 Print is still visible, although the coating is worn through to the metal in places. Heavy dark mark seen on the cloth. 5 Only very slight wearing of the coating seen. Print is clearly legible, although there is a heavy dark mark left on the cloth. 10 No wear seen on coating and the print is clearly legible. Overall, much less of a dark mark seen on the cloth.
[0115] The data with regard to the print durability appear to be comparable to those of the A-1100. After 17 days, there was no significant change in viscosity, as compared to the unblocked siland, which typically had only three hours of viscosity stability.
EXAMPLE 8
[0116] The effect of diols on adhesion and cracking of a marking coating was evaluated using a 90 bend test. The bend test is performed using 6061 aluminum coupons (3″L×1″W×{fraction (1/32)}″T) with a coating applied and cured as described earlier. The coupon is placed into a vise and bent in one motion to approximately a 90 angle. The area of interest is the coating closest to the bend, where the stress on the coating is at the maximum.
[0117] The following samples were prepared:
TABLE 8A Sample A B C D (Control) Sample III 10 10 10 10 Zn Octanoate 0.3 0.3 0.3 0.3 1,4 Butanediol 0.1 0.2 0.25 0
[0118] The samples were drawn down to thicknesses of ¼ and ½ mil and cured for different amounts of time (1, 5 and 10 minutes). Fracturing and delamination were evaluated using the 90° bend test described above, and print robustness was evaluated using the Crock test described above.
TABLE 8B ¼ Mil Wet Draw Down for 1,4 butanediol Time in Oven Fracturing/ Sample Delamination 1 minute 5 minutes 10 minutes A Fracturing NF Micro NF Delamination Yes Yes Yes Print Robustness Poor Decent Good B Fracturing NF Micro NF Delamination Yes Yes No Print Robustness Poor Decent Good C Fracturing NF Micro NF Delamination Yes Yes No Print Robustness Poor Decent Good D Fracturing NF Micro NF Delamination Yes No No Print Robustness Poor Decent Good
[0119] [0119] TABLE 8C ½ Mil Wet Draw Down for 1,4 butanediol Time in Oven Fracturing/ Sample Delamination 1 minute 5 minutes 10 minutes A Fracturing NF Micro NF Delamination No No No Print Robustness Poor Decent Good B Fracturing NF Mass NF Delamination Yes No No Print Robustness Poor Good Good C Fracturing NF Micro Micro Delamination Yes No No Print Robustness Poor Decent Good D Fracturing NF Mass NF Delamination Yes Yes No Print Robustness Poor Good Good
[0120] where
TABLE 8D Key Print Robustness Poor Print is completely removed Decent Some material is removed, print is still legible Good Although some black material is removed, print is still very legible Fracturing NF No fracturing seen Micro Micro-fracturing seen in sample Mass Massive fracturing seen Delamination Yes Material was removed when scraped with a dental tool, and then wiped with a finger. No Material was not removed by above procedure
[0121] The following samples were then prepared with Tone 0201:
TABLE 8E Sample A B C Sample III 10 10 10 Zn Octanoate 0.3 0.3 0.3 Tone 0201 0.5 0.6 0.2 Silquest A-1100 0.5 0.5 0.5
[0122] [0122] TABLE 8F ¼ mil Wet Draw Down For Tone 0201 Time in Oven Sample Fracturing/Delamination 1 minute 5 minutes 10 minutes A Fracturing Mass No No Delamination Yes No No Print Robustness Slight Good Excellent B Fracturing No No No Delamination No No No Print Robustness Fair Good Excellent C Fracturing Micro No No Delamination No No No Print Robustness Good Good Excellent
[0123] The following samples were prepared with Tone 0201 and Tone 1270:
TABLE 8G Sample A B C D E F Sample III 10 10 10 10 10 10 Tone 0201 0.1 0.25 0.5 Zn Octanoate 0.3 0.3 0.3 0.3 0.3 0.3 Tone 1270 0.1 0.25 0.5
[0124] [0124] TABLE 8H ¼ Mil Wet Draw Down For Tone 0201 and Tone 1270 Time in Oven Fracturing/ Sample Delamination 1 minute 5 minutes 10 minutes A Fracturing Mass Micro Mass Delamination No No No Print Robustness Poor Poor Poor B Fracturing Mass Micro NF Delamination No No No Print Robustness Poor Poor Fair C Fracturing Mass Mass NF Delamination No No No Print Robustness Poor Poor Decent D Fracturing Micro Micro Mass Delamination No No No Print Robustness Poor Poor Fair E Fracturing Mass Mass Mass Delamination No Small amount No Print Robustness Poor Poor Poor F Fracturing Micro Mass Micro Delamination No No No Print Robustness Poor Poor Poor
[0125] Delamination properties of samples A-F were also evaluated by a freeze/water adhesion study in which aluminum coupons with the coatings were submerged in an ice bath for the time indicated.
TABLE 8I Sample 1 Minute 5 Minutes 10 Minutes A Yes Yes Yes B Yes Yes Yes C Yes Yes No D Yes Yes Yes E Yes Yes Yes F Yes Yes No
[0126] where “Yes” means that the coating was removed by a scratch, and “No” means no coating was removed by a scratch.
[0127] The coating was not removed when the highest tested concentration of polyol was used and the cure time was 10 minutes.
EXAMPLE 9
[0128] The effect of adding a silane (Silquest A-1100) to a coating composition containing Tone 0201 was evaluated by preparing the following samples:
TABLE 9A Sample A B C Sample III 10 10 10 Zn Octanoate 0.3 0.3 0.3 Tone 0201 0.5 0.6 0.2 Silquest A-1100 0.5 0.5 0.5
[0129] [0129] TABLE 9B ¼ Mil Wet Draw Down thickness Time in Oven Sample Fracturing/Delamination 1 minute 5 minutes 10 minutes A Fracturing Mass No No Delamination Yes No No Print Robustness Slight Good Excellent B Fracturing No No No Delamination No No No Print Robustness Fair Good Excellent C Fracturing Micro No No Delamination No No No Print Robustness Good Good Excellent
[0130] Adding the silane enhanced the fracturing, delamination, and print robustness properties of the coating.
EXAMPLE 10
[0131] To study the effect of polyols on a marking composition, the following samples, without a polyol, were prepared:
TABLE 10A Sample A B C D E Sample III 10 10 10 10 10 3-aminopropyltriethoxysilane 0.3 (Witco Silquest A-1100) 3-aminopropyldimethylethoxysilane (UCT A0735) 0.3 3-aminopropylmethyldiethoxysilane (UCT A0742) 0.3 3-triethoxysilylpropyl-t-butylcarbamate 0.3 2-ethylhexylamine 0.3
[0132] Samples were weighed into scintillation vials and mixed by shaking the vials. When the samples were clear, they were drawndown onto clean aluminum coupons with a bar. The coupons were then placed into an oven at approximately 200° C. for about 2 minutes, and cooled to room temperature. For each sample, a coupon was lased to evaluate image quality, before and after crocking. Each lased sample was also tested for resistance to removal by Oxsol 100 by subjecting the samples to ten double rubs with an applicator soaked with Oxsol 100 (Oxsol wipe test).
[0133] Microphotographs were taken of lased samples before the samples were subjected to crocking. Sample D did not show any print durability and included black amorphous clouds. The clouds may be similar to black material created by the laser that is being deposited around the area where imaging was done. Sample E showed poor durability and color development, with lased spots having white halos.
[0134] The lased samples were then crocked. Samples D and E showed the worst results. For example, in sample D, a dot created by the laser was sometimes completely removed by crocking, and sample E showed heavy abrasion. Samples A, B, and C all showed decent dot retention. Results are tabulated below:
TABLE 10B Image Quality Image Durability Oxsol 100 wipe Sample before Crocking after crocking resistance A Nice Quality, good Little material Very slight film dot definition removed, very deterioration seen. readable. Film is still intact. B Nice Quality, good Little material No deterioration dot definition removed, very seen. readable. C Nice Quality, good Little material No deterioration dot definition removed, very seen. readable. D No image durability, Material completely Film is completely black “cloud” effect removed, removed. around where image Essentially no was made evidence a code was there. E Image has a whitish Image is essentially Film is completely hazy appearance. completely removed. Not a sharp print. removed. Film is also heavily abraded, the only coating to have this effect.
[0135] Compared to the blocked silane (D) and the amine (E) samples, the three silanes tested (A, B & C) showed better image quality, print durability, and resistance of the cured film to solvent dissolution. Since testing done was performed with a cure time of 2 minutes, the amine and the t-butylcarbamate blocked silane may need more time at this temperature to provide durable prints, if they are obtainable at all. The absence of the Tone polyol appears to have a negative effect to the primary amine and t-butylcarbamate blocked silane, in terms of print formation and durability.
EXAMPLE 11
[0136] Different lasers and wavelengths were evaluated to determine parameters that can create an image.
[0137] A fluid sample was prepared with 0.3 gram of Silquest A-1100 and 10 grams of a prepared solution (Sample I). Coatings of the fluid were made onto aluminum coupons using a ¼ wet draw down bar. Samples were cured for 5 minutes at ˜200 C.
[0138] Table 11A describes the lasers used in this evaluation, along with the results produced from that laser.
TABLE 11A Fluence Wavelength Beam Diameter Spot Size (approx. Power (approximate) Watts (Unfocused) (Microns) Density) Results 532 nm (Green) 10 mW 8 mm 3.5 110 kW/cm 2 No image created doubled YAG 632.8 nm (Red) 15 mW 8 mm 4.0 117 kW/cm 2 No image created Helium-Neon 831 nm (IR) Laser 1 W 50 50 kW/cm 2 No image created Diode 1112 nm 15 W Image created at 7+ Watts, 100 mm/sec. scan rate 10.6 μ CO 2 20 W focused 168 Image made with <0.1 mJ
[0139] Images were created at wavelengths of 10.6μ and 1112 nm, but not at shorter wavelengths. This is believed to be due to energy being applied to the coating, or not enough absorbance of the coating at that particular wavelength to convert the energy to heat and pyrolyze the coating.
EXAMPLE 12
[0140] Different powered lasers were evaluated to study the relationship between the size of a dot imaged and the amount of power to produce the dot. For example, if a high powered laser is used, ablation may dominate over pyrolysis, but if a relatively low powered laser is used for longer dwell times, then perhaps energy from the laser may be more efficiently used to produce an image.
[0141] Aluminum coupons were placed into a 1M NaOH solution for about 5 minutes. The NaOH solution was used to change the surface of the aluminum coupons and to “whiten” the background of the aluminum coupon, making it easier to detect imaged dots using a QEA system (Quality Engineering Associates, Inc., Burlington, Mass., software version 1.6.3C). After the coupons were removed from the solution, they were wiped down using a KimWipe® tissue and then wiped using a KimWipe® tissue soaked with a 50%:50% by volume solution of ethyl acetate and isopropanol. These procedures provided a white opaque background on the coupons.
[0142] A sample of 0.3 gram of Silquest A-1100 and 10 grams of Sample I was prepared. The materials were weighed into a scintillation vial and hand shaken to provide mixing. Using a ¼ mil drawdown bar, 3 drawdowns were prepared for each of the following pulse widths (μs) to be tested: 50, 100, 200, 300, 400, 500, 600, 700, and 800. The total number of drawdowns was 27. Samples were cured at 200 C. for 5 minutes.
[0143] A multi-tube laser system was used. The system includes seven laser tubes that direct seven laser beams to a focusing lens. The lens then directs and focuses the beams onto a substrate. Referring to Table 12A, the laser (Domino DDC-2) configuration was:
TABLE 12A Tube # Type of Tubes 1 Standard 2 Standard 3 Standard 4 Standard 5 LEEP 6 Standard 7 LEEP
[0144] The standard tubes output nominally 20 Watts, and the LEEP tubes output nominally 25 Watts. Typically, the LEEP tubes have a quicker rise and fall time; i.e., they reach full power quicker than the standard tubes. The feedrate of the samples was ˜3 meters/minute.
[0145] Measurements were taken using a QEA system (IAS 1000) on 18 dots (except for the 50 microseconds sample, in which 9, 17, and 18 dots were measured).
[0146] An average diameter (in mils) was calculated using the following formula
2 * ( AvgDotArea ( μ 2 ) / π 25.4
[0147] Table 12B shows the results for each pulsewidth:
TABLE 12B Beam fluence Pulsewidth Avg. Energy Avg. Energy at edge of (μs) diameter (Mils) (mJ) Density (J/cm 2 ) dot (J/cm 2 ) 800 12.8 16.48 19.85 0.08 700 12.8 14.48 17.45 0.07 600 12.8 12.48 15.04 0.06 500 12.2 10.48 13.90 0.10 400 12.4 8.48 10.89 0.07 300 11.4 6.47 9.83 0.15 200 10.2 4.45 8.45 0.35 100 7.3 2.27 8.40 1.96 50 4.6 0.68 6.35 3.76
[0148] where energy is the total energy received by a dot; average energy density is the total energy divided by the dot area; and beam fluence at edge of dot relates to how much laser energy is applied along the perimeter of the dot (Example 16).
[0149] [0149]FIG. 5 shows energy as a function of average diameter, and FIG. 6 shows dot diameter as a function of pulse width. It appears that for pulse widths greater than about 400 μs, there is little gain in dot area. At about 50 μs pulse width, the data was erratic, and the prints were difficult to read.
EXAMPLE 13
[0150] A protocol for heat curing samples is described below.
[0151] A coating fluid is applied to substrates using a draw down bar, which helps to provide a uniform coating thickness. The coated substrates are then placed in a wire basket. A layer of aluminum foil is placed on the bottom of the basket to prevent material from dripping onto an oven.
[0152] The basket is then placed into the Blue M oven (Model #DC-146C with a Type 0931X019 temperature controller) for a predetermined time and at a predetermined temperature. Typically, the oven temperature decreases when the samples are placed in the oven. The oven temperature, however, recovers relatively quickly. After curing, the basket is removed and cooled to room temperature. Testing is then conducted on the coated substrates.
EXAMPLE 14
[0153] The following samples were made to fill in controls for Tables 4A; 5A; 6A; 9A; and 10A.
[0154] All samples were drawn down onto 6061 aluminum coupons (1 in.×3 in.) to give a ¼ mil wet film thickness. The coated coupons were placed into a Blue M oven (Model #DC-146C with a Type 0931X019 temperature controller) for 2, 5, and 10 minutes at 200 C. Samples were removed from the oven and addressed with a Domino DDC-2 laser at 300 μs pulse width. A slow moving conveyor belt transported the samples under the laser head. Photographs were then taken of the samples using a microscope (Olympus, Model #SZX12 with Olympus DP10 digital capture). Samples were then crocked and wiped with solvent (Oxsol 100) as described above. Sample D can be used as a control sample for Tables 4A, 5A, and 6A (Sample I without a silane cross linking agent). Sample A can be used as a control sample for Tables 9A and 10A (Sample III only).
TABLE 14A Sample A B C D E Oxsol 100 5.00 5.00 5.00 5.00 5.00 Dow Corning 4-3136 5.00 5.00 5.00 5.00 5.00 Tone 0201 0.50 0.50 0.50 Zinc Octanoate 0.25 0.25 0.25 Silquest A-1100 silane 0.30
[0155] [0155] TABLE 14B Description of Results Time in Oven (Mins) A B C D E 2 Before Black Black Nice sharp Nice sharp Nice sharp Crock amorphous amorphous image. image. image. clouds seen, clouds seen, poor image poor image resolution resolution After Image Image Some Smudging Nice sharp Crock completely completely smudging seen around image. No removed-1 removed-1 seen, print. Still smudging stroke stroke although still readable, around print. very although readable light. 5 Before Black Black Nice sharp Nice sharp Nice sharp Crock amorphous amorphous image. image. image. clouds seen, clouds seen, poor image poor image resolution resolution After Image Image Only slight Smudging Nice sharp Crock completely completely smudging seen around image. No removed-2 removed-2 around print. print. Still smudging strokes strokes Very sharp readable, around print. and although readable. light. Darker than 2 minutes. 10 Before Slightly Nice sharp Nice sharp Nice sharp Nice sharp Crock better image. image. image. image. definition than 5 mins. Readable image After Nearly Image is still No Smudging Nice sharp Crock completely readable, smudging seen around image. No removed although around print, print. Still smudging after 10X much lighter very little readable, around print. rubs than before. removed to although cloth. Nice light. sharp image Darker than remains. 5 minutes.
[0156] [0156] TABLE 14C Dissolution of Cured Materials Time in oven (mins) A B C D E 2 Film Film Film Slight film No film completely completely completely deterioration deterioration removed removed removed and removal or removal seen 5 Film Film Slight film No film No film completely completely deterioration deterioration deterioration removed removed and removal or removal or removal seen 10 Film Film No film No film No film completely completely deterioration deterioration deterioration removed removed, or removal or removal or removal although slightly less area than 5 minute sample
[0157] Sample E gave good print durability and solvent resistance, e.g., those that can be used for industrial applications. Other samples are useful if cure cycles times greater than 2 minutes at 200° C. are used.
[0158] The resin with the combined effects of the polyol, zinc catalyst, and silane create a formula that results in good print durability, rub resistance and chemical resistance when cured for about 2 minutes in a ˜200° C. oven.
EXAMPLE 15
[0159] An experimental beverage can printing run was performed on cans coated with a composition including 3000 grams of Sample I and 90 grams of the Silquest A-1100 silane. The silane was added to the composition just prior to spraying.
[0160] The power of the laser used was as described above. At a pulse width of about 250 microseconds, and a can throughput of about 1250 cans per minute, the cans were marked with an excellent image. The above coating provided a legible print with minimal fracturing and delamination.
EXAMPLE 16
[0161] In a Gaussian laser beam, optical power is not uniform throughout the cross-section. The beam has the highest power per unit area at the center of the beam, and the power per unit area deceases away from the center of the beam according to a well-known bell curve. This curve is irradiance, typically expressed in W/cm 2 and described by the formula:
I ( r ) = 2 P π r o 2 - 2 ( r / r o ) 2
[0162] where r is the distance from the beam center; P is the total beam power; and r o is the 1/e 2 radius, i.e., the distance at which the power density is 1/e 2 , about 13% of its peak value.
[0163] To calculate how much power an area exposed to the beam sees, one can integrate the irradiance over the area.
[0164] The total power delivered to a circular area of radius R is:
W = ∫ 0 2 π ∫ 0 R I ( r ) r r θ = [ 1 - - 2 ( R / r o ) 2 ] P
[0165] To find the energy delivered to this area, one can integrate again over exposure time. If the power output of the laser is unchanging—that is, if P is constant—than one multiplies W by the exposure time T. If, however, the laser power is not constant—if P is a function of time—then the energy is:
E = [ 1 - - 2 ( R / r o ) 2 ] ∫ 0 T P ( t ) t
[0166] The power function P(t) of the DDC-2 laser is characterized by an exponential rise to peak power, a dwell at that power, and exponential decay back down to zero. The integration of this profile is known in the art.
[0167] Other embodiments are within the claims.
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A marking composition includes a polymerizable first material that comprises silicon and a second material capable of extending polymeric chains of the first material, wherein the marking composition is capable of undergoing a change that can be detected optically when the composition is contacted with energy.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This non-provisional patent application claims the benefit under § 119(e) of U.S. Provisional Patent Application Ser. No. 60/667,487, filed Apr. 1, 2005, which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates in general to poultry processing. More particularly, this invention relates to a system and method of processing poultry using electrolyzed water.
[0004] 2. Background of the Invention
[0005] The Center for Disease Control (CDC) estimates that 76 million cases of food-borne illnesses occur each year, while food poisoning claims the lives of an estimated 5200 Americans. Most cases of food-borne illnesses are related to surface or product contamination, and up to one-third of the illnesses are related to improperly handled poultry and produce. With United States weekly chicken broiler production now exceeding 150 million birds per week, and with over 9 billion birds processed each year, a significant challenge for poultry processors is the control of illness-causing pathogens, including Salmonella and E. coli.
[0006] The current method of controlling illness-causing pathogens in poultry processing utilizes antimicrobial sprays and washes, followed by quenching in a chiller. The two antimicrobial agents most commonly used to disinfect poultry carcasses prior to the chiller are sodium hypochlorite and trisodium phosphate, while chlorine and chlorine dioxide gases are bubbled into chiller water in an attempt to kill pathogens there. These disinfectants are increasingly ineffective in preventing cross-contamination in vats and chillers during processing. They are also toxic to plant workers and the environment. Chlorine off gassing poses a threat to worker health. Trisodium phosphate contaminates wastewater with dangerous phosphates that cannot be removed.
[0007] The monetary cost associated with the current methods of poultry processing are just as high as the costs to workers and the environment. Large quantities of chemicals must be purchased and disposed of. For instance, each poultry processing facility in the United States uses up to 7,500 gallons of toxic chlorinated water every hour. Thus processing plants pay twice: first for the chemicals and then for expensive wastewater management solutions. The shortcomings and expense of the disinfectants currently used by poultry processors attest to a real need for effective cleaning and disinfecting alternatives.
[0008] Electrolyzed water is useful for disinfecting and cleaning. Electrolyzed water is produced by electrolysis. A feed water solution containing a saline solution component is supplied to an electrolytic cell comprising both an anode chamber and a cathode chamber. When normal culinary tap water is combined with an electrolyte (i.e., salt) and placed in contact with an electrical probe or plate, electrolysis occurs once the probe or plate is electrically charged by a power source. The probes or plates are separated by a membrane that separates and isolates certain chemical ions. During the chemical reaction, positively charged ions naturally migrate to the negative electrode (i.e., cathode) and negatively charged ions including precursors for hypochlorous acid (HOCl) naturally migrate towards the positive electrode (i.e., anode). The feed water solution is cathodically electrolyzed in the cathode chamber to produce electrolyzed water as an antioxidant solution called alkaline catholyte, commonly referred to as Type B water. The feed water solution is anodically electrolyzed in the anode chamber to produce electrolyzed water as an oxidant solution called anolyte, whose pH is modified in the process, and is commonly referred to as Type A water. The anolyte is a strong oxidizing solution. More specifically, acidic electrolyzed water is normally generated from the anode electrode through electrolysis of a dilute aqueous sodium chloride (NaCl) solution. The Cl −1 ions are electrochemically oxidized to Cl 2 gas on the anode surface, which gas is partially hydrolyzed to hypochlorous acid (HOCl) in solution phase and to other ions.
[0009] The relatively high bactericidal activity of acidic electrolyzed water, or Type A water, is attributed to high oxidation-reduction potential (ORP), presence of dissolved Cl 2 , OCl − , and HOCl, and acidic pH. The high ORP of Type A water kills microbes by first damaging cell walls, thus allowing infiltration of the water solution inside the cell walls and causing an osmotic or hydration overload. The Type A water floods the cell faster than the cell can expel the fluid thus causing the cell to burst. Also contributing to the relatively high bactericidal activity is the presence of so-called active chlorine, which comprises dissolved Cl 2 , OCl − , and HOCl. The bactericidal activity of dissolved Cl 2 lessens over time as it evaporates or is otherwise lost from the Type A water during storage or a period of treatment. This loss may also affect other important properties of Type A water, such as its pH, ORP, and HOCl concentration. Finally, the low pH of Type A water effectively kills many pathogens.
SUMMARY OF THE INVENTION
[0010] The present invention relates to a system and method for processing poultry using electrolyzed water. Processing poultry with electrolyzed water overcomes many of the disadvantages of current poultry processing methods. Electrolyzed water is more pathogenically effective, safer for workers and the environment, and lower in cost.
[0011] The system and method of the present invention achieves an extremely high reduction in pathogen counts. It has been found that electrolyzed water is highly efficacious, achieving higher kill rates of harmful pathogens than alternative cleaners and disinfectants. In tests conducted at a major university and at an operating plant, electrolyzed water solutions achieved as high as a 6 log (99.9999%) reduction in Salmonella and E. coli on carcasses. Electrolyzed water is capable of killing bacteria, viruses, spores, and molds within seconds of contact. Furthermore, in contrast to other cleaners and disinfectants, pathogens are unlikely to become resistant to electrolyzed water over time.
[0012] Electrolyzed water also is capable of being produced on site without toxic chemicals. Only lab grade salt is added to the initial process as an electrolyte to assist in the electrolysis process. During the electrolysis process, a small amount of chlorine quickly gases off from the holding tank and dissipates into open atmosphere. The fluid is created in a room where venting can be accomplished without risk to operators, workers, or the environment.
[0013] Embodiments of the invention provide for a system for processing poultry comprising electrolyzed water and a plurality of application points for applying the electrolyzed water. Further embodiments of the invention provide for a system for processing poultry comprising an evisceration line, an inside/outside bird washer, and electrolyzed water. Embodiments of the invention also provide for a method of processing poultry comprising the step of applying electrolyzed water to a bird at a plurality of application points.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] Some of the features, advantages, and benefits of the present invention having been stated, others will become apparent as the description proceeds when taken in conjunction with the accompanying drawings in which:
[0015] FIG. 1 is a schematic diagram of a system in accordance with an embodiment of the present invention.
DETAILED DESCRIPTION
[0016] Although the following detailed description contains many specific details for purposes of illustration, anyone of ordinary skill in the art will appreciate that many variations and alterations to the following details are within the scope of the invention. Accordingly, the exemplary embodiment of the invention described below is set forth without any loss of generality to, and without imposing limitations thereon, the claimed invention.
[0000] Types of Electrolyzed Water
[0017] Electrolyzed water produced by electrolysis is classified into three types: Type A, Type B, and Type C. In the preferred embodiments described below, electrolyzed water is produced from an electrolyte solution made by combining tap or other water with a concentration of about 1% to 50% sodium chloride. However, a concentration of 10% to 30% sodium chloride is more preferable. In certain embodiments a concentration of about 20% is preferred. Furthermore, it should be noted that electrolyte solutions for producing electrolyzed water may include magnesium chloride (MgCl 2 ), sodium phosphate (NaH 2 PO 4 ), and amidosulfonic acid (H 3 NO 3 S). Some of these electrolyte solutions are described in U.S. Pat. No. 7,011,739, which is incorporated herein by reference.
[0018] Type A water is a disinfectant that kills a large variety of bacteria, viruses, molds, and spores within seconds of contact. It is capable of replacing chlorinated water, and can be more effective at killing pathogens without the toxicity. When negatively charged ions migrate to the anode, the fluid around the anode develops a reduced pH in the approximate range of 1.8 to 3.5 and an ORP in the approximate range of 1050 to 1400 + millivolts (mV). Type A water can be produced as a continuous stream of clear solution having a pH of 1.8-3.5, an ORP of 1,050-1,400 + mV, and containing 8-200 parts per million (ppm) of HOCl. When Type A water comes in contact with organic material its pH increases, its ORP drops, and the HOCl dissipates or gases off, thus returning to ordinary water having a small amount of free chlorine (Cl). Safety and toxicity tests have shown that Type A water is nontoxic at an HOCl concentration ranging from 10 to 120 ppm, a pH of 1.8, and an ORP ranging from 1050-1400 + mV.
[0019] Type B water is an extremely effective emulsifier and cleaner having antimicrobial properties. It is capable of saponifying surfaces upon contact. Type B water is an alkaline water stream and can be produced as a continuous stream of clear solution produced around the negative electrode, i.e., cathode, during electrolysis. Type B water is basic with a pH in the approximate range of 9.5 to 12.2. The ORP of Type B water is in the approximate range of 350 − -950 − mV. Type B water also contains sodium hydroxide (NaOH) ions in the approximate range of 8 to 200 ppm. NaOH has the ability to saponify, or create a microscopic “soap” film on the surface of a target. Type B water is effective in emulsifying oils and lipids and leaves no residue. Safety and toxicity tests show that Type B water is nontoxic at a pH of 9.5 to 12.2 and an ORP from 350 − to 950 − mV.
[0020] Type C water is essentially a form of stabilized Type A water with a longer shelf life. Type C solution has an ORP in the approximate range of 850-1080 + mV, a pH value in the approximate range of 3.6-7.0, and contains HOCl in the approximate range of 8-80 ppm.
[0021] Table 1 summarizes the typical physical characteristics of Type A, B, and C water produced from an electrolyte solution containing sodium chloride.
TABLE 1 Physical Characteristics of Type A, B, and C Water Type pH ORP (mV) HOCl (ppm) NaOH (ppm) Type A 1.8-3.5 1050-1400 + 8-200 — Type B 9.5-12.2 350 − -950 − — 8-200 Type C 3.6-7.0 850-1080 + 8-80 —
Effect of Electrolyzed Water
[0022] The examples that follow describe the effect of electrolyzed water against a variety of common pathogens found on poultry carcasses. Many variations on the specific perimeters of the examples are possible. Thus the examples are provided only for completeness, and not by way of limitation.
EXAMPLE 1
[0023] Both Type A and B water were applied to poultry carcasses. Type B water was applied in a shower; Type B water was applied again in a spray cabinet; and finally Type A water was applied in a spray cabinet. The spray application was accomplished with a spray manifold having eight spray heads in a single manifold.
[0024] The application of Type B water in the shower and spray cabinet was identical except for location. The Type B water had a pH of 11.0, an ORP of 900 − mV, and an initial NaOH concentration of 25 ppm. Type B water was sprayed from a spray nozzle onto the carcasses from multiple angles for approximately 1.5 seconds at 35 psi and 7 gpm at a temperature of 50° C. The temperature of the solution was greater than the fat temperature of the poultry carcasses before application. The spray washing with Type B water occurred immediately following de-feathering or de-flocking and saponified the surfaces of the carcasses so that any fecal matter or other substances would not adhere to the carcasses. Tests revealed no measurable discoloration, deterioration, or change in consistency or texture of the target tissue as a result of spraying with Type B water.
[0025] Within seconds after the second application of Type B water, the poultry was removed from the Type B spray cabinet and placed in the Type A spray cabinet for disinfecting. The Type A water had a pH of 2.5, an ORP of 1100 + mV, and an initial HOCl concentration of 25 ppm. Type B water was sprayed from a spray nozzle onto the carcasses from multiple angles for approximately 1.5 seconds at 35 psi and 7 gpm at a temperature of 50° C. The temperature of the solution was greater than the fat temperature of the poultry carcasses before application.
[0026] Table 2 summarizes the effect of the protocol of Example 1 on E. coli on chicken carcasses. CFU/cm2 stands for colony forming units per square centimeter, as understood by those of skill in the art. Any reduction in colony forming units is as compared to the control.
TABLE 2 Effect of Electrolyzed Water by Spraying Against E. coli on Broiler Chicken Carcasses Initial Reduction Treatment (Log 10 CFU/cm 2 ) (Log 10 CFU/cm 2 ) Control - Spray with Tap Water 2.12 — Spray with Type B, Spray with 1.67 0.45 Type B, Spray with Type A
EXAMPLE 2
[0027] Both Type A and B water were applied to poultry carcasses. Type B water was applied by electrostatic spraying followed by Type A water by immersion.
[0028] Type B water was applied by electrostatic sprayer immediately after de-feathering or de-flocking the birds. The Type B water had a pH of 9.0-9.5, and an ORP of 850 − mV, and an initial NaOH concentration 8-10 ppm. The Type B water was electrostatically sprayed on the carcass for 17 seconds, followed by a 45 minute dwell period at 4° C. in a chiller.
[0029] After removal from the chiller, Type A water was immediately applied to the carcasses by immersion or dipping. The Type A water had a pH of 1.9-2.4, an ORP of 1150 + mV, and an initial HOCl concentration of 8-10 ppm. The poultry carcasses were dipped into the Type A water for 60 minutes at a temperature of 20° C. The carcasses were agitated or shaken while immersed, which agitation was accomplished through an aeration device positioned underneath the carcasses being treated.
[0030] Table 3 summarizes the effect of the protocol of Example 2 on E. coli on chicken carcasses. CFU/cm2 stands for colony forming units per square centimeter, as understood by those of skill in the art, and ESS stands for electrostatic spray. Any reduction or increase in colony forming units is as compared to the no treatment control.
TABLE 3 Effect of Electrolyzed Water by Electrostatic Spraying or Immersion Against E. coli on Broiler Chicken Carcasses Initial Reduction Treatment (Log 10 CFU/cm 2 ) (Log 10 CFU/cm 2 ) Control - No Treatment 7.27 — Control - ESS with Tap Water 7.51 0.24 increase Control - Immersion with Tap 7.07 .20 Water Control - ESS, Immersion, ESS 7.06 0.21 with Tap Water ESS with Type B 7.62 0.35 increase Immersion with Type A 1.00 6.27
EXAMPLE 3
[0031] Type A water was applied to poultry carcasses. The carcasses were de-feathered or de-flocked and placed in a chiller. The Type A water was applied immediately after removal from the chiller and had a pH of 2.5, an ORP of 1150 + mV, and an initial HOCl concentration of 50 ppm. The poultry carcasses were dipped into the Type A water for approximately 10 minutes at a temperature of 2° C. The carcasses were agitated or shaken while immersed, which agitation was accomplished through an aeration device positioned underneath the carcasses being treated.
[0032] Table 4 summarizes the effect of the protocol of Example 3 on E. coli on chicken carcasses. CFU/cm2 stands for colony forming units per square centimeter, as understood by those of skill in the art. Any reduction in colony forming units is as compared to the chiller control.
TABLE 4 Effect of Electrolyzed Water by Immersion Against E. coli on Broiler Chicken Carcasses Initial Reduction Treatment (Log 10 CFU/cm 2 ) (Log 10 CFU/cm 2 ) Control - Chiller 2.47 — Control - Immersion with Tap 2.39 0.08 Water Immersion with Type A 0.80 1.67
[0033] Table 5 summarizes the effect of the protocol of Example 3 on total coliform on chicken carcasses. CFU/cm2 stands for colony forming units per square centimeter, as understood by those of skill in the art. Any reduction in colony forming units is as compared to the chiller control.
TABLE 5 Effect of Electrolyzed Water by Immersion Against Total Coliform on Broiler Chicken Carcasses Initial Reduction Treatment (Log 10 CFU/cm 2 ) (Log 10 CFU/cm 2 ) Control - Chiller 2.54 — Control - Immersion with Tap 2.50 0.04 Water Immersion with Type A 0.71 1.83
[0034] Table 6 summarizes the effect of the protocol of Example 3 on Salmonella on chicken carcasses. Any reduction the percent of positive samples is as compared to the chiller control.
TABLE 6 Effect of Electrolyzed Water by Immersion Against Salmonella on Broiler Chicken Carcasses Treatment Percent Positive Percent Reduction Control - Chiller 32.00% — Control - Immersion with Tap 16.67% 47.91% Water Immersion with Type A 8.89% 72.22%
EXAMPLE 4
[0035] Type C water was applied to poultry carcasses. The carcasses were de-feathered or de-flocked and placed in a chiller. The Type C water was applied immediately after removal from the chiller. The Type C water had a pH of 2.5, an ORP of 1150 + mV, and an initial HOCl concentration of 50 ppm. The poultry carcasses were dipped into the Type C water for approximately 60 minutes at a temperature of 2° C. The carcasses were agitated or shaken while immersed, which agitation was accomplished through an aeration device positioned underneath the carcasses being treated.
[0036] Table 7 summarizes the effect of the protocol of Example 4 on E. coli on chicken carcasses. CFU/cm2 stands for colony forming units per square centimeter, as understood by those of skill in the art. Any reduction in colony forming units is as compared to the control.
TABLE 7 Effect of Electrolyzed Water by Immersion Against E. coli on Broiler Chicken Carcasses Initial Reduction Treatment (Log 10 CFU/cm 2 ) (Log 10 CFU/cm 2 ) Control - Immersion with Tap 1.29 — Water Immersion with Type C 0.37 0.92
Use of Electrolyzed Water in Poultry Processing Plants
[0037] It has been discovered that different types of electrolyzed water are best applied at different points during poultry processing. Birds traveling through a plant undergo a series of processes are various points. Type B water contains sodium hydroxide and acts as a saponifying agent. Type B water works to remove organic material from the surface of the bird. It also makes the surface of the bird slippery, which helps to prevent organic material and bacteria from adhering to the carcass. Thus, Type B water is best applied where the birds are dirty, are about to undergo major trauma, or have recently undergone major trauma. Type A water contains hypochlorous acid and acts as a disinfecting agent. Type A water is best applied were the bird is relatively clean or where the dwell time of the solution on the bird is relatively long. Because organic material acts to deactivate Type A water, it preferably should not be applied at a point in the plant where the surface of bird has a relatively large amount of organic material thereon.
[0038] FIG. 1 is a schematic diagram of a poultry processing system using Type A and B water at appropriate points. As understood by those of skill in the art, a poultry processing plant can be arranged in any number of ways, the plant of FIG. 1 serving only as an example.
[0039] The birds enter the plant at picking room 9 , where the birds preferably have their feathers and feet removed. The surfaces of the birds are dirty with organic matter upon entry to the plant and after de-feathering. Type B water may be applied by nozzles at point 11 . This application may occur within picking room 9 , before de-feathering, or before the birds enter the picking room. Type B water may also be applied by nozzles at point 13 . This application may occur within picking room 9 , after de-feathering, or after the birds leave the picking room. Type B water is again applied by nozzles at point 15 . This application occurs before entering evisceration line 17 , where the carcasses are cut and the guts removed. Evisceration results in both major trauma to the bird and possible fecal contamination. Type B water is applied by nozzles after evisceration line 17 at point 19 . The birds next travel to USDA check line 21 . Either Type A or Type B water may be applied by nozzles at point 23 . The choice depends mostly upon the dwell time until the carcasses reach cropper 25 . Cropper 25 removes the crops from the carcasses and, in so doing, inflicts major trauma on the birds. Type B water is applied by nozzles after cropper 25 at point 27 . Next the birds enter one or more inside/outside bird washers (IOBW) 29 . IOBW 29 washes the birds with Type A water by nozzles. The birds are again sprayed with Type A water by nozzles at point 31 before traveling to chiller 33 . Chiller 33 could be chlorinated as in the prior art. More preferably, chiller 33 contains Type A water, in which the birds are immersed. Finally, after exiting chiller 33 , the birds are sprayed again with Type A water by nozzles at point 35 before traveling to other areas of the plant. Electrolyzed water may of course be used in further processing of the birds, such as before packaging. Type B water preferably should be used where trauma and organic matter are encountered (for example skinning, deboning, and cutting into parts) and Type A water preferably would be used where a relatively long dwell time is encountered or the birds are relatively clean.
[0040] In the system of FIG. 1 , electrolyzed water is preferably applied by nozzles at an approximate pressure of between 20-100 psi. More preferably, IOBW 29 operates at 70-100 psi, while the remaining nozzles operate at 20-40 psi. The volume of electrolyzed water preferably ranges from approximately 0.25 to 1.5 gpm per nozzle, but can vary significantly depending on the number of birds processed and the number of nozzles used. The nozzles of the system of FIG. 1 are preferably of the standard variety, but also may be electrostatic sprayers. Electrostatic sprayers break down the droplet size to about 30 microns in diameter, and add either a positive or negative charge to the surface of each droplet. The electrical charge of the spray can increase the volume of solution that adheres to the carcass, thereby increasing the effect.
[0041] The temperature of the electrolyzed water used in the system of FIG. 1 preferably ranges from approximately 2-60 degrees Centigrade. More preferably, electrolyzed water applied by the nozzles ranges from approximately 10-30 degrees Centigrade, while the electrolyzed water in the chiller ranges from approximately 2-10 degrees Centigrade. For purposes of choosing between Type A and B water, a dwell time of 40 seconds or more would militates towards the use of Type A. The system of FIG. 1 is preferably equipped with valves that permit the application of either Type A or B water at any application point, the valves permitting maximum flexibility in configuration of the system. Also within the scope of the system of FIG. 1 is the substitution of Type C water at one or more points where Type A water is specified.
[0042] In the drawings and specification, there have been disclosed typical preferred embodiments of the invention, and although specific terms are employed, the terms are used in a descriptive sense only and not for purposes of limitation. The invention has been described in considerable detail with specific reference to these illustrated embodiments. It will be apparent, however, that various modifications and changes can be made within the spirit and scope of the invention as described in the foregoing specification and as defined in the appended claims.
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Embodiments of the invention provide for a system for processing poultry comprising electrolyzed water and a plurality of application points for applying the electrolyzed water. Further embodiments of the invention provide for a system for processing poultry comprising an evisceration line, an inside/outside bird washer, and electrolyzed water. Embodiments of the invention also provide for a method of processing poultry comprising the step of applying electrolyzed water to a bird at a plurality of application points.
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CROSS REFERENCE TO RELATED APPLICATION
This application is a continuation-in-part of my U.S. patent application Ser. No. 07/822,320 filed Jan. 16, 1992 and having the same title as this present application, and now abandoned.
TECHNICAL FIELD
This invention relates to boats or ships of the type having a hull that extends underwater and more particularly to a boat construction and a method for reducing frictional resistance to motion of such watercraft. The invention may also be used to inhibit adherence of barnacles to the hulls of boats or ships.
BACKGROUND OF THE INVENTION
Motor powered or wind powered movement of boats is greatly impeded by friction or drag arising from the contact of the moving hull with adjacent water. Friction can be reduced to some extent by configuring the hull with hydrodynamic principles in mind but this may adversely affect other characteristics of the boat. For example, flattening of the hull reduces drag by reducing the area of the hull that is in contact with water but also roughens the travel of the boat particularly in the the presence of waves.
Certain prior forms of watercraft reduce frictional drag by creating and entrapping a cushion of air beneath the hull or at least a portion of the hull. Confining the air cushion requires that there be a sizable concavity in the underside of the hull or that skirts extend downward from the hull along the boundaries of the air cushion. The rim of the concavity or the lower edges of the skirts must lie in a horizontal plane in order to entrap the air cushion and thus the technique mandates an essentially flat bottomed hull configuration. Thus these prior air cushions are not applicable to all forms of hull configuration and are generally limited to small craft of the type that plane along the water surface when traveling at high speed.
Air cushioning is carried to an extreme in a class of watercraft known as surface effect ships or hovercraft. Such vessels have a skirt encircling the underside of the craft and are supported above the water during operation by forcing a downflow of air into the region encircled by the skirt. This again dictates that the craft have an essentially flat and horizontal underside. Reduction of friction is gained at the cost of substantially increased power requirements and a loss of precision in controlling movement of the craft.
It would be advantageous if friction resistance to movement of a boat could be reduced without introducing constraints on the configuration of the boat hull. This would increase the efficiency of boats having, for example, V-shaped hulls or U-shaped hulls without compromising the operational advantages of such hulls such as stability, passenger comfort, cargo capacity and manuverability.
Frictional resistance to the motion of boats and ships is also increased by barnacles which adhere to the hull. Coating of the hull with barnacle repelling paints or the like is only temporarily effective and can cause environmental problems by releasing harmful constituents of the paints into the water.
The present invention is directed to overcoming one or more of the problems discussed above.
SUMMARY OF THE INVENTION
In one aspect of the present invention, a boat of the type having a hull region that is submerged during floatation of the boat has a plurality of spaced apart airflow apertures arranged in an array that extends both transversely and longitudinally at the submerged region of the hull. The array includes forward apertures that are closest to the bow of the boat, rearward apertures that are closest to the stern and additional apertures situated in the region between the forward and rearward apertures at a plurality of locations that are progressively further from the bow. The apertures are sized and positioned to generate an unconfined layer of intermixed air bubbles and water that extends along at least a portion of the submerged region of the hull in contact with the hull. The boat further includes means for emitting a flow of air at the airflow apertures.
In another aspect, the invention provides a boat having a hull with a plurality of airflow apertures arranged in an array that extends outward and upward from the keel region at both of the opposite side surfaces of the hull at a plurality of locations along the length of the hull including at locations which are progressively more distant from the bow of the boat. Means are provided .for directing an outflow of air through the airflow apertures to generate an unconfined layer of air bubbles adjacent the hull including at the side surfaces of the hull.
In still another aspect, the invention provides a method of reducing frictional resistance to motion of a boat of the type having a hull region that is submerged during travel of the boat. Steps in the method include directing a flow of air to the submerged region of the hull and maintaining a layer of intermixed air bubbles and water adjacent at least a portion of the submerged region of the hull by releasing the airflow into the adjacent water at a plurality of spaced apart locations along the hull including at a series of locations that are progressively more distant from the bow of the boat and at locations that extend upward at each side of the hull.
In a further aspect, the invention provides a boat having a hull region which is submerged during flotation of the boat and having an array of spaced apart flow emitting apertures which extends longitudinally along the submerged region. The boat further includes at least one container for storing a fluid which inhibits adherence of barnacles to the hull and means for directing a flow of the fluid out of the apertures and into the water that is adjacent the hull.
The invention creates a layer or film of bubbles adjacent the submerged region of a boat hull by releasing a flow of air at numerous spaced apart locations on that region of the hull. This substantially reduces frictional drag by, in effect, lubricating the interface of the boat hull and adjacent water. The reduction of friction results in reduced drive power requirements and/or greater speed with a given motor power output. The air bubbles may travel freely along the hull and up the sides of the hull towards the water surface and thus the boat hull need not have a concave undersurface or other specialized configuration for the purpose of entrapping air. Consequently, the invention is compatible with boats of virtually any configuration and size including deep draft boats having V-shaped or U-shaped hull cross sections. In the preferred form of the invention the boat is further equipped with means for releasing a flow of barnacle inhibiting fluid through the array of airflow apertures when the boat is docked or at anchor.
The invention, together with further aspects and advantages thereof, may be further understood by reference to the following description of preferred embodiments and by reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an elevation view of a boat in accordance with a preferred embodiment of the invention.
FIG. 2 is a view of the underside of the boat of FIG. 1.
FIG. 3 is a front view of the boat of the preceding figures.
FIG. 4 is a section view of a portion of the hull of the boat taken along line 4--4 of FIG. 2.
FIG. 5 is a section view taken along line 5--5 of FIG. 4.
FIG. 6 is an elevation section view of a portion of the bow region of the boat of the preceding figures taken along line 6--6 of FIG. 2.
FIG. 7 is a plan section view of the bow region of the boat taken along line 7--7 of FIG. 6.
FIG. 8 is a schematic diagram of airflow generating and distributing components of the boat of the preceding figures.
FIG. 9 is a cross section view of the hull of another boat in accordance with a second embodiment of the invention.
FIG. 10 is an enlarged view of a portion of the underside of the boat hull of FIG. 9 taken along line 10--10 thereof.
FIG. 11 is an elevation section view taken along line 11--11 of FIG. 10.
FIG. 12 is an elevation section view illustrating a modification of the structure depicted in FIG. 11.
FIG. 13 is a front view of the hull of another boat in accordance with a third embodiment of the invention and schematically depicts certain further components of the boat.
FIG. 14 is a view of the undersurface of the boat hull of FIG. 13 taken along line 14--14 thereof.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring jointly to FIGS. 1, 2 and 3 of the drawings, for purposes of example the invention is shown embodied in a boat 16 of the small craft type. It should be recognized that the invention is equally applicable to large vessels. Compatibility with boats, ships, barges and the like of diverse sizes and configurations is an important advantage of the invention.
The boat 16 of this example is of conventional design except as hereinafter described and thus has a hull 17, steering rudder 18 and a propeller 19 which is turned by motor 21 that is of the inboard type in this embodiment. The invention can also be embodied in sailing ships.
In accordance with the method of the invention, frictional resistance to powered travel of the boat 16 is reduced by directing a flow of air from air intakes 22 into the submerged region 23 of hull 17 that is below the surface of the water 24 that supports the boat. A layer 26 or film of intermixed air bubbles and water is created adjacent the submerged region 23 of the hull by releasing the airflow into the water 24 at a plurality of spaced apart locations along the hull region 23 which locations are defined by spaced apart airflow apertures 27 27 in the hull.
Apertures 27 are arranged in an array which extends transversely on the hull 17 at locations that are forward from the stern 28 of the boat. In this embodiment, the airflow apertures 27 are situated within a series of spaced apart grooves 29 formed in the underside of hull 17 and which extend upward and outward from the keel region 31 of the hull at each side of the hull. Referring to FIGS. 4 and 5 in combination, each such groove 29 has an upwardly extending forward surface 32 that faces away from the bow 33 of the boat 16 and along which the spaced apart airflow apertures 27 are situated. The opposite back surface 34 of the groove is impacted by air emitted from apertures 27 and is inclined relative to the forward surface 32 to channel the airflows back along the following portions of hull 17.
The apertures 27 are axial passages in a series of flanged fittings 36 which extend through the hull at the groove front surfaces 32 and each of which is engaged by a threaded coupling 37 which is at the end of one of a series of flexible air hoses 38. The abutment of fittings 36 and hull 17 is sealed by welding, adhesive or other means to prevent water leakage into the hull.
With reference to FIGS. 2 and 8 in combination, this embodiment of the invention has two air intakes 22 and manifolding 39 which includes a pair of air ducts 41 that extend rearward, preferably along the keel region 31 of the boat 16. Ducts 39 may be angled as necessary to avoid motor 21 or other components of the boat 16. The flexible air hoses 38 which supply air to apertures 27 are coupled to ducts 41. In the present example the air hoses 38 at one side of keel region 31 are coupled to one of the ducts 41 and the hoses at the opposite side of the keel region couple to the other duct although this is not essential in all cases. The manifolding 39 may include only a single duct or additional ducts depending on the configuration of the interior of the boat 16.
In this example of the invention, each duct 41 receives pressurized air from a separate one of the intakes 22 through a separate one of a pair of air compressor pumps 42 and a separate one of a pair of flow control valves 43 which enable the operator to block the flow path from intakes 22 to apertures 27 when it is desired to inactivate the friction reducing system such as when rapid slowing of boat motion is desired.
Referring jointly to FIGS. 6 and 7, the air compression means 42 may be of any of various types and in the present example are bladed rotary fans 44 driven by electric motors 46 through belts 47, the motors being operated with current from the electrical system of the boat 16. The previously described air ducts 41 extend to the bow region 48 of the boat 16 and each is communicated with a separate one of the air intakes 22 which in the present embodiment are openings formed in the bow region of hull 17 above the level of the surface of the water which supports the boat and at opposite sides of the keel region of the boat. Air intake 22 openings are larger than the passages within ducts 41 and are communicated with the ducts through air scoop structure 49 which forms flow passages that diminish in size in the direction of the upper ends 51 of the ducts 41. The rotary fans 44 are situated within the upper ends 51 of ducts 41 and are supported in coaxial relationship with the ducts by brackets 52. The pulleys 53 through which drive belts 47 are coupled to fans 44 are preferably of a spoked or apertured type in order to minimize obstruction of the air flow path. Screens 54 are preferably disposed at the entrances to the upper ends 51 of ducts 41, above fans 44, to prevent entry of sizable objects into the ducts that might clog the air flow passages.
As the large intake 22 openings and air scoop structure 49 face in the direction of travel of the boat 16, high speed motion of the boat supplements the action of fans 44 in producing an inflow of air. In fact, at very high speeds an airflow adequate to reduce frictional drag significantly may be realized without the fans 44 or other motor driven air compression means.
FIGS. 9, 10 and 11 depict another boat 16b embodying advantageous variations of the invention. The boat 16b in this case is of the type which has an inner hull 56 that is spaced from the outer hull 17b. In double hulled vessels of this kind, the airflow delivery manifolding 39b can be situated between the two hulls 56 and 17b to avoid complication of the structure of the inner hull 56. In the present example, manifolding 39b includes a single large air duct 41b that extends along the keel region 31b of the boat 16b between the two hulls 17b and 56 and connects with each of the air hoses 38b that supply the airflow apertures 27b.
An air compressor 42b driven by a motor 46b receives air from an intake 22b and transmits pressurized air to duct 41b through a flow control valve 43b. In instances where the compressor 42b is of the positive displacement type such as in this embodiment or if the rotary fans of the previously described embodiment are situated below the waterline, a one way flow valve or check valve 57 may be situated in the air flow path between the compressor and apertures 27b to protect the compressor and motor from an inflow of water during periods when the motor and compressor are shut down. This also reduces the loss of buoyancy that is brought about by such water entry. Alternately, an individual one way check valve 57 can be situated in each of the air flow apertures 27 or in hoses 38b to prevent or to minimize the buoyancy reduction.
The airflow apertures 27 of the previously described embodiments of the invention include groups of such apertures that are situated together in grooves in the boat hull. In the embodiment of FIGS. 10 and 11, each such aperture 27b is situated in an individual indentation 29b in the boat hull 17b to enable a more distributed positioning of the air outflows on the hull and to thereby provide for a more uniform layer of air bubbles adjacent the hull. Each such indentation 29b has a vertically extending forward surface 32b that faces away from the bow of the boat and in which one of the airflow aperture fittings 36b is situated. The back surface 34b of each indentation 29b slopes outward to channel air backward on to the following surface of hull 17b.
The indentations 29b of the embodiment of FIGS. 10 and 11 are integrally formed in the boat hull 17b at the time of fabrication of the hull. Referring now to FIG. 12, essentially similar indentations 29c can be retrofitted onto pre-existing hulls 17c of conventional design by forming the indentations 29c in plates 58 which can be secured to the hull 17c by bolts, welds or the like. Openings 59 are cut into the hull 17c to receive the indentations 29c.
FIGS. 13 and 14 depict another embodiment of the invention which is also easily installed on pre-existing conventional hulls 17d as well as being suitable for new hulls. In this embodiment, spaced apart air pipes 61 extend along the underside of the hull 17d and the airflow emitting apertures 27d are situated in the pipes. The pipes 61 are secured to hull 17d by welds 62 or other means. Preferably the air pipes 61 extend longitudinally along the hull 17d to minimize drag. Air from an intake 22d is supplied to the pipes 61 through a flow control valve 43d, motor driven compressor 42d and one way flow valve 57d in this embodiment.
The air bubble generating system of any of the above described embodiments of the invention can also be adapted to inhibit adherence of barnacles to a hull while the boat is docked or anchored. Referring to FIG. 13, a flow of barnacle repelling fluid from a storage container 63 may be added to the airflow or may replace the airflow by opening a flow control valve 64 which communicates the container with the intake of compressor 42d in this instance.
The barnacle repelling fluid should be of a type that does not have adverse environmental effects. As one example, an airflow with an enriched carbon dioxide gas content produces the desired effect without causing any pollution or contamination of the water.
While the invention has been described with reference to certain specific embodiments for purposes of example, many variations and modifications are possible and it is not intended to limit the invention except as defined in the following claims.
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Frictional resistance to motion of a boat is reduced by generating an unconfined layer of intermixed air bubbles and water adjacent at least a portion of the hull of the boat including at upcurving side surfaces of the hull. In the preferred form of the invention, an array of spaced apart airflow apertures in the hull extends outward and upward at each side of the keel at a plurality of locations along the hull. Air is forced through the apertures by a compressor or a forward facing air scoop or by a combination of both. In the preferred embodiment, barnacle inhibiting fluid may be released through the array of apertures when the boat is docked or at anchor.
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FIELD OF THE INVENTION
The present invention relates to a new cutting device which can be used without modification for cutting any natural or artificial materials. The device comprises a plurality of blades placed in a frame which is supported for being moved in a reciprocating rectilinear movement or beneath a guiding frame, the guiding frame being itself vertically movable by use of jacks or cylinders.
BACKGROUND OF THE INVENTION
Multi-blade frame machines of this type are known and have been described for example in German Pat. No. 2,161,393, French Pat. No. 1,440,801, French Pat. No. 1,193,333, Belgium Pat. No. 661,521, and French Pat. No. 586,320, the disclosure of which is made an integral part of the present patent application.
However, it has not been possible up to now to make a multi-purpose machine for industrially sawing materials having an hardness as different as soft stone and granite by using diamond blades. Moreover, even though diamond sawing is well known in stone and marble sawing, there is presently ineffectiveness in performances of the tools and in the output production of corresponding sawing machines. Reasons for such ineffectiveness are as follows:
1--Diamond blade sawing of granite in particular sawing into thin slices, by use of existing multi-blade frame machines, cannot be embodied because of the too short useful life of the sawing tools. The only presently competitive method consists of interposing metal shot between the blades and the bottom of the sawing line.
2--Present designs of such machines accommodate only insignificant variations in the cutting parameters, and therefore it is not practicable to combine the cutting parameters for optimization of the cutting conditions.
3--In presently known machines, moving parts are guided by metal-on-metal contact of surfaces having a plurality of shapes, and despite their tolerances, the wear of the parts causes decreasing accuracy, followed by tansmittal of vibrations and impacts to the cutting tools, while simultaneously shortening the operating or useful life of the tools.
Prior art has also taught, for making bearing means or for guiding slides, devices of a fluid type which prevent or at least limit the friction between parts having to be relatively displaced. This is for example the case of German Pat. No. 904,946. French Pat. No. 69 17777, French Pat. No. 1,299,218, U.S. Pat. No. 3,466,951 and French Pat. No. 1,372,163, the disclosure of which is included in the present patent application.
OBJECTS AND SUMMARY OF THE INVENTION
The present invention creates a new machine which can be provided with one or a plurality of blades, and makes it possible to saw natural or artificial materials, whatever is their hardness to the diamond tool; and improves the quality of the sawn surfaces as well as the cutting conditions, the output production and therefore the production costs. It is also noted that improvements in the sawing quality make possible, by obtaining a better state of surface, to save an appreciable time on the ulterior surfacing and polishing steps.
According to the invention, in a device for cutting stone, marble, granite and the like materials by means of diamonded blades displaced in a reciprocating movement by a blade carrying frame, the blade carrying frame being itself connected to a reciprocating movement motor unit, at least the blade carrying frame is connected to a sliding frame through vibration damping elements. This embodiment makes possible to surprisingly avoid that the diamond sawing blades are submitted to vibrations during a sawing operation, and it results therefrom a very good cutting speed, a cutting accuracy which has never been previously reached and a lower wearing of the sawing blades, the diamond particles of which are not torn away nor otherwise deteriorated, with only a regular wear of the blades occurs.
Various further features of the present invention are moreover shown in the following detailed disclosure.
BRIEF DESCRIPTION OF THE DRAWINGS
Embodiments of the invention are shown as non limiting examples in the accompanying drawings, wherein:
FIG. 1 is a diagrammatic elevation view with parts broken away of a reciprocating sawing machine embodying the invention;
FIG. 2 is a front elevation view corresponding to FIG. 1;
FIG. 3 is a cross section of FIG. 1 taken substantially along line III--III of FIG. 1;
FIG. 4 is a detail of one of the components shown in FIG. 3;
FIG. 5 is diagrammatic cross-section of another detail of embodiment;
FIG. 6 shows the detail of the crankshaft connection for the embodiment of FIG. 1;
FIG. 7 is an alternative embodiment to that of FIG. 3.
DETAILED DESCRIPTION OF THE INVENTION
The machine shown in the drawings comprises rear uprights 1, 1a and front uprights 2, 2a which are for example placed at angles of a right angled trapezium. The uprights 1, 1a and 2, 2a are connected together by upper side members 3 and upper cross members 4. The uprights 1, 1a and 2, 2a are surrounded by guiding units 5 to which is fixed a slide carrying frame 6. The slide carrying frame 6 supports by means of suspension brackets 7 a blade carrying frame 8. The blades 9 of the frame 8 are provided for sawing a block 10, for example a block of granite.
The blade carrying frame 8 is laterally provided with at least one pin 11 for pivotally mounting a head of a connecting rod 12. The foot of the connecting rod 12 is pivotally mounted on a pin 13 provided at end of a crank-shaft 14. The crank-shaft 14 is wedged on a shaft 15 carrying an inertia wheel 16 driven by an electric motor 17. The electric motor 17 is preferably of a variable speed type.
The up and down movement of the blade carrying frame 8 is controlled by the movement of the slide carrying frame 6. In the example shown in the drawings, the movement of slide carrying frame 6 is provided by means of screws 18 placed in the uprights 1, 1a and 2, 2a. The rotation speed of the screws 18 is synchronized by transmission boxes 19 connected together by means of shafts 20 driven by a motor-reductor unit 21.
According to the present invention, for preventing propagation of the vibrations, a fluid type connection is provided between the various means submitted to a relative movement.
The blade carrying frame 8 is connected near its ends by means of the suspension brackets 7, to sliding devices 22. As shown in FIG. 3, an embodiment of each sliding device 22 comprises a profile member 23 on which slides 24, 25 are mounted. The slides 24, 25 are maintained between a set of shoes 26, three shoes in the present example. The shoes 26 are placed in a casing 27 which is itself fixed to the side members of the slide carrying frame 6.
Each shoe defines, in the side thereof facing the slide 24, at least one housing 28 which is fed with pressurized fluid, for example oil, through a channel 29. Ducts 30 are provided for feeding each housing 28.
The above mentioned embodiment enables to maintain the slides 24, 25 in a state closely related to a levitation state and has for its result to greatly reduce friction upon displacement of the blade carrying frame 8 relatively to the slide carrying frame 6, and most especially to prevent transmission of the vibrations caused, in particular, by friction between the blades 9 and the block 10 during the sawing operation, and the vibrations caused by the vertical and horizontal driving systems of the blade carrying frame 8.
A device similar to the sliding device 22 can be similarly embodied between the guiding units 5 and the uprights 1, 1a and 2, 2a.
As also shown in FIG. 3, the pin 11 on which is pivotally mounted the head of the connecting rod 12 comprises a fluid bearing box 31 containing curved shoes 32 forming a housing 33 which communicates with duct 34 for supplying a pressurized fluid.
By providing a similar construction for the pin 13 of the foot of the connecting rod 12, the motor unit 17, 16 is isolated from the blade carrying frame and, therefore, the vibrations emanating from either the blade carrying frame or the motor unit are suitably damped and/or filtered.
It is further possible to mount also the shaft 15 on fluid bearings as above described.
For preventing vibrations from being transmitted from or to the motor-reductor unit 21, the screws 18, the rotation of which causes a fall then a raise of the slide carrying frame 6, are connected to the slide carrying frame 6 by means of nuts 35 (FIG. 5) having a plurality of channels 36 connected to at least one collecting chamber 37 into which a pressurized fluid is supplied through a duct 38.
The drawings show that the channels 36 terminate at the bottom of the screw threads of the nut 35, which makes that the nut, the threads of which are machined relatively to these of the screw 18 is not in direct physical contact with the screw.
In order to prevent dirt from entering the fluid circuit and the threads of the nuts 35 and screws 18, the nuts 35 are provided with sealing bellows 39 or similar means.
The device of the invention which provides isolation of the various mobile parts, the one with respect to the other by means which damp and/or filter the vibrations makes possible to use cutting blades of the diamond type (i.e. blades in which abradant elements formed by diamonds are maintained in a matrix), from which a risk of tearing away of the diamonds is either prevented or at least greatly reduced. Vibrations are actually positively suppressed.
In order that the diamond blades are used at best of their characteristics, motor 17 is a variable speed type, which enables variation of the beating rate which is for example adjusted in dependence of the nature of the material of the block 10 to be sawn. As shown in FIG. 6, it is possible to realize at least the crank-shaft 14 in the form of a telescopic element of a known structure for varying the stroke of the blades, i.e. in particular for optimizing the stroke in function of the block 10 and the compositions of the tool for using always the blades at optimum sawing conditions. In this case, the speed of the motor 17 is adjusted so that the maximum linear speed reached by the blades will not exceed a predetermined threshold.
The motor-reductor unit 21 is itself preferably made also in the form of a variable speed unit in order that the speed of fall of the blades which determines the depth of each work-pass during their sliding movement does not exceed a predetermined threshold.
Although the screw 18 and nut 35 arrangement of FIG. 5 has been shown as a screw-jack, it is also possible to use known hydraulic sliding cylinders, the important point being that the cutting blades will always exert a constant unitary pressure on the material to be cut.
Although not shown in the drawings, it is obviously possible to displace the blade carrying frame 8 by means of hydraulic cylinders, preferably of the double action type, acting either directly on the blade carrying frame 8 or on the sliding devices 22. An hydraulic motor of a known type can be used instead of the motor-reductor unit 17 and inertia wheel 16 of FIG. 1.
In the embodiment of FIG. 7, which is a variation of the embodiment of FIG. 3, similar parts having the same reference numerals as in FIG. 3, the shoes 26 as well as the shoes 32 and the nut channels 36 can be formed by polar parts of electromagnetic windings which generate magnetic fields for maintaining in a levitation state the parts which must be isolated in order to prevent transmission of vibrations.
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The device for cutting blocks of granite, marble, stone and other like materials by means of diamond blades displaced in a reciprocating movement by a blade carrying frame, said blade carrying frame being itself connected to a reciprocating motor unit, characterized in that at least the blade carrying frame is connected to a sliding frame by means of vibration damping means.
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of Korean Patent Application No. 10-2014-0163737, filed on Nov. 21, 2014 in the Korean Intellectual Property Office, the entire disclosure of which is incorporated herein by reference for all purposes.
TECHNICAL FIELD
[0002] The present disclosure relates to a substrate for surface enhanced Raman scattering, a fabricating method for the same and an analyzing method using the same.
BACKGROUND
[0003] Raman scattering or the Raman Effect is an inelastic photon scattering phenomenon. When photons are scattered from an atom or molecule, most photons are elastically scattered (Rayleigh scattering), such that the scattered photons have the same energy (frequency and wavelength) as the incident photons. A small fraction of the scattered photons (approximately 1 in 10 million) are scattered by an excitation, with the scattered photons having a frequency different from, and usually lower than, that of the incident photons. In a gas, Raman scattering can occur with a change in energy of a molecule due to a transition to another (usually higher) energy level.
[0004] Raman Effect (Raman shift) is exhibited in almost organic molecules including not only by polar molecules but also by non-polar molecules which have induction polarizability when Raman spectroscopy using Raman scattering is applied. It is thus more suitable for the detection of biomolecules such as proteins, genes and the like since it is not affected by interference caused by water molecules.
[0005] On the other hand, specific wavelengths of Raman emission spectrum represents chemical composition and structure features so that it can be used to directly analyze materials using Raman signals.
[0006] Surface enhanced Raman scattering is associated with surface plasmon resonance phenomena caused with excitation by electromagnetic radiation. Signal intensities are greatly amplified with the electromagnetic resonance.
[0007] It has been studied in a variety of structures for inducing this surface enhanced Raman scattering, and recently technologies relating to substrates for surface enhanced Raman scattering are being developed with utilization metal nanoparticles or metal nanowires.
[0008] Ag nanowire arrays by a glass capillary: A portable, reusable and durable SERS substrate in Scientific Reports 2, Article number: 987, doi: 10.1038/srep00987 discloses a technique for aligning Ag nanowires along the direction of a capillary on the inner wall of the capillary.
[0009] Assembly of Ag Nanowires into 3D Woodpile-like Structures to Achieve High Density Spots for Surface-Enhanced Raman Scattering in Langmuir, 2013, 29 (23), pp 7061-7069, DOI: 10.1021/la4012108 discloses a method for alternatively laminating Ag nanowires according to the Langmuir-Blodgett method.
[0010] KR Patent No. 10-1073853 discloses a manufacturing method of a nano structured net-shaped film on a substrate. It teaches a method for forming the nano structure by a filtration method. However, it requires a transcription process after filtration and does not teach its application as a substrate for surface enhanced Raman scattering. It discloses that the nano substrate is a carbon nanotube which is manufactured by transcription of a membrane in which the nano structure net-shaped film is formed on the substrate such as a silicon oxide and then separating the membrane using surface tension difference between the membrane and the substrate ( FIG. 1 ). Thus, its technical field is different from a substrate for surface enhanced Raman scattering of the present disclosure.
[0011] US Patent Publication No. 2012-0300203 discloses a method for the formation of a substrate with filtering capabilities by utilizing a nanoparticle ink. This teaches that nanoparticles with much smaller size than a fiber strand are densely adhered on a fiber strand which is a part of the substrate with filtering capabilities.
[0012] The present disclosure is to provide a substrate for surface enhanced Raman scattering which is prepared by using filtering functions and is able to suitable for Raman signal analyses, a fabricating method for the same and an analyzing method using the same.
SUMMARY
[0013] This summary is provided to introduce a surface enhanced Raman scattering having excellent surface enhanced Raman scattering (SERS) effects using a substrate with filtering capabilities, a fabricating method for the same and an analyzing method using the same. This Summary is not intended to identify key features or essential features of the claimed subject matter, nor is it intended to be used as an aid in determining the scope of the claimed subject matter.
[0014] In one general aspect, there is provided a substrate for surface enhanced Raman scattering including: a substrate including a plurality of pores; and metal-containing nanowires configured not to pass through the pores and to be aggregated on the substrate, wherein the metal-containing nanowires form nanogaps configured to induce surface plasmon resonance with adjacent metal-containing nanowires.
[0015] In another general aspect, there is provided a Raman scattering apparatus including the substrate for surface enhanced Raman scattering of the present disclosure described above.
[0016] In still another general aspect, there is provided a method for fabricating the substrate for surface enhanced Raman scattering of the present disclosure. The method may include preparing a substrate including a plurality of pores; filtering a solution including metal-containing nanowires to aggregate the metal-containing nanowires on the substrate; and drying the substrate, wherein the metal-containing nanowires do not pass the pores and form nanogaps configured to induce surface plasmon resonance with adjacent metal-containing nanowires.
[0017] In still another general aspect, there is provided an analyzing method using a substrate for surface enhanced Raman scattering, the analyzing method including preparing a substrate for surface enhanced Raman scattering of the present disclosure; forming a mixed solution by mixing a material to be analyzed to a solution including metal-containing nanowires; filtrating the mixed solution to the substrate; drying the substrate; and detecting a Raman signal by light irradiation into the material to be analyzed, wherein the metal-containing nanowires do not pass the pores and form nanogaps configured to induce surface plasmon resonance with adjacent metal-containing nanowires.
[0018] In still another general aspect, there is provided an analyzing method using a substrate for surface enhanced Raman scattering, the analyzing method including preparing a substrate for surface enhanced Raman scattering of the present disclosure; filtrating a material to be analyzed to the substrate; and detecting a Raman signal by light irradiation into the material to be analyzed.
[0019] The present disclosure may provide a substrate for surface enhanced Raman scattering having excellent surface enhanced Raman scattering effects in a simple way by utilizing a substrate having a filtering function and a method for efficiently analyzing a material to be analyzed using the same.
[0020] Other features and aspects will be apparent from the following detailed description, the drawings, and the claims.
BRIEF DESCRIPTION OF DRAWINGS
[0021] FIG. 1A illustrates an example of a substrate for surface enhanced Raman scattering and an example of a part of its fabrication process.
[0022] FIG. 1B illustrates an example of a part of the fabrication process for a substrate for surface enhanced Raman scattering.
[0023] FIG. 2 illustrates an example of a substrate for surface enhanced Raman scattering.
[0024] FIG. 3A illustrates an example of metal-containing nanowires aggregated on a substrate for surface enhanced Raman scattering.
[0025] FIG. 3B illustrates the example of metal-containing nanowires aggregated on a substrate for surface enhanced Raman scattering of FIG. 3A at a higher magnification.
[0026] FIG. 3C illustrates the example of metal-containing nanowires aggregated on a substrate for surface enhanced Raman scattering of FIG. 3A at a higher magnification.
[0027] FIG. 3D illustrates the example of metal-containing nanowires aggregated on a substrate for surface enhanced Raman scattering of FIG. 3A at a higher magnification.
[0028] FIG. 4A illustrates another example of metal-containing nanowires 122 having different sizes of nanoparticles deposited on a substrate for surface enhanced Raman scattering.
[0029] FIG. 4B illustrates another example of metal-containing nanowires 122 having different sizes of nanoparticles deposited on a substrate for surface enhanced Raman scattering.
[0030] FIG. 4C illustrates another example of metal-containing nanowires 122 having different sizes of nanoparticles deposited on a substrate for surface enhanced Raman scattering.
[0031] FIG. 4D illustrates another example of metal-containing nanowires 122 having different sizes of nanoparticles deposited on a substrate for surface enhanced Raman scattering.
[0032] FIG. 5 is a block view illustrating an example of a method for fabricating a substrate for surface enhanced Raman scattering.
[0033] FIG. 6 is a block view illustrating an example of an analyzing method using a substrate for surface enhanced Raman scattering.
[0034] FIG. 7 is a block view illustrating an example of an analyzing method using a substrate for surface enhanced Raman scattering.
[0035] FIG. 8 is a transmission electron microscope image of an example of metal-containing nanowires.
[0036] FIG. 9 is a reflectance graph of an example of a substrate for surface enhanced Raman scattering.
[0037] FIG. 10 is a graph comparing Raman signals using an example of a substrate for surface enhanced Raman scattering.
[0038] Throughout the drawings and the detailed description, the same reference numerals refer to the same elements. The drawings may not be to scale, and the relative size, proportions, and depiction of elements in the drawings may be exaggerated for clarity, illustration, and convenience.
DETAILED DESCRIPTION
[0039] The following detailed description is provided to assist the reader in gaining a comprehensive understanding of the methods, apparatuses, and/or systems described herein. However, various changes, modifications, and equivalents of the methods, apparatuses, and/or systems described herein will be apparent to one of ordinary skill in the art. The sequences of operations described herein are merely examples, and are not limited to those set forth herein, but may be changed as will be apparent to one of ordinary skill in the art, with the exception of operations necessarily occurring in a certain order. Also, descriptions of functions and constructions that are well known to one of ordinary skill in the art may be omitted for increased clarity and conciseness.
[0040] The terms used in the description are intended to describe certain embodiments only, and shall by no means restrict the present disclosure. Unless clearly used otherwise, expressions in the singular number include a plural meaning. In the present description, an expression such as “comprising” or “consisting of” is intended to designate a characteristic, a number, a step, an operation, an element, a part or combinations thereof, and shall not be construed to preclude any presence or possibility of one or more other characteristics, numbers, steps, operations, elements, parts or combinations thereof.
[0041] Hereinafter, certain embodiments of the present disclosure will be described in detail with reference to the accompanying drawings. Identical or corresponding elements will be given the same reference numerals, regardless of the figure number, and any redundant description of the identical or corresponding elements will not be repeated.
[0042] FIGS. 1A and 1B illustrate an example of a substrate for surface enhanced Raman scattering and an example of a part of its fabrication process.
[0043] Referring to FIG. 1A , a substrate for surface enhanced Raman scattering includes substrates 110 and metal-containing nanowires 122 . The substrates 110 are represented by the thickest lines and medium thick lines, and the metal-containing nanowires 122 are represented by the thin lines.
[0044] The substrate 110 may include a plurality of pores so that a solution 120 is filtered therethrough. When the solution 120 including the metal-containing nanowires 122 is filtered through the substrate 110 , materials, except the metal-containing nanowires 122 , which are the solution including a stabilizer may be filtered through the plurality of pores in the substrate 110 .
[0045] The substrate 110 may be one chosen from glass fiber, alumina, Teflon (polytetrafluoroethylene, PTFE), polycarbonate (PC), cellulose and paper, but it is not limited thereto. The substrate 110 may be any substrate having filtering capabilities regardless of material.
[0046] A glass fiber filter is used as an example of the substrate 110 . The glass fiber has advantages of allowing various organic solvents to be used, not large signal noises and low cost, etc.
[0047] When any process including a drying process such as heat treatment is performed to the substrate for surface enhanced Raman scattering, heat resistance may be needed to withstand high temperatures. The heat resistance is needed since temperature of gas or solution to be analyzed may be high when a Raman signal is analyzed or it may need ability to withstand high temperatures during analysis. When the glass fiber is used as an example of the substrate 110 in the present disclosure, a substrate for surface enhanced Raman scattering having excellent heat resistance under such conditions can be manufactured.
[0048] The metal-containing nanowires 122 may have an enough length not to pass through the pores.
[0049] The metal-containing nanowires 122 may be aggregated in irregular directions on the substrate 110 to form a plurality of cross points (junctions).
[0050] Since hot spots at which plasmon resonance occurs are formed near the cross points, they may contribute Raman signal enhancement with light irradiation.
[0051] The metal-containing nanowires 122 aggregated on the substrate 110 may be formed by vacuum filtering the solution 120 including the metal-containing nanowires 122 such as nanowire ink on the substrate 110 . Since the metal-containing nanowires 122 have an enough length not enough to pass through the pores of the substrate 110 , most of them may not pass the substrate 110 with vacuum filtration and thus be aggregated on the substrate 110 .
[0052] Size and density of the metal-containing nanowires 122 may be adjusted to form nanogaps which induce the surface plasmon resonance with adjacent metal-containing nanowires 122 .
[0053] The density of the metal-containing nanowires 122 may be adjusted by utilizing various factors, for example a concentration of the metal-containing nanowires 122 in the solution 120 and filtration volume of the solution 120 .
[0054] Aggregation of the metal-containing nanowires 122 means thickly formed and laminated metal-containing nanowires 122 on the substrate 110 .
[0055] A thickness of the metal-containing nanowires 122 to be aggregated may be adjusted using a concentration of the metal-containing nanowires 122 in the solution 120 and filtration volume of the solution 120 .
[0056] FIG. 1B illustrates a vacuum filtration apparatus.
[0057] The solution 120 including the metal-containing nanowires 122 is filtered through the substrate 110 and filtrate 124 is collected in a container. The metal-containing nanowires 122 are aggregated on the substrate 110 since they cannot pass through the substrate 110 .
[0058] The filtrate 124 may include a coating material such as polyvinylpyrrolidone (PVP) which is used for dispersion stability of the metal-containing nanowires 122 . The coating material may be removed using heat treatment or may be used for controlling the nanogaps. For example, when the density of the metal-containing nanowires 122 increases, the nanogaps are gradually reduced and the metal-containing nanowires 122 become thus in contact with each other and the nanogaps are eventually disappeared. Thus, when the coating material is not removed, the nanogaps may be present in minimized sizes.
[0059] The coating material may cause noises when a Raman signal is analyzed using the substrate for surface enhanced Raman scattering. In this case, after gaps between the metal-containing nanowires are formed using the coating material, the coating material is removed and then a material to be analyzed is adsorbed to perform Raman signal analysis.
[0060] In an embodiment of the present disclosure, most of the metal-containing nanowires 122 do not pass through the substrate 110 and are thus aggregated thereon due to their enough length. The metal-containing nanowires 122 aggregated on the substrate 110 may form numerous cross points which become hot spots since nanogaps are formed around the cross points.
[0061] The hot spots may be formed vertically or horizontally. As the metal-containing nanowires 122 are laminated thicker and thicker, Raman intensity may be enhanced. However, the Raman intensity is not enhanced further from a certain thickness or above. In this description, it is referred to as the thickness where the Raman signal enhancement is saturated. When the thickness where the Raman signal does not enhance is known in advance, it may be utilized in the fabrication process. For example, the thickness where the Raman signal does not enhance is recorded and determined and the thickness of the metal-containing nanowires 122 to be aggregated may be then determined based thereon. In this case, laser focal length dependency becomes lowered during analysis using Raman signals.
[0062] Since each of the metal-containing nanowires 122 has irregularly its own orientation instead of a particular orientation, there is little outcome difference associated with laser orientation.
[0063] FIG. 2 illustrates an example of a substrate for surface enhanced Raman scattering.
[0064] The structure in FIG. 2 is to illustrate for improvement of the surface enhanced effect compared to the structure in FIG. 1 .
[0065] Referring to FIG. 2 , the substrate for surface enhanced Raman scattering further includes an insulating film 130 and metal-containing nanoparticles 140 . The structure of the substrate 110 is omitted in FIG. 2 for brief description.
[0066] The insulating film 130 may be formed on the metal-containing nanowires 122 . The insulating film 130 may be formed between the metal-containing nanowires 122 and the metal-containing nanoparticles 140 to form nanogaps therebetween.
[0067] The insulating film 130 may be formed of any one chosen from alumina, metal oxide, metal sulfide, metal halide, silica, zirconium oxide and iron oxide, but it is not limited thereto.
[0068] The metal-containing nanoparticles 140 may be formed on the insulating film 130 and be spaced apart with each other. The metal-containing nanoparticles 140 may form nanogaps to induce surface plasmon resonance.
[0069] The spaced-apart distance of the metal-containing nanoparticles 140 may be adjusted during the manufacturing process to form nanogaps.
[0070] The nanogaps may be formed at least one area chosen from between the metal-containing nanowires 122 , between the metal-containing nanowires 122 and the metal-containing nanoparticles 140 , and between the metal-containing nanoparticles 140 .
[0071] Two types of nanogaps may be formed between the metal-containing nanowires 122 of which one is formed due to irregular distance between the metal-containing nanowires 122 having irregular orientation and the other is formed around cross points which are formed when the metal-containing nanowires 122 having irregular orientation are aggregated.
[0072] The nanogaps between the metal-containing nanowires 122 and the metal-containing nanoparticles 140 are formed naturally due to the present of the insulating film 130 . Plasmon resonance properties such as wavelength of the plasmon resonance may be controlled by controlling the thickness of the insulating film 130 .
[0073] The metal-containing nanoparticles 140 are formed to be spaced apart with each other on the insulating film 130 so that nanogaps may be formed between the metal-containing nanoparticles 140 and the adjacent metal-containing nanoparticles 140 .
[0074] As described above, the nanogaps can be formed at various areas in the substrate for surface enhanced Raman scattering so that intensity and uniformity may be improved with increased density of hot spots during light irradiation.
[0075] When a material is analyzed using the substrate for surface enhanced Raman scattering of the present disclosure, the material may be adsorbed to the nanogaps so that large-scaled material with a low concentration can be analyzed.
[0076] The metal in the metal-containing nanowires 122 or in the metal-containing nanoparticles 140 may be any one chosen from Ag, Al, Au, Co, Cu, Fe, Li, Ni, Pd, Pt, Rh, Ru and an alloy thereof, but it is not limited thereto.
[0077] FIGS. 3A, 3B, 3C and 3D illustrate an example of metal-containing nanowires aggregated on a substrate for surface enhanced Raman scattering at different magnifications.
[0078] FIG. 3A illustrates the metal-containing nanowires 122 aggregated on the substrate 110 , FIG. 3B and FIG. 3C are a top view and a side view of the metal-containing nanowires 122 aggregated on the substrate 100 , respectively, and FIG. 3D is a SEM image of the metal-containing nanowires 122 .
[0079] Referring to FIG. 3A , it is noted that the metal-containing nanowires 122 are uniformly distributed on the substrate with a diameter of 48 mm.
[0080] As also shown in FIG. 3B and FIG. 3C , since the pore size of the substrate 110 is less than the length of the metal-containing nanowires 122 , most of the metal-containing nanowires 122 do not pass through the substrate 110 and are aggregated on the substrate 110 . Only other materials, except the metal-containing nanowires 122 , are filtered with vacuum filtration which allows for the metal-containing nanowires 122 to be aggregated closely and densely.
[0081] Referring to FIG. 3D , the metal-containing nanowires 122 are arranged irregularly to form numerous cross points near which hot spots are formed. It is also noted that the metal-containing nanowires 122 are laminated in multiple layers.
[0082] A 0.7 μm-sized glass fiber filter is used as an example of the substrate 110 and nanowire ink including Ag nanowires with a diameter of about 40 nm and a length of about 50 μm is used. Ag nanowires are aggregated on the substrate 110 with vacuum filtration.
[0083] When a material is analyzed using the substrate for surface enhanced Raman scattering of the present disclosure, the material may be adsorbed to the nanogaps so that large-scaled material with a low concentration can be analyzed.
[0084] FIGS. 4A, 4B, 4C, and 4D illustrate examples of metal-containing nanowires 122 having different sizes of nanoparticles deposited on a substrate for surface enhanced Raman scattering.
[0085] FIG. 4A illustrates the metal-containing nanoparticles 140 which are deposited in a thickness of 9 nm with Ag, and FIGS. 4B, 4C and 4D illustrate the metal-containing nanoparticles 140 which are deposited in a thickness of 13 nm, 15 nm, 19 nm, respectively.
[0086] It may be noted that the metal-containing nanoparticles 140 are formed in a 3-D semi sphere shape due to low wetting between the alumina insulating film 130 and Ag which grows thereon. It is determined by the SEM image that when Ag is deposited in a thickness of 19 nm in an embodiment, height of the semi sphere shaped Ag is 50 nm.
[0087] In another general aspect, there is provided a Raman scattering apparatus including any one substrate for surface enhanced Raman scattering among the substrates described above. The Raman scattering apparatus may include a light source, a substrate for surface enhanced Raman scattering, and a detector configured to detect Raman scattering, wherein the substrate for surface enhanced Raman scattering may include one substrate for surface enhanced Raman scattering among the substrates described above. Detailed description about the light source and the detector may be omitted since they may be ones known in the art.
[0088] FIG. 5 is a block view illustrating an example of a method for fabricating a substrate for surface enhanced Raman scattering.
[0089] Referring to FIG. 5 , in S 200 , a substrate 110 may be prepared. The substrate 110 may include a plurality of pores.
[0090] In S 210 , a solution 120 including metal-containing nanowires 122 may be filtered to aggregate the metal-containing nanowires 122 on the substrate 110 .
[0091] A vacuum filtration may be used in an embodiment of the present disclosure.
[0092] A thickness of the metal-containing nanowires 122 to be aggregated may be adjusted by utilizing a concentration of the metal-containing nanowires 122 in the solution 120 and filtration volume of the solution 120 .
[0093] A density of the metal-containing nanowires 122 to be aggregated may be adjusted by utilizing a concentration of the metal-containing nanowires 122 in the solution 120 and filtration volume of the solution 120 .
[0094] In S 220 , the substrate 110 , on which the metal-containing nanowires 122 are aggregated, may be dried.
[0095] When the substrate 110 is dried, materials which are not filtered off and remained, except the metal-containing nanowires 122 , may be removed. Heat treatment may be used to accelerate drying. In an embodiment of the present disclosure, the substrate 110 may be placed on a hot plate heated to 150° C. to 170° C. to dry within 5 minutes.
[0096] In S 220 , a substrate for surface enhanced Raman scattering may be fabricated. However, the steps of from S 230 to S 240 may be further performed to obtain enhanced Raman signals.
[0097] In S 230 , an insulating film 130 may be formed on the metal-containing nanowires 122 .
[0098] The insulating film 140 may be formed by using any one of vacuum deposition and solution processing, but it is not limited thereto.
[0099] The vacuum deposition may be any one chosen from atomic layer deposition, chemical vapor deposition, sputtering and thermal vapor deposition, but it is not limited thereto.
[0100] The solution processing may be any one chosen from spin coating, dip coating and dropping.
[0101] In an embodiment of the present disclosure, the thermal vapor deposition is used.
[0102] In S 240 , the metal-containing nanoparticles 140 may be formed. The metal-containing nanoparticles 140 may be formed by vacuum depositing a metal. The vacuum deposition may be one chosen from sputtering, evaporation and chemical vapor deposition, but it is not limited thereto.
[0103] Thickness or density of the metal-containing nanoparticles 140 may be adjusted by controlling deposition conditions such as a deposition time and the like during deposition process.
[0104] FIG. 6 is a block view illustrating an example of an analyzing method using a substrate for surface enhanced Raman scattering.
[0105] Referring to FIG. 6 , in S 300 , a substrate 110 may be prepared. Materials and properties of the substrate 110 are the same as described above.
[0106] In S 310 , a material to be analyzed may be added to a solution 120 including metal-containing nanowires 122 . Kinds, sizes and properties of the metal-containing nanowires 122 are the same as described above. As described above, a coating material such as polyvinylpyrrolidone (PVP) may be mixed to the solution 120 to ensure dispersion stability of the metal-containing nanowires 122 . The coating material may be removed using heat treatment or may be used to control nanogaps.
[0107] In S 320 , the mixed solution 120 may be filtered. Vacuum filtration is used in an embodiment of the present disclosure. When the mixed solution 120 is filtered, the material to be analyzed may be positioned on the nanogaps between metal-containing nanowires 122 naturally without any separate process. For example, the material to be analyzed may be placed at hot spots to efficiently provide enhanced Raman signal during analyzing the Raman signals.
[0108] In S 330 , the substrate 110 may be dried. During drying the substrate 110 , materials, except the material to be analyzed and the metal-containing nanowires 122 which are not filtered through and thus remained, may be removed. According to an embodiment, the coating material present on the surface of the metal-containing nanowires 122 may be remained to control nanogaps.
[0109] In S 340 , Raman signals of the material to be analyzed may be detected using laser irradiation to the substrate 110 . As described above, the material to be analyzed may be also present between the nanogaps to provide enhanced Raman signals.
[0110] FIG. 7 is a block view illustrating an example of an analyzing method using a substrate for surface enhanced Raman scattering.
[0111] Referring to FIG. 7 , in S 400 , a substrate for surface enhanced Raman scattering having above described structural properties may be prepared. The substrate for surface enhanced Raman scattering may be prepared by utilizing the method described above.
[0112] In S 410 , the material to be analyzed may be filtered. The material to be analyzed may be adsorbed to one area among various nanogaps during the filtration.
[0113] In S 420 , Raman signals of the material to be analyzed may be detected using laser irradiation to the substrate 110 . As described above, the material to be analyzed may be also present between the nanogaps to provide enhanced Raman signals.
[0114] FIG. 8 is a transmission electron microscope image of an example of metal-containing nanowires.
[0115] Referring to FIG. 8 , cross points (circular dotted line), which are formed when the metal-containing nanowires 122 are crossed each other, may be clearly provided.
[0116] FIG. 9 is a reflectance graph of an example of a substrate for surface enhanced Raman scattering.
[0117] The substrate for surface enhanced Raman scattering in FIG. 9 only includes a substrate 110 and metal-containing nanowires 122 .
[0118] The substrate 110 used in FIG. 9 is a glass fiber filter with a thickness of 0.7 μm. The metal-containing nanowires 122 in the solution 110 have a diameter of about 40 nm and a length of abut 50 μm and Ag is used. Vacuum filtration is used to aggregate the metal-containing nanowires 122 on the substrate 110 .
[0119] The substrate for surface enhanced Raman scattering of the present disclosure has excellent optical properties including less than 5% of reflectance at a wavelength range of 400-700 nm which is a visible range. Such a low reflectance is due to effective light absorption through numerous different nanogaps between Ag nanowires 122 .
[0120] FIG. 10 is a graph comparing Raman intensities using an example of a substrate for surface enhanced Raman scattering.
[0121] Referring to FIG. 10 , Raman intensities were compared using the substrate for surface enhanced Raman scattering, which was prepared at the same conditions described in FIG. 9 , and the substrate for surface enhanced Raman scattering, which was prepared by further including the insulating film 130 of 10 nm of alumina (Al 2 O 3 ) and the metal-containing nanoparticles 140 of 9 nm of Ag on the substrate for surface enhanced Raman scattering of FIG. 9 .
[0122] The former was represented by Ag NWs, while the latter was represented by Ag NWs_Al 2 O 3 10 nm_Ag NPs 9 nm.
[0123] Both substrates were immersed in 2 mM of a benzenethiol (BT) solution for about 1 hour and then rinsed with ethanol so that benzenethiol molecules were adsorbed on the substrate 110 in a single layer. Raman intensity of the both substrates for surface enhanced Raman scattering were determined using Raman spectroscopy. Wavelength and intensity of incident laser were 632.8 nm and 0.4 mW, respectively. Ag NWs_Al2O3 10 nm_Ag NPs 9 nm showed 5 times or more of Raman intensity compared to Ag NWs.
Example 1
[0124] Excitation laser wavelength): 632.8 nm
[0125] Objective lens: 50×
[0126] Spot size: 2 μm
[0127] Power: 0.4 mW
[0128] While this disclosure includes specific examples, it will be apparent to one of ordinary skill in the art that various changes in form and details may be made in these examples without departing from the spirit and scope of the claims and their equivalents. The examples described herein are to be considered in a descriptive sense only, and not for purposes of limitation. Descriptions of features or aspects in each example are to be considered as being applicable to similar features or aspects in other examples. Suitable results may be achieved if the described techniques are performed in a different order, and/or if components in a described system, architecture, device, or circuit are combined in a different manner, and/or replaced or supplemented by other components or their equivalents. Therefore, the scope of the disclosure is defined not by the detailed description, but by the claims and their equivalents, and all variations within the scope of the claims and their equivalents are to be construed as being included in the disclosure.
DESCRIPTION OF REFERENCE NUMERALS
[0129] 110 : Substrate
[0130] 120 : Solution
[0131] 122 : Metal-containing nanowire
[0132] 124 : Filtrate
[0133] 130 : Insulator
[0134] 140 : Metal-containing nanoparticles
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The present disclosure relates to a substrate for surface enhanced Raman scattering, a fabricating method for the same and an analyzing method using the same. The present disclosure may provide a substrate for surface enhanced Raman scattering having excellent surface enhanced Raman scattering effects by randomly stacking of Ag nanowires in a simple way by utilizing a substrate having a filtering function, and a method for efficiently analyzing a material to be analyzed using the same.
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CROSS-REFERENCE TO RELATED PATENT APPLICATIONS
[0001] This patent application claims the benefit of U.S. Provisional Patent Application No. 60/386,980 and 60/387,235, both filed on Jun. 7, 2002.
FIELD OF THE INVENTION
[0002] This invention pertains to filters, and more particularly to an environmentally friendly filter cartridge.
BACKGROUND OF THE INVENTION
[0003] Most conventional filters and filter cartridges present a disposal problem. Driven by ease of installation, many applications have gone to self-contained spin-on cartridges. These have a metal outer case, a metal base plate, and other metal components within the filter. Replaceable cartridges also have significant metal components, often in the form of centertubes or support grids for supporting the filter element, and metal endcaps. Thus, significant elements of a filter will not burn thus preventing the use of incineration for relatively complete disposal of the spent filters or filter cartridges.
BRIEF SUMMARY OF THE INVENTION
[0004] In view of the foregoing, it is a general aim of the present invention to provide an environmentally friendly filter cartridge, capable of being incinerated, and which is economical to manufacture and provides for simple and reliable installation. The cartridge is environmentally friendly in that it contains no metallic parts.
[0005] In practicing the invention, the cartridge can be made from a limited class of materials, preferably all incinerateable. The materials include the media (normally cellulose or perhaps polyester with plastic backing), two plastic endcaps, two rubber gaskets, and potting compound (epoxy, plastisol, hot melt or urethane), all of which are incinerateable. The cartridge itself has no centertube; to the extent internal support is required, it is built into the housing, which is compatible with the cartridge. The fact that the cartridge will burn and it is lightweight (due to no metal parts) simplifies disposal.
[0006] It is a feature of the invention that pre-molded plastic endcaps are utilized in the filter along with structures which compensate for the reduction in strength of plastic endcaps over conventional metal endcaps.
[0007] In a particular embodiment, the invention provides an environmentally friendly filter cartridge containing no metal parts. The cartridge includes a cylindrical filter element having an internal bore, which has no integral supporting centertube. A pre-molded plastic endcap, having an open center corresponding to the internal bore of the filter, it is ealed to the filter element at a first end thereof. An annular groove formed near the outer periphery of the first endcap has a radial seal gasket fitted therein. The radial seal gasket has a peripheral mounting bead sized to be stretched and snap fit into the annular groove. The radial seal gasket has a depending skirt coaxial with the filter element and positioned at about the outer periphery of the filter element. A second pre-molded plastic endcap is provided having a closed end. The second end of the filter element is sealed to the second endcap. The second endcap also has an annular groove at the outer periphery thereof. In this case a disc-like axial seal is stretch fit into the groove to project from the outer periphery of the second endcap to provide an axial seal. A pressure equalizing aperture is formed in the second endcap for equalizing the pressure differential across the second endcap during filter operation. Support shoulders associated with the lower portion of the second endcap serve to resist crushing forces applied to the second endcap during filter operation.
[0008] Subsidiary features of the invention include a handle also formed in the second endcap for facilitating user manipulation of the filter cartridge.
[0009] The filter cartridge, according to the invention, is used in a housing, which receives the filter cartridge. The housing has a centertube fixed therein for supporting the inner bore of a cartridge when inserted in the housing. A cover is threaded onto the housing in such a way as to compress the axial seal gasket between the cover and the housing. The pressure equalization apertures serves to equalize the pressures between the upper endcap and the cover to prevent bowing of the plastic of the second endcap under operating pressure.
[0010] In certain applications, the upper endcap has a plurality of tapered ribs positioned near the periphery thereof and oriented to assist in centering the cartridge in the housing. Shoulders formed on the tapered ribs interfit with an annular ridge in the housing for supporting the shoulders to resist crushing pressures on the filters under operating conditions.
[0011] In certain instances, the filter also has a plurality of keys associated with the second endcap. The key positions are on the underside of the endcap facing toward the centertube. The housing centertube has a top surface having a plurality of keyed positions. A slot is formed in a selected one of the keyed positions to correspond with the position of the key on the inside of the second endcap.
[0012] Other aspects, objectives and advantages of the invention will become more apparent from the following detailed description when taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is an elevational view of a filter constructed in accordance with the present invention;
[0014] FIG. 2 is an elevational section taken through the filter of FIG. 1 in a plane parallel to the paper surface;
[0015] FIG. 3 is a partial enlarged view showing the upper endcap with key;
[0016] FIG. 4 is a diagram illustrating a plurality of key positions;
[0017] FIG. 5 is a partial enlarged view illustrating the lower endcap and radial seal gasket;
[0018] FIG. 6 is a partial diagram illustrating the upper endcap, with filter removed, to better show the tapered centering guides and shoulders; and
[0019] FIG. 7 is an elevational cross-section showing a housing used with the filter of FIG. 1 .
[0020] While the invention will be described in connection with certain preferred embodiments, there is no intent to limit it to those embodiments. On the contrary, the intent is to cover all alternatives, modifications and equivalents as included within the spirit and scope of the invention as defined by the appended claims.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0021] Turning then to FIG. 1 , there is shown, in elevation, a cartridge 20 constructed in accordance with the present invention. This disclosure of the cartridge 20 is intended to be general, since the cartridge 20 can be configured for different applications. More particularly the cartridge can have elements configured such that it will be used as a fuel filter, a full flow oil filter, a hydraulic filter, or a bypass oil filter. The cartridge features, which will be described in detail herein, will be common to any of the foregoing applications. The universal housing, which will also be described below, is readily reconfigureable for the foregoing applications, without the necessity for change of the characteristics of the filter cartridge. Referring back to FIG. 1 , it will be seen that the filter cartridge 20 includes a filter element 21 having a lower endcap 22 , which carries a radial seal gasket 23 . An upper endcap 24 , also secured to the filter element 21 , provides a number of features, including a mechanism for supporting an axial seal gasket 26 , an integrally molded handle 27 on the top of the endcap 24 , and centering beveled projections 28 , which both serve to center the cartridge 20 as it is inserted into the housing and which also have lower shoulders 29 b thereon which tend to support the plastic endcap 24 on the housing to resist crushing forces in filter operation. Also of note is a pressure equalization aperture 30 formed in the upper endcap 24 , which serves to equalize the differential pressure across the endcap 24 to prevent bowing and possible fracture of the endcap 24 .
[0022] The cross-sectional view of FIG. 2 reveals additional constructional details of the filter of FIG. 1 . There it will be seen that the lower endcap 22 , which is made of pre-molded plastic, provides an upstanding annular channel 31 into, which a first end of the filter element 21 is fit and potted. Potting can be accomplished with any conventional potting material used in this art, which includes epoxy, plastisol, hot melt or urethane. The particular potting material used may depend upon the nature of the application to which the filter is put. The potting tends to seal the lower portions of all of the pleats into a unitary endcap. The lower endcap 22 has a central opening 35 for passing fluid which is passed through the filter to the central bore thereof to a housing outlet (not shown in FIG. 2 ).
[0023] The filter element 20 has an outer circumference and an open inner bore 21 a . Normally flow through the filter is from the outside in, making the internal bore 21 a the area which receives and passes to an external conduit the filtered fluid. It is possible, of course, to operate the filter in the opposite direction in which the internal bore 21 a would be the filter inlet, and clean filtered fluid would be obtained at the outside periphery of the filter.
[0024] The lower endcap 22 also has an annular groove 32 formed therein near the periphery of the filter. The radial seal gasket 23 has an enlarged in-turned annular bead 34 which is sized to be stretched and snap fit into the groove 32 . In that way the gasket 23 is positively and reliably locked in place on the endcap 22 . The gasket 23 has a depending skirt 23 a which depends from the endcap 22 and has a radius very near the outside radius of the filter element 21 , so that the axial seal performs its sealing function near the outside of the filter cartridge 20 for reasons to be explained below.
[0025] FIG. 2 also shows the upper endcap 24 which, like the endcap 22 , is a pre-molded plastic element. In the case of the upper endcap 24 , the endcap has a closed end. An internal annular channel 36 is provided for receiving the second end of the filter element 21 . Like the first end, the second end is also potted into the associated channel in the endcap.
[0026] The upper endcap 24 has an annular groove 38 preferably located at the outer periphery thereof. A disc-like rubber annular gasket 26 , which serves as an axial seal gasket, is sized so that it can be stretched and snap fit into the groove 38 . In this way, the gasket is reliably and securely positioned for automatic installation with the cartridge 20 .
[0027] FIG. 2 also illustrates the centering ribs 28 (see also FIG. 6 for an enlarged view). It will be seen that the ribs 28 each have an angled face 29 which, as suggested in FIG. 7 , causes the filter cartridge to self center as it is slid into the housing. The housing has a circular ridge 29 a (see also FIG. 7 ) over which the angled projections 29 ride to ultimately seat the lower shoulders 29 b on a ledge 29 c formed in the housing. The dimensions are such that the upper endcap 24 firmly seats the shoulders 29 b on the ledge 29 c so that additional downward force on the endcap 24 created by pressures during operation of the filter will not drive the endcap 24 into the housing and crush the filter. These ribs 28 , in conjunction with the pressure relief port 30 in the upper endcap 24 , are significant features in allowing the use of a plastic endcap in an application which heretofore had required the structural stability of a metal endcap.
[0028] Also of note in FIG. 2 is the integrally molded handle 27 formed on the upper surface of the upper endcap 24 . Also, as a subsidiary feature, the inside surface of the upper endcap 24 is provided with a key feature generally indicated at 62 , which will be described in greater detail below.
[0029] FIG. 7 shows an exemplary housing into which the filter of FIG. 1 can be fit. In the illustrated housing, inlet fluid is provided through an inlet port 42 . The housing also has an outlet port 44 , which is connected by an internal passage 44 a in the housing to the center lower portion of the filter, in fluid communication with the bore 21 a . The housing has a removable cap 45 which is threaded onto the housing to compress the axial seal gasket 26 set in the annular groove 38 on the periphery of the upper endcap 24 . Also of note is the bottom 49 of the housing, which may be removably secured in place by fasteners such as bolts. This allows the installation of different housing bottoms for different applications, such as a bottom including a sump for a fuel filter application, or a concave bottom for high pressure lubrication applications.
[0030] The lower portion of the housing has an annular flange 46 which provides a sealing surface acted upon by the skirt 23 a of the radial seal gasket 23 which, it is recalled, is carried in the groove 32 of the lower endcap 22 . The seating of the radial seal gasket 23 into the groove 32 is better illustrated in the enlarged partial view of FIG. 5 , while the interaction between the radial seal 23 and the housing flange 46 is best shown in FIG. 7 . Use of a radial seal in this position is significant in that the gasket is positioned near the outer periphery of the filter so that the pressure differential serves to enhance the sealing action. The gasket 23 seals radially between itself, the endcap 22 that supports it, and the housing flange 46 . This seal separates the filtered and unfiltered fluid. Use of a radial seal for this component utilizes the pressure differential across the filter to assist the sealing function by forcing the radial seal gasket 23 against both the endcap 22 , which supports it and the housing flange 46 of the filter housing. In addition, placing the seal at the external periphery tends to put a pressure differential across the lower endcap which is positive at the outside of the filter (and therefore the inside of the endcap) and negative at the bottom of the endcap. This pressure differential tends to put the pleated paper filter in tension, which the media is capable of resisting. Moving the skirt 23 a of the gasket inboard would tend to put at least part of the media in compression, which is not so readily resisted by pleated paper media. Keeping the media in tension is particularly important in resisting what would otherwise be crushing forces encountered in a plugged filter condition.
[0031] Returning to the upper endcap 24 , it will be seen that at least one pressure relief port 30 is formed in the upper endcap 24 . The purpose of this port is to equalize the pressure across the upper endcap 24 to prevent bowing or possible fracture of the endcap 24 . This is accomplished by, in effect, allowing a small portion of the unfiltered fluid on the outside of the cartridge to move through the pressure relief aperture 30 to the top of the endcap 24 . The purpose is to allow the pressure to equalize across the gasket at the top and to avoid putting undue stresses on the endcap 24 or the axial seal gasket 26 .
[0032] The pressure downstream of the media is always less than the upstream pressure (when the filter is flowing fluid). This differential pressure can be quite high in cases where the filter is plugged, the velocity is high, or the fluid is cold and viscous. When a pressure relief aperture 30 is provided, this pressure is carried to the top of the upper endcap 24 and causes an unbalanced force to be placed on the upper endcap 24 , tending to force it into the housing. In practicing this aspect of the invention, this force is counterbalanced in the housing. The unbalanced force is due mainly to the center of the endcap 24 which has the upstream pressure on one side, and downstream pressure on the bottom side. The unbalanced force is in the downward direction and tries to push the cartridge into the housing and crush the element. The cartridge has the aforementioned shoulders 29 b on the bottoms of the ribs 29 , and these seat against a stop 29 c to provide a positive stop for the top endcap and thus seat the overall filter in the housing.
[0033] FIGS. 3 and 4 illustrates a keying feature which can be used in the practice of the present invention. The inside 24 a of the upper endcap 24 is provided with a plurality of key positions, best illustrated in FIG. 4 . It will be seen that at a given radius from the center of the endcap 24 , a plurality of key positions 60 are provided. The illustrated embodiment includes eight key positions in a single ring. More or fewer key positions per ring, as well as additional rings can also be provided, but it is believed that the eight key positions, which can provide the sixteen possibilities illustrated in FIG. 4 , is adequate for most applications.
[0034] Referring primarily to FIG. 3 , it will be seen that a single key 62 is provided on the underside of the illustrated endcap in a given position. While only a single key is shown, as contrasted with the three keys of FIG. 4 it is believed that the single key will adequately illustrate the invention without overcomplicating the drawings. The key is in a fixed angular position with respect to the key circle 63 (the circle in which the keys are located). The key 62 projects into the internal bore 21 a of the filter element 21 . FIG. 3 shows a portion of the housing centertube 64 having a top surface 65 which is substantially solid except for a key opening 66 . The upper surface 65 of the centertube has a plurality of key positions in a key circle 67 in the same pattern as illustrated in FIG. 4 . However, instead of projections 62 , the keys in the upper surface 65 are apertures to receive the projections. FIG. 3 shows a single aperture 66 positioned in the key circle 67 to engage the single projection 62 positioned in the key circle 63 . Thus, when the filter is installed in the housing, the keys will align and allow the filter to reach the seated position, allowing the cover to be placed on the housing and operation to continue. If the wrong filter inserted, the filter will not seat, and the user will be incapable of completing assembly.
[0035] This feature is particularly significant when using a universal housing as illustrated in this application. For example, two housings might be used side-by-side to provide a primary and a secondary fuel filter system. Both housings would be of the same diameter and height, but would require different filter cartridges. The keys will prevent the cartridges for one of the housings from being installed incorrectly in the other housing. It would be a simple matter to have several different key configurations to suit various applications and indeed various customers.
[0036] The assembly of the filter will now be briefly described, primarily with reference to FIG. 2 . Basically the endcaps 22 , 24 are potted onto the filter element 21 in whichever sequence the manufacture desires. Using conventional techniques, an end of the filter element is placed, for example, in the channel 31 of the lower endcap, and potting material (epoxy, plastisol, hot melt or urethane) is introduced into the channel 31 to seal the ends of all the pleats and join them to the endcap 22 . A similar operation is performed on the other end in connection with endcap 24 . The gaskets 26 , 23 can be preinstalled before potting, or are preferably installed after potting by simply stretching the gaskets and snapping them into place. The filter is then ready for packaging and ready for use by the ultimate consumer. The fact that the gaskets are so reliably joined to the filter makes changing a cartridge filter constructed in accordance with this invention about as simple as changing a spin-on filter. The result, however, is that the spent filter can be disposed of by incineration, rather than contributing to landfill waste.
[0037] All references, including publications, patent applications, and patents, cited herein are hereby incorporated by reference to the same extent as if each reference were individually and specifically indicated to be incorporated by reference and were set forth in its entirety herein.
[0038] The use of the terms “a” and “an” and “the” and similar referents in the context of describing the invention (especially in the context of the following claims) are to be construed to cover both the singular and the plural, unless otherwise indicated herein or clearly contradicted by context. The terms “comprising,” “having,” “including,” and “containing” are to be construed as open-ended terms (i.e., meaning “including, but not limited to,”) unless otherwise noted. Recitation of ranges of values herein are merely intended to serve as a shorthand method of referring individually to each separate value falling within the range, unless otherwise indicated herein, and each separate value is incorporated into the specification as if it were individually recited herein. All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g., “such as”) provided herein, is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention unless otherwise claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the invention.
[0039] Preferred embodiments of this invention are described herein, including the best mode known to the inventors for carrying out the invention. Variations of those preferred embodiments may become apparent to those of ordinary skill in the art upon reading the foregoing description. The inventors expect skilled artisans to employ such variations as appropriate, and the inventors intend for the invention to be practiced otherwise than as specifically described herein. Accordingly, this invention includes all modifications and equivalents of the subject matter recited in the claims appended hereto as permitted by applicable law. Moreover, any combination of the above-described elements in all possible variations thereof is encompassed by the invention unless otherwise indicated herein or otherwise clearly contradicted by context.
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A filter cartridge which is environmentally friendly in that it is made up of components which are all incinerateable. The ends of a filter element are sealed using potting compound and plastic endcaps. The upper endcap, which is closed, has a pressure relief aperture associated therewith to prevent bowing. In a plugged filter condition the high downward pressure introduced on the upper endcap is compensated by providing the cartridge with centering ribs which bottom on an associated ledge in the housing to provide a positive stop for the top endcap, preventing it from being driven down into and through the filter element. Rubber gaskets are associated with the respective endcaps, and are reliably secured to the endcaps by being snap fit into grooves molded into the plastic of the endcaps. The lower endcap utilizes a simple radial seal gasket which is both highly effective and also positioned to avoid structural crushing forces on the cartridge. A keying system prevents the installation of improper filters.
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FIELD OF THE INVENTION
The field of the present invention is that of end-of-arm tooling devices (EOAT) for a robot or like mechanical manipulators.
DISCLOSURE STATEMENT
Present-day industrial robots are capable of highly repetitive motion, but in most cases have relatively poor accuracy. Most industrial robots with repeatabilities in the range of 0.05 inches may have absolute positioning accuracies of only 0.25 inch. Repeatability refers to the positional deviation from the average position achieved by repetitive motion between a start point and a target point. The target location is typically "taught" using an on-line process in which the manipulator is physically moved by the programmer to assigned locations. This "teaching" is used for programming critical points in most industrial manufacturing robot applications and is a reliable but time-consuming process. A robot's accuracy refers to its ability to reach a location specified by coordinates often specified by some off-line process such as a computer-assisted design/computer-assisted manufacturing (CAD/CAM) process. The accuracy of the robot is determined by several factors. Mechanical inaccuracies can be caused by backlash in the joints and bending of the length of the manipulator. The controller may contribute inaccuracies due to round-off errors. The resolution of the manipulator's positional feedback system also affects accuracy performance capability.
A major reason industrial robots are not used in many manufacturing operations is inaccuracy. If the accuracy of the robot were enhanced, significant amounts of development time could be eliminated in cases where repeated installations of applications are to be installed. A more accurate industrial robot could allow the off-line programming of an application, further reducing development time.
Still another problem with many prior end-of-arm tooling devices is that to make the device compliant requires separate drive systems for each individual finger. Typically, not only did this require separate drive systems, but further required complex control programming.
SUMMARY OF THE INVENTION
The present invention overcomes the above-noted problems by providing an EOAT with a compliant finger drive transmission and, in a preferred embodiment, an encoder system that will allow the EOAT to grip an object off-center from the EOAT and measure the offset to determine the accuracy. With these capabilities, the present EOAT may be used to obtain offset measurement on gauges of known size and location and to calibrate the robot's position in the "real world." In this manner, the present invention provides an EOAT which increases the robot's accuracy, making off-line robotic programming more practical.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a rear perspective view of a preferred embodiment gear box of an EOAT of the present invention.
FIG. 2 is a front perspective view of the gripper portion of the EOAT of the present invention.
FIGS. 3 and 4 are schematic views of the present invention EOAT.
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIGS. 1 through 4, the end-of-arm tooling device (EOAT) 7 has a frame 12. The frame 12 has an end providing for a face plate 13 for connection to a robot or like manipulator (not shown). The EOAT 7 is powered by a variable torque motor 11, typically pneumatic or electrical, which may be physically connected with the EOAT 7 or taken from a power take-off shaft from a wrist of the robot itself.
The motor 11 provides a first torsional input to a first shaft 10. Shaft 10 is fixably connected with a cross shaft 20. The cross shaft 20 has rotatably attached thereto a first planet bevel gear 21 and a second planet bevel gear 22. Meshed with the planet bevel gears 21 and 22 are a first output bevel gear 31 and a second output bevel gear 42. The output gear 42 is fitted over the shaft 10 directly or by means of a bearing. The output gear 42 is physically connected with a gear 44. The gear 44 meshes with a reversing gear 50 which is fixably connected to a shaft 52. Shaft 52 has at its end a fixably connected gear 62.
Output gear 31 is fixably connected with a gear 61. The gear 61 is also rotatably mounted directly or via a bearing over shaft 10. The gear 61 is engaged with a rack gear 71. In like manner, the gear 62 is engaged with a rack gear 72. The rack gear 71 has fixably connected thereto a jaw member 81 (not shown in FIG. 2) and is spring biased to an open position by a spring 85. In like manner, the rack gear 72 has an associated jaw 82 which is spring biased to the open position by a spring 85.
The end-of-arm tooling device is capable of inducing friction upon the movement of the jaws 81,82 by a variable induced friction device 100. Friction device 100 induces friction via a friction pad 101 which is biased by a spring 104 away from the rack gear 71. A chamber 102 has a slidably-mounted piston which is responsive to pneumatic pressure to move the friction pad 101 toward the rack gear 71. By varying the pneumatic pressure, the imposed friction force upon the movement of the jaw 81 is varied. A friction device 100 is also provided for the jaw 82. It has been found that the preferred friction setting often is a function of workpiece weight.
To determine the location of the jaws 81, 82 and to provide a signal in response thereto, there are encoders 91 and 92 which determine the angular rotational position of gears 61 and 62, respectively. The information from the encoders 91, 92 is fed back to a robotic controller (not shown). The robotic controller also controls the torque input of the motor 11 and the amount of imposed friction provided by the friction devices 100. (Note: In FIGS. 1, 2 and 4, the motor 11, friction devices 100 and biasing springs 85 have been eliminated for clarity of illustration.)
In operation, the robot will position the EOAT 7 in the general vicinity of the workpiece 150. Usually, the robot will be programmed to position the EOAT so that the jaw members 82 and 81 will be an equal distance from the workpiece 150. Due to discrepancy in the positioning of the robot and/or discrepancies in the location of the workpiece 150, typically one jaw will be closer to the workpiece 150 than the other jaw.
The motor 11 will turn the shaft 10. The gears 21, 22, 31 and 42 act as a bevel differential and, therefore, as long as there are no objects preventing movement of the jaws 81 and 82, both jaws will move inward against their biasing provided by spring 85. The spring biasing is provided to prevent backlash in the gearing.
The encoders 91 and 92 will feed information to the robot to allow the robot to know how far the jaws 81 and 82 have moved. As mentioned previously, the shaft 10 will turn, causing the cross-shaft 20 to turn with it. Planet gears 21 and 22 essentially will not rotate; therefore, they will act as if they are fixed to the cross-shaft 20 and rotate the gears 42 and 31. The gear 31 causes rotation of the gear 61, which in turn moves the rack 71 and jaw 81. To get the opposite direction in the movement of jaw 82, there is a reversing gear 50 which meshes with the gear 44 which, as mentioned previously, is fixed with the gear 42. The above, in turn, causes rotation of gear 61, which therefore causes movement in the rack 72.
If, for instance, the jaw 81 contacts the workpiece 150, it will be urged toward the workpiece 150 until a certain torque value is reached. Thereupon, the gear 61 will be stalled out, stalling gear 31. With the end of rotation gear of gear 31, the planet gears will now rotate upon their respective rotational axes which are parallel with the cross-shaft 20 and divert all of the torque from the motor 11 to the gear 42, which in turn will cause the continued movement of the jaw 82. If it were desired to make a three-jaw EOAT, another differential would be connected between the gears 44 and 50. The output of that differential would be fed to gear 50 and to the gear 62 which controls the operation of the other associated jaw 82.
As mentioned previously, when the jaw 81 hits the workpiece 150, all torque will then be automatically transferred to jaw 82, which will then continue its motion until it hits the workpiece 150. The encoder 91 will allow the controller to know that jaw 81 has stopped, thereby informing the robot of the location of workpiece 150. The jaw 82 will continue to move until it hits the workpiece 150 at which point the encoder 92 will inform the robot on the whereabouts of the other side of the workpiece.
The information by the encoders 91 and 92 may be utilized in a few different manners. One manner is to allow the robotic controller to know about the location of the workpiece 150. Conversely, the workpiece 150 may be a test location piece, and the robot may be programmed to grab the workpiece with the jaws 81 and 82 and therefore know the exact location of the robot's arm by the readings provided by the encoders 91 and 92 and then recalibrate the robot controller's guidance system.
The information may also be utilized in other instances to tell the approximate size of the workpiece 150 in situations where the robot may be utilized on different size workpieces and therefore interpret this information to determine which part that the robot jaws 91 and 92 are gripping.
Additionally, there is provided, as mentioned previously, the friction device 100. These variable friction devices 100 are beneficial in that after the jaws 81 and 82 have gripped the device, the friction device 100 will lock the racks and therefore prevent any movement of the racks upon movement of the robot arm after the EOAT 7 has picked up the workpiece, thereby insuring a firm grip upon the workpiece.
In instances where very light workpieces are being utilized, the motor 11 will be put on a low torque and the friction device 100 will be held off to provide little or no induced friction. Upon engagement of the first jaw 81, all torque will then be transferred to the jaw 82. Initially, low torque will be utilized when picking up delicate workpieces; however, to add speed, a high torque setting will be initialized after one of the jaws 81, 82 has made contact with the workpiece 150. After the second jaw makes contact with the workpiece, the friction device 100 will then lock the jaws 81, 82 in position to insure a firm grip upon the workpiece. This locking will only occur after the encoders 91 and 92 have sensed that there is no further movement on the jaws after their contact with the workpiece.
Accordingly, while my invention has been described in terms of a specific embodiment thereof, it will be appreciated that other forms could readily be adapted, and therefore the scope of my invention is to be considered limited only by the following claims.
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An end-of-arm tooling device for a robot or like manipulator is provided which, in a preferred embodiment, includes a differential separating a first torsional input into first and second torsional outputs, and two jaws for interacting with a workpiece powered by a separate one of the first and second torsional outputs, and wherein, upon interaction with the workpiece at a predetermined torque level by one of the jaws, the jaw's motion will be stopped and torque will be continually transferred to the remaining jaw.
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CROSS-REFERENCED APPLICATIONS
This application is a Continuation-in-Part of U.S. patent application Ser. No. 13/656,286, filed on Oct. 19, 2012, and claims priority to U.S. Provisional Application No. 61/618,276, filed on Mar. 30, 2012, both of which are incorporated herein by reference thereto in their entireties.
BACKGROUND OF THE DISCLOSURE
1. Field of Disclosure
The present disclosure relates to a hair care composition containing an inorganic fluoride for straightening, smoothing, defrizzing, curling and/or relaxing of hair, and its method of use in a variety of hair care products, e.g., straightener solution, shampoo, conditioner, hair color binding treatment, hair volumizing treatment, combinations thereof, etc.
2. Description of Related Art
During the past few years, there has been a growing trend in the market for semi-permanent curl reduction and change in the configuration of hair with minimum hair damage. These products affect the style configuration of hair with discernible curl reduction and easiness of styling attributes including shine, luster, smoothness, volume reduction, and feel of hair.
Conventional techniques for temporary smoothing and removing curls have been by applying pomades on hair, followed by combing with uncontrollable hot, heated metal combs. These techniques have many serious drawbacks, including scalp burning and hair damage from excessive heat.
Recently, improvements have been made to conventional techniques for smoothing and straightening hair that use controllable flat irons and curling irons. However, the straightening and smoothing effects on hair by these improved methods are only temporary, and total reversion occurs when the person perspires, or is exposed to high humidity, and especially after a single shampoo.
The technique of achieving semi-permanent results of straightening and smoothing was introduced by Brazilian hair stylists using solutions that contained formaldehyde in amounts from 0.2-1.5%, to reduce curl, with longevity of about four to six shampoos. A technique known as “escova progressiva,” where the hair was shampooed several times with high pH shampoos of about a pH of 8.5 to swell the hair, and then a “defrizz lotion” containing the formaldehyde and thermal protectors was applied on the hair and processed for 20-30 minutes. The hair was then blow dried and flat ironed. The results from this Brazilian process resulted in temporarily straight, silky, shiny and smooth hair. In order to attain semi-permanent results lasting beyond two to three shampoos, this process required weekly repeat applications.
Recently, several products have entered the market labeled as “keratin treatments.” These products have one or more keratin crosslinkers, solubilized keratin protein fractions, emollients, surfactants/emulsifiers, and preservatives. The keratin crosslinkers include monoaldehydes, dialdehydes and polyaldehydes at concentrations of 2% to 10%. The chemical crosslinking and hardening of the proteins with the aldehydes is due to the Maillard reaction. The monoaldehydes are referred to as formol, methanal, or acetaldehyde. These aldehyde-based keratin treatment products have many disadvantages. The major disadvantage with the aldehyde products is their toxicological profiles, creating safety and health concerns.
Formaldehyde, also known as “formol,” “methanal,” or “methylene glycol,” is a suspected carcinogen. Formaldehyde can cause contact dermatitis. Some hair stylists have become ill from repeated exposure to these hair treatments.
Formaldehyde is a colorless, strong-smelling and hazardous chemical that is found in hair smoothing treatments, including the Brazilian Blowout®, owned by Crème De Le Crem Inc. of West Hollywood, Calif. The Brazilian Blowout is regarded as being a more effective and less time-consuming choice than other hair-straightening methods, including conventional relaxers, Japanese thermal processing or keratin based treatments.
In 2011, the Brazilian Blowout has faced warnings and investigations by the Occupational Safety and Health Administration (OSHA) and the U.S. Food and Drug Administration (FDA) for mislabeling its products as “formaldehyde free,” when in fact their products contain methylene glycol, a liquid form of the chemical that emits formaldehyde gas when heated. Thus, salon workers and users of the product are exposed to formaldehyde during the entire hair straightening process (typically lasting two hours), especially during some of the key steps of the process, such as blow drying and flat ironing.
Formaldehyde can cause immediate reactions to the immune system, and it is a cancer hazard. It is listed as a human carcinogen in the 12 th Report on Carcinogens published by the National Toxicology Program. Exposure to formaldehyde can be highly irritating to the eye, nose and throat, which can cause coughing and sneezing. Formaldehyde can cause severe allergic reactions of the skin, eyes, and respiratory tract, and long term exposure to low levels in the air can cause asthma-like respiratory problems and skin irritations such as dermatitis and itching. In women, exposure to formaldehyde can also cause menstrual disorders.
If hair salons do choose to use the hair straightening treatments that contain formaldehyde, they must comply with strict requirements set out in OSHA's formaldehyde standard, which sets a permissible exposure limit for formaldehyde in the workplace at 0.75 parts of formaldehyde per million parts of air (0.75 ppm). Furthermore, the standard requires that employers test the air to find out the level of formaldehyde present in the air when the product is being used.
The difficulty and costs of complying with standards for formaldehyde places a significant burden on salon owners who choose to use hair smoothing products that contain or emit formaldehyde. Due to the health concerns of using hair straightening products that contain formaldehyde, some salons have stopped offering the Brazilian Blowout treatment, at the cost of losing customers.
Products containing more than 0.10% formaldehyde are prohibited in the marketplaces of several countries. Since these products are unstable, they are formulated with a large excess of formaldehyde exceeding the permissible level. At levels of less than 2% formaldehyde, limited crosslinking and polymerization occurs on hair with some level of curl relaxation with shiny and better fiber alignment shown as frizz reduction. The curl reversion is almost quantitative within two or three shampoos, but the cuticular attributes have a few more shampoos of longevity. At higher concentrations of formaldehyde (4-8%), high crosslinking and fast rates of polymerization occur with a discernable curl reduction of hair. Also, at these high levels, there is no need for a waiting period of 72 hours, and hair can be shampooed on the same or next day.
Even though the hair appears shiny and healthy, the formaldehyde polymerization seals the cuticle and traps some of the formula agents into the hair shaft or cortex, making the hair unhealthy. This is due to the water displacement and changes to the melanin, cortical cells, and matrix of hair. Over time, the changes in the cortical cells and microfilaments are irreversible and result in hair damage. Repeat treatments can amplify this damage, which results in fiber failure and hair breakage.
The present inventors have unexpectedly discovered that the application of an inorganic fluoride, such as a sodium fluoride, is a unique non-toxic, non-carcinogenic, product that can be used to straighten, smooth, defrizz or curl hair. It is unexpected since sodium fluoride has never been associated with hair care and nothing found in the literature would suggest to one of ordinary skill in the art the use of such an inorganic fluoride in hair care formulation for the purpose of straightening, smoothing, defrizzing, or curling hair. Moreover, the use of sodium fluoride, as an inorganic salt, in a hair care product ingredient is completely counterintuitive. That is, one would typically avoid the use of inorganic salts generally in hair care formulations, since these salts are known to cause build-up on the hair and many hair cleansing products (e.g., chelating shampoos) are formulated to remove inorganic salts from the hair rather than add such salts to the hair.
SUMMARY
The present disclosure provides a composition to apply to hair that contains fluoride for straightening, smoothing, defrizzing, and/or relaxing hair, and its method of use in a variety of hair care products, e.g., straightener solution, shampoo, conditioner, hair color binding treatment, volumizing treatment, a combination thereof, etc.
A hair care composition comprising: a crosslinking component comprising an inorganic fluoride; and a conditioning component, wherein the composition has a ratio of crosslinking component to conditioning component in the range of about 10:90 to about 95:5, preferably about 75:25.
The inorganic fluoride is present in the crosslinking component in a concentration of between about 0.1 to about 15%. The crosslinking component has a pH range of between about 3.0 to about 8.5, preferably between about 4.5 to about 5.5.
The crosslinking component further comprising at least one additional component selected from the group consisting of: a thickener, a preservative, a humectant, a pH adjuster, soothing agent, emollients, emulsifiers, fragrance and water.
The crosslinking component comprises: the inorganic fluoride having a concentration in the range between about 0.1 to about 15%; the preservative having a concentration in the range between about 0.2 to about 1%; the humectant having a concentration in the range between about 0.1 to about 1%; and the water to bring the concentration up to 100%. The crosslinking component further comprising a pH adjuster to bring the crosslinking component to a pH in the range between about 3.0 to about 8.5.
The inorganic fluoride is at least one selected from the group consisting of: sodium fluoride, potassium fluoride, ammonium fluoride, lithium fluoride, stannous fluoride, aluminum fluoride, zirconium fluoride, nickel fluoride, tin fluoride, ammonium hexafluorophosphate, sodium monofluorophosphate, stannous fluorozirconate, and stannous chlorofluoride.
The preservative is at least one selected from the group consisting of: phenoxyethanol, sorbitol, potassium sorbate, sodium sorbate, methyl paraben, propyl paraben, imidazolidynyl urea, and DMDM hydantoin.
The humectant is at least one selected from the group consisting of: glycerine, propylene glycol, dipropylene glycol, diglycerin, panthenol, sodium PCA, sugar alcohols, lecithin, hydrolyzed wheat proteins, hydrolyzed rice proteins, hydrolyzed keratin proteins, hydrolyzed silk proteins, lipids and polyols.
The thickener is at least one selected from the group consisting of: polysaccharide, cellulose, cellulose, derivatives, natural gums, natural polymers, synthetic polymers and inorganic gel mineral silicates.
The pH adjuster is at least one selected from the group consisting of: phosphoric acid, citric acid, tartaric acid, lactic acid, acetic acid, and bases that include sodium hydroxide, potassium hydroxide, sodium carbonate, ammonium hydroxide, isopropanolamine, and monoethanolamine.
The inorganic fluoride is present in the crosslinking component in a concentration of between about 0.1 to about 3.0%, more preferably between about 0.4 to about 1.25%.
The conditioning component comprises at least one selected from the group consisting of: amodimethicone, cyclomethicone, dimethicone, behentrimonium methosulfate, citrimonium chloride, citrimonium bromide, cocotrimonium methosulfate, olealkonium chloride, phenyltrimethicone, pantethine, panthenylethylether, silicone quaternium, gelatin, keratin amino acids, and polyquaternium.
A method for treating hair comprising: applying a premixed composition comprising (a) a crosslinking component comprising an inorganic fluoride and (b) a conditioning component to a user's hair, wherein the hair is straightened, smoothed, defrizzed or curled and wherein the premixed composition has a ratio of crosslinking component to conditioning component in the range of about 10:90 to about 95:5.
The fluoride is preferably a salt with an alkali metal (such as sodium fluoride, potassium fluoride, or lithium fluoride), or as ammonium fluoride, stannous fluoride, or with hexafluorophosphate.
The compositions of the present disclosure can be applied to any type of hair, with excellent results in hair straightening, smoothing, defrizzing, and/or relaxing.
The hair care compositions of the present disclosure are formaldehyde-free, even when heated by blow drying or flat ironing.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the results for Example 1, with a sample of a control (untreated hair) and three samples of normal hair treated with 1% sodium fluoride at pH 4.8, for very curly normal hair.
FIG. 2 shows the results for Example 2, with a sample of a control (untreated hair) and three samples of 20 volume color treated hair treated with 1% sodium fluoride at pH 4.8, for very curly 20 volume hair.
FIG. 3 shows the results for Example 3, with a sample of a control (untreated hair) and three samples of 40 volume bleached hair treated with 1% sodium fluoride at pH 4.8, for very curly 40 volume bleached hair.
FIG. 4 shows the results for Example 4, with a sample of a control (untreated hair) and three samples of wavy 20 volume hair treated with 1% sodium fluoride at pH 4.8, for wavy 20 volume hair.
FIG. 5 shows the results for Example 5, with a sample of a control (untreated hair) and three samples of normal hair treated with 2% sodium fluoride at pH 4.8, for very curly normal hair.
FIG. 6 shows the results for Example 6, with a sample of a control (untreated hair) and three samples of 40 volume bleached hair treated with 1.5% sodium fluoride at pH 4.8, for 40 Volume bleached hair.
FIG. 7 shows the results for Example 7, with a sample of a control (untreated hair) and three samples treated at pH 4.8, where A=1.0% sodium fluoride, B=1.5% sodium fluoride, and C=2.0% sodium fluoride.
FIG. 8 shows the results for Example 8, with a sample of a control (untreated hair) and two samples of normal curly hair treated with Brazilian Blow Out (O=Original Formula 7-8% formaldehyde and Z=Zero Formaldehyde Formula).
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The present inventors have unexpectedly discovered that due to the small molecular size of the fluoride, and its affinity for multiple cross-linking sites, the fluoride can produce cross-linkage in hair and cause temporary or permanent restructuring of the hair; i.e. causes straightening, smoothing, defrizzing and/or curling of the hair fiber.
More particularly, the use of sodium fluoride can be used in hair products for straightening, smoothing, defrizzing and/or curling. Sodium fluoride has excellent water solubility.
Unexpectedly, the present inventors have discovered that the fluoride can be used to crosslink other molecules to the hair to provide long lasting conditioning or volume to the hair. It can also be used to bind hair dye molecules in the hair for longer lasting coloring of the hair.
Sodium fluoride is an alternative to conventional hair products using formaldehyde.
Our data show that compositions for hair treatment having about 0.1 to about 15%, preferably about 0.1 to about 3.0%, and more preferably about 0.60 to about 1.25% sodium fluoride at pH 4.8, along with a polysaccharide thickener (such as AMIGEL®) has a perceptible effect on curl reduction, and that smoothening or better alignment of hair fibers is observed for all normal and porous hair types.
The compositions of the present disclosure include:
Composition
Inorganic fluoride compound M-Fluoride
0.1-15%
Preservative
0.2-1%
Humectant
0.1-1%
pH adjuster
to pH 3.0-8.5
M = Sodium, Potassium, Ammonium, Lithium, Stannous, Hexafluorophosphate
The treatment composition below was used for several performance examples:
Composition
w/w
Sodium fluoride (protein crosslinker)
1-2
Phenoxyethanol (preservative)
0.2%
Glycerine (humectant)
0.5%
AMIGEL ® (polysaccharide thickener)
0.6%
Phosphoric acid (QS)
to pH 4.8
Water (QS)
to 100%
FIGS. 1 to 7 show the effects of a sodium fluoride composition on several hair types, normal and porous hair including 20 volume color treated and bleached hair. The results from Examples 1 to 7 below are shown in FIGS. 1 to 7 , respectively.
In each of the following examples, the hair was treated as follows: The hair was shampooed and blotted dry. The hair was combed and the treatment composition was applied on the hair for 35 minutes at room temperature with a brush and then it was treated as in the directions below for each of Examples 1 to 7.
All samples marked “CNTL” are untreated hair.
For all hair samples marked “A”, the treatment composition was applied for 35 minutes and then the hair was rinsed with tap water. The hair was air-dried naturally.
For all hair samples marked “B”, the treatment composition was applied for 35 minutes and then the hair was rinsed with tap water. The hair was blow dried to about 90% and then flat ironed at 430° F. The hair was then rinsed with tap water.
For all hair samples marked “C”, the treatment composition was applied for 35 minutes and then the hair blow dried at a medium setting to about 90%, and then flat ironed at 430° F. The hair was then rinsed with tap water, and the hair was air-dried naturally.
Example 1
Normal Hair
For Example 1, shown in FIG. 1 , a composition of the present disclosure containing 1% sodium fluoride at pH 4.8 was applied to very curly normal hair.
Example 2
20 Volume Color Treated Hair
For Example 2, shown in FIG. 2 , a composition of the present disclosure containing 1% sodium fluoride at pH 4.8 was applied to very curly 20 volume hair.
Example 3
40 Volume Bleached Hair
For Example 3, shown in FIG. 3 , a composition of the present disclosure containing 1% sodium fluoride at ˜pH 4.8 was applied to very curly 40 volume bleached hair.
Example 4
20 Volume Hair
For Example 4, shown in FIG. 4 , a composition of the present disclosure containing 1% sodium fluoride at ˜pH 4.8 was applied to wavy 20 volume hair.
Example 5
Normal Hair
For Example 5, shown in FIG. 5 , a composition of the present disclosure containing 2% sodium fluoride at a pH of approximately 4.8 was applied to very curly normal hair.
Example 6
40 Volume Bleached Hair
For Example 6, show in FIG. 6 , a composition of the present disclosure containing 1.5% sodium fluoride at a pH of approximately 4.8 was applied to 40 volume bleached hair.
Example 7
Normal Curly Hair
For Example 7, samples A, B, and C were treated as follows: The treatment composition was applied to the hair for 35 minutes. The hair was blow dried at medium heat setting to about 90% dry, and then flat-ironed at 430° F. The hair was then rinsed with tap water, and the hair was air dried naturally.
A=1.0% sodium fluoride at a pH of approximately 4.8
B=1.5% sodium fluoride at a pH of approximately 4.8
C=2.0% sodium fluoride at a pH of approximately 4.8
Example 8
Brazilian Blow Out on Normal Curly Hair
Samples O and Z were treated as follows: The treatment composition was applied to the hair for 35 minutes, and then the hair was blow dried at a medium heat setting to about 90% dry. The hair was then flat-ironed at 430° F., and then was rinsed with tap water. The hair was then air dried naturally.
O=Brazilian Blowout Original Formula 7-8% Formaldehyde content
Z=Brazilian Blowout Zero Formaldehyde Formula
As used in this application, the word “about” for dimensions, weights, and other measures, means a range that is ±10% of the stated value, more preferably ±5% of the stated value, and most preferably ±2% of the stated value, including all sub ranges there between.
In practice of the present disclosure one or more other extended cosmetic compositions can be included for their generally acceptable recognized purposes. These can include soothing agents, such as aloe or allantoin gelatin; auxiliary emollients, such as squalene, mineral oil, argan oil, coconut oil, jojoba oil, walnut oil or liquid silicones; fatty alcohol based thickeners, such as cetyl alcohol, cetearyl alcohol, or stearic acid; low to no foaming cationic, nonionic or amphoteric emulsifiers; or preservatives, such as phenoxyethanol, sorbitol, potassium sorbate, sodium sorbate, methyl paraben, propyl paraben, Imidazolidynyl urea, or DMDM hydantoin.
The composition may also contain a fragrance to neutralize any malodors of the composition.
Cream Based Composition 1 (Leave On or Rinse Off)
(W/W %) Water 70 Methyl paraben 0.15 Ethyl paraben 0.02 Isopropyl Palmitate 0.61 Petrolatum 2.45 Glyceryl Stearate 2.04 Cetearyl Alcohol 2.04 Cyclopentasiloxane 1.02 Fragrance 0.20 Phenoxyethanol 0.50 Polyquaternium-37 1.23 Sodium Fluoride 0.5-8 pH adjustor - QS to pH Water QS to 100%
Cream Based Composition 2 (Rinse Off)
(W/W %) Water 60 Cetyl Alcohol 3.50 Stearyl Alcohol 3.00 Dicetyldimonium Chloride 2.00 Propylene Glycol 0.10 Polyquaternium-7 2.00 Stearyl Alcohol (and) Ceteareth-20 2.00 Cyclopentasiloxane 1.30 Amodimethicone 1.00 Hydrolyzed Keratin 1.00 Stearamidopropyl Dimethylamine 0.50 Fragrance 0.20 Aminopropyl Phenyl Trimethicone 0.20 Glycerin 0.50 Methylparaben 0.10 Phenoxyethanol 0.50 Sodium Fluoride 0.5-8 pH adjustor - QS to pH Water QS to 100%
Cream Based Composition 3 (Leave On or Rinse Off)
(W/W %) Water 70 Cetearyl Alcohol (and) Ceteareth-20 1.80 Hydrolyzed Keratin 2.00 Amodimethicone 1.00 Hydrolyzed Keratin 2.00 Cyclopentasiloxane (and) Dimethicone 0.50 Cetrimonium Chloride 0.50 Fragrance/Parfum 0.20 Hydrolyzed Collagen 0.20 Propylene Glycol 0.10 Glycerine 0.20 Methylparaben 0.10 (Wheat) Germ Oil 0.001 Argania Spinosa Kernel Oil 0.001 Sodium Fluoride 0.5-8 pH adjustor - QS to pH Water QS to 100%
Gel Based Composition 3 (Leave On or Rinse Off)
(W/W %) Water 70 Polyquaternium-7 4.00 Silkworm Extract 3.00 Hydrolyzed Keratin 3.00 Glycerin 2.00 Cetrimonium Chloride 0.80 Guar Hydroxypropyltrimonium Chloride 0.60 Phenoxyethanol 0.50 Panthenol 0.50 Sodium Fluoride 0.5-8 pH adjustor - QS to pH Water QS to 100%
Non Ionic Surfactant Smoothing Shampoo
(W/W %) Water 75 Non ionic Surfactants 5-15 Foam Boosters 0.5-10 Opacifier 0.50-3 Fragrance (Parfum) 0.20-0.90 Anionic Surfactant/Fatty alcohol 0.15-2 Fatty Alcohol 0.2-0.5 Sodium Fluoride 0.01-2 Preservative 0.10-0.25 Thickener 0.05-3 Citric Acid 0.10-0.5 Chelating Agent 0.08-0.30 Sodium Citrate (and) Water (Aqua) QS to pH 4.5-5.5 Water QS to 100%
Anionic Surfactant Smoothing Shampoo
(W/W %)
Water
75
Anionic Surfactants
5-15
Foam Boosters
0.5-10
Opacifier
.50-3
Fragrance (Parfum)
0.20-0.90
Anionic Surfactant/Fatty
0.2-0.5
Sodium Fluoride
0.01-2
Preservative
0.10-0.25
Thickener
0.05-3
Citric Acid
0.10-0.5
Chelating Agent
0.08-0.30
Sodium Citrate (and) Water (Aqua)
QS to pH 4.5-5.5
Sodium Chloride
QS to Viscosity 6,000-9,000 cps
Water
QS to 100%
TABLE I PERFORMANCE EFFECTS OF 1% NaF Versus pH ON CURLY/FRIZZY HAIR (NORMAL CURLY, COLOR TREATED AND BLEACHED HAIR TYPE) COMPOSITION I NaF 1.00% Amigel Thickener 0.60% Glycerol 0.50% Phenoxyethanol 0.20% pH Adjustor pH adjustment only QS DI Water QS. Process A: The hair swatches are shampooed with a Clarifying shampoo, towel blot and dried at medium heat with blow dryer. The composition I product was applied liberally to the hair with a tint brush and processed for 35 minutes. The excess product was towel blotted and the hair is dried to about 95% with a blow dryer at low heat followed with flat ironing @ 430° F. using 7-8 passes. The hair was rinsed after 48 hours. The performance % Curl Reduction, Shine and Smoothness was evaluated. PERFORMANCE pH Lo (cm) Ls (cm) Lt (cm) % Curl Reduction Shine Smoothness NORMAL CURLY HAIR 3.51 18.2 27.1 22.2 44.94% +++ ++++ (H 2 PO 4 ) 3.99 18.2 27.3 22.3 45.05% +++ ++ 4.5 18.2 26.8 25.3 82.56% +++ ++++ 5.02 18.2 27.2 19.8 17.78% ++ ++ 5.95 18.2 25.4 19.6 19.44% ++ ++ 6.93 18.2 27.9 20.3 21.65% +++ ++ 7.99 18.2 27.2 22.1 36.79% +++ ++++ NORMAL CURLY HAIR 3.82 16.6 23.3 19.1 37.31% + +++ (CITRIC ACID) 4.1 16.6 24.6 20.2 45.00% ++ ++++ 4.51 16.6 25.3 18.7 24.14% +++ +++ 5.03 16.6 26.3 17.6 10.31% +++ ++ 6.02 16.6 24.7 19.1 30.86% +++ ++++ 7.03 16.6 24.1 18.2 21.33% +++ +++ 8.06 16.6 25.2 18.3 32.69% ++++ ++ 20 VOL COLOR 3.01 20.0 26.00 22.50 41.66% +++ +++ TREATED HAIR 3.99 20.0 25.00 21.50 30.00% +++ +++ (H2PO4) 4.49 19.0 25.50 22.00 46.15% ++++ ++++ 5.02 19.0 26.00 22.00 42.85% ++++ +++ 6.93 18.0 24.00 22.50 75% +++ +++ 7.99 18.0 26.00 23.00 62.50% +++ ++++ 2X 40 VOL BLEACHED 3.01 20.0 26.00 24.00 66.66% ++ + HAIR 3.99 22.0 29.00 23.00 14.28% ++ ++ (H2PO4) 4.49 21.0 27.00 25.50 75.00% +++ ++++ 5.02 21.0 25.00 22.00 25.00% ++ ++++ 6.93 20.0 25.50 23.00 54.55% +++ +++ 7.99 21.0 27.00 24.00 50.00% +++ ++++ Process B: The hair swatches are shampooed with Clarifying shampoo, towel blot and dried at medium heat with blow dryer. The composition I product was applied liberally to the hair with a tint brush and processed for 35 minutes. The excess product was towel blotted and hair was blow dried straight at high heat setting using a brush. The hair was rinsed after 48 hrs. The performance % Curl Reduction, Shine and Smoothness was evaluated. PERFORMANCE pH Lo (cm) Ls (cm) Lt (cm) % Curl Reduction Shine Smoothness NORMAL CURLY HAIR 3.51 16.3 27.3 21.2 44.55% +++ +++ (H 2 PO 4 ) 3.99 16.3 26.1 18.3 20.41% +++ +++ 4.49 16.3 26.7 18.9 25.00% ++++ ++++ 5.02 16.3 23.6 17.5 16.44% ++ ++ 5.95 16.3 26.8 18.2 18.10% ++ ++ 6.93 16.3 27.1 19.2 26.85% ++ +++ 7.99 16.3 27.5 20.3 35.71% +++ ++++ NORMAL CURLY HAIR 3.82 13.8 26.8 17 24.62% +++ ++ (CITRIC ACID) 4.1 13.8 23.9 14.9 10.89% ++++ ++++ 4.51 13.8 23.7 15.4 16.16% ++++ ++++ 5.03 17.5 26.5 18.7 13.33% ++ ++ 6.02 13.8 22.6 15.8 22.73% ++ ++ 7.03 13.8 23.7 14.2 4.04% +++ +++ 8.06 13.8 24.2 17.4 34.62% +++ +++ 20 VOL COLOR 3.01 14.0 22.0 18.5 56.25% ++ ++ TREATED HAIR 3.99 17.5 24.0 20.5 46.15% ++ ++ (H2PO4) 4.49 18.5 24.0 20.0 27.27% ++++ ++++ 5.02 15.0 24.0 19.0 44.44% +++ +++ 6.93 13.0 23.0 18.5 55.00% ++ ++ 7.99 16.0 24.0 19.5 43.75% +++ + 2X 40 VOL BLEACHED 3.01 17.5 24.0 19.5 30.77% ++ + HAIR 3.99 18.0 25.0 19.5 21.43% ++ +++ (H2PO4) 4.49 16.0 24.5 20.0 47.06% +++ ++++ 5.02 16.0 24.0 19.0 37.50% ++ ++ 6.93 19.0 25.0 22.5 58.33% ++ +++ 7.99 17.0 25.0 20.0 37.50% +++ ++ Process C: The hair swatches are shampooed with Clarifying shampoo, towel blot and dried at medium heat with blow dryer. The composition I product was applied liberally to the hair with a brush and processed for 35 minutes. The excess product was towel blotted and air dried from the hair. The hair was rinsed after 48 hrs. The performance % Curl Reduction, Shine and Smoothness was evaluated. PERFORMANCE pH Lo (cm) Ls (cm) Lt (cm) % Curl Reduction Shine Smoothness NORMAL CURLY HAIR 3.51 17.5 26.2 20.5 34.48% + + (H 2 PO 4 ) 3.99 13.8 24.5 17.5 34.58% + + 4.49 17.5 24.3 18.4 13.24% + +++ 5.02 13.8 24 16.7 28.43% + ++ 5.95 17.5 24.5 19.2 24.29% ++ + 6.93 17.5 24.3 18.5 14.71% +++ ++ 7.99 17.5 24.3 18.4 13.24% ++ + NORMAL CURLY HAIR 3.82 17.5 25.8 19.4 22.89% + ++ (CITRIC ACID) 4.1 17.5 25.6 19 18.52% + + 4.51 17.5 26.2 17.9 4.60% +++ +++ 5.03 17.5 25.1 17.8 3.95% + + 6.02 14.8 25 17.8 29.41% + + 7.03 14.8 25.6 16.8 18.52% +++ +++ 8.06 14.8 26.8 18.6 31.67% ++ ++ 20 VOL COLOR 3.01 15.0 25.0 18.0 30.00% ++ ++ TREATED HAIR 3.99 14.0 23.0 16.0 22.22% +++ +++ (H2PO4) 4.49 18.5 25.0 19.0 7.69% +++ +++ 5.02 18.0 25.0 18.5 7.14% ++ ++ 6.93 18.0 25.0 18.0 0.00% +++ ++ 7.99 13.0 24.0 16.0 27.27% +++ +++ 2X 40 VOL BLEACHED 3.01 17.0 25.0 20.0 37.50% + + HAIR (H2PO4) 3.99 16.0 25.0 18.5 27.78% +++ +++ 4.49 16.0 24.0 18.0 25.00% +++ ++++ 5.02 18.0 26.0 19.0 12.50% +++ ++++ 6.93 16.0 24.0 18.5 31% ++ ++ 7.99 21.0 28.0 21.0 0.00% +++ +++ Process D: The hair swatches are shampooed with Clarifying shampoo, towel blot and dried at medium heat with blow dryer. The Composition I was applied liberally to the hair with a brush and processed for 35 minutes. The hair was rinsed with luke warm water. The hair is dried to about 95% with a blow dryer at low heat followed with flat ironing @ 430° F. using 7-8 passes. The hair was rinsed after 48 hours. The performance % Curl Reduction, Shine and Smoothness was evaluated. PERFORMANCE pH Lo (cm) Ls (cm) Lt (cm) % Curl Reduction Shine Smoothness NORMAL CURLY HAIR 3.51 15.3 23.2 16.5 15.19% +++ ++++ (H 2 PO 4 ) 3.99 15.3 25.4 17.7 23.76% +++ ++++ 4.49 15.3 26.1 19.7 40.74% ++++ ++++ 5.02 15.3 22.8 17.3 26.67% ++ +++ 5.95 15.3 23.8 17.5 25.88% +++ +++ 6.93 15.3 23.6 19.3 48.19% ++++ ++++ 7.99 15.3 22.7 16.8 20.27% +++ ++++ NORMAL CURLY HAIR 3.82 14.8 26.3 16.2 12.17% ++ ++ (CITRIC ACID) 4.1 14.8 24.2 18.7 41.49% +++ +++ 4.51 14.8 25 17.7 28.43% +++ +++ 5.03 14.8 24.8 17.2 24.00% ++ ++ 6.02 14.8 25.8 18.5 33.64% + + 7.03 14.8 26 18.2 30.36% ++ ++ 8.06 14.8 25.2 17.4 25.00% ++ ++ 20 VOL COLOR 3.01 16.0 27.0 20.0 36.36% ++ ++ TREATED HAIR 3.99 14.0 24.0 19.0 50.00% + ++ (H2PO4) 4.49 17.0 24.0 20.0 42.86% +++ ++++ 5.02 14.0 25.0 19.0 45.45% ++ ++ 6.93 15.0 24.0 20.0 55.56% ++ +++ 7.99 17.0 25.0 21.0 50.00% +++ ++ 2X 40 VOL BLEACHED 3.01 19.0 26.0 24.5 78.57% + + HAIR (H2PO4) 3.99 21.0 26.0 22.5 30.00% +++ ++++ 4.49 19.0 24.0 22.0 60.00% +++ ++++ 5.02 19.0 24.0 22.0 60.00% ++ ++ 6.93 21.0 27.0 24.0 50% ++ ++ 7.99 19.0 24.5 22.0 54.55% +++ +++ % Curl Reduction Evaluation: L0 = Initial Length of curly hair LS = Length of hair @ 100% Curl reduction LT = Length of treated Curly hair % Curl reduction = Lt − Lo × 100/Ls − L0 Shine and Smoothness Evaluation: Grading 0% ± 0-20% + 20-40% ++ 40-60% +++ 60-80% ++++ 80-100% +++++
The tabulated data of Table I above shows that the overall performance of curl reduction, shine and smoothness on hair depends on the pH of Composition I and method of application. The performance appears to be dependent on the pH and independent of the type of pH adjustor. The optimum performance of Composition I pH range on Normal, Color treated and Bleached hair, appears to be between 4-5. Also, the performance effects are dependent on the method of application of composition I. Application methods A and D are preferable over methods B and C. Both methods A and D have high heat flat ironing greater than 400° F. with Composition I or rinsed off the hair. Curl reduction, increase in Smoothness and Shine of 40-80% have been observed on Normal, Color treated and Bleached hair.
TABLE IA pH PERFORMANCE EFFECTS OF 1% NaF ON VERY CURLY/FRIZZY HAIR (NORMAL, COLOR TREATED AND BLEACHED HAIR TYPE) COMPOSITION I NaF 1.00% Amigel Thickener 0.60% Glycerol 0.50% Phenoxyethanol 0.20% 10% Phosphoric QS to pH Acid DI Water QS to 100% Process A: The hair swatches are shampooed with Clarifying shampoo, towel blot and dried at medium heat with blow dryer. The Composition I Product was applied liberally to the hair with a tint brush and processed for 35 minutes. The excess product was towel blotted and the hair is dried to about 95% with a blow dryer at low heat followed with flat ironing @ 430° F. using 7-8 passes. The hair was rinsed after 48 hours. The performance % Curl Reduction, Shine and Smoothness was evaluated. Hair Type pH Lo (cm) Ls (cm) Lt (cm) % Curl Reduction Shine Smoothness Normal 4.24 16.0 23.00 19.00 42.86% + + 4.53 15.5 23.00 18.00 33.33% + + 4.77 17.5 24.00 19.00 23.08% + + 20Vol Color Treated 4.24 21.0 26.50 22.50 27.27% +++ +++ 4.53 18.0 26.00 20.50 31.25% ++ ++ 4.77 19.0 25.00 19.50 8.33% ++ ++ 2X 40 VOL BLEACHED 4.24 17.5 24.00 19.50 30.77% +++ +++ HAIR 4.53 21.5 25.00 22.00 14.29% ++++ ++++ 4.77 18.5 23.50 20.00 30.00% ++++ ++++ Process B: The hair swatches are shampooed with Clarifying shampoo, towel blot and dried at medium heat with blow dryer. The composition I product was applied liberally to the hair with a tint brush and processed for 35 minutes. The excess product was towel blotted and hair was blow dried and straightened at high heat setting using a brush. The hair was rinsed after 48 hrs. The performance % Curl Reduction, Shine and Smoothness was evaluated. Hair Type pH Lo (cm) Ls (cm) Lt (cm) % Curl Reduction Shine Smoothness Normal 4.24 13.5 20.0 16.5 30.00% + + 4.53 14.5 22.0 17.0 33.33% + + 4.77 13.0 23.0 18.0 50.00% + + 20Vol Color Treated 4.24 18.0 25.0 20.0 28.57% +++ +++ 4.53 15.5 22.5 17.5 28.57% ++ ++ 4.77 14.5 22.5 16.0 18.75% ++ ++ 2X 40 VOL BLEACHED 4.24 20.5 26.0 21.5 18.18% +++ +++ HAIR 4.53 19.5 26.0 22.0 38.46% ++ ++ 4.77 20.0 25.5 21.0 18.18% ++ ++ Process C: The hair swatches are shampooed with Clarifying shampoo, towel blot and dried at medium heat with blow dryer. The Composition I product was applied liberally to the hair with a brush and processed for 35 minutes. The excess product was towel blotted and air dried from the hair. The hair was rinsed after 48 hrs.The performance % Curl Reduction, Shine and Smoothness was evaluated. Hair Type pH Lo (cm) Ls (cm) Lt (cm) % Curl Reduction Shine Smoothness Normal 4.24 17.0 27.0 20.0 30.00% ++ ++ 4.53 16.0 25.0 18.5 27.78% ++ ++ 4.77 16.0 25.0 18.0 22.22% ++ ++ 20Vol Color Treated 4.24 17.5 25.0 19.5 26.67% +++ +++ 4.53 16.0 24.0 18.0 25.00% +++ +++ 4.77 17.5 25.0 19.0 20.00% +++ +++ 2X 40 VOL BLEACHED 4.24 19.0 23.5 20.5 33.33% ++++ ++++ HAIR 4.53 19.5 22.5 20.0 16.67% +++ +++ 4.77 19.0 22.5 19.5 14.29% +++ +++ % Curl Reduction Evaluation: L0 = Initial Length of curly hair LS = Length of hair @ 100% Curl reduction LT = Length of treated Curly hair % Curl reduction = Lt − Lo × 100/Ls − L0 Shine and Smoothness: Grading 0% ± 0-20% + 20-40% ++ 40-60% +++ 60-80% ++++ 80-100% +++++
The tabulated data on Table IA shows that the optimum pH of Composition I for maximum performance is about 4.50. This is in agreement with the previous data of Table I. Exceptional curl reduction, smoothing and shine is observed on all hair types including Normal, Color treated and multi bleached hair.
TABLE II Multi Treatment Effects of NaF versus Performance. Performance Effects of 1 Treatment, 1 Wash, 5 Wash, 10 Wash and 2nd Treatment with 0.75% NaF Composition II-B on very curly/frizzy hair (Normal, Color treated and 2X Bleached Hair Type) COMPOSITION II-B NaF 0.75% Amigel Thickener 0.60% Glycerol 0.50% Phenoxyethanol 0.20% 50% Phosphoric Acid pH adjustment only QS DI Water QS. Process A: The hair swatches were shampooed with an alkaline shampoo (pH = 8.10), towel blot and dried at medium heat with blow dryer. The composition II-8 product was applied liberally to the hair with a tint brush and processed for 35 minutes. The excess product was towel blotted and the hair is dried to about 95% with a blow dryer at low heat followed with flat ironing @ 430° F. using 7-8 passes. The hair was rinsed after 48 hours. One of the swatch was rinsed and evaluated, the second swatch was washed 1 times and evaluated, the third swatch washed 5 times and evaluated, the fourth swatch was washed 10 times and evaluated and the fifth swatch was washed 10 times and 2nd treatment was repeated and after 48 Hours rinsed and evaluated for performance; % Curl Reduction; Shine and Smoothness. % Curl PERFORMANCE pH L o (cm) L s (cm) L t (cm) Reduction Shine Smoothness NORMAL CURLY HAIR 1 Treatment 4.53 13.5 17.5 14.0 12.50% +++ ++ 1 Wash 4.53 13.5 17.0 13.5 0.00% ++ ++ 5 wash 4.53 13.5 17.0 13.5 0.00% ++ ++ 10 Wash 4.53 13.0 17.5 13.0 0.00% ++ ++ 2nd 4.53 14.0 18.5 15.0 22.22% +++ +++ treatment 20 VOL /6R 1 Treatment 4.53 13.5 18.5 14.0 10.00% +++ +++ COLOR TREATED HAIR 1 Wash 4.53 13.5 18.5 14.0 10.00% ++ ++ 5 wash 4.53 13.5 19.0 14.0 9.09% ++ ++ 10 Wash 4.53 13.5 18.5 13.5 0.00% ++ ++ 2nd 4.53 13.5 18.0 14.5 22.22% +++ +++ treatment 2X BLEACHED HAIR 1 Treatment 4.53 15.0 20.5 16.0 18.18% ++++ ++++ 40 VOL 1 Wash 4.53 15.0 20.0 16.0 20.00% +++ +++ 5 wash 4.53 16.0 21.0 16.0 0.00% ++ ++ 10 Wash 4.53 15.0 20.5 15.0 0.00% ++ ++ 2nd 4.53 16.0 20.5 18.5 55.56% ++++ ++++ treatment % Curl Reduction Evaluation: L o = Initial Length of curly hair L s = Length of hair @ 100% Curl reduction L t = Length of treated Curly hair % Curl reduction = L t - L o L s - L o × 100 Shine and Smoothness Evaluation: Grading 0% ± 0-20% + 20-40% ++ 40-60% +++ 60-80% ++++ 80-100% +++++
The tabulated data on Table II shows that the performance longevity of a single treatment with Composition II-B can last multiple shampoos. In addition, the performance of repeat or double treatments increases significantly the performance in curl reduction, shine and smoothness.
TABLE III Phase II-B- Effects of NaF pH on performance Curl Reduction Study at Higher pH Range with 0.50% NaF Composition II-B on very curly/frizzy hair (Normal, Color treated and 2X Bleached Hair Type) COMPOSITION II-B NaF 0.50% Amigel Thickener 0.60% Glycerol 0.50% Phenoxyethanol 0.20% 50% Phosphoric Acid pH adjustment only QS DI Water QS. Process A: The measurement of the initial length (L 0 ) and (L 100 ) of each swatch was taken. The hair swatches were shampooed with Clarifying Shampoo, towel blot and dried at medium heat with blow dryer. The Composition 11 “B” with different pH range was applied liberally to the hair with a tint brush and processed for 35 minutes. The excess product was towel blotted and the hair is dried to about 95% with a blow dryer at high heat followed by flat ironing @ 430° F. using 7-8 passes. The hair was rinsed after 48 hours and air dried. % Curl Reduction was calculated with the final length (L t ) of each swatch after treatment. The results are as follows. % Curl pH Range pH L o (cm) L s (cm) L t (cm) Reduction 4.51 Normal hair 4.51 12.5 17.5 13.5 20.00% 20 Vol/CT 4.51 15.0 20.0 16.5 30.00% 2X Bleached 4.51 15.0 16.5 16.0 66.67% 8.67 Normal hair 8.67 13.0 20.0 14.0 14.29% 20 Vol/CT 8.67 14.0 19.5 16.0 36.36% 2X Bleached 8.67 15.5 16.5 16.0 50.00% 9.05 Normal hair 9.05 12.5 18.5 14.5 33.33% 20 Vol/CT 9.05 14.0 19.0 15.5 30.00% 2X Bleached 9.05 15.5 16.5 16.2 70.00% % Curl Reduction Evaluation: L o = Initial Length of curly hair L s = Length of hair @ 100% Curl reduction L t = Length of treated Curly hair % Curl reduction = L t - L o L s - L o × 100
The data of Table III shows the performance of Composition IIB, 0.50% NaF above pH 8.05 shows no advantages. This is probably due to unfavorable crosslinking between unprotonated amino R′—N—R″ (R′═H, C=0 or R″═H, C=0) peptide side terminals and the Fluoride ion that occurs at high pH. Whereas the pH decreases the protonation of the amino group and specifically the peptide side terminals of Lysine, Arginine R—NH3+ and will favor crosslinking with the Fluoride ion. These side terminal crosslinks R—NH 3 F, —N—H2F, —N—HF or possible amide crosslinks F—N—C═O are more favorable at low pH. Alternatively, favorable crosslinking may occur with the side OH side terminals of Threonine and Serine or indirect crosslinking followed by dehydration for Threonine side terminal.
TABLE IV Effects of NaF Concentration on Performance versus Formaldehyde @ 0.5% PERFORMANCE EFFECTS OF % MCLA ON VERY CURLY/FRIZZY HAIR (NORMAL CURLY, COLOR TREATED AND 2X BLEACHED HAIR TYPE) COMPOSITION II NaF 0.5-2.5% Amigel Thickener 0.60% Glycerol 0.50% Phenoxyethanol 0.20% 10% Phosphoric Acid pH adjustment only QS DI Water QS. Process A: The hair swatches are shampooed with Clarifying shampoo, towel blot and dried at medium heat with blow dryer. The Composition II product was applied liberally to the hair with a tint brush and processed for 35 minutes. The excess product was towel blotted and the hair is dried to about 95% with a blow dryer at low heat followed with flat ironing @ 430° F. using 7-8 passes. The hair was rinsed after 48 hours. The performance % Curl Reduction, Shine and Smoothness was evaluated. % Curl PERFORMANCE % NaF Swatch pH Lo (cm) Ls (cm) Lt (cm) Reduction Shine Smoothness NORMAL CURLY HAIR 0.50% A 4.49 14.0 25.0 17.0 27.27% xxx xxx 0.75% M 4.52 15.0 24.0 18.0 33.33% xx xx 1.00% B 4.51 14.5 23.0 17.0 29.41% xxx xxx 1.50% C 4.49 14.0 23.0 16.5 27.78% xx xx 2.00% D 4.51 14.0 25.0 16.5 22.73% xx xx 2.50% E 4.48 14.0 25.0 16.5 22.73% xx xx 0.5% Formaldehyde 0.00% FORM 4.5 15.0 24.0 18.5 38.89% xx xx 20 VOL COLOR 0.50% A 4.49 16.0 24.0 18.5 31.25% xxx xxx TREATED HAIR 0.75% M 4.52 13.0 20.5 15.0 26.67% xx xx 1.00% B 4.51 16.0 23.0 18.0 28.57% xx xx 1.50% C 4.49 16.0 24.0 18.0 25.00% xx xx 2.00% D 4.51 16.0 22.0 18.0 33.33% xx xx 2.50% E 4.48 16.0 23.5 18.5 33.33% xxx xxx 0.5% Formaldehyde 0.00% FORM 4.5 13.0 21.0 15.5 31.25% xx xx 2X 40 VOL BLEACHED 0.50% A 4.49 19.0 23.0 20.5 37.50% xxx xx HAIR 0.75% M 4.52 18.0 23.0 20.0 40.00% xxx xxx 1.00% B 4.51 20.5 25.0 22.0 33.33% xxx xxx 1.50% C 4.49 21.0 25.0 22.5 37.50% xxx xxx 2.00% D 4.51 20.0 23.0 21.0 33.33% xx xx 2.50% E 4.48 18.0 23.0 20.0 40.00% xx xx 0.5% Formaldehyde 0.00% FORM 4.5 18.0 23.0 20.5 50.00% xxx xxx Process D: The hair swatches are shampooed with shampoo, towel blot and dried at medium heat with blow dryer. The composition II product was applied liberally to the hair with a brush and processed for 35 minutes. The hair was rinsed with luke warm water. The hair is dried to about 95% with a blow dryer at low heat followed with flat ironing at 430° F. using 7-8 passes. The hair was rinsed after 48 hours. The performance % Curl Reduction, Shine and Smoothness was evaluated. % % Curl PERFORMANCE MCLA pH Lo (cm) Ls (cm) Lt (cm) Reduction Shine Smoothness NORMAL CURLY HAIR 0.50% A 4.49 13.50 20.00 14.50 15.38% xxx xxx (H 2 PO 4 ) 0.75% M 4.52 15.00 25.00 18.00 30.00% xx xx 1.00% B 4.51 13.50 20.50 15.00 21.43% xx xx 1.50% C 4.49 12.00 20.00 14.00 25.00% xx xx 2.00% D 4.51 13.00 21.00 15.00 25.00% xx xx 2.50% E 4.48 12.00 21.50 14.50 26.32% xxx xxx 0.5% Formaldehyde 0.00% FORM 4.5 12.00 19.00 14.50 35.71% xx xx 20 VOL COLOR TREATED 0.50% A 4.49 17.00 24.50 18.00 13.33% xxx xxx HAIR 0.75% M 4.52 14.00 22.00 16.00 25.00% xx xx 1.00% B 4.51 15.00 23.00 17.00 25.00% xxx xxx 1.50% C 4.49 16.00 23.00 17.00 14.29% xx xxx 2.00% D 4.51 16.00 23.00 17.00 14.29% xx xxx 2.50% E 4.48 15.50 23.00 17.00 20.00% xx xxx 0.5% Formaldehyde 0.00% FORM 4.5 14.00 22.00 17.00 37.50% xx xx 2X 40 VOL BLEACHED 0.50% A 4.49 15.00 19.00 16.50 37.50% xx xxx HAIR 0.75% M 4.52 20.00 23.50 21.00 28.57% xx xxx 1.00% B 4.51 16.00 20.00 17.00 25.00% xx xxx 1.50% C 4.49 16.00 20.00 17.00 25.00% xx xxx 2.00% D 4.51 15.00 19.00 16.00 25% xx xxx 2.50% E 4.48 15.00 20.00 16.50 30.00% xx xxx 0.5% Formaldehyde 0.00% FORM 4.5 20.00 24.00 21.50 37.50% xx xxx % Curl Reduction Evaluation: L0 = Initial Length of curly hair LS = Length of hair @ 100% Curl reduction LT = Length of treated Curly hair % Curl reduction = Lt − Lo × 100/Ls − L0 Shine and Smoothness Evaluation: Grading 0% ± 0-20% + 20-40% ++ 40-60% +++ 60-80% ++++ 80-100% +++++
The tabulate data of Table IV shows that the performance on normal hair is not affected greatly with the concentration increase of NaF from 0.5-2.50%. However, on porous hair 20 volume and twice 40 volume bleached hair, NaF concentration effects are observed. The data shows equivalent performance to 0.5% Formaldehyde is obtained with 0.23% F (0.50% NaF). This observation can be explained due to the presence of larger number of Ionic sites in hair which result in greater crosslinking and overall performance of curl reduction and smoothing effects. It also suggests that the crosslinking reactions of the fluoride and formaldehyde with hair may not entirely be the same. The specificity of crosslinking with the fluoride is greater than formaldehyde, thus more predictable results can be obtained.
TABLE V Performance Evaluation using Treatment Processes E, F and G (Normal, Color treated and 2X Bleached Hair Type) COMPOSITION II-B NaF 0.75% Amigel Thickener 0.60% Glycerol 0.50% Phenoxyethanol 0.20% 50% Phosphoric Acid pH adjustment only QS DI Water QS. PERFORMANCE pH L o (cm) L s (cm) L t (cm) % Curl Reduction Shine Smoothness NORMAL CURLY HAIR Process E 4.49 13.0 20.0 14.5 21.43% ++ ++ Process F 4.49 13.0 20.0 15.0 28.57% +++ +++ Process G 4.49 13.0 20.0 15.0 28.57% +++ +++ 20 VOL /6R Process E 4.49 10.0 13.5 11.0 28.57% ++ ++ COLOR TREATED HAIR Process F 4.49 10.0 13.5 11.0 28.57% ++++ ++++ Process G 4.49 13.0 20.0 15.0 28.57% ++++ ++++ 2X BLEACHED HAIR Process E 4.49 14.0 18.0 16.0 50.00% ++ ++ Process F 4.49 14.0 18.0 16.0 50.00% ++++ ++++ 40 VOL Process G 4.49 14.0 18.0 16.0 50.00% ++++ ++++ DIFFERENT PROCESSES TESTED Process E: Wash hair with clarifying shampoo. Towel blot excess water and blow dry in medium heat up to 95% dry. Apply the Fluoride product thoroughly and comb hair through to ensure that all hair fibers are saturated with the product. Process for 35 min. Keep the hair straight during process time. Rinse with luke warm water and towel blot excess water. Apply a Moisturizing Leave-on Conditioner and detangle the hair with the comb. Blow dry hair in high heat. Take thin sections and flat iron at approximately 430° F. with 7-8 passes, make sure that all the fibers are passed through the heat evenly. After 48 hours wash hair with Sulfate Free Shampoo and Conditioner. Process F Wash hair with clarifying shampoo. Towel blot excess and blow dry in medium heat up to 95% dry. Apply the Fluoride product thoroughly and comb hair through to ensure that all hair fibers are saturated with the product. Process for 35 min. Keep the hair straight during process time. Towel blot excess product and apply a deep conditioning masque. Comb through so that all the fibers are covered with masque. Process for 10 min and rinse with Luke warm water. Towel blot excess water and Blow dry in high heat. Take thin sections and flat iron at approximately 430° F. with 7-8 passes, make sure that all the fibers are passed through the heat evenly. After 48 hours wash hair with Sulfate Free Shampoo and Conditioner. Process G Wash hair with Clarifying shampoo. Towel blot excess and blow dry in medium heat up to 95% dry. Apply the Fluoride product thoroughly with a tint brush. Comb hair through to ensure that all hair fibers are saturated with the product. Process for 35 min. Keep the hair straight during process time. Towel blot excess product and apply a Leave-On Conditioner. Comb through so that all the fibers are saturated. Towel blot excess and blow dry up to 95% dry. Take very thin sections and flat iron at approximately 430° F. with 7-8 passes, make sure that all the fibers are passed through the heat evenly. Section Hair and apply the deep conditioning masque and process for 10 minutes. Rinse with Luke warm water and style as desired. % Curl Reduction Evaluation: L o = Initial Length of curly hair L s = Length of hair @ 100% Curl reduction L t = Length of treated Curly hair % Curl reduction = L t - L o L s - L o × 100 Shine and Smoothness Evaluation: Grading 0% ± 0-20% + 20-40% ++ 40-60% +++ 60-80% ++++ 80-100% +++++
The data in Table V shows the different methods of treatment application to enhance the conditioning effects with the fluoride treatment. All treatment methods E, F and G increase the conditioning and smoothing effects of hair. Based on the results it appears that method G is the best where the fluoride is crosslinked first to the hair and the conditioning agents are further crosslinked by the fluoride. This multi-crosslinking effect of fluoride between the hair and the conditioning agent creates longer lasting effects between washes. Comparative results with just hair conditioning treatments of masking or rinse off conditioners shows a temporary effect that does not last more than one or two shampoos. The fluoride crosslinked hair will have a strong affinity to bind different molecules, such as conditioning, antistatic, volumizing ingredients, keratin proteins and non-keratinous proteins. The crosslinking of fluoridated keratin reacts with functional groups of strong cationic character, such amino, mono or divalent cations forming strong ligand structures within the hair. The formation of these additional structures will restructure hair and produce effects of increased softness, manageability and tensile strength.
Methods of Sodium Fluoride Application on Hair for Maximum Conditioning/Smoothing Effects
Process E:
Wash the hair with Clarifying shampoo. Towel blot excess and blow dry in medium heat up to 95% dry. Apply the Fluoride composition product on hair thoroughly. and comb through to ensure that all the fibers are saturated with the product. Process for 35 min. Keep the hair straight during process time. Rinse with luke warm water and towel blot excess water. Apply a Leave-on Conditioner and detangle the hair with the comb. Blow dry with medium heat. Take thin sections and iron hair with a preheated flat iron with a minimum of 7-8 passes, making sure that all the fibers are passed through evenly. After 48 hours wash hair with Sulfate Free Shampoo and Conditioner.
Process F:
Wash the hair with Clarifying shampoo. Towel blot excess and blow dry in medium heat up to 95% dry. Apply the Fluoride composition product on hair thoroughly and comb through to ensure that all the fibers are saturated with the product. Process for 35 min. Keep the hair straight during process time. Towel blot excess product and apply a deep conditioner, reconstructor or conditioning masque with a tint brush. Comb through so that all the fibers are covered with deep conditioner, reconstructor or conditioning masque. Process for 10 min and rinse with luke warm water. Towel blot excess water and blow dry with high heat. Take thin sections and iron hair with a pre-heated flat iron with a minimum of 7-8 passes, making sure that all the fibers are passed through evenly. After 48 hours wash hair with Sulfate Free Shampoo and Conditioner.
Process G:
Wash hair with Clarifying shampoo. Towel blot excess and blow dry hair in medium heat up to 95% dry. Apply the fluoride composition product on hair thoroughly and comb through to ensure that all the fibers are saturated with the product. Process for 35 min. Keep the hair straight during process time. Towel blot excess product and apply a Leave-On Conditioner. Comb through so that all the fibers are saturated. Towel blot excess and blow dry up to 95% dry. Take very thin sections and iron hair with a pre heated flat iron with a minimum of 7-8 passes, making sure that all the fibers are passed through evenly. Section Hair and apply a deep conditioner, reconstructor or conditioning masque and process for 10 minutes. Rinse with luke warm water and style as desired.
Moisturizing Leave on Conditioner Formula
Water
Amodimethicone
Glycine
Hydrolyzed Keratin
Hydrolyzed Silk
Hydrolyzed Vegetable Protein
Retinyl Palmitate
Ascorbic Acid
Benzophenone-4
Butylene Glycol
Ceteareth 25
Cetrimonium Chloride
Lecithin
Polyquaternium-11
Propylene Glycol
Steartrimonium Chloride
Sucrose
Tetrasodium EDTA
VP/VA Copolymer
Isopropyl alcohol
Fragrance
Deep Conditioning Masque Formula
Water
PPG-3 Benzyl Ether Myristate
Cyclopentasiloxane
Dimethicone
Cetearyl Alcohol
Behentrimonium Chloride
Panthenol
Hydrolyzed Keratin
Sodium PCA
Sodium Lactate
VP/DMAPA/Acrylates Copolymer
Cetrimonium Chloride
Phenoxyethanol
Caprylyl Glycol
Ethylhexyl glycerine
Hexylene Glycol
Fragrance
During our testing it was discovered that the cross linker composition containing sodium fluoride had insufficient conditioning for combing and flat ironing of hair during the treatment. The conditioning was improved by applying conditioning compositions on the hair after the application of the crosslinker composition but suffered from inconsistent results due to the heterogeneous product on the hair. It was found for optimum consistent performance a homogeneous cross linker composition with conditioning agents was necessary. The key conditioning agents, such as phenyl trimethicone, amodimethicone, polyquaternium-67 and cetrimonium chloride, were required but not limited. However, the ready to use crosslinker/conditioning composition presented stability/performance issues. We currently believe that this was due to a change of the crosslinking affinity of the fluoride to the hair by the conditioning agents. In order to alleviate this premixing of the crosslinking composition with a conditioning composition was developed where the cross linker composition part 1 is mixed with the conditioning composition part 2 at ratios by weight of 10:90, 40:60, 55:45, 75:25 and 95:5. Where the preferable composition would be 75:25. Two treatment processes H and I resulted in excellent smoothing results in our studies for up to three months. Both processes include the rinse off and a leave on conditioner for final sealing and smoothing of hair. For extended smoothing results the leave-on conditioner is used once or twice a week after shampooing and conditioning the hair.
Process H:
Wash hair with clarifying shampoo. Towel blot and blow dry hair to about 90%. Premix Composition Part 1 and Part 2 at ratio of about 75:25 by weight.
Apply the premixed product on the hair. Comb through to ensure that all the fibers are saturated with the product. Process for 35 min. Keep the hair straight during the processing time. Towel blot excess product and blow dry hair to about 90%. Take thin sections and flat iron at approximately 430° F. with about 7-8 passes, make sure that all the fibers are passed through the heat evenly. Apply a deep conditioning masque through the hair and wait for approximately 7-10 minutes.
Comb through so that all the fibers are covered with the deep conditioner. Process for 10 min and rinse with luke-warm water and style as desired. After 48 hours wash hair with sulfate free shampoo and conditioner and style as desired.
Process G:
Wash the hair with clarifying shampoo. Towel blot and blow dry hair to about 90%. Premix Composition Part 1 and Part 2 at ratio of about 75:25 by weight.
Apply the premixed product on the hair. Comb through to ensure that all the fibers are saturated with the product. Process for 35 min. Keep the hair straight during the processing time. Towel blot excess product and blow dry hair to about 90%. Take thin sections and flat iron approximately 430° F. with about 7-8 passes, make sure that all the fibers are passed through the heat evenly. Apply a leave-on conditioner through the hair and wait for approximately 7-10 minutes. Comb hair through so that all the fibers are covered with the conditioner. Process for about 10 minutes, remove excess and style as desired. After about 48 hours wash hair with sulfate free shampoo and conditioner and style as desired.
Composition Part 1
(w/w) %
Water
95.17
Phosphoric Acid
1.70
NaF
1.33
Phenoxyethanol
0.80
Glycerine
0.50
Hydroxypropyl Guar
0.50
pH = 4.50
Composition Part 2
(w/w) %
Water
85.22
Alcohol Denatured
4.62
Cetrimonium Chloride
1.24
Phenyltrimethicone
1.00
Phenoxyethanol
0.80
Amodimethicone
0.63
Trideceth-12
0.27
Polyquaternium-67
0.55
VP/VA Copolymer
0.30
Polyquaternium-11
0.30
Fragrance
0.10
Steartrimonium Chloride
0.023
Isopropyl Alcohol
0.012
pH = 5.65
Leave-On Conditioner
(w/w) %
Water
93.69
Hydrolyzed Quinoa Protein
1.00
Phenoxyethanol
0.50
Glycerin
0.50
Hydroxyethyl Cetyldimonium phosphate
1.00
Cetrimonium Chloride
0.75
Polyquaternium-28
1.00
Amodimethicone Trideceth-12
1.00
Stearyldimonium hydroxyl propyl Lauryl
0.50
Panthely Hydroxypropyl Sreardimonium Chloride
0.20
Polyquaternium-22
0.20
Fragrance
0.05
VP/DMAPA Acrylates Copolymer
0.10
Dimethicone/Silica
0.02
Phosphoric acid
QS to pH
pH = 5.73
TABLE VI Detection of Fluoride Ion in Normal, Colored and Bleached Single Treated Hair Fibers with Composition II, 0.75% Na F @ pH 4.51 Analysis of fluoride ion in single treated hair initially and after multiple washes with smoothing shampoo and conditioner. μg Fluoride/g Hair 1 10 15 0.75% NaF Treatment 3 Wash 5 Washes Washes Washes Normal Control 0 0 0 0 0 Normal Treated 3529 2875 2662 2564 2046 Color Treated 0 0 0 0 0 Control Color Treated 3380 3673 3892 3393 2796 Treated 2x Bleached Control 0 0 0 0 0 2x Bleached Treated 1876 1374 802 845 1007 Hair type: Normal, 20vol/6R Color Treated and 2X Bleached hair. Variations: 1 treatment; 3 wash; 5 wash; 10 wash and 15 washes Buffer Solution: 25 ml. TISAB II + 25 ml. DI H 2 O for immersing the hair sample for 48 hours. Standards for Calibration: 2, 4, 6, 10, 20 (μg/ml) Fluoride Ion Detection Limit = <0.1 (μg/ml) Fluoride Ion Procedure: All the hair swatches were washed with an Alkaline Shampoo at pH 8.09. The controls and the samples to be treated were dried to 95% with blow dryer, at medium heat setting. The hair swatches (approximately 5 inch in width) were treated with composition II (0.75% NaF) pH = 4.51. Processed for 35 min. Towel blot excess. Dried up to 95% dry with blow dryer at medium heat followed with flat ironing small sections of hair at approximately 430° F. with 7-8 passes. After 48 hours the hair was rinsed with copious amounts of water and hair was dried at ambient conditions and cut into small 1/16″ sections. The hair was further equilibrated under ambient conditions for 8 hours and hair samples weighed about 0.5 grams and were immersed into 50 ml of buffer solutions 1:1 Total Ionic Strength Adjustment Buffer (TISAB II): Deionized Water for 48 hours. Direct analysis of the Fluoride Ion was carried out in the leached solutions using the Fluoride Ion Selective Electrode potentiometric method (ASTM D 1179-72) approved by the American Society of Testing and Materials. The hair swatches were washed 3x, 5x, 10x and 15 x, and the hair was dried with blow dryer between the washes. The multi washed hair samples were analyzed as above.
The data in Table VI shows that fluoride is detected in normal, colored and bleached hair treated hair. Based on the assay results about 3,400 μmoles F/g hair is detected in water/buffer leaches of normal and color treated hair. This is compared to 1,800 μmoles F/g hair for bleached hair. This detection of fluoride in treated hair even after fifteen washes suggest that stable crosslinking has occurred and it is resistant to conventional shampooing and conditioning. The detection of fluoride in the buffer/water leaches is about 42-46% after fifteen shampoos showing slow rate of depletion or leaching of fluoride from hair. Based on these observations long lasting results of up to fifteen or more shampoos should be expected from a single treatment.
TABLE VII
pH EFFECTS OF 1% NaF ON THE TENSILE STRENGTH OF
NORMAL, COLOR TREATED AND 2X BLEACHED HAIR
20% INDEX
2x
pH
Normal Hair
20 Volume Hair
Bleached Hair
3.51
0.977
0.932
0.788
T-Test @pH 3.51
P = 0.0028*
P = 0.041*
P = 0.00024*
4.49
0.982
0.936
0.759
T-Test @pH 4.51
P = 0.00005*
P = 0.036*
P = 0.00413*
6.01
0.980
0.925
0.756
T-Test @pH 6.20
P = 0.0040*
P = 0.069
P = 0.0058*
7.62
0.966
0.910
0.744
T-Test @pH 7.62
P = 0.132
P = 0.0082*
P = 0.0118*
Brazilian Blowout
0.820
Solution; @pH 3.77
8% Formaldehyde
T-Test
P = 0.0143*
Untreated Hair
0.959
0.834
0.707
*statistically significant difference from untreated hair
Procedure:
Hair for tensile testing was prepared with five bundles of twelve hair fibers (total of 60 fibers) of similar texture with Normal, 20 Volume, 2x Bleached hair. The bundles were immersed in water for 1-2 hours and the initial wet tensile strength of all the bundles was evaluated at 20% extension using an Instron Model 1122C5054 at 0.5 inch/minute. The bundles after 24 hours were washed, blow dried with a paddle brush to about 95% and the NaF Composition I at pH 4.50 was applied with the tint brush and processed for 35 minutes. After the excess product was towel blotted and blow dried to about 95% with medium heat using a paddle brush, each bundle were flat ironed at approximately 430° C. with 7-8 passes. After 24 hours, the fibers were soaked in DI water and after 45 minutes the tensile strength of bundles was determined under the identical conditions. The tensile strength of bundles was determined versus untreated fibers with composition I. The wet tensile strength of each bundle was calculated as 20% index given below:
20% Index = Force of hair fibers after treatment/Force of hair fibers after treatment
The tensile strength studies showed that statistically a single treatment of normal, colored and bleached hair with the fluoride composition I statistically and significantly improved the tensile strength. The wet strength is attributed by adding support to the alpha helical crosslinks of cystine. This is not an expected effect for wet strength since all secondary bonds should be minimized in water. It is interesting that formaldehyde has significantly decreased the tensile strength of hair which suggests the weakening of these crosslinks. This supports our understanding that the crosslinking reactions and mechanism between the fluoride and formaldehyde is different.
Differential Scanning Calorimetry (DSC) of Hair
Differential scanning calorimetry (DSC) techniques published earlier by Cao (J. Cao, Melting study of the a crystallites in human hair by DSC, Thermody. Acta, 335 (1999) and F. J. Wortmann, (F. J Wortmann, C. Springob, and G. Sendlebach, Investigations of cosmetically treated human hair by DSC in water, IFFCC.Ref 12 (2000) are used to study the structural changes of hair by measuring the thermal decomposition pattern or behavior. The thermal stability of hair is evaluated by measuring the amount of thermal energy required for denaturation or phase transition. The technique measures the amount of heat transferred into and out of a sample in a comparison to a reference. The heat transfer in (endothermic) and out (exothermic) is detected and recorded as a thermogram of heat flow versus temperature.
The technique gives valuable information on the morphological components of hair of Feughelman's accepted two phase filament matrix model for hair (M Feugelman, A two phase structure for keratin fibers, Text. Res. 1, 29, 223-228, 1959). This two phase model includes the crystalline filaments (alpha helical proteins) or traditionally referred to as microfibrils which are embedded in an amorphous matrix.
The DSC data technique yields thermogram data on the denaturation temperature T m and the denaturation enthalpy (delta H) of hair. It is concluded that the thermogram data of the denaturation temperature T m of hair is dependent on the crosslink density of the matrix in which surrounds the microfibrils or crystalline filaments. Also, the denaturation enthalpy (delta H) depends on the strength of the crystalline filaments or microfibrils. It has been shown that cosmetic treatments, such as bleaching or perming, effect these morphological components selectively and differently at different rates causing changes in denaturation temperatures and in heat flow.
DSC was use to analyze the effects of NaF treatment on Normal, 20 volume color treated and four times bleached hair. The treatment included Process A using Composition I at 1% NaF at pH 4.50. The hair after 48 hours was rinsed and dried at ambient temperature conditions and relative humidity (20° C., 65% RH). The hair samples were cut into small pieces of about 2 mm in length and about 4-7 mg weighed into aluminum pans followed with capping. The hair samples were analyzed using Perkin Elmer Diamond DSC instrument and a method of 50° C. to 280° C. at 20° C./minute using an empty capped aluminum pan as reference.
The obtained DSC thermograms for treated and untreated hair samples showed single endothermic (absorbed thermal energy) denaturation temperatures T m ranging from 178 to 189° C. and delta H from 154 to 340 (J/g). The comparative tabulated data below for normal untreated and treated hair shows differences in the denaturation temperatures of 178.88 and 184.33° C., respectively, with no differences in the delta H. This is due to changes in the crosslink density of the matrix attributed by an increase in the crosslink density of the matrix proteins with NaF. Based on the delta H it is assumed that the intermediate filaments or alpha helical protein regions or microfilaments are not affected. The results for 20 volume color treated and untreated hair show significant statistically changes in the delta H (p=0.00019) of 226.53 and 270.01 (J/g) and no changes in the denaturation temperature. This observation suggests that the effects of NaF on 20 volume color treated hair are primarily on the alpha helical protein regions with no effect on the matrix proteins. The multi bleached hair fibers show statistically differences in the denaturation temperatures 187.76 and 181.49° C. and delta H 260.28 and 318.16 (J/g) between untreated and treated samples. This observation suggests that both the matrix proteins and the alpha-helical proteins are affected by the NaF treatment. This data is in good agreement with previously reported data by Humphries et al. JSCC, 1972 on oxidized and colored dried hair showing higher denaturation temperatures and delta H. The explanation may be explained by an increase in crosslinked bridges between the polypeptide chains giving more structural support. This appears to be the same observation with the NaF increasing the overall support for hair through crosslinking on the matrix proteins and alpha helical regions of the hair.
Endotherm
HAIR
Peak Temperature (C°)
Delta H (J/g)
Normal
178.88 ± 1.80
154.98 ± 6.23
Normal (Treated)
184.33 ± 1.88
159.06 ± 3.65
T-Test Normal Hair
P = 0.06892
P = 0.315
20 Volume
181.84 ± 2.63
226.53 ± 1.14
20 Volume (Treated)
182.94 ± 3.07
270.01 ± 2.53
T-Test 20 Volume Hair
P = 0.588
P = 0.00019
4x Bleached Hair
187.76 ± 1.51
260.28 ± 10.19
4X Bleached Hair (Treated)
181.49 ± 0.93
318.16 ± 22.07
T-Test Bleached Hair
P = 0.00033
P = 0.015
It should be understood that the foregoing description is only illustrative of the present disclosure. Various alternatives and modifications can be devised by those skilled in the art without departing from the disclosure. Accordingly, the present disclosure is intended to embrace all such alternatives, modifications, and variances that fall within the scope of the disclosure.
|
A hair care composition comprising: a crosslinking component comprising an inorganic fluoride; and a conditioning component, wherein the composition has a ratio of crosslinking component to conditioning component in the range of about 10:90 to about 95:5.
| 0 |
FIELD OF THE INVENTION
[0001] The present invention relates to chemical mechanical polishers used for polishing semiconductor wafers in the semiconductor fabrication industry. More particularly, the present invention relates to a new and improved slurry delivery system for delivering slurry to a chemical mechanical polisher for the polishing of semiconductor wafers.
BACKGROUND OF THE INVENTION
[0002] Apparatus for polishing thin, flat semiconductor wafers are well-known in the art. Such apparatus normally includes a polishing head which carries a membrane for engaging and forcing a semiconductor wafer against a wetted polishing surface, such as a polishing pad. Either the pad or the polishing head is rotated and oscillates the wafer over the polishing surface. The polishing head is forced downwardly onto the polishing surface by a pressurized air system or similar arrangement. The downward force pressing the polishing head against the polishing surface can be adjusted as desired. The polishing head is typically mounted on an elongated pivoting carrier arm, which can move the pressure head between several operative positions. In one operative position, the carrier arm positions a wafer mounted on the pressure head in contact with the polishing pad. In order to remove the wafer from contact with the polishing surface, the carrier arm is first pivoted upwardly to lift the pressure head and wafer from the polishing surface. The carrier arm is then pivoted laterally to move the pressure head and wafer carried by the pressure head to an auxiliary wafer processing station. The auxiliary processing station may include, for example, a station for cleaning the wafer and/or polishing head, a wafer unload station, or a wafer load station.
[0003] More recently, chemical-mechanical polishing (CMP) apparatus has been employed in combination with a pneumatically-actuated polishing head. CMP apparatus is used primarily for polishing the front face or device side of a semiconductor wafer during the fabrication of semiconductor devices on the wafer. A wafer is “planarized” or smoothed one or more times during a fabrication process in order for the top surface of the wafer to be as flat as possible. A wafer is polished by being placed on a carrier and pressed face down onto a polishing pad covered with a slurry of colloidal silica or alumina in deionized water.
[0004] CMP polishing results from a combination of chemical and mechanical effects. A possible mechanism for the CMP process involves the formation of a chemically altered layer at the surface of the material being polished. The layer is mechanically removed from the underlying bulk material. An altered layer is then regrown on the surface while the process is repeated again. For instance, in metal polishing, a metal oxide may be formed and removed separately. The chemical mechanical polishing method can be used to provide a planar surface on dielectric layers, on deep and shallow trenches that are filled with polysilicon or oxide, and on various metal films.
[0005] Referring next to FIG. 1, a conventional CMP apparatus 50 includes a conditioning head 52 , a polishing pad 56 , and a slurry delivery arm 54 positioned over the polishing pad. The conditioning head 52 is mounted on a conditioning arm 58 which is extended over the top of the polishing pad 56 for making a sweeping motion across the entire surface of the polishing pad 56 . The slurry delivery arm 54 is equipped with slurry dispensing nozzles 62 which are used for dispensing a slurry solution on the top surface 60 of the polishing pad 56 . Surface grooves 64 are further provided in the top surface 60 to facilitate even distribution of the slurry solution and to help entrapping undesirable particles that are generated by coagulated slurry solution or any other foreign particles which have fallen on top of the polishing pad 56 during a polishing process. The surface grooves 64 , while serving an important function of distributing the slurry, also presents a processing problem when the pad surface 60 gradually wears out after prolonged use.
[0006] The slurry solution is typically distributed to the slurry dispensing nozzles 62 through tubing (not illustrated), by operation of a pump (not illustrated). The force generated by the pump forcing the slurry through the tubing tends to crack the tubing, and this causes premature drying of some of the slurry in the tubing and formation of particles in the tubing before the slurry is dispensed onto the wafer. These slurry particles tend to scratch the wafer during the CMP process. Additionally, air enters the slurry through the cracked tubing, forming air bubbles which tend to adversely affect the CMP operation.
[0007] Accordingly, a slurry delivery system is needed for removing particles and air bubbles from a CMP slurry as the slurry is transported from a slurry source to a CMP dispensing nozzle or nozzles.
[0008] An object of the present invention is to provide a slurry delivery system for delivering a polishing slurry to a slurry dispensing nozzle of a chemical mechanical polisher, wherein the slurry is devoid of air bubbles when dispensed onto a wafer for polishing.
[0009] Another object of the present invention is to provide a slurry delivery system for delivering a polishing slurry to a slurry dispensing nozzle of a chemical mechanical polisher, wherein the slurry is devoid of particles when dispensed onto a wafer for polishing.
[0010] Still another object of the present invention is to provide a slurry delivery system which is capable of removing air bubbles and particles from a polishing slurry before the slurry is deposited onto a semiconductor wafer for chemical mechanical polishing of the wafer.
[0011] Yet another object of the present invention is to provide a slurry delivery system which facilitates a substantial reduction in wafer scratching during chemical mechanical polishing of the wafer.
[0012] A still further object of the present invention is to provide a slurry delivery system which optimizes the performance of a chemical mechanical polisher in the polishing of semiconductor wafers.
[0013] Another object of the present invention is to provide a slurry delivery system which may be programmed to deliver selected quantities of slurry to a chemical mechanical polisher.
[0014] Yet another object of the present invention is to provide a slurry delivery system which may be operably connected to a chemical mechanical polisher in pairs in order to provide a continuous supply of slurry to the chemical mechanical polisher.
SUMMARY OF THE INVENTION
[0015] In accordance with these and other objects and advantages, the present invention comprises a slurry delivery system which removes air bubbles and particles from a polishing slurry and delivers the slurry to a CMP apparatus for the chemical mechanical polishing of semiconductor wafers. The slurry delivery system of the present invention comprises a bag housing fitted with a slurry intake conduit and a slurry outlet conduit. An expandible and collapsible pump bag is provided in fluid communication with the conduits inside the bag housing, and the interior of the pump bag is sealed from the bag housing. As an air/vacuum controller withdraws air from the housing, the pump bag enlarges due to the negative pressure in the housing, and slurry is drawn into the pump bag through the slurry intake conduit. As the air/vacuum controller subsequently introduces air into the housing, the pump bag collapses and the slurry is expelled from the pump bag through the slurry outlet conduit. A purge valve is provided upstream of the pump bag to remove air bubbles from the slurry and vent the air to the atmosphere. A filter is provided typically in the slurry intake conduit to filter particles from the slurry before entry into the pump bag.
[0016] A pair of the slurry delivery systems of the present invention may be connected to the chemical mechanical polisher in parallel with each other, in order to provide a continuous supply of the polishing slurry to the CMP apparatus. Accordingly, as the first system undergoes the suction phase to draw slurry from the intake conduit into the pump bag, the second system undergoes the output phase to expel the slurry from the pump bag and outlet conduit to the CMP apparatus, and vice-versa. The systems may be programmed to deliver selected quantities of the slurry to the CMP apparatus.
[0017] The purge valve is located at a higher level than and upstream of the bag housing, typically at the junction between the slurry intake conduit and the bag housing, to facilitate the destruction of air bubbles in the slurry as the air bubbles rise in the slurry from the intake conduit into the purge valve. In a preferred embodiment of the invention, the purge valve includes a rotation floater which is rotatably mounted in a purge valve housing. A spring-loaded valve ball is slidably disposed in the purge valve housing above the rotation floater. During the suction phase of the pump bag, the rotation floater engages a floater support and the valve ball engages a ball stop shoulder in the purge valve housing to prevent flow of slurry out of the slurry intake conduit and into the purge valve. During the output phase of the pump bag, the rotation floater disengages the floater support and the valve ball disengages the ball stop shoulder. Accordingly, as slurry flows into the purge valve housing and past the rotation floater, the rotation floater rotates and destroys air bubbles in the slurry. The air from the broken air bubbles rises beyond the valve stop shoulder and valve ball and is vented from the system through the vent port.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The invention will now be described, by way of example, with reference to the accompanying drawings, in which:
[0019] [0019]FIG. 1 illustrates a typical conventional chemical mechanical polishing (CMP) apparatus;
[0020] [0020]FIG. 2 is a schematic view of a slurry delivery system of the present invention, with the pump bag of the system shown in the suction phase of operation;
[0021] [0021]FIG. 3 is a schematic view of the slurry delivery system of the present invention, with the pump bag of the system shown in the output phase of operation;
[0022] [0022]FIG. 4 is a schematic view of the purge valve element of the slurry delivery system of the present invention, with the rotation floater and valve ball components in the closed positions during the suction phase of the pump bag;
[0023] [0023]FIG. 5 is a schematic view of the purge valve element of the slurry delivery system of the present invention, with the rotation floater and valve ball components in the open positions during the output phase of the pump bag;
[0024] [0024]FIG. 6 is a top view of the rotation floater of the purge valve;
[0025] [0025]FIG. 7 illustrates utilization of a pair of slurry delivery systems of the present invention in parallel with each other to provide a continuous flow of slurry to a CMP apparatus (not shown);
[0026] [0026]FIG. 8 is a graph illustrating staggered or alternate operation of a pair of slurry delivery systems to provide a continuous flow of slurry to a CMP apparatus; and
[0027] [0027]FIG. 9 is a schematic illustrating a piping configuration for multiple slurry delivery systems connected to each other in parallel.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0028] The present invention has particularly beneficial utility in removing air bubbles and particles from a polishing slurry and delivering the slurry to a chemical mechanical polishing (CMP) apparatus used in the polishing of semiconductor wafers. However, the invention is not so limited in application and while references may be made to such polishing slurry and CMP apparatus, the invention is more generally applicable to removing air bubbles and particles from liquids and transporting the liquids in a variety of industrial and mechanical applications.
[0029] Referring initially to FIGS. 2 and 3, an illustrative embodiment of the slurry delivery system of the present invention is generally indicated by reference numeral 10 . The slurry delivery system 10 is designed to remove particulate impurities and air bubbles from a polishing slurry as it pumps the slurry from a slurry supply reservoir 17 to a CMP apparatus 68 . The slurry delivery system 10 includes a slurry intake conduit 16 which leads from the slurry supply reservoir 17 . A downward bend 16 a in the slurry intake conduit 16 defines a sloped segment 16 b of the slurry intake conduit 16 . A particle filter 20 of selected design and pore size is provided in the slurry intake conduit 16 , typically in the sloped segment 16 b . An intake check valve 18 is provided in the slurry intake conduit 16 , typically between the slurry supply reservoir 17 and the bend 16 a . The sloped segment 16 b of the slurry intake conduit 16 enlarges to define a purge housing 22 , which extends into the upper end of a sloped bag housing 12 and includes a discharge end 23 that terminates in the housing interior 14 of the bag housing 12 . A purge valve 24 , the details of which will be hereinafter further described, is confluently connected to the upper end of the purge housing 22 .
[0030] The sloped segment 40 b of a slurry outlet conduit 40 angles downwardly and exits from the lower end of the sloped bag housing 12 , with the intake end 41 of the slurry outlet conduit 40 extending into the housing interior 14 of the bag housing 12 . The sloped segment 40 b of the slurry outlet conduit 40 angles at a bend 40 a to define the remaining straight segment of the slurry outlet conduit 40 , which is confluent with the slurry dispensing arm (not illustrated) of the CMP apparatus 68 , according to the knowledge of those skilled in the art. An output check valve 42 is provided in the slurry outlet conduit 40 .
[0031] A resilient pump bag 46 , which may be constructed from a Teflon sheet, includes an upper open end which is connected in gas-tight communication to the discharge end 23 of the purge housing 22 , inside the housing interior 14 . The opposite, lower open end of the pump bag 46 is, in like manner, connected in gas-tight communication to the intake end 41 of the slurry outlet conduit 40 , inside the housing interior 14 . Accordingly, the junctions between the pump bag 46 and the discharge end 23 of the purge housing 22 and between the pump bag 46 and the intake end 41 of the slurry outlet conduit 40 provide a gas-tight seal between the bag interior 48 of the pump bag 46 and the housing interior 14 of the bag housing 12 . An air/vacuum controller 44 is confluently connected to the housing interior 14 of the bag housing 12 for alternately introducing air into the housing interior 14 and withdrawing air from the housing interior 14 . Because the bag housing 12 forms a gas-tight seal with the purge housing 22 and with the sloped segment 40 b of the slurry outlet conduit 40 , the air introduced into the housing interior 14 by operation of the air/vacuum controller 44 is incapable of escaping from the housing interior 14 except back through the air/vacuum controller 44 . The air/vacuum controller 44 may be actuated through a tool PC (not shown) for the CMP apparatus 68 or a system PC (not shown).
[0032] Referring next to FIGS. 4 and 5, the purge valve 24 includes a valve housing 25 which is confluently attached to the upper end of the purge housing 22 (FIGS. 2 and 3). A rotational floater 26 , which may be constructed of Teflon, is vertically displaceably mounted in the valve housing 25 . The rotational floater 26 includes a floater body 27 from which extend multiple floater vanes 28 . The floater vanes 28 extend from the floater body 27 at an angle, typically toward a counterclockwise direction when the rotational floater 26 is viewed from above, as shown in FIG. 6. Alternatively, the floater vanes 28 may extend from the floater body 27 at an angle in a clockwise direction when the rotational floater 26 is viewed from above. A circumferential floater seal 29 extends from the floater body 27 , and a tapered or cone-shaped floater base 30 extends downwardly from the floater body 27 . The floater base 30 extends through a flow opening 32 which extends through the center of a floater support 31 that spans the interior of the valve housing 25 . Accordingly, the rotational floater 26 is capable of movement between a lower position in which the floater seal 29 disengages the valve housing 25 and the floater base 30 is seated in the flow opening 32 , as shown in FIG. 4, and an upper position in which the floater seal 29 engages the valve housing 25 and the floater base 30 withdraws from the flow opening 32 , as shown in FIG. 5. When the rotational floater 26 is positioned in the lower configuration of FIG. 4, a spring 35 biases a valve ball 34 against a ball stop shoulder 36 above the rotational floater 26 and blocks flow of air or liquid from the valve housing 25 through a vent port 37 in the upper end of the valve housing 25 . When the rotational floater 26 is positioned in the upper configuration of FIG. 5, the valve ball 34 is pushed against the spring 35 and disengages the ball stop shoulder 36 to facilitate flow of air from the valve housing 25 through the vent port 37 , as hereinafter further described.
[0033] In operation of the slurry delivery system 10 , and referring again to FIGS. 2 and 3, a supply of polishing slurry 19 is pumped from the slurry supply reservoir 17 to the CMP apparatus 68 and simultaneously, particles and air bubbles are removed from the slurry 19 before the slurry 19 reaches the CMP apparatus 68 . Accordingly, with the intake check valve 18 in the open configuration and the output check valve 42 in the closed configuration, the pump bag 46 is initially operated in a suction phase, illustrated in FIG. 2, to draw slurry 19 from the slurry supply reservoir 17 into the bag interior 48 of the pump bag 46 . This is accomplished by causing the air/vacuum controller 44 to withdraw air from the housing interior 14 of the bag housing 12 . The resulting negative air pressure in the housing interior 14 (typically about −1 psi) causes the pump bag 46 to expand therein, such that slurry 19 is drawn from the slurry supply reservoir 17 , through the slurry intake conduit 16 , the open intake check valve 18 and particle filter 20 , and into the purge housing 22 and bag interior 48 , respectively. Simultaneously, the purge valve 24 assumes the closed configuration of FIG. 4, wherein the floater seal 29 of the rotational floater 26 disengages the valve housing 25 and the floater base 30 is inserted in the flow opening 32 , and the valve ball 34 , under actuation by the spring 35 , is biased against the ball stop shoulder 36 to prevent fluids or air from exiting the purge valve 24 through the vent port 37 . The particle filter 20 removes from the slurry 19 particles exceeding a selected size depending on the pore size of the particle filter 20 .
[0034] After the suction phase is completed, the pump bag 46 is operated in an output phase, shown in FIG. 3, to expel the slurry from the bag interior 48 , through the slurry output conduit 40 and open output check valve 42 and ultimately, to the CMP apparatus 68 . Accordingly, with the intake check valve 18 in the closed configuration and the output check valve 42 in the open configuration, the air/vacuum controller 44 is operated to inject air into the housing interior 14 until the air pressure in the housing interior 14 reaches a pressure of typically about 1 psi. The air in the housing interior 14 compresses or collapses the pump bag 46 , which expels the slurry 19 from the bag interior 48 , through the slurry outlet conduit 40 and open output check valve 42 and ultimately, to the CMP apparatus 68 .
[0035] As the pump bag 46 begins the output phase, any air bubbles (not shown) in the slurry 19 are forced upwardly through the slurry 19 in the bag interior 48 and purge housing 22 . Some of the slurry 19 flows upwardly into the valve housing 25 , first through the flow opening 32 and then between the floater seal 29 and valve housing 25 . This upward flow of the slurry 19 causes the rotational floater 26 to rotate in the clockwise direction when viewed from the top, as shown in FIG. 6, as the flowing slurry 19 impinges on the floater vanes 28 . The rotating action of the rotational floater 26 causes the floater vanes 28 to rupture and destroy any air bubbles rising through the slurry 19 . The slurry 19 typically rises to the top of the rotational floater 26 in the valve housing 25 , as indicated by the slurry level 38 in FIG. 5, at which time the rotational floater 26 rises in the slurry and engages the valve housing 25 . Air in the valve housing 25 , including air released from the ruptured air bubbles, impinges on the valve ball 34 due to the upward pressure of the air imparted by the contracting pump bag 46 . Accordingly, the air flows beyond the ball stop shoulder 36 and escapes the valve housing 25 through the vent port 37 . When the pump bag 46 subsequently begins a second suction phase and enlarges due to the negative pressure induced in the housing interior 14 , the rotational floater 26 and valve ball 34 again assume the closed positions of FIG. 4 as the slurry 19 is drawn from the valve housing 25 and into the bag interior 48 due to the negative pressure generated in the bag interior 48 .
[0036] The quantity of slurry 19 drawn into the bag interior 48 from the slurry supply reservoir 17 , and thus, pumped to the CMP apparatus 68 may be varied by controlling the expansion volume of the pump bag 46 during the suction phase thereof. This is, in turn, determined by the volume of air withdrawn from the housing interior 14 by operation of the air/vacuum controller 44 . The lower the pressure induced in the housing interior 14 by operation of the air/vacuum controller 44 , the larger the expansion volume of the pump bag 46 and the larger the quantity of slurry 19 drawn into the bag interior 48 for subsequent pumping to the CMP apparatus 68 . Conversely, the higher the pressure induced in the housing interior 14 by operation of the air/vacuum controller 44 , the smaller the expansion volume of the pump bag 46 and the smaller the quantity of slurry drawn into the bag interior 48 .
[0037] Referring next to FIGS. 7 and 8, in typical application two slurry delivery systems, indicated by reference numerals 10 a and lob, respectively, are connected to each other in parallel as illustrated in FIG. 7. Accordingly, a pump controller 76 operates the air/vacuum controller 44 , the intake check valve 18 and the output check valve 42 (FIGS. 2 and 3) components of each slurry delivery system 10 a and lob in conjunction with a shuttle valve 74 to alternately shuttle flow of slurry through the system 10 a and system lob (designated “pump A” and “pump B”, respectively, in FIG. 8). Such alternating operation of the systems 10 a and 10 b provides a continuous flow or output of particle and air bubble free slurry 19 from a slurry supply reservoir 70 to a CMP apparatus 72 , as indicated by the graph in FIG. 8.
[0038] [0038]FIG. 9 schematically illustrates a piping configuration for a selected number (n) of multiple slurry delivery systems connected to each other in parallel. Three of the slurry delivery systems 78 are designated by the reference numerals 78 a , 78 b and 78 c , respectively, and the nth slurry delivery system 78 is designated by the reference numeral 78 n . The slurry delivery systems 78 are connected through a slurry intake conduit 80 , slurry intake valve 82 , service conduit 84 and respective branch conduits 86 to a slurry supply reservoir 96 which contains a supply of polishing slurry 98 . Each of the slurry delivery systems 78 is operated in conjunction with the slurry intake valve 82 by a central controller (not illustrated). An auto stop valve 100 is provided in each branch conduit 86 , between the corresponding slurry delivery system 78 and a slurry output line 92 . Typically, each pair of branch conduits 86 serviced by adjacent slurry delivery systems 78 is connected to the same CMP apparatus (not shown), which continuously receives some of the slurry 98 by alternate operation of the paired slurry delivery systems 78 . Each of the branch conduits 86 is further connected to a slurry output conduit 92 which distributes the remaining slurry 98 back to the slurry supply reservoir 96 through a slurry return conduit 94 . One or multiple operator positions 88 may be provided for each system 78 . An auto stop valve 100 is typically included in each branch conduit 86 for automatically terminating flow of the slurry 98 through a branch conduit 86 in the event of a leakage or blockage in the branch conduit 86 . For example, in the event of a blockage or leakage in the branch conduit 86 a , the auto stop valve 10 a terminates flow of the slurry 98 through the branch conduit 86 a to continue supply of the slurry 98 to the slurry delivery systems 78 a , 78 b , 78 c and 78 n , respectively. Typically at least about 10% of the total volume of the slurry 98 is continuously distributed back to the slurry supply reservoir 96 in order to prevent crystallization of the slurry 98 during circulation.
[0039] While the preferred embodiments of the invention have been described above, it will be recognized and understood that various modifications can be made in the invention and the appended claims are intended to cover all such modifications which may fall within the spirit and scope of the invention.
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A slurry delivery system for a chemical mechanical polisher, comprising a bag housing fitted with a slurry intake conduit and a slurry outlet conduit. An expandible and collapsible pump bag is provided in fluid communication with the conduits inside the bag housing, and the interior of the pump bag is sealed from the bag housing. As an air/vacuum controller withdraws air from the housing, the pump bag enlarges and slurry is drawn into the pump bag. As the air/vacuum controller subsequently introduces air into the housing, the pump bag collapses and the slurry is expelled from the pump bag through the slurry outlet conduit. A purge valve is provided upstream of the pump bag to remove air bubbles from the slurry and vent the air to the atmosphere.
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This is a continuation of application Ser. No. 08/009,865, filed Jan. 27, 1993 now U.S. Pat. No. 5,461,956.
BACKGROUND OF THE INVENTION
This invention relates to bread slicing machines, and more particularly to a variable thickness bread slicer as for delicatessens, bakery stores, restaurants and the like, where it is desirable to be able to slice bread in varying thicknesses.
Conventional bread slicers are typically set up to slice loaves of bread to a specific thickness. Standard bread slice thickness is one-half inch, deli bread thickness is one-quarter to three-eighths inch, and garlic bread or French bread is up to one inch in thickness. In small bakeries where the bread is sold to customers directly, or other similar situations, it would be desirable to be able to adjust the slicer from one thickness to another quickly, even for successive loaves of bread for successive customers. However, known slicers require substantial disassembly and reassembly by a knowledgeable person over a period of 15 to 30 minutes, to change the slicing thickness. Indeed, some slicers are not subject to any variation at all.
There is a need in the market for a powered bread slicer which can slice one loaf to a particular slice thickness, e.g., one-half inch, readily slice the next loaf to another thickness, e.g., three-eighths inch, slice the third loaf to a third thickness, e.g., one inch or so, and so forth, without significant time delay or complexity.
SUMMARY OF THE INVENTION
This invention provides a power bread slicer capable of slicing successive loaves of bread to varying selected slice thicknesses, even by persons untrained in mechanical apparatus. The operator simply selects any of a multitude of potential thicknesses and activates the slicer. The bread loaf is advanced by a pusher, step-by-step, to be fed to a rotating or pivotally reciprocating cutting knife. Each step is of selected thickness. The knife may be a revolving circular knife which rotates through a slicing stroke and a return stroke, after each feed step, until the pusher is adjacent the knife, at which time the knife remains retracted while the pusher advances the cut loaf to a discharge position past the knife, and returns to the first side of the knife. The slicer works effectively on crusty breads such as garlic breads or French breads, as well as on soft, somewhat wet breads, such as conventional American bread.
These and other features, objects and advantages of the invention will become apparent upon studying the following detailed specification in conjunction with the drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective, front view of the novel bread slicer;
FIG. 2 is a perspective view comparable to FIG. 1, but with the protective covers raised;
FIG. 3 is a front, elevational, cutaway view showing operative mechanical components of the slicer;
FIG. 4 is a sectional view of the bread slicer taken along the lines IV--IV in FIG. 3;
FIG. 5 is a top, elevational, cutaway view showing operative mechanical components of the slicer;
FIG. 6 is a sectional view of the bread slicer taken along the lines VI--VI in FIG. 5;
FIG. 7 is a front elevational, somewhat schematic view of the bread advancing mechanism;
FIGS. 8a and 8b are clarifications of the area indicated by VIII in FIG. 7 in different portions of a slicing cycle;
FIGS. 9a-9c are a circuit diagram for the apparatus;
FIGS. 10a and 10b are a circuit diagram for the microprocessor/stepper driver assembly; and
FIG. 11 is a flow chart of a control routine for the apparatus.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now specifically to the drawings, the bread slicer assembly 10 includes a frame and housing subassembly 12 supporting the other functioning components. These other functioning components include a generally horizontal slide platform subassembly 14 of generally V-shaped configuration, to retain a loaf of bread, and made up of a V-shaped infeed table 16 and a V-shaped outfeed table 18 on opposite sides of a vertical plane containing a circular rotational slicer knife 24. This circular knife is rotationally mounted at its center at one upper end of a pivotal cutoff arm 28 (FIG. 6), by having a stub shaft 26 on the knife rotationally mounted on bearings in arm 28. This arm is pivotally mounted at its opposite lower end to a rotating shaft 30. An endless belt drive 34 extends around pulleys on stub shaft 26 and shaft 30 to form part of a drive connection. Another endless belt drive 38 extends around a pulley on shaft 30 and a pulley on the output shaft extending from drive motor 40. Motor 40 can be a conventional electric motor, e.g., one-half h.p., to rotationally drive the knife. The knife has scallops on its outer edge to slice bread, when operated to shift transversely to the platform, in the manner explained more fully hereinafter.
Cutoff arm 28 can pivot between an upper knife retracted condition, through an arcuate cutoff stroke ending at a lower position, with the knife edge below the slide subassembly and any bread thereon (FIG. 4).
A pivotal safety cover 44 for the knife is pivotally mounted to the housing at the upper rear edge of the cover, to move between a lower knife covering position (FIG. 1) and a raised knife revealing position (FIG. 2). In the lower knife covering position, an inverted, V-shaped opening in the side walls of the cover, on each side of the knife, enables passage of a loaf of bread B through cover 44 to be operated upon by knife 24. Astraddle knife 24 is a pair of downwardly biased, bread hold down fingers 50 (FIG. 2) to prevent the bread from rising with the raising of, i.e., retraction of, knife 24 after a cut is made.
Cutoff arm 28 is reciprocably operated by cutoff drive motor 70 (FIG. 3) through a belt drive 72, a conventional single revolution cutoff clutch 74 and a crank arm 73, connecting rod 200 to pivot arm 28 from its upward position, through an arc, to its full downward position and back to its upward position where it engages the cutoff arm return proximity switch 29 (FIG. 5) to be arrested, awaiting reactivation.
Pivotally mounted adjacent to, and extending over, infeed table 16 is a three dimensional, open bottom, horizontally elongated cover 80 mounted at its upper rear edge on pivot hinge 82 to housing 12. It pivots between an upper position uncovering infeed table 16 to a lowered position covering table 16 and a loaf of bread B thereon. A bread pusher assembly 60 is covered by a stationary cover 81 when in a retracted position at the outer end of the bread loaf (FIG. 1). Cover 80 has an open discharge end adjacent opening 46 in cover 44 to allow bread to be advanced to the knife. This cover 80 is preferably transparent, as of polycarbonate, to enable viewing of the bread B. A second open bottom cover 86 is pivotally mounted at its upper rear edge on hinge 88 to housing 12, to pivot between an upper condition (FIG. 2) uncovering outfeed table 18, and a lowered position (FIG. 1). It has an open bread receiving end adjacent opening 46 in cover 44 to receive and cover the bread B after it is sliced.
There are three safety lockout switches actuated by the three respective covers, namely switch 90 for cover 80, switch 94 for blade cover 44, and switch 92 for cover 86, to prevent knife 24 from operating and cutoff arm 28 from lowering if any of the three covers is raised.
Extending above the slide platform 14 is a pusher assembly 60 including a vertical pusher plate 60a and a fork assembly 60b. Pusher assembly 60 is capable of moving from an initial position at one end, here the left end of the infeed table and slide platform, spaced from knife 24 more than the length of a loaf of bread B, toward the knife and ultimately to a final position just on the opposite side of knife 24, i.e., at the outfeed table, as shown by the phantom lines in FIG. 2. A heel holder plate 20, which is mounted for reciprocal travel over outfeed table 18 (FIG. 7), maintains the slices together on the outfeed table.
Pusher assembly 60 is connected by a hitch 61 to underlying belt 98 (FIGS. 7, 8a and 8b) to be above platform 14, and particularly above infeed table 16 and outfeed table 18. It is mounted on endless belt drive 98 (FIG. 7), to be advanced toward and just beyond knife 24, as described hereinafter. Endless member 98 extends around a first pulley 100 beneath the outer end of infeed table 16, and a second pulley 102 beneath outfeed table 18. Endless drive member 98 is driven forwardly toward knife 24 in preselected increments by a variable step, incremental, stepper motor 104 (FIGS. 7 and 9a-9c) of conventional type, e.g., 200 steps per revolution. It operates a gear box which drives pulley 102. The retracted position of pusher assembly 60 is controlled by a limit switch serving as an end-of-travel switch 108 which is engaged by hitch 61 mounted on drive member 98. The furthermost advanced position of pusher 60 is controlled by two limit switches, switch 112A near the knife, and switch 112B below drive member 98, near pulley 100. Switch 112A is actuated by hitch 61, and switch 112B is actuated by actuator 110, either switch, if actuated, causing the arm 28 to be retained in the retracted position. After final retraction of the arm, the pusher assembly moves just past the knife for fully shifting the complete loaf of bread onto the outfeed table. When the outfeed table cover 86 is lifted for removal of the bread, and then closed again, pusher assembly 60 returns to the infeed table. In brief, the initial position of pusher assembly 60 is at the outer (left) end of infeed table 16 while the furthermost position of pusher assembly 60 is just beyond knife 24 above outfeed table 18.
Only pusher plate 60a is directly coupled with hitch 61. Fork assembly 60b travels in a channel 60c (FIG. 7) and is frictionally engaged with openings in pusher plate 60a. Fork assembly 60b is arrested in motion at the end of channel 60c adjacent to knife 24 prior to reaching the knife, as illustrated in FIG. 8b. This allows the tines of fork assembly 60b to penetrate deeper into a loaf of bread than a typical slice thickness yet avoid contact with the knife. The fork assembly tines are reinserted in the openings of pusher plate 60a, as pusher plate 60a is retracted to the infeed table, as illustrated in FIG. 8a.
An elongated lower crumb tray 75a for collecting dropping crumbs is extendible from a first position inside housing 12 (FIG. 1) beneath the slide platform, to a removed condition from the housing for dumping (FIG. 2 shows partial removal). A generally vertically extending crumb chute 75b guides crumbs into crumb tray 75a.
At the infeed table, immediately before and adjacent knife 24, are two photoelectric sensors 19 (FIG. 2) to detect the presence of the leading end of a loaf of bread ready to be sliced. If covers 80, 44 and 86 are closed, this sensor can activate slicer drive motor 40A and cutoff arm drive 70, 72, 74. A resilient wiper (not shown) mounted toward the rear of pusher plate 60a wipes crumbs from the Plexiglas covering sensors 19.
Stepper motor 104 is controllable in conventional fashion using a stepper motor driver, and preferably through a microprocessor control 125, to allow it to take a predetermined number of the 200 or so incremental steps possible per revolution. This enables manual presetting of the dimension of each advancing step sequentially taken by the motor, so as to set the dimensional distance that pusher 60 moves in each increment. This manual setting is readily performed by the human operator by rotating an exposed arcuate surface portion 114 (FIG. 2) of a conventional thumb wheel, for example, to a "1/2" inch designation indicia thereon, e.g., for the one-half inch unit, or to another increment dimension desired, for the thickness of the bread slice. The thumb wheel is exposed at 114 on control panel 116 which also includes an on-off switch 115, start button 118, stop button 120 and indicator light 122. Suitable control circuitry may be that set forth in FIGS. 9a-9c and 10a-10b, or the equivalent.
Referring low to FIGS. 9a-10b, a control 125 is shown connecting AC voltage across lines 134 and 136 whenever on-off switch 115 is placed in the ON position. A control relay 146 is energized whenever switches 90, 92 and 94 are closed, indicating that the covers 80 and 86 for the infeed and outfeed tables, as well as the safety cover 44 for the knife, are closed. Also, with switches 90, 92 and 94 closed, power is fed to the output contacts C1 and C2 of the microprocessor to energize a relay 148 provided that an output designated OUT 1 of a microprocessor and stepper driver 130 provides a suitable output command, to thereby apply power to knife drive motor 40A, and knife motor brake 40B through relay contact 148a. An output designated OUT 2 of microprocessor/stepper driver 130 supplies power to a relay 149 which opens contacts 149A and 149B, which removes the drive inhibit of DC driver control 127. DC driver control 127 supplies an adjustable DC voltage level to cutoff arm drive motor 70. A variable potentiometer 150 provides adjustable control of the speed of motor 70 in order to allow regulation of the speed at which the arm is moved through the bread. A cooling fan motor 152 is energized whenever switch 115 is in the ON position in order to supply cooling air to control 125. Indicator 122 provides a red warning indication whenever microprocessor/stepper driver 130 determines that a cover is not properly closed.
Microprocessor/stepper driver 130 receiving inputs from start switch 118, stop/return switch 120, a contact 146b of relay 146, thumb wheel switch 114, retracted-position limit switch 108, redundant photoelectric bread sensors 19a, 19b, redundant end of travel limit switches 112a, 112b and cutoff arm return proximity switch 29 (FIG. 9b). Such input devices receive supply voltage from input DC supply lines 140 and 138. Microprocessor/stepper driver 130 receives supply voltage from DC power supply 126 via supply lines 138 and 140. Microprocessor/stepper driver 130 provides an output OUT 5 to single revolution cutoff clutch solenoid 74 and an output OUT 4 to counter 151. Output 151 is a 6-digit, manually reset counter which counts entire cycles of the apparatus. Microprocessor/stepper driver 130 produces step outputs (01-06) 166 that are capable of driving stepper motor 104.
Microprocessor/stepper driver 130 responds to the state of the inputs being provided to it and produces outputs to relays 148 and 149, to single revolution cutoff clutch solenoid 74 and to stepper motor 104. A control program 200 (FIG. 11) establishes the number of steps that stepper motor 104 is to be incremented. Hence, the data inputs of thumb wheel switch 114 determine the distance that belt 98 will be incremented, and hence the thickness of each bread slice.
Operation of control program 200, with covers 44, 80 and 86 being closed, i.e., lowered, is started by the on-off switch 115 being actuated, applying power at 201 to the equipment. The microprocessor/stepper driver 130 then initiates a self check sequence at 202. During the self check sequence, the position of the pusher plate 60a is first checked to see whether it is in the outer extreme position. If the pusher plate is not in the correct position, the microprocessor/stepper driver 130 with retract the pusher plate until it is in the extreme outer position. Then the pusher assembly is advanced to the end limit switches 112a and 112b. After actuating both limit switches in sequence, the pusher is then retracted back to the extreme outer position, ready for operation. If, during the self check, it is determined at 204 that either end limit switch 112a or 112b fails to operate, the microprocessor/stepper driver will enter a lockout mode 206 in which operation is stopped, and the operator is alerted to a malfunction. The equipment must be turned off to reset the microprocessor/stepper driver in order to exit the lockout mode.
Self check sequence 202 cannot be bypassed. By leaving any of the covers 44, 80, 86 open when turning on the machine, which is determined at 208 and places the control in a stop mode 210, the self check sequence can be also interrupted during its cycle by pushing the stop button 120. Once the microprocessor/stepper driver is in stop mode 210, only by closing the doors and pressing the start button will the microprocessor finish its self check sequence.
Once it is determined at 204 that there were no failures during the self check mode, the apparatus is in a ready mode 212. During this mode, a loaf of unsliced bread is placed on slide platform 14, and specifically on infeed table 16, while cover 80 is raised. The outer end of the loaf is abutted against pusher plate 60, which is at its outer extreme position, with the tines of fork assembly 60b engaging the loaf. The thumb wheel 114 is set to the desired cut size and the cover 80 is then lowered, as well as cover 44 and cover 86 being closed, i.e., lowered. The equipment may then be actuated by pushing start button 118. Knife 24 is at this time in the retracted elevated condition, i.e., not the cutoff condition. Pusher assembly 60 advances bread B toward knife 24 until the product detection scanner 19 detects the leading edge of the loaf of bread. At this point, the stepper motor will stop, with the leading edge of the loaf being just in front of knife 24. At this time, the apparatus enters a slice mode 214. In the slice mode, the knife drive motor 40a and slicer arm drive 127 and 70 are powered up, and the knife brake 40b energized, releasing the knife. Once the slicer motor comes up to speed, the stepper motor 104 will index one unit width forward, the unit width dimension having been determined by the previous setting on the thumb wheel 114.
The slicer arm will then actuate to lower the knife to cut the first slice, and this intermittent incremental sequence will continue until the end limit switch 112 for pusher 60 is actuated. When end limit switch 112 is actuated, the control enters a last slice mode 216 in which it is determined whether the last slice of bread is of a suitable thickness to be sliced again into two slices. Microprocessor/stepper driver 130 counts the number of pulses between the initiating of the last indexing of belt 98 and the actuation of limit switch 112. This count is converted into belt travel and, hence, thickness of the last bread slice. If the determined thickness of the last bread slice is more than 80 percent greater than the thickness entered by the operator using thumb wheel switch 114, then single revolution cutoff clutch 74 is again actuated to make one additional slice.
At this point, a last push mode 218 is entered. The arm and knife drive turn off, and the brake solenoid 40B de-energizes, stopping the bread knife rotation. Then pusher 60 will advance past knife 24 to push the remainder of the loaf onto the outfeed table beneath cover 86. The operator will then lift cover 86 and remove the sliced bread. The operator can now return the heel holder 20 to its position closer to knife 24. Reclosing of door 86 will initiate a return mode 220 and enable pusher 60 to return to its initial retracted position (FIG. 2) for receipt of the next loaf of bread in front of it. At any point, operation of the apparatus can be interrupted by pressing stop button switch 120. Further, opening any of the three covers at any time will deactuate power to the knife drive. A flow chart illustrating the detailed operation of control program 200 is appended to this specification as Appendix A and is incorporate by refence.
In the illustrated embodiment, cutoff arm drive motor 70 is a one-eighth horsepower DC motor that operates from an input that varies from 0 to 90 VDC. Stepper motor 104 is commercially available and is marketed by Oriental Motors under Model No. PH296-02GK with a six-to-one ratio gear, also marketed by Oriental Motors under Model No. 4GK6KA. Stepper motor 104 produces one-sixth revolution through the gear reducer for each 200 pulses from controller 132, which represents one inch of travel of belt 98. The index speed of belt 98 is six inches per second at 800 pulses per second from controller 130. Microprocessor/stepper driver includes a central processor unit, or CPU, 160 and optical isolator circuits 162a-162d for coupling inputs IN01-IN13 to CPU 160 (FIG. 10a). CPU 160 supplies a stepper driver circuit 164 with commands, with circuit 164 supplying step 01-06 commands 166 to stepper motor 104 (FIG. 10b). CPU 160 drives relays outputs OUT 1-OUT 3 through a buffer circuit 166 and through relays 168a-168d. CPU 160 drives transistor outputs OUT 5 and OUT 6 through a buffer circuit 170 and through overload devices 172a and 172b. In the illustrated embodiment, CPU 160 is a model 6800 microprocessor chip set marketed by Motorola, Inc. Stepper driver circuit 164 is marketed by Miquest Corp. under Model MI348. Optical isolator circuits 162a-162d and buffer circuits 166 and 170 are conventional devices.
Although the invention is illustrated as implemented on a microprocessor control, it is adaptable to being implemented using a programmable logic controller and an intelligent stepper driver to directly actuate stepper motor 104. Such modification would be readily apparent to the skilled artisan.
This novel apparatus can be installed in a small store, bakery, delicatessen, or the like, to enable slices of various thickness to be readily created from a loaf of unsliced bread, enabling a person to cut the bread to a standard one-half inch thickness, a deli one-quarter to three-eighths inch thickness, a garlic bread thickness of up to one inch, or as desired, simply by rotating thumb wheel 114 to the desired setting, placing the loaf of bread on the infeed table, closing cover 80, and engaging start button 18. The slicer knife 24 then repeatedly slices the loaf to the predetermined slice width until the loaf is totally sliced or until the operator stops the machine. Cover 86 is lifted and the sliced bread removed.
The specific embodiment of the invention disclosed above could conceivably be modified in various ways within the scope of the inventive concept, to suit a particular situation. This preferred form of the invention is deemed illustrative, with it being intended that the invention is not to be limited to this specific embodiment depicted, but only by the scope of the appended claims and the reasonably equivalent structures to those defined therein.
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A powered bread slicer capable of slicing successive loaves of bread to selected different slice thicknesses. A rotating circular bread slicing knife is mounted on a pivotal, reciprocal arm for shifting the knife from a retracted position through slicing positions between and transverse to an infeed table and an out feed table, and return to the retracted position. The slice thickness is selected, as for standard one-half inch thickness, deli one-quarter to three-eighths inch thickness, garlic or French bread up to one inch thickness, or otherwise. A variable stepper motor incrementally advances a loaf pusher one step at a time, the dimension of the step being of the selected slice thickness dimensional. The distance by the travelled loaf pusher to reach the end of its travel is monitored to determine whether the bread heal is thick enough to slice once more. This decision is a function of the selected slice thickness dimension. A detector sensing the leading end of the loaf initially activates the slicer knife drive and the support arm drive. A pusher detector adjacent the knife prevents knife advancement with presence of the pusher adjacent the knife, allowing the pusher to move past the knife to push the fully sliced loaf completely onto the discharge table, and then return to the infeed table.
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[0001] This is a continuation of copending application Ser. No. 09/455,011, filed Dec. 3, 1999, which is a continuation of copending application Ser. No. 09/286,195, filed Apr. 5, 1999, now U.S. Pat. No. 6,042,598, which is a continuation of application Ser. No. 09/022,510, filed Feb. 12, 1998, now U.S. Pat. No. 5,910,154, which is a continuation of application Ser. No. 08/852,867, filed May 8, 1997, now U.S. Pat. No. 5,911,734. Each of the above applications and patents is hereby expressly and fully incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates generally to treating plaque deposits and occlusions within major blood vessels, more particularly to an apparatus and method for preventing detachment of mobile aortic plaque within the ascending aorta, the aortic arch, or the carotid arteries, and to an apparatus and method for providing a stent and a filter in a percutaneous catheter for treating occlusions within the carotid arteries.
BACKGROUND OF THE INVENTION
[0003] Several procedures are now used to open stenosed or occluded blood vessels in a patient caused by the deposit of plaque or other material on the walls of the blood vessels. Angioplasty, for example, is a widely known procedure wherein an inflatable balloon is introduced into the occluded region. The balloon is inflated, dilating the occlusion, and thereby increasing intraluminal diameter. Plaque material may be inadvertently dislodged during angioplasty, and this material is then free to travel downstream, possibly lodging within another portion of the blood vessel or possibly reaching a vital organ, causing damage to the patient.
[0004] In another procedure, stenosis within arteries and other blood vessels is treated by permanently or temporarily introducing a stent into the stenosed region to open the lumen of the vessel. The stent typically comprises a substantially cylindrical tube or mesh sleeve made from such materials as stainless steel or nitinol. The design of the material permits the diameter of the stent to be radially expanded, while still providing sufficient rigidity such that the stent maintains its shape once it has been enlarged to a desired size.
[0005] Generally, a stent having a length longer than the target region is selected and is disposed on a catheter prior to use. The catheter typically has a flexible balloon, near its distal end, designed to inflate to a desired size when subjected to internal pressure. The stent is mounted to the catheter and compressed over the balloon, typically by hand, to assure that the stent does not move as it passes through the blood vessel to the desired location within the patient. Alternatively, self-expanding stents may also be used.
[0006] The stent is typically introduced into the desired blood vessel using known percutaneous methods. The catheter, having the stent securely crimped thereon, is directed to the region of the blood vessel being treated. The catheter is positioned such that the stent is centered across the stenosed region. The balloon is inflated, typically by introducing gas or fluid such as saline solution, through a lumen in the catheter communicating with the balloon. Balloon inflation causes the stent to expand radially, thereby engaging the stenosed material. As the stent expands, the material is forced outward, dilating the lumen of the blood vessel.
[0007] Due to substantial rigidity of the stent material, the stent retains its expanded shape, providing an open passage for blood flow. The balloon is then deflated and the catheter withdrawn.
[0008] Because the stent is often constructed from a mesh material, the stent typically compresses longitudinally as it expands radially. Stenotic material trapped between the stent and the vessel wall may extend into the openings in the mesh and may be sheared off by this longitudinal compression to create embolic debris free. When this material travels downstream, it can cause serious complications. For example loose embolic material released within the ascending aorta, the aortic arch, or the carotid arteries may travel downstream to the brain, possibly causing stroke, which can lead to permanent injuries or even death of the patient.
[0009] Thus, there is a need for an apparatus and method for delivering a stent into an arterial occlusion which substantially reduces the risk of embolic material escaping to the vessel and causing a blockage at a downstream location. There is also an apparatus and method for substantially preventing detachment of plaque deposited on the walls of the ascending aorta, the aortic arch, the descending aorta, and the carotid arteries. In addition, there is a need for an apparatus and method to substantially contain loose embolic material within the aorta and the carotid arteries during an interventional procedure, preventing it from reaching the brain.
SUMMARY OF THE INVENTION
[0010] The present invention provides an apparatus and method for preventing embolic material from escaping a site of intervention within the aorta, the carotid arteries, and other arteries generally, thereafter causing damage to vital organs, such as the brain. More particularly, the present invention involves an apparatus and method for introducing a stent into a region of a major blood vessel within the human body having plaque deposits, such as the ascending aorta, the descending aorta, aortic arch, common carotid artery, external and internal carotid arteries, brachiocephalic trunk, middle cerebral artery, anterior cerebral artery, posterior cerebral artery, vertebral artery, basilar artery, subclavian artery, brachial artery, axillary artery, iliac artery, renal artery, femoral artery, popliteal artery, celiac artery, superior mesenteric artery, inferior mesenteric artery, anterior tibial artery, and posterior tibial artery, thereby opening occlusions and/or preventing embolic material from breaking free within the blood vessel.
[0011] In a first embodiment, the invention includes a guidewire having an expandable filter attached to it, and a stent catheter. The catheter has an inflatable balloon mounted on or near its distal end, and an inflation lumen extending through the catheter between a proximal region of the catheter and the balloon. A stent is provided on the outer surface of the catheter, substantially engaging the balloon. Generally, the stent comprises an expandable substantially rigid tube, sheet, wire or spring, but preferably a cylindrical mesh sleeve. See Palmaz, U.S. Pat. No. 4,733,665, incorporated herein by reference.
[0012] Alternatively, the stent may be a self-expanding sleeve, preferably from nitinol. In this case, the stent catheter does not require an inflatable balloon. Instead the stent is compressed over the catheter and a sheath or outer catheter is directed over the stent to hold it in the compressed condition until time of deployment.
[0013] The guidewire has a filter assembly attached at or near its distal end, which includes an expansion frame which is adapted to open from a contracted condition to an enlarged condition. Filter material, typically a fine mesh, is attached to the expansion frame to filter undesirable embolic material from blood.
[0014] The guidewire with the expansion frame in its contracted condition is provided through a sheath or cannula, or preferably is included directly in the stent catheter. The catheter typically has a second lumen extending from its proximal region to its distal end into which the guidewire is introduced. The filter assembly on the distal end of the guidewire is then available to be extended beyond the distal end of the catheter for use during stent delivery.
[0015] The device is typically used to introduce a stent into a stenosed or occluded region of a patient, preferably within the carotid arteries. The catheter is introduced percutaneously into a blood vessel and is directed through the blood vessel to the desired region. If the filter device is provided in a separate sheath, the sheath is percutaneously inserted into the blood vessel downstream of the region being treated, and is fixed in position.
[0016] The filter assembly is introduced into the blood vessel, and the expansion frame is opened to its enlarged condition, extending the filter mesh substantially across the blood vessel until the filter mesh substantially engages the walls of the vessel.
[0017] The catheter is inserted through the region being treated until the stent is centered across the plaque deposited on the walls of the blood vessel. Fluid, preferably saline solution, is introduced through the inflation lumen, inflating the balloon, and expanding the stent radially outwardly to engage the plaque. The stent pushes the plaque away from the region, dilating the vessel. The balloon is deflated, and the catheter is withdrawn from the region and out of the patient. The stent remains substantially permanently in place, opening the vessel and trapping the plaque beneath the stent.
[0018] When the stenosed region is opened, embolic material may break loose from the wall of the vessel, but will encounter the filter mesh and be captured therein, rather than traveling on to lodge itself elsewhere in the body. After the stent is delivered, the expansion frame is closed, containing any material captured in the filter mesh. The filter assembly is withdrawn back into the sheath or the catheter itself, which is then removed from the body.
[0019] If a self-expanding stent is used, the stent catheter with the compressed stent thereon is inserted into a sheath, which restrains the stent in a compressed condition. The catheter is introduced into the patient's blood vessel and directed to the target region. Once the stent is localized across the stenosed region and the filter assembly is in position, the sheath is drawn proximally in relation to the catheter. This exposes the stent, which expands to engage the wall of the blood vessel, opening the lumen. The filter assembly is then closed and the catheter withdrawn from the patient.
[0020] The filter assembly has a number of preferred forms. For example, the expansion frame may comprise a plurality of struts or arms attached to and extending distally from the distal end of the guidewire. The struts are connected to each other at each end and have an intermediate region which is biased to expand radially. Filter mesh is attached typically between the intermediate region and the distal ends of the struts, thereby defining a substantially hemispherical or conical shaped filter assembly.
[0021] To allow the filter assembly to be inserted into the lumen of the sheath, the intermediate region of the expansion frame is compressed. When the filter assembly is ready to be introduced into a blood vessel, the guidewire is pushed distally. The expansion frame exits the lumen, and the struts automatically open radially. This expands the filter mesh to substantially traverse the vessel. After the stent is delivered, the guidewire is pulled proximally to withdraw the filter assembly. The struts contact the wall of the filter lumen, forcing them to compress, closing the frame as the filter assembly is pulled into the sheath.
[0022] In another embodiment, the expansion frame includes a plurality of struts attached to the distal end of the sheath. The struts extend distally from the sheath and attach to the distal end of the guidewire which is exposed beyond the sheath. At an intermediate region, the struts are notched or otherwise biased to fold out radially. Filter mesh is attached to the struts between the intermediate region and the distal end of the guidewire.
[0023] The filter assembly is directed into position in the blood vessel, either exposed on the end of the sheath or preferably within a second sheath which is withdrawn partially to expose the filter assembly. With the sheath fixed, the guidewire is pulled proximally. This compresses the struts, causing them to bend or buckle at the intermediate region and move radially outwardly, expanding the filter mesh across the blood vessel. After use, the guidewire is pushed distally, pulling the struts back down and closing the filter mesh.
[0024] In an alternative to this embodiment, the struts attached to the distal end of the sheath and to the distal end of the guidewire are biased to expand radially at an intermediate region. The filter mesh is attached to the struts between the intermediate region and the distal end of the guidewire. Prior to introduction into a patient, the guidewire is rotated torsionally in relation to the sheath, twisting the struts axially around the guidewire and compressing the filter mesh. Once in position in the blood vessel, the guidewire is rotated in the opposite direction, unwinding the struts. The struts expand radially, opening the filter mesh. After use, the guidewire is rotated once again, twisting the struts and closing the filter mesh for removal.
[0025] In yet another embodiment, the filter assembly comprises a plurality of substantially cylindrical compressible sponge-like devices attached in series to the guidewire. The devices have an uncompressed diameter substantially the same as the open regions of the blood vessel. They are sufficiently porous to allow blood to pass freely through them but to entrap undesirable substantially larger particles, such as loose embolic material.
[0026] The devices are compressed into the lumen of the sheath prior to use. Once in position, they are introduced into the blood vessel by pushing the guidewire distally. The devices enter the vessel and expand to their uncompressed size, substantially engaging the walls of the blood vessel. After use, the guidewire is pulled proximally, forcing the devices against the distal end of the sheath and compressing them back into the lumen.
[0027] In a second embodiment, a stent catheter and filter assembly are also provided. Unlike the previous embodiments, the filter assembly is not primarily mechanically operated, but is instead, generally fluid operated. Typically, the stent catheter includes a second balloon on or near the distal end of the catheter. A second inflation lumen extends through the catheter from the proximal region of the catheter to the balloon. The balloon is part of the expansion frame or alternatively merely activates the expansion frame, opening the filter assembly to the enlarged condition for use and closing it after being used.
[0028] In one form, the balloon has an annular shape. Filter mesh is attached around the perimeter of the balloon, creating a conical or hemispherical-shaped filter assembly. A flexible lumen extends between the balloon and the inflation lumen within the catheter. Optionally, retaining wires are connected symmetrically between the balloon and the catheter, thereby holding the balloon substantially in a desired relationship to the catheter.
[0029] When deflated, the balloon substantially engages the periphery of the catheter, holding the filter mesh closed and allowing the catheter to be directed to the desired location. Once the catheter is in position, the balloon is inflated. The balloon expands radially until it engages the walls of the blood vessel, the filter mesh thereby substantially traversing the vessel. After use, the balloon is deflated until it once again engages the perimeter of the catheter, thereby trapping any embolic material between the filter mesh and the outer wall of the catheter.
[0030] Alternatively, the balloon of this embodiment may be provided on the catheter proximal of the stent for retrograde use. In this case, the filter mesh is extended between the balloon and the outer surface of the catheter, instead of having a closed end.
[0031] In a third embodiment of the present invention, a method is provided in which a stent catheter is used to prevent the detachment of mobile aortic deposits within the ascending aorta, the aortic arch or the carotid arteries, either with or without an expandable filter assembly. A stent catheter, as previously described, is provided having an inflatable balloon and a stent thereon, or alternatively a self-expanding stent and a retaining sheath. The catheter is percutaneously introduced into a blood vessel and is directed to a region having mobile aortic plaque deposits, preferably a portion of the ascending aorta or the aortic arch.
[0032] The stent is positioned across the desired region, and the balloon is inflated. This expands the stent to engage the plaque deposits and the walls of the blood vessel, thereby trapping the plaque deposits. The balloon is deflated, and the catheter is removed from the blood vessel. Alternatively if a self-expanding stent is used, the sheath is partially withdrawn proximally, and the stent is exposed, allowing it to expand. The stent substantially retains its expanded configuration, thereby containing the plaque beneath the stent and preventing the plaque from subsequently detaching from the region and traveling downstream.
[0033] Optionally, a filter device similar to those already described may be introduced at a location downstream of the treated region. The filter device may be provided in a sheath which is inserted percutaneously into the blood vessel. Preferably, however, a filter device is attached to the stent catheter at a location proximal to the stent. Instead of attaching the filter assembly to a guidewire, it is connected directly to the outer surface of the catheter proximal to the stent. A sheath or cannula is typically provided over the catheter to cover the filter assembly.
[0034] Once the catheter is in position within the vessel, the sheath is withdrawn proximally, the filter assembly is exposed and is expanded to its enlarged condition. In a preferred form, the expansion frame includes biased struts similar to the those described above, such that when the filter assembly is exposed, the struts automatically expand radially, and filter mesh attached to the struts is opened. After the stent is deployed, the sheath is moved proximally, covering the expansion frame and compressing the struts back into the contracted condition. The catheter and sheath are then withdrawn from the patient.
[0035] Thus, an object of the present invention is to provide an apparatus and method for substantially preventing mobile aortic plaque deposited within the ascending aorta, the aortic arch, or the carotid arteries from detaching and traveling to undesired regions of the body.
[0036] Another object is to provide an apparatus and method for treating stenosed or occluded regions within the carotid arteries.
[0037] An additional object is to provide an apparatus and method for introducing a stent to treat a stenosed or occluded region of the carotid arteries which substantially captures any embolic material released during the procedure.
BRIEF DESCRIPTION OF THE DRAWINGS
[0038] For a better understanding of the invention, and to show how it may be carried into effect, reference will be made, by way of example, to the accompanying drawings, in which:
[0039] [0039]FIG. 1 is a longitudinal view of an embodiment being inserted into a blood vessel, namely a stent catheter in a stenosed region and a filter device downstream of the region.
[0040] [0040]FIG. 2 is a longitudinal view of another embodiment, showing the filter device included in the stent catheter.
[0041] [0041]FIG. 3 is a longitudinal view of an embodiment of the filter assembly in its enlarged condition within a blood vessel.
[0042] [0042]FIGS. 4A, 4B and 4 C show a longitudinal view of an embodiment of the filter assembly in a contracted condition, a partially expanded condition, and an enlarged condition respectively within a blood vessel.
[0043] [0043]FIGS. 5A, 5B and 5 C show a longitudinal view of another embodiment of the filter device in a contracted condition, a partially opened condition, and an enlarged condition across a blood vessel respectively.
[0044] [0044]FIGS. 6A and 6B are longitudinal views, showing the orientation of the filter mesh in an antegrade approach to a stenosed region and in a retrograde approach respectively.
[0045] [0045]FIG. 7 is a longitudinal view of another embodiment of the filter assembly.
[0046] [0046]FIGS. 8A and 8B are longitudinal views of another embodiment of the filter assembly, showing the filter mesh without gripping hairs and with gripping hairs respectively.
[0047] [0047]FIG. 9 is a longitudinal view of another embodiment of the filter assembly including sponge-like devices.
[0048] [0048]FIG. 10 is a longitudinal view of another embodiment, namely a filter assembly attached to the outer surface of a stent catheter.
[0049] [0049]FIGS. 11A and 11B show a filter assembly attached to the outer surface of a stent catheter, with a sheath retaining the filter assembly in the contracted condition, and with the filter assembly in the enlarged condition respectively.
[0050] [0050]FIGS. 12A and 12B are longitudinal views of another embodiment including an inflatable filter assembly, shown in a contracted condition and an enlarged condition respectively.
[0051] [0051]FIG. 13 is a longitudinal view of an inflatable filter assembly attached to the catheter proximal of the stent shown in an enlarged condition.
[0052] [0052]FIG. 14 depicts a longitudinal view of a stent deployment device having a distal filter disposed within a carotid artery.
[0053] [0053]FIGS. 15 and 15A show detailed longitudinal views of a guidewire filter in accordance with the present invention.
[0054] [0054]FIGS. 16, 16A, 16 B, and 16 C show longitudinal and cross-sectional views of an eggbeater filter in accordance with the present invention.
[0055] [0055]FIGS. 17 and 17A show longitudinal views of a filter scroll in accordance with the present invention.
[0056] [0056]FIGS. 18, 18A, and 18 B show longitudinal views of a filter catheter in accordance with the present invention.
[0057] [0057]FIG. 19 shows an alternate construction for an eggbeater filter as disclosed herein.
[0058] [0058]FIG. 20 shows a longitudinal view of an imaging guidewire having an eggbeater filter and restraining sheath.
[0059] [0059]FIG. 21 shows human aortic anatomy and depicts several routes for deployment of an aortic filter upstream of the carotid arteries.
[0060] [0060]FIG. 22 depicts a longitudinal view of a generalized filter guidewire.
[0061] [0061]FIGS. 23 and 23A depict longitudinal views of a compressible, expansible sheath disposed over a guidewire in accordance with the present disclosure.
DETAILED DESCRIPTION
[0062] Turning to FIG. 1, a first embodiment of the present invention is shown, namely a stent catheter 10 and a filter device 30 . The stent catheter 10 typically includes a catheter body 12 , an inflatable balloon 16 , and a stent 20 . The catheter body 12 typically comprises a substantially flexible member having a proximal end (not shown) and a distal end 14 . The balloon is mounted on a region at or near the distal end 14 of the catheter body 12 . An inflation lumen 18 extends longitudinally from a region at or near the proximal end of the catheter body 12 to the balloon 16 .
[0063] The stent 20 is introduced over the balloon 16 , typically by manually compressing it onto the balloon 16 . The stent 20 may comprise a tube, sheet, wire, mesh or spring, although preferably, it is a substantially cylindrical wire mesh sleeve, that is substantially rigid, yet expandable when subjected to radial pressure. Many known stent devices are appropriate for use with the present invention, such as those discussed elsewhere in this disclosure. Generally the stent is furnished from materials such as stainless steel or nitinol, with stainless steel being most preferred.
[0064] Alternatively, a self-expanding stent (not shown) may also be used, such as those disclosed in Regan, U.S. Pat. No. 4,795,458, Harada et al., U.S. Pat. No. 5,037,427, Harada, U.S. Pat. No. 5,089,005, and Mori, U.S. Pat. No. 5,466,242, the disclosures of which are incorporated herein by reference. Such stents are typically provided from nitinol or similar materials which are substantially resilient, yet compressible. When an expandable stent is used, the stent catheter does not generally include an inflatable balloon for the stent. Instead, the stent is compressed directly onto the catheter, and a sheath is placed over the stent to prevent it from expanding until deployed.
[0065] In addition to the catheter 10 , the present invention typically includes a filter device 30 . The filter device 30 generally comprises an introducer sheath 32 , a guidewire 40 , and an expandable filter assembly 50 , although alternatively the guidewire 40 and the filter assembly 50 may be provided directly on the catheter 10 as will be described below (see FIG. 2). The sheath 32 has a proximal end 34 and a distal end 36 , and generally includes a hemostatic seal 38 mounted on its proximal end 34 . The guidewire 40 , typically a flexible, substantially resilient wire, having a distal end 42 and a proximal end 44 , is inserted into the proximal end 34 of the sheath 32 through a lumen 33 . A hub or handle 46 is generally mounted on the proximal end 44 for controlling the guidewire 40 .
[0066] Generally, attached on or near the distal end 42 of the guidewire 40 is an expandable filter assembly 50 which generally comprises an expansion frame 52 and filter mesh 60 . The expansion frame 52 is generally adapted to open from a contracted condition while it is introduced through the lumen 33 of the sheath 32 to an enlarged condition once it is exposed within a blood vessel 70 , as will be discussed more particularly below. The filter mesh 60 is substantially permanently attached to the expansion frame 52 .
[0067] The construction of the stent catheter 10 should already be familiar to those skilled in the art. The catheter body 12 is typically made from substantially flexible materials such as polyethylene, nylon, PVC, polyurethane, or silicone, although materials such as polyethylene and PVC are preferred. The balloon 16 for delivering the stent 20 is generally manufactured from a substantially flexible and resilient material, such as polyethylene, polyester, latex, silicone, or more preferably polyethylene and polyester. A variety of balloons for angioplasty or stenting procedures are available which have a range of known inflated lengths and diameters, allowing an appropriate balloon to be chosen specifically for the particular blood vessel being treated.
[0068] The sheath 32 for the filter device 30 generally comprises a conventional flexible sheath or cannula for introducing catheters or guidewires into the blood stream of a patient. Exemplary materials include polyethylene, nylon, PVC, or polyurethane with polyethylene and pvc being most preferred. The hemostatic seal 38 generally is an annular seal designed to prevent the escape of blood from the vessel through the sheath 32 , and includes materials such as silicone, latex, or urethane, or more preferably silicone. The hemostatic seal 38 is substantially permanently adhered to the proximal end 34 of the sheath 32 using known surgically safe bonding materials.
[0069] The guidewire 40 is generally manufactured from conventional resilient wire such as stainless steel or nitinol, although stainless steel is preferred, having a conventional hub or handle 46 formed integral with attached to its proximal end 44 .
[0070] Turning now to FIG. 3, the filter assembly 50 of the present invention is generally shown extending from the distal end 36 of a sheath or catheter 32 and in an enlarged condition within a blood vessel 70 . The filter assembly 50 includes an expansion frame 52 comprising a plurality of struts, ribs or wires 54 , each strut 54 having a substantially fixed proximal end 56 and a distal end 58 , which may or may not be fixed. The proximal ends 56 are typically connected to the distal end 42 of the guidewire 40 , or alternatively to the outer surface of a distal region (not shown in FIG. 3) of the guidewire 40 , typically using conventional bonding methods, such as welding, soldering, or gluing. The distal ends 58 of the struts 54 are connected to the filter mesh 60 , or alternatively to the distal end of the guidewire (not shown). The struts generally comprise substantially resilient materials such as stainless steel or nitinol, with stainless steel being preferred.
[0071] Generally, the filter mesh 60 comprises a fine mesh having an open region 64 substantially engaging the wall 72 of the blood vessel 70 and a closed region 62 , shown here as the apex of a cone. An appropriate mesh is selected, having a pore size that permits blood to flow freely through the mesh, while capturing therein undesired particles of a targeted size. Appropriate filter materials are disclosed in co-pending applications Barbut et al., U.S. application Ser. No. 08/553,137, filed Nov. 7, 1995, Barbut et al., U.S. application Ser. No. 08/580,223, filed Dec. 28, 1995, Barbut et al., U.S. application Ser. No. 08/584,759, filed Jan. 9, 1996, Barbut et al., U.S. application Ser. No. 08/640,015, filed Apr. 30, 1996, Barbut et al., U.S. application Ser. No. 08/645,762, filed May 14, 1996, and Maahs, U.S. application Ser. No. 08/842,727, filed Apr. 16, 1997. The disclosure of these references and any others cited herein are expressly incorporated herein by reference. An exemplary embodiment of the mesh has a mesh area of 3-8 sq. in., a mesh thickness of 60-200 μm, a thread diameter of 30-100 μm, and a pore size of 60-100 μm. Polyethylene meshes, such as Saati Tech and Tetko, Inc. meshes, provide acceptable filter materials, as they are available in sheet form and can be easily cut and formed into a desired shape. The mesh is formed into a desired filter shape and is sonic welded or adhesive bonded to the struts 54 .
[0072] The present invention is then typically used to introduce a stent into a stenosed or occluded region of a patient, preferably for treating a region within the carotid arteries. Referring again to FIGS. 1 and 2, the catheter 10 is first introduced into a blood vessel 70 using known percutaneous procedures, and then is directed through the blood vessel to the stenosed region of the target blood vessel. The catheter 10 is typically introduced in an upstream-to-downstream (antegrade) orientation as shown in FIGS. 1 and 14, although the catheter may also be introduced in a downstream-to-upstream (retrograde) orientation as will be described below. In a preferred example, the catheter 10 is inserted into a femoral artery and directed using known methods to a carotid artery, as shown in FIG. 14, or alternatively is introduced through a lower region of a carotid artery and directed downstream to the stenosed location 74 .
[0073] The sheath 32 is percutaneously introduced into the blood vessel 70 downstream of the stenosed region 74 , and is deployed using conventional methods. The distal end 42 of the guidewire 40 is directed through the lumen 33 of the sheath 32 until the filter assembly 50 is introduced into the blood vessel 70 by pushing distally on the hub 46 on the guidewire 40 . When the distal end 42 of the guidewire 40 enters the blood vessel 70 , the expansion frame 52 is opened to its enlarged condition, extending substantially across the entire cross-section of the vessel 70 . The filter mesh 60 attached to the frame 52 substantially engages the luminal walls 72 of the vessel 70 , thereby capturing any undesirable loose material passing along the blood vessel 70 from the treated region 74 .
[0074] The catheter 10 is inserted through the stenosed region 74 until the stent 20 is centered across the plaque or embolic material 76 deposited on the walls 72 of the blood vessel 70 . If the region 74 is substantially blocked, it may be necessary to first open the region 74 using a balloon catheter prior to insertion of the stent catheter (not shown in FIG. 3), as will be familiar to those skilled in the art. Once the stent 20 is in the desired position, fluid, saline, or radiographic contrast media, but preferably radiographic contrast media, is introduced through the inflation lumen 18 to inflate the balloon 16 . As the balloon 16 expands, the pressure forces the stent 20 radially outwardly to engage the plaque 76 . The plaque 76 is pushed away from the region 74 , opening the vessel 70 . The stent 20 covers the plaque 76 , substantially permanently trapping it between the stent 20 and the wall 72 of the vessel 70 . Once the balloon 16 is fully inflated, the stent 20 provides a cross-section similar to the clear region of the vessel 70 . The balloon 16 is then deflated by withdrawing the fluid out of the inflation lumen 18 and the catheter 12 is withdrawn from the region 74 and out of the patient using conventional methods. The stent 20 remains in place, substantially permanently covering the plaque 76 in the treated region 74 and forming part of the lumen of the vessel 70 .
[0075] As the stenosed region 74 is being opened, or possibly as the catheter 12 is being introduced through the region 74 , plaque may break loose from the wall 72 of the vessel 70 . Blood flow will carry the material downstream where it will encounter the filter mesh 60 and be captured therein. Once the catheter 12 is removed from the treated region 74 , the expansion frame 52 for the filter mesh 60 is closed to the contracted position, containing any material captured therein. The filter assembly 50 is withdrawn into the lumen 33 of the sheath 32 , and the filter device 30 is removed from the body.
[0076] In another embodiment, shown in FIG. 2, the guidewire 40 and the filter assembly 50 are included within the stent catheter 10 , rather than being provided in a separate sheath, thus eliminating the need for a second percutaneous puncture into the patient. As already described, the catheter 12 is provided with an inflatable balloon 16 furnished near its distal end 14 and with a stent 20 compressed over the balloon 16 . In addition to the inflation lumen 18 , a second lumen 19 extends through the catheter 12 from a proximal region (not shown) to its distal end 14 . A guidewire 40 , having a filter assembly 50 on its distal end 42 , is introduced through the lumen 19 until its distal end 42 reaches the distal end 14 of the catheter 12 . As before, the filter assembly 50 comprises an expansion frame 52 and filter mesh 60 , which remain within the lumen 19 of the catheter 12 until deployed.
[0077] As described above, the stent catheter 10 is percutaneously introduced and is directed through the blood vessels until it reaches the stenosed region 74 and the stent 20 is centered across the plaque 76 . The guidewire 40 is pushed distally, introducing the filter assembly 50 into the blood vessel 70 . The expansion frame 52 is opened to the enlarged condition until the filter mesh 60 engages the walls 72 of the blood vessel 70 . The balloon 16 is then inflated, pushing the stent 20 against the plaque 76 , opening the treated region 74 . As before, the stent 20 substantially permanently engages the plaque 76 and becomes part of the lumen 72 of the vessel 70 . After the balloon 16 is deflated, the expansion frame 52 of the filter assembly 50 is closed to the contracted condition, and the filter assembly 50 is withdrawn into the lumen 19 . The stent catheter 10 is then withdrawn from the patient using conventional procedures.
[0078] Alternatively, a self-expanding stent may be substituted for the expandable stent described above. Generally, the stent is compressed onto a catheter, and a sheath is introduced over the catheter and stent. The sheath serves to retain the stent in its compressed form until time of deployment. The catheter is percutaneously introduced into a patient and directed to the target location within the vessel. With the stent in position, the catheter is fixed and the sheath is withdrawn proximally. Once exposed within the blood vessel, the stent automatically expands radially, until it substantially engages the walls of the blood vessel, thereby trapping the embolic material and dilating the vessel. The catheter and sheath are then removed from the patient.
[0079] The filter assembly 50 generally described above has a number of possible configurations. Hereinafter reference is generally made to the filter device described above having a separate sheath, although the same filter assemblies may be incorporated directly into the stent catheter.
[0080] Turning to FIGS. 4A, 4B, and 4 C, another embodiment of the filter device 30 is shown, namely a sheath 32 having a guidewire 40 in its lumen 33 and a filter assembly 50 extending from the distal end 36 of sheath 32 . The filter assembly 50 comprises a plurality of struts 54 and filter mesh 60 . The guidewire 40 continues distally through the filter mesh 60 to the closed end region 62 . The proximal ends 56 of the struts 54 are attached to the distal end 36 of the sheath 32 , while the distal ends 58 of the struts 54 are attached to the distal end 42 of the guidewire. In FIG. 4A, showing the contracted condition, the struts 54 are substantially straight and extend distally. At an intermediate region 57 , the open end 64 of the filter mesh 60 is attached to the struts 54 using the methods previously described. The filter mesh 60 may be attached to the struts 54 only at the intermediate region 57 or preferably continuously from the intermediate region 57 to the distal ends 58 .
[0081] In addition, at the intermediate region 57 , the struts 54 are notched or otherwise designed to buckle or bend outwards when compressed. Between the intermediate region 57 of the struts 54 and the distal end 36 of the sheath 32 , the guidewire 40 includes a locking member 80 , preferably an annular-shaped ring made of stainless steel, fixedly attached thereon. Inside the lumen 33 near the distal end 36 , the sheath 32 has a recessed area 82 adapted to receive the locking member 80 .
[0082] The guidewire 40 and filter assembly 50 are included in a sheath 32 as previously described, which is introduced into a blood vessel 70 , as shown in FIG. 4A, downstream of the stenosed region (not shown). With the sheath 32 substantially held in position, the guidewire 40 is pulled proximally. This causes the struts 54 to buckle and fold outward at the intermediate region 57 , opening the open end 64 of the filter mesh 60 as shown in FIG. 4B. As the guidewire 40 is pulled, the locking member 80 enters the lumen 33 , moving proximally until it engages the recessed area 82 , locking the expansion frame in its enlarged condition, as shown in FIG. 4C. With the expansion frame 52 in its enlarged condition, the open end 64 of the filter mesh 60 substantially engages the walls 72 of the blood vessel 70 .
[0083] After the stent is delivered (not shown), the expansion frame 52 is closed by pushing the guidewire 40 distally. This pulls the struts 54 back in towards the guidewire 40 , closing the open end 64 of the filter mesh 60 and holding any loose embolic material within the filter assembly 50 .
[0084] As a further modification of this embodiment, the entire sheath 32 and filter assembly 50 may be provided within an outer sheath or catheter (not shown) to protect the filter assembly 50 during introduction into the vessel. Once the device is in the desired location, the sheath 32 is held in place and the outer sheath is withdrawn proximally, exposing the filter assembly 50 within the blood vessel 70 . After the filter assembly 50 is used and closed, the sheath 32 is pulled proximally until the filter assembly 50 completely enters the outer sheath, which may then be removed.
[0085] Turning to FIGS. 5A, 5B and 5 C, another embodiment of the filter assembly 50 is shown. The proximal ends 56 of the plurality of struts 54 are substantially fixed to the distal end 36 of the sheath 32 . The distal ends 58 may terminate at the open end 64 of the filter mesh 60 , although preferably, the struts 54 extend distally through the filter mesh 60 to the closed end region 62 , where they are attached to the distal end 42 of the guidewire 40 .
[0086] Referring to FIG. 5A, the filter assembly 50 is shown in its contracted condition. The guidewire 40 has been rotated torsionally, causing the struts 54 to helically twist along the longitudinal axis of the guidewire 40 and close the filter mesh 60 . The filter assembly 50 is introduced into a blood vessel 70 as already described, either exposed on the end of the sheath 32 or, preferably, within an outer sheath (not shown) as described above.
[0087] Once in position, the sheath 32 is fixed, and the guidewire 40 is rotated torsionally in relation to the sheath 32 . As shown in FIG. 5B, the struts 54 , which are biased to move radially towards the wall 72 of the vessel 70 , unwind as the guidewire 40 is rotated, opening the open end 64 of the filter mesh 60 . Once the struts 54 are untwisted, the expansion frame in its enlarged condition causes the open end 64 of the filter mesh 60 to substantially engage the walls 72 of the vessel 70 , as shown in FIG. 5C.
[0088] After the stent is delivered (not shown), the guidewire 40 is again rotated, twisting the struts 54 back down until the expansion frame 52 again attains the contracted condition of FIG. 5A. The sheath 32 and filter assembly 50 are then removed from the blood vessel 70 .
[0089] Another embodiment of the filter assembly 50 is shown in FIGS. 6A and 6B. The struts 54 at their proximal ends 56 are mounted on or in contact with guidewire 40 , and their distal ends 58 are connected to form the expansion frame 52 , and are biased to expand radially at an intermediate region 57 . The proximal ends 56 are attached to the distal end 42 of the guidewire 40 with the distal ends 58 being extended distally from sheath 32 . Filter mesh 60 is attached to the struts 54 at the intermediate region 57 . If the filter assembly 50 is introduced in an antegrade orientation as previously described, the filter mesh 60 is typically attached from the intermediate region 57 to the distal ends 58 of the struts 54 , as indicated in FIG. 6A. Alternatively, if introduced in a retrograde orientation, it is preferable to attach the filter mesh 60 between the intermediate region 57 to the proximal ends 56 of the struts 54 , as shown in FIG. 6B, thus directing the interior of the filter mesh upstream to capture any embolic material therein.
[0090] The filter assembly 50 is provided with the struts 54 compressed radially in a contracted condition in the lumen 33 of the sheath 32 (not shown). The filter assembly 50 is introduced into the blood vessel 70 by directing the guidewire distally. As the expansion frame 52 enters the blood vessel, the struts 54 automatically expand radially into the enlarged condition shown in FIGS. 6A and 6B, thereby substantially engaging the open end 64 of the filter mesh 60 with the walls 72 of the blood vessel 70 . To withdraw the filter assembly 50 from the vessel 70 , the guidewire 40 is simply pulled proximally. The struts 54 contact the distal end 36 of the sheath 32 as they enter the lumen 33 , compressing the expansion frame 52 back into the contracted condition.
[0091] [0091]FIG. 8A presents another embodiment of the filter assembly 50 similar to that just described. The expansion frame 52 comprises a plurality of struts 54 having a filter mesh 60 attached thereon. Rather than substantially straight struts bent at an intermediate region, however, the struts 54 are shown having a radiused shape biased to expand radially when the filter assembly 50 is first introduced into the blood vessel 70 . The filter mesh 60 has a substantially hemispherical shape, in lieu of the conical shape previously shown.
[0092] Optionally, as shown in FIG. 8B, the filter mesh 60 may include gripping hairs 90 , preferably made from nylon, polyethylene, or polyester, attached around the outside of the open end 64 to substantially minimize undesired movement of the filter mesh 60 . Such gripping hairs 90 may be included in any embodiment presented if additional engagement between the filter mesh 60 and the walls 72 of the vessel 70 is desired.
[0093] [0093]FIG. 7 shows an alternative embodiment of the filter assembly 50 , in which the expansion frame 52 comprises a strut 54 attached to the filter mesh 60 . The open end 64 of the filter mesh 60 is biased to open fully, thereby substantially engaging the walls 72 of the blood vessel 70 . The mesh material itself may provide sufficient bias, or a wire frame (not shown) around the open end 64 may be used to provide the bias to open the filter mesh 60 .
[0094] The filter mesh 60 is compressed prior to introduction into the sheath 32 . To release the filter assembly 50 into the blood vessel 70 , the guidewire 40 is moved distally. As the filter assembly 50 leaves the lumen 33 of the sheath 32 , the filter mesh 60 opens until the open end 64 substantially engages the walls 72 of the blood vessel 70 . The strut 54 attached to the filter mesh 60 retains the filter mesh 60 and eases withdrawal back into the sheath 32 . For removal, the guidewire 40 is directed proximally. The strut 54 is drawn into the lumen 33 , pulling the filter mesh 60 in after it.
[0095] In a further alternative embodiment, FIG. 9 shows a filter assembly 50 comprising a plurality of substantially cylindrical, expandable sponge-like devices 92 , having peripheral surfaces 94 which substantially engage the walls 72 of the blood vessel 70 . The devices 92 are fixed to the guidewire 40 which extends centrally through them as shown. The sponge-like devices have sufficient porosity to allow blood to pass freely through them and yet to entrap undesirable substantially larger particles, such as loose embolic material. Exemplary materials appropriate for this purpose include urethane, silicone, cellulose, or polyethylene, with urethane and polyethylene being preferred.
[0096] In addition, the devices 92 may have varying porosity, decreasing along the longitudinal axis of the guidewire. The upstream region 96 may allow larger particles, such as embolic material, to enter therein, while the downstream region 98 has sufficient density to capture and contain such material. This substantially decreases the likelihood that material will be caught only on the outer surface of the devices, and possibly come loose when the devices is drawn back into the sheath.
[0097] The devices 92 are compressed into the lumen 33 of the sheath 32 (not shown), defining the contracted condition. They are introduced into the blood vessel 70 by pushing the guidewire 40 distally. The devices 92 enter the vessel 70 and expand substantially into their uncompressed size, engaging the walls 72 of the vessel 70 . After use, the guidewire 40 is pulled proximally, compressing the devices 92 against the distal end 36 of the sheath 32 and directing them back into the lumen 33 .
[0098] Turning to FIG. 10, another embodiment of the present invention is shown, that is, a stent catheter 10 having a filter assembly 50 provided directly on its outer surface 13 . The stent catheter 10 includes similar elements and materials to those already described, namely a catheter 12 , an inflatable balloon 16 near the distal end 14 of the catheter 12 , and a stent 20 compressed over the balloon 16 . Instead of providing a filter assembly 50 on a guidewire, however, the filter assembly 50 typically comprises an expansion frame 52 and filter mesh 60 attached directly to the outer surface 13 of the catheter 12 . Preferably, the expansion frame 52 is attached to the catheter 12 in a location proximal of the stent 20 for use in retrograde orientations, although optionally, the expansion frame 52 may be attached distal of the stent 20 and used for antegrade applications.
[0099] The filter assembly 50 may take many forms similar to those previously described for attachment to a guidewire. In FIG. 10, the expansion frame 52 includes a plurality of radially biased struts 54 , having proximal ends 56 and distal ends 58 . The proximal ends 56 of the struts 54 are attached to the outer surface 13 of the catheter 12 proximal of the stent 20 , while the distal ends 58 are loose. Filter mesh 60 , similar to that already described, is attached to the struts 54 between the proximal ends 56 and the distal ends 58 , and optionally to the outer surface 13 of the catheter 12 where the proximal ends 56 of the struts 52 are attached.
[0100] Prior to use, a sheath 132 is generally directed over the catheter 12 . When the sheath engages the struts 54 , it compresses them against the outer surface 13 of the catheter 12 . The catheter 12 and the sheath 132 are then introduced into the patient, and directed to the desired location. Once the stent 20 is in position, the catheter 12 is fixed and the sheath 132 is drawn proximally. As the struts 58 enter the blood vessel 70 , the distal ends 58 move radially, opening the filter mesh 60 . Once the filter assembly 50 is fully exposed within the blood vessel 70 , the distal ends 58 of the struts 54 , and consequently the open end 64 of the filter mesh 60 , substantially engage the walls 72 of the blood vessel 70 .
[0101] After the stent is deployed, the sheath 132 is pushed distally. As the struts 54 enter the lumen 133 of the sheath 132 , they are compressed back against the outer surface 13 of the catheter 12 , thereby containing any captured material in the filter mesh 60 . The catheter 12 and sheath 132 are then withdrawn from the vessel 70 .
[0102] Turning to FIGS. 11A and 11B, an alternative embodiment of the expansion frame 50 is shown. The proximal ends 56 of the struts 54 are attached or in contact with the outer surface 13 of the catheter 12 . The struts 54 have a contoured radius biased to direct an intermediate region 57 radially. Filter mesh 60 is attached between the intermediate region 57 and the proximal ends 56 , or between the intermediate region and the distal end (not shown). FIG. 11A shows the filter assembly 50 in its contracted condition, with a sheath 132 covering it. The sheath 132 compresses the struts 54 against the outer surface 13 of the catheter 12 , allowing the device to be safely introduced into the patient. Once in position, the sheath 132 is pulled proximally as shown in FIG. 11B. As the distal end 136 of the sheath 132 passes proximal of the filter assembly 50 , the struts 54 move radially, causing the intermediate region 57 of the struts 54 and the open end of the filter mesh 60 to substantially engage the walls 72 of the blood vessel 70 . After use, the sheath 132 is directed distally, forcing the struts 54 back against the catheter 12 and containing any material captured within the filter mesh 60 .
[0103] In another embodiment of the present invention, shown in FIGS. 12A and 12B, a stent catheter 10 , similar to those previously described, is provided with a fluid operated filter assembly 50 attached on or near the distal end 14 of the catheter 12 . The catheter 12 includes a first inflation lumen 18 for the stent balloon 16 , and a second inflation lumen 19 for inflating an expansion frame 52 for the filter assembly 50 . The expansion frame 52 generally comprises an inflatable balloon 102 , preferably having a substantially annular shape. The balloon 102 generally comprises a flexible, substantially resilient material, such as silicone, latex, or urethane, but with urethane being preferred.
[0104] The second inflation lumen 19 extends to a region at or near to the distal end 14 of the catheter 12 , and then communicates with the outer surface 13 , or extends completely to the distal end 14 . A conduit 104 extends between the balloon 102 and the inflation lumen 19 . The conduit 104 may comprise a substantially flexible tube of material similar to the balloon 102 , or alternatively it may be a substantially rigid tube of materials such as polyethylene. Optionally, struts or wires 106 are attached between the balloon 102 and the catheter 12 to retain the balloon 12 in a desired orientation. Filter mesh 60 , similar to that previously described, is attached to the balloon 102 .
[0105] Turning more particularly to FIG. 12A, the filter assembly 50 is shown in its contracted condition. The balloon 102 is adapted such that in its deflated condition it substantially engages the outer surface 13 of the catheter 12 . This retains the filter mesh 60 against the catheter 12 , allowing the catheter 12 to be introduced to the desired location within the patient's blood vessel 70 . The catheter 12 is percutaneously introduced into the patient and the stent 20 is positioned within the occluded region 74 . Fluid, such as saline solution, is introduced into the lumen 19 , inflating the balloon 102 . As it inflates, the balloon 102 expands radially and moves away from the outer surface 13 of the catheter 12 .
[0106] As shown in FIG. 12B, once the balloon 102 is fully inflated to its enlarged condition, it substantially engages the walls 72 of the blood vessel 70 and opens the filter mesh 60 . Once the stent 20 is delivered and the stent balloon 16 is deflated, fluid is drawn back out through the inflation lumen 19 , deflating the balloon 102 . Once deflated, the balloon 102 once again engages the outer surface 13 of the catheter 12 , closing the filter mesh 60 and containing any embolic material captured therein. The catheter 12 is then withdrawn from the patient.
[0107] Alternatively, the filter assembly 50 just described may be mounted in a location proximal to the stent 20 as shown in FIGS. 13A and 13B. The open end 64 of the filter mesh 60 is attached to the balloon 102 , while the closed end 62 is attached to the outer surface 13 of the catheter 12 , thereby defining a space for capturing embolic material. In the contracted condition shown in FIG. 13A, the balloon 102 substantially engages the outer surface 13 of the catheter 12 , thereby allowing the catheter 10 to be introduced or withdrawn from a blood vessel 70 . Once the stent 20 is in position across a stenosed region 74 , the balloon 102 is inflated, moving it away from the catheter 12 , until it achieves its enlarged condition, shown in FIG. 13B, whereupon it substantially engages the walls 72 of the blood vessel 70 .
[0108] A detailed longitudinal view of a filter guidewire is shown in FIG. 15. Guidewire 40 comprises inner elongate member 207 surrounded by a second elongate member 201 , about which is wrapped wire 211 in a helical arrangement. Guidewire 40 includes enlarged segment 202 , 208 which houses a series of radially biased struts 203 . Helical wires 211 separate at cross-section 205 to expose the eggbeater filter contained within segment 202 . Guidewire 40 includes a floppy atraumatic tip 204 which is designed to navigate through narrow, restricted vessel lesions. The eggbeater filter is deployed by advancing distally elongate member 201 so that wire housing 211 separates at position 205 as depicted in FIG. 15A. Elongate member 207 may be formed from a longitudinally stretchable material which compresses as the struts 203 expand radially. Alternatively, elongate member 207 may be slideably received within sheath 201 to allow radial expansion of struts 203 upon deployment. The filter guidewire may optionally include a coil spring 206 disposed helically about elongate member 207 in order to cause radial expansion of struts 203 upon deployment.
[0109] A typical filter guidewire will be constructed so that the guidewire is about 5F throughout segment 208 , 4F throughout segment 209 , and 3F throughout segment 210 . The typical outer diameter in a proximal region will be 0.012-0.035 inches, more preferably 0.016-0.022 inches, more preferably 0.018 inches. In the distal region, a typical outer diameter is 0.020-0.066 inches, more preferably 0.028-0.036 inches, more preferably 0.035 inches. Guidewire length will typically be 230-290 cm, more preferably 260 cm for deployment of a balloon catheter. It should be understood that reducing the dimensions of a percutaneous medical instrument to the dimensions of a guidewire as described above is a significant technical hurdle, especially when the guidewire includes a functioning instrument such as an expansible filter as disclosed herein. It should also be understood that the above parameters are set forth only to illustrate typical device dimensions, and should not be considered limiting on the subject matter disclosed herein.
[0110] In use, a filter guidewire is positioned in a vessel at a region of interest. The filter is deployed to an expanded state, and a medical instrument such as a catheter is advanced over the guidewire to the region of interest. Angioplasty, stent deployment, rotoblader, atherectomy, or imaging by ultrasound or Doppler is then performed at the region of interest. The medical/interventional instrument is then removed from the patient. Finally, the filter is compressed and the guidewire removed from the vessel.
[0111] A detailed depiction of an eggbeater filter is shown in FIGS. 16, 16A, 16 B, and 16 C. With reference to FIG. 16, the eggbeater filter includes pressure wires 212 , primary wire cage 213 , mesh 52 , and optionally a foam seal 211 which facilitates substantial engagement of the interior lumen of a vessel wall and conforms to topographic irregularities therein. The eggbeater filter is housed within catheter sheath 32 and is deployed when the filter is advanced distally beyond the tip of sheath 32 . This design will accommodate a catheter of size 8F (0.062 inches, 2.7 mm), and for such design, the primary wire cage 213 would be 0.010 inches and pressure wires 212 would be 0.008 inches. These parameters can be varied as known in the art, and therefore should not be viewed as limiting.
[0112] [0112]FIGS. 16A and 16B depict the initial closing sequence at a cross-section through foam seal 214 . FIG. 16C depicts the final closing sequence.
[0113] [0113]FIGS. 17 and 17A depict an alternative filter guidewire which makes use of a filter scroll 215 disposed at the distal end of guidewire 40 . Guidewire 40 is torsionally operated as depicted at 216 in order to close the filter, while reverse operation ( 217 ) opens the filter. The filter scroll may be biased to automatically spring open through action of a helical or other spring, or heat setting. Alternatively, manual, torsional operation opens the filter scroll. In this design, guidewire 40 acts as a mandrel to operate the scroll 215 .
[0114] An alternative embodiment of a stent deployment blood filtration device is depicted in FIGS. 18, 18A, and 18 B. With reference to FIG. 18, catheter 225 includes housing 220 at its proximal end 221 , and at its distal end catheter 225 carries stent 223 and expandable filter 224 . In one embodiment, expandable filter 224 is a self-expanding filter device optionally disposed about an expansion frame. In another embodiment, filter 224 is manually operable by controls at proximal region 221 for deployment. Similarly, stent 223 can be either a self-expanding stent as discussed above, or a stent which is deployed using a balloon or other radially expanding member. Restraining sheath 222 encloses one or both of filter 224 and stent 223 . In use, distal region 226 of catheter 225 is disposed within a region of interest, and sheath 222 is drawn proximally to first exposed filter 224 and then exposed stent 223 . As such, filter 224 deploys before stent 223 is radially expanded, and therefore filter 224 is operably in place to capture any debris dislodged during stent deployment as depicted in FIG. 18A. FIG. 18B shows an alternative embodiment which employs eggbeater filter 224 in the distal region.
[0115] An alternative design for the construction of an eggbeater filter is shown in FIG. 19. This device includes inner sheath 231 , outer sheath 230 , and a plurality of struts 232 which are connected to outer sheath 230 at a proximal end of each strut, and to inner sheath 231 at a distal end of each strut. Filter expansion is accomplished by moving inner sheath 231 proximal relative to outer sheath 230 , which action causes each strut to buckle outwardly. It will be understood that the struts in an eggbeater filter may be packed densely to accomplish blood filtration without a mesh, or may include a mesh draped over a proximal portion 233 or a distal portion 234 , or both.
[0116] In another embodiment, a filter guidewire is equipped with a distal imaging device as shown in FIG. 20. Guidewire 40 includes eggbeater filter 224 and restraining sheath 222 for deployment of filter 224 . The distal end of guidewire 40 is equipped with imaging device 235 which can be any of an ultrasound transducer or a Doppler flow velocity meter, both capable of measuring blood velocity at or near the end of the guidewire. Such a device provides valuable information for assessment of relative blood flow before and after stent deployment. Thus, this device will permit the physician to determine whether the stent has accomplished its purpose or been adequately expanded by measuring and comparing blood flow before and after stent deployment.
[0117] In use, the distal end of the guidewire is introduced into the patient's vessel with the sheath covering the expandable filter. The distal end of the guidewire is positioned so that the filter is downstream of a region of interest and the sheath and guidewire cross the region of interest. The sheath is slid toward the proximal end of the guidewire and removed from the vessel. The expandable filter is uncovered and deployed within the vessel downstream of the region of interest. A percutaneous medical instrument is advanced over the guidewire to the region of interest and a procedure is performed on a lesion in the region of interest. The percutaneous medical instrument can be any surgical tool such as devices for stent delivery, balloon angioplasty catheters, atherectomy catheters, a rotoblader, an ultrasound imaging catheter, a rapid exchange catheter, an over-the-wire catheter, a laser ablation catheter, an ultrasound ablation catheter, and the like. Embolic material generated during use of any of these devices on the lesion is captured before the expandable filter is removed from the patient's vessel. The percutaneous instrument is then withdrawn from the vessel over the guidewire. A sheath is introduced into the vessel over the guidewire and advanced until the sheath covers the expandable filter. The guidewire and sheath are then removed from the vessel.
[0118] Human aortic anatomy is depicted in FIG. 21. During cardiac surgery, bypass cannula 243 is inserted in the ascending aorta and either balloon occlusion or an aortic cross-clamp is installed upstream of the entry point for cannula 243 . The steps in a cardiac procedure are described in Barbut et al., U.S. application Ser. No. 08/842,727, filed Apr. 16, 1997, and the level of debris dislodgment is described in Barbut et al., “Cerebral Emboli Detected During Bypass Surgery Are Associated With Clamp Removal,” Stroke, 25(12):2398-2402 (1994), which is incorporated herein by reference in its entirety. FIG. 21 demonstrates that the decoupling of the filter from the bypass cannula presents several avenues for filter deployment. As discussed in Maahs, U.S. Pat. No. 5,846,260, incorporated herein by reference, a modular filter may be deployed through cannula 243 either upstream 244 or downstream 245 . In accordance with the present disclosure, a filter may be deployed upstream of the innominate artery within the aorta by using a filter guidewire which is inserted at 240 through a femoral artery approach. Alternatively, filter guidewire may be inserted through route 241 by entry into the left subclavian artery or by route 242 by entry through the right subclavian artery, both of which are accessible through the arms. The filter guidewire disclosed herein permits these and any other routes for accessing the ascending aorta and aortic arch for blood filtration.
[0119] In another embodiment, a generalized filter guidewire is depicted in FIG. 22. FIG. 23 shows guidewire 40 having sleeve 250 disposed thereabout. Sleeve 250 includes longitudinally slitted region 251 which is designed to radially expand when compressed longitudinally. Thus, when the distal end of sleeve 250 is pulled proximally, the slitted region 251 buckles radially outwardly as shown in FIG. 23A to provide a form of eggbeater filter. The expanded cage thus formed may optionally include mesh 52 draped over a distal portion, a proximal portion, or both.
[0120] In use, a stent catheter, such as those previously described, is used in a retrograde application, preferably to prevent the detachment of mobile aortic plaque deposits within the ascending aorta, the aortic arch, or the descending aorta. Preferably, the stent catheter is provided with a filter assembly, such as that just described, attached to the catheter proximal of the stent. Alternatively, a stent catheter without any filter device, may also be used. The stent catheter is percutaneously introduced into the patient and directed to the desired region. Preferably, the catheter is inserted into a femoral artery and directed into the aorta, or is introduced into a carotid artery and directed down into the aorta. The stent is centered across the region which includes one or more mobile aortic deposits.
[0121] If a filter assembly is provided on the catheter, it is expanded to its enlarged condition before the stent is deployed in order to ensure that any material inadvertently dislodged is captured by the filter. Alternatively, a sheath having a guidewire and filter assembly similar to those previously described may be separately percutaneously introduced downstream of the region being treated, and opened to its enlarged condition.
[0122] The stent balloon is inflated, expanding the stent to engage the deposits. The stent forces the deposits against the wall of the aorta, trapping them. When the balloon is deflated, the stent substantially maintains its inflated cross-section, substantially permanently containing the deposits and forming a portion of the lumen of the vessel. Alternatively, a self-expanding stent may be delivered, using a sheath over the stent catheter as previously described. Once the stent has been deployed, the filter assembly is closed, and the stent catheter is withdrawn using conventional methods.
[0123] Unlike the earlier embodiments described, this method of entrapping aortic plaque is for a purpose other than to increase luminal diameter. That is, mobile aortic deposits are being substantially permanently contained beneath the stent to protect a patient from the risk of embolization caused by later detachment of plaque. Of particular concern are the ascending aorta and the aortic arch. Loose embolic material in these vessels presents a serious risk of entering the carotid arteries and traveling to the brain, causing serious health problems or possibly even death. Permanently deploying a stent into such regions substantially reduces the likelihood of embolic material subsequently coming loose within a patient, and allows treatment without expensive intrusive surgery to remove the plaque.
[0124] While the invention is susceptible to various modifications, and alternative forms, specific examples thereof have been shown in the drawings and are herein described in detail. It should be understood, however, that the invention is not to be limited to the particular forms or methods disclosed, but to the contrary, the invention is to cover all modifications, equivalents and alternatives falling within the spirit and scope of the appended claims.
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The invention provides a nested tubing cannula which comprises outer and inner elongate tubular members, both having a proximal end, a distal end, and a lumen therebetween. The inner tubular member is sealed at its distal end and is nested substantially coaxially within the lumen of the outer tubular member, so that the gap between the inner and the outer tubular member defines a second lumen whereas the first lumen is the lumen of the inner tubular member. A tubular sleeve is disposed coaxially between the inner and outer tubular members. A balloon is mounted on a distal region of the outer tubular member and is in communication with the first lumen. The cannula further comprises a port proximal or distal the balloon occluder and is in communication with the second lumen. Methods for making the devices herein are disclosed.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] This invention relates to surgical apparatus, particularly an integrated cable, crimping and tensioning system.
[0003] 2. Description of the Prior Art
[0004] Surgical cable is used in reconstructive spine surgery, such as fusion and spine trauma surgery, total hip replacement, fracture fixation, surgical closures, and the like. Cable and wire may be used to encircle broken bones to hold them together for healing. The cable may be monofilament or multifilament.
[0005] In general, surgical cable and wire require a length of cable to be applied about the skeletal member, a device or tensioner to apply tension to the cable to hold the skeletal member in the desired position, and a crimp or device to lock the cable in the preferred position. One conventional cable employs a titanium cable and a double lumen crimp. The crimp is a short rod with the double lumen passing longitudinally therethrough. The cable is passed through one lumen of the crimp, around the skeletal repair site and back through the other lumen. A tensioner is used to set the cable in place and a crimp is placed perpendicularly in the cable between the ends of the double lumen crimp. See U.S. Pat. No. 5,116,340 to Songer et al. Songer also discloses a tensioner device like a pair of pliers having opposed jaws for deforming the crimp on the cable. One of the opposing handles has a winding reel for creating the desired tension in the cable before the crimp is set. The cable may have an eyelet on one end through which the other end passes so that the deformed crimp is stopped by the larger eyelet.
[0006] A problem area for cable is the relative stiffness of the metal wires or strands and the relatively large diameter. These aspects detract from the ability to thread the cable through small skeletal openings and making sharp changes in direction. U.S. Pat. No. 5,997,542 to Burke addresses this problem and discloses another cable with one portion being more flexible and of smaller diameter than the rest of the cable. The smaller portion is used as a lead to thread the cable about the bones for placement. Burke also teaches an enlarged end on the cable by swaging or crimping the end of the cable in a blind bore of an enlargement.
[0007] Blackman et al, U.S. Pat. No. 6,146,386, discloses a surgical cable system with a tensioner operated by hand grips and ratchet. The cable is looped about bone anchors and tension is applied to displace the bones. Once the bones are properly located, the bone anchors fix the bones in place and the cable is removed from the body.
[0008] Wagner et al, U.S. Pat. No. 6,391,030, discloses a cable system with a cable, a tensioner and a connector for securing the cable in place about skeletal bones. The connector serves as a crimp to fix the size of the cable loop. The connector is separate from the cable and in one modification, the end of the cable has an enlargement to prevent disconnection. The connector has a pin that is rotatable to allow passage of the cable in one position and to secure the cable within the connector in another position. The pin is deformed upon locking the cable to prevent dislodgement.
[0009] Ferree, U.S. Pat. No. 6,514,255, discloses a cable system having a body which is movably mounted on a spinal rod and connected to a looped cable that extends around a vertebrae The body is moved to the preferred location on the rod and the cable loop is tightened to fix the body to the spinal rod and apply pressure to the hold the bones and body in place.
[0010] These prior art systems all apply the tensioner directly to the end of the cable and crimp which induces a certain amount of slack in the fixed cable. Usually, this is caused by the space needed to position the working end of the tensioner immediately adjacent the tissue and/or the several manipulative steps needed to crimp the cable and/or the stiffness of the cable in transitioning from the radius of the bone and into the crimp. More than one setting of the crimp is sometimes necessary to arrive at the preferred fixing of the cable tension.
SUMMARY OF THE PRESENT INVENTION
[0011] Accordingly, it is an objective of this invention to provide a surgical cable system in which the first fixation of the permanent crimp is the final fixation at the proper cable tension and loop size.
[0012] It is another objective of the invention to provide a more flexible cable by increasing the number of filaments and decreasing filament size.
[0013] It is yet another objective of this invention to provide a permanent fastener with a low profile and passageway wherein the cable does not change direction, significantly, and reduces friction.
[0014] It is a further objective of this invention to provide a provisional clamp to remove the working end of the tensioner from the location of the permanent clamp during tensioning of the cable. The provisional fastener provides for one-way travel of the cable to maintain cable tension during adjustment of tension and relieves tension from the permanent clamp until that clamp is set.
[0015] It is another objective of this invention to provide a tensioner instrument for manually setting the tension on the cable. The instrument provides for one way movement of the cable that is precisely controlled and provides increased range of cable translation per cycle.
[0016] It is a still further objective of this invention to teach a method of placing a crimped surgical cable with a minimum number of adjustments. The components of the invention operate thusly; one end of the surgical cable is fixed to a permanent clamp and the free end of the cable is threaded around the skeletal processes to be held in place; the free end of the cable is then inserted through the permanent clamp; the provisional clamp is placed on the free end of the cable extending from the permanent fastener; the end of the cable extends through the provisional clamp longitudinally; the tensioner is placed on the provisional fastener and grips the free end of the cable; the hand grips of the tensioner are moved together to pull the free end of the cable to tighten the loop about the skeletal processes; the provisional fastener is constructed to allow the cable to move through the provisional fastener in one direction, only; as the hand grips are squeezed, the diameter of the loop is reduced and the proper tension is established in the cable; when the doctor or operator is satisfied with the placement, the tensioner is removed from the provisional fastener; the button on the side of the permanent fastener is moved to engage the cable in a non-slip crimp within the permanent clamp, the tension in the provisional clamp is then released so that the provisional fastener is slid off the free end of the cable; the excess cable is then cut. In this manner, the tension in the cable is maintained by both the provisional fastener and the tensioner with the permanent fastener and stop being free of tension until after the crimp is set.
SHORT DESCRIPTION OF THE DRAWINGS
[0017] FIG. 1 is a side view of the permanent clamp and surgical cable of this invention;
[0018] FIG. 2 is an exploded perspective of the permanent clamp;
[0019] FIG. 3 is a cross section of the permanent clamp;
[0020] FIG. 4 a perspective of the tensioner of this invention;
[0021] FIG. 5 is a front view of the tensioner of this invention;
[0022] FIG. 6 is a longitudinal cross section of the tensioner;
[0023] FIG. 7 is a partial cross section of the tensioner of FIG. 5 ; and
[0024] FIG. 8 is a cross section of the provisional clamp of this invention.
DETAILED DESCRIPTION OF THE INVENTION
[0025] A number of embodiments of the present invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, it is to be understood that the invention is not to be limited by the specific illustrated embodiment but only by the scope of the appended claims.
[0026] The integrated cable system is composed of a surgical cable 11 , a tensioner 12 , a provisional clamp 13 and a permanent clamp 14 . The cable may be a monofilament steel wire or a multifilament cable. The preferred cable has approximately 133 filaments of titanium alloy and a superior flexibility.
[0027] One end of the cable 11 is affixed to the permanent clamp 14 , shown in FIGS. 1-3 . Depending on the materials used, the clamp may be swaged onto the cable or soldered or welded or otherwise suitably joined. The permanent clamp has a rectangular body of low profile with a top wall 15 , a bottom wall 16 , opposite side walls 17 , 18 connecting the top and bottom walls, and opposite front wall 19 and rear wall 20 connecting the top and bottom walls and perpendicularly connected to the side walls. The cable exits the rear wall 20 in line with the longitudinal axis of the clamp.
[0028] Near the front wall 19 , a cable bore 21 extends through the permanent clamp from the bottom wall 16 through the top wall 5 . The axis of the bore, as illustrated, is at an angle with the front wall 19 . The angle is oriented to lessen the change in direction of the cable as it transits the permanent clamp. After the cable 11 has encircled the desired bones or bone fragments, the lead end of the cable is passed through the cable bore 21 and extends above the top wall. The cable bore 21 is of a diameter closely approximating the diameter of the cable 11 . A lateral bore 22 passes through the side walls 17 and 18 tangentially intersecting cable bore 21 within the permanent clamp. Within the lateral bore 21 is a clamp mandrel 23 . The mandrel 23 is movable from an open position to a clamping position which deforms the cable and/or obstructs cable bore and prevents retrograde movement of the cable 11 out of the permanent clamp 14 . The end 24 of the mandrel is exposed in the open end 25 of the lateral bore and may be moved by either a push-pull motion along the axis of the mandrel or a rotational move about the axis. In the preferred embodiment, the mandrel 23 is composed of a split tube 26 . The split tube 26 has semi-circular legs 27 , 28 which extend across the tangential opening in the cable bore. The space between the semi-circular legs provides resilience in the split tube and allows the cable to pass through the cable bore during tensioning. The clamp is applied when the stop 29 is pushed into the split tube 26 causing the semi-circular legs to expand and wedge the cable 11 against the cable bore 21 .
[0029] In operation, the cable is looped about the bones and through the permanent clamp. The cable and permanent clamp may be pre-assembled with the free end of the cable inserted through the clamp forming an adjustable loop. The leading end of the cable is threaded through the provisional clamp 13 and into the tensioner 12 . The provisional clamp 13 , shown in FIG. 8 , has an inner tubular core 32 with a through bore 33 extending from the distal end 30 to the proximal end 31 . The distal end 30 contacts the permanent clamp 14 , about the cable bore 21 , and the proximal end 31 contacts the tensioner 12 . The proximal end of the core is formed as a disk 39 . Between the distal and proximal ends of the core, there is an area 34 of reduced diameter having a proximal annular ledge 35 . The inner core 32 has a transverse slit 36 oriented at an angle to the through bore with the lower end 37 of the slit intersecting the through bore 33 . Within the slit 36 is a roller bearing 38 movable from one end of the slit to the other. When the roller bearing 38 is at the lower end 37 of the slit 36 it obstructs the through bore 33 .
[0030] An outer sleeve 40 surrounds the core 32 and is telescopically movable along the axis of the inner core. Near the rearward end, an external flange 45 projects outwardly. Near the forward end of the sleeve there is an internal shoulder 41 . Resting on the shoulder 41 is a ring 42 . Between the ring 42 and the ledge 35 is a coil spring 49 encircling the reduced diameter area of the core. The ring 42 is in contact with the opposite ends of the roller bearing 38 thereby biasing the bearing toward the lower end of the slit 36 which permits movement of the cable from the permanent clamp toward the tensioner but prevents retrograde movement. Upon movement of the cable toward the tensioner 12 , the ring will compress the spring slightly and upon release of the tension the roller bearing 38 is spring biased to wedge the cable in the through bore 33 .
[0031] To release the cable in the provisional clamp, the disk 39 and flange 45 are used to telescope the inner core and outer sleeve into a compact position. This moves a portion of the slit 36 below the ring 42 allowing the roller bearing freedom to move away from the cable an out of the through bore.
[0032] The tensioner 12 , shown in FIG. 4-7 , has an elongated central shaft 50 with a cable guide 51 on the distal end and a head 61 on the other end. The cable guide 51 contacts the provisional clamp 13 . The cable guide 51 has an aperture therethrough with an axis parallel to the longitudinal axis of the shaft 50 . The cable 11 is threaded through the cable guide and extends along the shaft to the cable chuck 52 . At the proximal end of the shaft, the head 61 is connected to hand grips 53 and 54 by links 55 and 56 , respectively. A pivot pin 57 connects one end of link 55 to the shaft and a pivot pin 58 connects the other end to the hand grip 53 . A pivot pin 59 connects one end of link 56 to the shaft and a pivot pin 60 connects the other end to hand grip 54 .
[0033] The cable chuck 52 is slidably mounted on the shaft 50 between the cable guide 51 and the head 61 . The cable chuck has a body 62 and a tubular extension 63 which telescopes along the shaft 50 for directional control of the chuck and compression of a coil spring 80 surrounding the shaft. The distal ends of the hand grips 53 , 54 are pivotally connected to the cable chuck body 62 by pivot pins 64 . The proximal ends of the hand grips are free and spring biased to move away from each other limited by the length of the links 55 , 56 . The coil spring 80 has one end resting on a shoulder 81 inside the tubular extension of the chuck. The other end of the spring engages a flange 82 on the shaft. The relative movement of the shaft and the tubular extension 63 compresses the spring 80 as the hand grips move together. Release of the hand grips permits unloading of the spring and outward movement of the hand grips.
[0034] The chuck body 62 has a bore 65 through which the cable 11 passes. Within the body 62 , is the clutch 70 which engages the cable 11 in the bore 65 allowing tension to be exerted by the tensioner 12 , when the hand grips move toward each other, resulting in the reduction of the size of the cable loop about the bones or bone fragments.
[0035] The clutch 70 is housed in a passage 71 in the chuck body that intercepts the bore 65 at an acute angle. A clutch pin 72 is biased into the bore 65 by spring 73 . The passage is closed by screw 74 . Also, within the passage 71 is a transverse rod 75 resting between the clutch pin 72 and the spring 73 . The rod extends through an aperture in the chuck body and is connected to a clutch arm 76 . A leaf spring 77 extends between the end of the clutch arm 76 and the hand grips. As the hand grips close, the clutch arm 76 releases the rod 75 and allows the spring 73 to bias the clutch pin 72 to obstruct the cable bore 65 . When the hand grips are closed and released to open, the leaf spring 77 pushes the clutch arm 76 to move the rod 75 to engage the spring 73 and remove the bias from the clutch pin 72 permitting the tensioner to move along the cable for a sequential cycle. When the clutch 70 in the tensioner 12 is released, the provisional clamp 13 maintains the cable position and prevents retrograde movement of the cable 11 . The surgeon then pulls on the cable in the area between the hand grips to remove the slack from the tensioned cable and the steps are repeated until the cable is.
[0036] The components of the cable system operate most effectively when used together however, the cable, the permanent clamp, the provisional clamp and the tensioner may be employed separately, either singly or in combinations, with other conventional components.
[0037] During a surgical procedure, the skeletal bones are accessed and the desired position of the permanent clamp is selected. Depending on circumstances, the permanent clamp and the provisional clamp may be pre-installed on the cable loop. In some instances, the tensioner may also be connected to the cable. The loop is placed about the boney processes to be stabilized and the permanent clamp is placed at the desired final position. The slack is taken out of the loop which places the permanent clamp in a relatively immobile site resting on a portion of the boney processes. The increased flexibility of the cable construction permits sharper radius turns without producing slack. The provisional clamp is in contact with the permanent clamp and the tensioner is in contact with the provisional clamp. This provides a substantial span of cable oriented in a straight line which results in less distortion between the cable and the permanent clamp which, in turn, results in a tighter loop being formed. There is no deforming pressure between the cable and the permanent clamp, at this time, and this also contributes to a tighter loop.
[0038] The shaft of the tensioner is placed on the provisional clamp and, in effect, becomes immobile because of the position of the permanent clamp. As the hand grips are squeezed, the shaft remains stationary and the chuck moves away from the cable guide. Both the roller bearing in the provisional clamp and the clutch in the tensioner grip the cable and provide one-way movement of the cable in response to the movement of the chuck. When the hand grips approach each other, the squeezing pressure is released and the hand grips spring apart. This motion releases the clutch in the tensioner however, the cable is still wedged in the provisional clamp. Also, the chuck has traveled down the cable to begin a new cycle of tightening of the loop.
[0039] When the boney processes are in satisfactory stabilized position, the clutch in the tensioner is released freeing the tensioner to move along the cable. The permanent clamp is manually fixed on the cable. The provisional clamp is manually released to move along the cable and the excess cable above the permanent clamp is cut. The incision is then closed.
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A surgical cable system for fixing bones in a spatial relationship is composed of a multistrand cable having improved flexibility with a fastener on one end and a free end. The fastener has an aperture through which the free end of the cable is inserted after being looped around the bones. The fastener has a stop in the aperture to crimp the cable to permanently fix the loop in the desired position. The tension on the cable is set using a provisional fastener and a tensioner instrument. The provisional fastener serves to separate the permanent fastener from the tensioner and align the cable to reduce friction and slack for more precise control of the tension and the size of the loop. The tensioner has a fixed length shaft providing small precise adjustments in the cable.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a blade for use in a radial keratotomy procedure and, more particularly, to a blade for making an intrastromal incision within a cornea.
2. Description of Related Art
Radial keratotomy is a procedure first performed in the 1950's to achieve corneal flattening to correct myopia. Significant advances have been made since the mid-1970's with respect to corneal mapping, instruments and type and nature of incisions to be made to improve the vision of patients. Generally, four or eight evenly spaced incisions extending radially from a predetermined optical zone are made. To correct certain problems of astigmatism, a variety and number of transverse incisions may be made.
The main function of radial keratotomy is that of achieving corneal flattening to correct myopia; correction of astigmatism may also be achieved in appropriate situations. If the incisions extend into or are close to the optical zone, glare and distortion may be present. The degree of glare and distortion may also be a function of the degree of intensity of the ambient light. Generally, more effective corneal flattening is achieved the further into the optical zone the incisions are made but such intrusions may result in unacceptable side effects to the patient. Accordingly, the degree of correction to be made must be tempered by the overall benefit to the patient.
SUMMARY OF THE INVENTION
After a traditional radial keratotomy procedure has been performed, the incisions normally end at the edge of a predetermined optical zone. The horizontal base of an L-shaped blade is inserted into an incision to rest on the groove formed. The base of the blade extends approximately 1 mm from the arm of the blade and is terminated by a very sharp vertical apex or edge of approximately 450 microns in length. In this position, the base (and cutting edge) is located between Bowman's and Descemet's membranes. Radial movement of the blade toward the optical center will incise the stroma but leave Bowman's and Descemet's membranes intact. The resulting incision formed to a greater or lesser extent within the optical zone will result in further corneal flattening but avoid creation of any further glare or vision distortion as Bowman's membrane remains intact within the optical zone. This procedure can also be used to enhance an existing undercorrection of a previously performed radial keratotomy procedure.
It is therefore a primary object of the present invention to provide additional myopic correction through radial keratotomy without adding glare or central vision distortion.
Anther object of the present invention is to provide a blade for performing intrastromal radial keratotomy.
Yet another object of the present invention is to provide a blade for performing a cut within the optical zone but without incising the epithelium or Bowman's membrane.
Still another object of the present invention is to provide a configuration of a blade for intrastromal radial keratotomy that self limits the extent of an intrastromal cut that can be made.
A further object of the present invention is to provide a diamond L-shaped blade for making intrastromal cuts to produce corneal flattening.
A yet further object of the present invention is to provide a cutting edge disposed between Bowman's and Descemet's membranes for making intrastromal cuts.
A still further object of the present invention is to provide a method for providing additional correction for myopia without adding glare or central vision distortion.
A still further object of the present invention is to provide a method for making intrastromal incisions within a cornea.
These and other objects of the present invention will become apparent to those skilled in the art as the description thereof proceeds.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention will be described with greater specificity and clarity with reference to the following drawings, in which:
FIG. 1 illustrates a blade holder for supporting a blade to be used for intrastromal radial keratotomy;
FIG. 2 is a side view of the blade;
FIG. 3 is a front view of the blade;
FIG. 4 is a rear view of the blade;
FIG. 5 illustrates a variant configuration of the blade shown in FIG. 2;
FIG. 6 is a plan view illustrating the optical zone and various incisions that might be made in a cornea as part of a radial keratotomy procedure; and
FIG. 7 is a cross-sectional view of a representative cornea and illustrating use of the blade of the present invention to make an intrastromal cut.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
In the 1950's when SATO (Japan) did his original radial keratotomy (RK) incisions, they were done from the endothelial side of the cornea. He used a special blade to cut from inside to outside dividing the endothelium, Descemet's membrane and the stroma leaving Bowman's membrane and the epithelium intact (presumably to protect against infections). Since the importance of the endothelium is now better understood, the modern RK approach is to go through the epithelium, Bowman's membrane, and the stroma in order to keep Descemet's membrane and the endothelium intact. The main objection to this approach is that glare and central vision distortion become noticeable if the radial incisions are carried too far centrally. While thinking through this evolutionary process, the inventor developed the hypothesis that perhaps it may not be necessary to incise or divide either the Bowman's membrane or the Descemet's membrane to achieve corneal flattening. And, perhaps, the desired corneal flattening could be achieved by making incisions only through the corneal stroma in and proximate the optical zone. The inventor thereafter began to devise a blade that could perform such intrastromal cuts and to develop the procedures for using such a blade.
Referring to FIG. 1, there is illustrated a blade holder 10 supporting a blade 12 for use in making intrastromal cuts in the cornea as part of a radial keratotomy procedure. It is to be noted that the blade and blade holder are not to scale and are depicted for illustrative purposes only. Ophthalmologists and those skilled in the art of instruments for use in RK procedures will readily appreciate and understand that various mechanisms may be employed to removably engage the blade with the blade holder; moreover, it may be advantageous to mount the blade holder in an existing handle presently in use or in a to-be-developed handle or use the blade holder in the manner of a handle. Moreover, these persons will also readily understand how to manipulate the blade holder/handle in order to cause the blade to perform its intended surgical function.
Blade 12 will be described with greater specificity with joint reference to FIGS. 2, 3, and 4. The blade is L-shaped and includes a horizontal base 14 extending from a vertical arm 16. The end or apex of the base is terminated by a vertical edge 18 sharpened (or faceted) to the highest degree possible. Preferably, edge 18 is a diamond edge brazed to base 14 if the base and arm are of stainless steel or of material other than diamond. That is, the blade may be of stainless steel, tungsten carbide, ceramic, sapphire or other suitable material. Recent work on the blade has suggested that the whole blade be of diamond, in which case edge 18 would be formed by faceting.
The purpose of blade 12 is that of augmenting an existing RK incision to cut the stroma lamellae without a commensurate cut in Bowman's membrane or in the epithelium. Thus, blade 12 is dimensioned for such specific purpose. Since such augmenting cuts to be made are on the order of 0.5 to 1 millimeters in length, the length of base 14 extending from arm 16 should be no more than 1 millimeter. Preferably, the length of the base should be commensurate with the length of the cut to be made. Such dimension will limit the length of the cut to the length of the base as the arm will interferingly engage with the end of the incision existing in Bowman's membrane. To ensure against perforation or cutting of Descemet's membrane or Bowman's membrane, the height of base 14 (and vertical length of the cutting edge) should be somewhat less than the thickness of the stroma; investigations to date suggest a height of about 450 microns since the thickness of most corneas is 500+ microns. While the cutting edge is illustrated as being vertical, it can be forwardly or rearwardly slanted to accommodate special procedures that may exist or may be developed. The thickness of the blade, or at least of base 14, is preferably about 0.17 millimeters. The width of arm 16 should be kept to 1 millimeter or less (possibly 0.75 or 0.50 millimeters consistent with the required structural strength). The preferred length of the arm should be on the order of 3.5 to 6 millimeters. To prevent injury at the bottom of the incision upon removal of blade 12, the bottom rear corner 20 is preferably slightly beveled, or rounded as indicated. If the blade is of diamond, the corner can be polished if it is bevelled; if the corner is rounded by a laser cut, it will be rough. Furthermore, lower edge 22 of base 14 should be polished to minimize drag and enhance travel along the groove of the incision.
A variant 30 of blade 12 is illustrated in FIG. 5. In this variant, the length of lower edge 22 is significantly reduced by sloping rear edge 32. Because of the shortened lower edge, unwanted rocking of the blade may occur. If the height of blade 12 is significantly less than the intrastromal depth, the possibility of rocking the blade may be used to advantage to permit varying or variable depth cuts to be made to accommodate or conform with unique procedures or procedures to be developed.
FIG. 6 depicts a planform of incisions potentially to be made in the cornea, as will be dictated by the specific RK procedure(s) to be performed. That is, 4, 8, or even 16 radial incisions 40 may be made. Alternatively, or in combination, transverse incisions 42, parallel incisions 44,46, angled incisions 48 or specific pattern incisions (not illustrated) may be made. The type and nature of incisions will primarily be dictated by the topography of the cornea and other factors well known to ophthalmologists practicing RK.
Through the use of blade 12, in combination with a traditional RK procedure, and assuming that an optical zone 50 of 3 millimeters is dictated, the following heretofore unavailable procedure could be undertaken. Traditional radial incisions made with a conventional RK blade would extend only to a 5 millimeter optical zone 52. Each of these incisions would be extended intrastromally by inserting base 14 of blade 12 into each incision and centrally extending it between Bowman's membrane and Descemet's membrane from the perimeter of the 5 millimeter optical zone 52 for a distance of 1 millimeter to the perimeter of the 3 millimeter optical zone 30. Thereby, the 5 millimeter optical zone would have an intact Bowman's membrane and epithelium without the otherwise associated glare and central vision distortion; moreover, patient recovery would be proportionately more rapid.
In the event an initial RK procedure to a 3 millimeter optical zone results in one diopter or less of undercorrection, the correction can be enhanced through use of blade 12. In such situation, the original RK incisions are prised open to a radial length of approximately 1.5 millimeters. Blade 12 is placed into the incision until bottom edge 22 rests along the groove of the incision. By advancing the blade toward the center of the cornea, the cutting edge, facing the corneal center, will cut the intrastromal lamellae under Bowman's membrane to cause collapse of the corneal zone. The optical zone would be reduced to approximately 2 millimeters, or to the extent controlled by the surgeon or by the interference between the front edge of arm 16 and the end of the original incision through Bowman's membrane. By selecting a blade 12 having a specific length base 14, essentially absolute control over the length of the intrastromal cut to be made can be controlled due to the interference between arm 16 and the end of the original incision. It has also been learned that transverse incisions can be extended across an existing incision by cutting only the stroma and not Bowman's membrane (note incision 48). Thereby, gaping of Bowman's membrane and the epithelium at the intersection is prevented.
Referring to FIG. 7, there is illustrated a partial representative cross-sectional view of a cornea 60. An endothelial layer 62 is adjacent Descemet's membrane 64. An epithelial layer 66 is adjacent Bowman's membrane 68. Stroma 70 is disposed between Bowman's and Descemet's membranes and is of a thickness somewhat greater than 450 microns. Using a conventional RK blade and traditional RK procedure an incision 72 through epithelial layer 66, Bowman's membrane 68 and stroma 70 is made radially centrally to a 5 millimeter optic zone (OZ); this zone is represented by numeral 52 in FIGS. 6 and 7.
Assuming that the procedure dictated an optic zone (OZ) of 3 millimeters (as represented by numeral 50), blade 12 is inserted into incision 72 until it rests upon groove 74 at the bottom of the incision adjacent or close to Descemet's membrane. Translating blade 12 radially centrally, will result in edge 18 performing a cut through stroma 70 in radial alignment with incision 72. The length of this cut can be controlled by the physician if his hand is sufficiently steady and he has developed the requisite skill. Alternatively, the length of the cut can be selected by employing a blade 12 having a base 14 extending from arm 16 a distance commensurate with the length of the cut to be made. Then, upon translation of blade 12 centrally radially within incision 72, translation will be inhibited upon interference between the leading edge 76 of arm 16 with end 78 of incision 72. By having base 14 extend for 1 millimeter from leading edge 76 of arm 16, the cut made will be 1 millimeter long and the original incision will be extended through the stroma to the perimeter of the 3 millimeter optic zone (OZ), as represented by numeral 50 in FIGS. 6 and 7.
The above described procedure for extending incisions or cuts through only the stroma of radial incisions can be equally and similarly applied to other non radial incisions, irrespective of their orientation. Again, the length of such extended incisions or cuts in the stroma can be a function of the skill of the surgeon or more pragmatically dictated by the length of the base of the blade. Furthermore, the depth of the extension cut to be made is a function of the height of the base of the blade and specific procedures can be developed to take advantage of such facility.
While the invention has been described with reference to several particular embodiments thereof, those skilled in the art will be able to make the various modifications to the described embodiments of the invention without departing from the true spirit and scope of the invention. It is intended that all combinations of elements and steps which perform substantially the same function in substantially the same way to achieve the same result are within the scope of the invention.
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The horizontal base of an L-shaped blade is inserted within an existing incision performed as part of a traditional radial keratotomy procedure to permit an intrastromal cut to be made to urge corneal collapse and provide myopia correction without incurring glare and central vision distortion for the patient. The base of the blade extends approximately 1 mm to a very sharp vertical edge from the vertical arm attached to a blade holder to permit up to an equivalent length intrastromal cut until the end of the arm reaches the end of the preexisting incision through Bowman's membrane and the epithelium. The height of the base and length of the cutting edge is approximately 450 microns to prevent cutting or perforation of either of Bowman's or Descemet's membranes.
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FIELD OF INVENTION
This invention relates to transit packaging having a reduced content. In particular, this invention relates to transit packaging for tapered containers, namely thin walled plastic containers, bowl shaped containers or glass containers shipped in a multi-pack format.
BACKGROUND OF INVENTION
Tapered containers, namely thin walled plastic containers, bowl shaped containers and glass containers are widely used in the food industry. In particular, edible oil products such as margarine and whipped toppings are currently packaged in bowl shaped containers. These containers must be packaged for transit in a multipack format. The multi-pack format requires outer packing support for loading onto pallets. Full corrugated boxes are normally used to package bowl shaped containers for transit.
There is an ongoing trend to reduce total package content by 10%. Currently, two U.S. states have enacted laws requiring 10% package reductions.
Current attempts at package reductions merely replaces the corrugated boxes with trays on which the containers are nested and then shrink wrapping the unit. However, a problem is created regarding the structural integrity of the trays. Such trays are generally not self-supportive when loaded onto pallets resulting in the pallet loads being unstable. With unstable pallet loads, there is a higher rate of damage during transit.
Shrink wrapping is not energy efficient. Extensive energy is required to heat the wrap. Much of the energy is lost as heat.
U.S. Pat. Nos. 3,826,357 and 4,998,615 are examples of packaging which addresses the structural problem. Dividers or stacker elements are required to be used in order to improve the stackability of the packages. By adding dividers and stacker elements, significant improvements in packaging reductions cannot be achieved.
Canadian Patent No. 1,191,819, describes a multipackage assembly is described. The packages are sandwiched between two sheet of cardboard and held together by strips of a frangible adhesive. This type of packaging has met the requirements of reduced packaging. However, this type of packaging is only suitable for regular parallelepiped cartons. Tapered containers packaged in this type of packaging are flimsy and do not handle and stack well.
In still other types of packaging such as described in U.S. Pat. No. 4,787,509, yogurt containers are wrapped with a single sheet of cardboard and attached to the sheet by a frangible adhesive. This type of packaging is only capable of packaging a small number of containers in a single package.
SUMMARY OF THE INVENTION
The disadvantages of the prior art may be overcome by providing a transit packaging which has a reduced content which also provides structural integrity for maintaining stable pallet loads.
It is desirable to provide a transit package comprising a cardboard sheet which extends partially about a plurality of containers. The sheet has a base and two ends with a plurality of straps which wrap about the sheet and containers forming an integral and structural package.
It is further desirable to provide a transit packaging which also includes a top sheet of cardboard for overlying the containers and which is wrapped by straps.
It is further desirable to provide a means for retaining the containers onto the cardboard sheet to prevent sliding movement.
It is further desirable to provide a frangible adhesive for releasably retaining the containers onto the cardboard sheet.
It is further desirable to provide a spacing retainer sheet to retain the containers onto the cardboard sheet.
It is still further desirable to provide an indentable footprint on the cardboard sheet to receive containers and once the containers are impressed onto the footprint sliding movement of the containers is prevented.
According to one aspect of the invention, there is provided a transit packaging comprising a blank of a corrugated cardboard having flutes in a longitudinal direction and having opposed end panels foldable to extend in the same direction and substantially perpendicular to the blank, a retainer for retaining like containers onto the blank in a rectangular pattern between the end panels, and a plurality of straps for wrapping about the blank once the like containers are presented to the retainer means and the end panels are folded. The plurality of straps urge at least outer longitudinal columns of the like containers together forming a structural package.
According to one aspect of the invention, there is provided a transit packaging comprising a blank of a corrugated cardboard having flutes in a longitudinal direction, a first and second transverse score at opposite end regions of the blank defining end panels of the packaging, a plurality of longitudinally aligned pairs of notches at opposite ends of the blank, a retainer means on the blank, the retainer means for retaining like containers onto the blank preventing relative sliding movement, and a plurality of straps, each positioned in one of the aligned pairs of notches, for wrapping about the blank when the like containers are retained on the blank.
According to another aspect of the invention, there is provided a method of packaging like containers using a blank of a corrugated cardboard. The blank has flutes in a longitudinal direction, opposed end panels foldable to extend substantially parallel to each other and a plurality of longitudinally aligned pairs of notches at opposite ends of the blank. The method comprises the steps of retaining like containers onto the blank in a rectangular pattern between the opposed end panels, plowing the end panels upwardly, and wrapping a plurality of straps about the blank with each of the straps positioned in one of the aligned pairs of notches.
DESCRIPTION OF THE DRAWINGS
The present invention will be better understood and more particularly described in the detailed description below and the following figures:
FIG. 1 is an illustration of a perspective view of a first embodiment of the transit packaging of the present invention in a packaged condition.
FIG. 2 is an illustration of a top view of the blank for the transit packaging of the embodiment of FIG. 1 in an unfolded flat condition.
FIG. 3 is an illustration of a top view of the transit packaging of the embodiment in FIG. 1, partially filled.
FIG. 4 is an illustration of a side view of two transit packagings of the embodiment in FIG. 1, stacked one upon the other with cut out lines illustrating like containers.
FIG. 5 is an illustration of a perspective view of a second embodiment of a 3×3 transit packaging of the present invention.
FIG. 6 is an illustration of a perspective view of a 2×3 transit packaging of the second embodiment.
FIG. 7 is an illustration of a top view of a third embodiment of the transit packaging of the present invention.
FIG. 8 is an illustration of a partial side view of a blank and retainer sheet of the embodiment in FIG. 7.
FIG. 9 is an illustration of a side view of a blank and retainer sheet of the embodiment of FIG. 7 as the end panel is plowed upwards.
FIG. 10 is an illustration of a side view of a blank and retainer sheet of the embodiment of FIG. 7 with the end panel folded upwards.
FIG. 11 is an illustration of a side view of the embodiment of FIG. 7 in the folded position.
FIG. 12 is an illustration of a top view of a blank of a fourth embodiment of the transit packaging of the present invention.
FIG. 13 is an illustration of a cross-sectional view of transit packaging of the embodiment of FIG. 12 with a container placed in the base member.
FIG. 14 is an illustration of a top view of a blank of a fifth embodiment of the transit packaging of the present invention. (Although seveal emobodiements are illustrated, like references refer to like parts of the figures).
DETAILED DESCRIPTION OF THE INVENTION
The transit packaging of the present invention is generally illustrated in FIG. 1 as 10. The packaging comprises a blank 12 having a base member 14 and two end panels 16 and 18.
Referring to FIG. 2, the blank 12 is illustrated in a flat condition. The central portion comprises the base member 14 while the end portions make up the end panels 16 and 18. At each end region of the blank 12, between base portion 14 and end panel 16 is score 20, and between base portion 14 and end panel 18 is score 22. Scores 20 and 22 are applied in a conventional manner.
Blank 12 is preferably made of corrugated cardboard. Corrugated cardboard has a longitudinal direction 21, which is the direction of the flutes or internal reinforcing member. In order to maintain structural integrity of the packaging, the longitudinal direction should be in a direction from end panel 18 to base member 14 to end panel 16. Scores 20 and 22 should be in a transverse direction perpendicular to the longitudinal direction.
End panels 16 and 18 are provided with a plurality of aligned pairs of notches 24. The distance between the base of each notch 24 and score 20 and score 22 is approximately equal to the height of the containers 26. The end panels 16 and 18 have a height when folded upwards greater than the height of the containers 26.
Containers 26 are like containers which are used to package foodstuffs, such as edible oil products and whipped toppings. The containers are generally characterized by a bowl shaped tapered bottom.
In the first embodiment, in FIGS. 1-4 the blank 12 of the transit packaging comprises a plurality of strips 28 of a frangible thermo-adhesive applied to blank 12.
Containers 26 are arranged on base member 14 in a rectangular pattern or array of rows and columns, wherein rows are in the transverse direction and columns are in the longitudinal direction. Since containers 26 are like in shape and have a tapered bowl shape, only the tops or lids of each containers 26 abut one another.
Strips 28 retain the containers 26 onto blank 12 preventing lateral or sliding movement.
Referring to FIG. 3, the end panels 16 and 18 are plowed upwardly about scores 20 and 22, respectively, until substantially perpendicular to the base member 14. The aligned notches 24 on end panels 16 are in alignment with the aligned notches on end panel 18. The number of aligned notches 24 in end panels 16 and 18 is normally equal to the number of columns of containers 26.
Straps 30 are then wrapped about the package and positioned to rest in two aligned notches 24 of end panels 16 and 18 and tightened to firmly retain containers 26 on the base member 14. Notches 24 prevent the straps 30 from slipping or moving.
The number of straps is preferably equal to the number of columns of containers 26.
Referring to FIG. 4, once strapped together, the group of containers 26 is ready for loading onto pallets and ready for transport. The packaging 10 provides sufficient strength or structural integrity such that like packages may be stacked one upon another. The strips of adhesive 28 retain the individual containers onto the base member 14 preventing the containers 26 from slipping out.
The quantity of packaging of the present invention is dramatically reduced from the prior art carton method of packaging for transit. The structural integrity is maintained minimizing damage during transit.
Referring to FIGS. 5 and 6, a second embodiment is illustrated. In the second embodiment, the blank 12 is identical to the blank of the first embodiment. A top panel 32 is placed over the containers 26 prior to strapping straps 30 about the packaging. The top panel can be made from corrugated cardboard, cardboard, paper board or fiber board.
When a top panel 32 is used and the number of columns is greater than 2, it is possible for the number of straps to be alternated with the number of columns, but keeping straps for each outer column. In this case, the amount of packaging can be reduced by a number of straps.
For example in FIG. 5, an array of containers in a 3×3 package is illustrated with only two straps 30. In FIG. 6, a 3×2 package is illustrated, again with only two straps 30.
Referring now to FIGS. 7 to 11, a base having an alternate retainer is illustrated. The blank 12 has a retainer sheet 34 adhered between end panel 16 and end panel 18. Retainer sheet 34 has a plurality of holes 36 or openings corresponding to the number of containers to be packaged. In the illustrated packaging, six containers are to be packaged and therefore retainer sheet 34 has six punched holes or openings 36.
Each end of retainer sheet 34 has two scores 38 and 40 extending in a transverse direction. The two scores 38, 40 are applied from opposite sides of the retainer sheet 34. When retainer sheet 34 is adhered to end panel 16 at 42, scores 38, 40 will straddle score 20. Similarly for the opposite end, scores 38, 40 will straddle score 22.
As illustrated in FIGS. 9 and 10, as end panel 16 is plowed upwardly, blank 12 will bend along score 20. The opposite scores 38, 40 will bend, spacing retainer sheet 34 from base member 14. In this condition, containers 126 may be inserted into holes or openings 36 and will be prevented from sliding relative to the base member 14. The containers 126 are then strapped, either with or without a top panel, with straps 30 to present a structural package.
Alternatively, the containers 126 may be placed on the base member 14 in holes or openings 36. The thickness of the spacing retainer sheet 34 will prevent the containers 126 from sliding. The end panels 16 and 18 are plowed upwardly, retainer sheet 34 folds and becomes spaced from the base member 14 sliding relative to the containers 126 for retaining the containers within the openings. The containers 126 are then strapped, either with or without a top panel, with straps 30 to present a structural package.
The packaging of FIGS. 7 to 11 is particularly useful for containers relatively taller than containers 26. Containers 126 may be glass containers with a tapered shape.
Referring to FIGS. 12 and 13, a further embodiment of a transit packaging having a retainer for retaining a container relative to the base member is illustrated. In this embodiment, the base member 14 of blank 12 is provided with a plurality of footprints which corresponds to the shape of the base of the container to be packaged. In the case of the bowl shaped containers 26, the footprint comprises two concentric circular scores 44 and 46 and a plurality of radially extending kiss cuts 48.
Referring to FIG. 13, as container 26 is urged downwardly, the kiss cuts 48 will allow the base of container 26 to contour the upper layer 50 of base member 14 pressing upon the corrugated layer 52 of base member 14, the footprint becomes indented to complementarily receive the base of container 26 thereon.
A container 26 is placed on each of the footprints and then the end panels 16 and 18 are plowed upwardly, ready for strapping, either with or without a top panel, with straps 30 to present a structural package.
Referring to FIG. 14, a further embodiment is illustrated. In this embodiment, the blank 12 has a retainer comprising a regular pattern of holes 54. Each hole has a plurality of tabs 56 which extend inwardly of the hole 54. The die cuts wich define the tab extend outwardly of the radius of hole 54.
In use, the containers 26 or 126 are placed on the hole 54. The ends 16 and 18 are plowed upwardly. The containers 26 or 126 will extend through the holes and frictionally engage tabs 56 retaining the containers 26 or 126 onto blank 12.
The packages 10 of the present invention are loaded onto pallets. The pallet loads can optionally be wrapped with a shrink wrap to protect the pallet load from damage. The pallet load is shipped to the desired destination. The packages 10 may be unloaded and transported to the retail destination. At the retail destination, the packages 10 may be stacked on a shelf and then the straps 30 may be cut and removed. Since the containers 26, 126 are retained on the base member 14, the packages 10 may still be maneuvered without upsetting the containers 26, 126. One of the end panels 16, 18 may be cut away exposing the face of the containers 26, 126. Alternatively, the packages 10 may be stacked and presented from the end where the containers 26, 126 are exposed.
The containers 26, 126 may be removed by the consumer. If the adhesive strips 28 are used, the adhesive is frangible allowing easy removal. If the spacing retainer sheet 34 is used the containers 126 may be removed from openings 36. If the footprints 44, 46, 48 are used, the containers are not attached to the base member and can be removed therefrom.
It is now apparent to a person skilled in the art that the transit packaging of the present invention could be readily modified. It is understood that certain changes in style, size and components may be effective without departure from the spirit of the invention and within the scope of the appended claims.
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A transit packaging having a reduced content includes a blank of a corrugated cardboard having flutes in a longitudinal direction. A first and second transverse score are made at opposite end regions of the blank defining side panels of the packaging. A plurality of longitudinally aligned pairs of notches are at opposite ends of the blank. A retainer releasably retains like containers onto the blank preventing relative sliding movement. A plurality of straps, each positioned in one of the aligned pairs of notches, wraps about the blank when the like containers are retained on the blank.
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PRIORITY TO RELATED APPLICATION(S)
This application claims the benefit of European Patent Application No. 06127078.1, filed Dec. 22, 2006, which is hereby incorporated by reference in its entirety.
BACKGROUND OF THE INVENTION
Vasopressin is a 9 amino acid peptide mainly produced by the paraventricular nucleus of the hypothalamus. Three vasopressin receptors, all belonging to the class I G-protein coupled receptors, are known. The V1a receptor is expressed in the brain, liver, vascular smooth muscle, lung, uterus and testis, the V1b or V3 receptor is expressed in the brain and pituitary gland, the V2 receptor is expressed in the kidney where it regulates water excretion and mediates the antidiuretic effects of vasopressin.
In the periphery vasopressin acts as a neurohormone and stimulates vasoconstriction, glycogenolysis and antidiuresis. In the brain vasopressin acts as a neuromodulator and is elevated in the amygdala during stress (Ebner, K., C. T. Wotjak, et al. (2002). “Forced swimming triggers vasopressin release within the amygdala to modulate stress-coping strategies in rats.” Eur J Neurosci 15(2): 384-8). The V1a receptor is extensively expressed in the brain and particularly in limbic areas like the amygdala, lateral septum and hippocampus which are playing an important role in the regulation of anxiety. Indeed V1a knock-out mouse show a reduction in anxious behavior in the plus-maze, open field and light-dark box (Bielsky, I. F., S. B. Hu, et al. (2003). “Profound Impairment in Social Recognition and Reduction in Anxiety-Like Behavior in Vasopressin V1a Receptor Knockout Mice.” Neuropsychopharmacology ). The downregulation of the V1a receptor using antisense oligonucleotide injection in the septum also causes a reduction in anxious behavior (Landgraf, R., R. Gerstberger, et al. (1995). “V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats.” Regul Pept 59(2): 229-39). The V1a receptor is also mediating the cardiovascular effects of vasopressin in the brain by centrally regulating blood pressure and heart rate in the solitary tract nucleus (Michelini, L. C. and M. Morris (1999). “Endogenous vasopressin modulates the cardiovascular responses to exercise.” Ann N Y Acad Sci 897: 198-211). In the periphery it induces the contraction of vascular smooth muscles and chronic inhibition of the V1a receptor improves hemodynamic parameters in myocardial infarcted rats (Van Kerckhoven, R., I. Lankhuizen, et al. (2002). “Chronic vasopressin V(1A) but not V(2) receptor antagonism prevents heart failure in chronically infarcted rats.” Eur J Pharmacol 449(1-2): 135-41).
SUMMARY OF THE INVENTION
The present invention provides novel spiro-piperidine derivatives as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use for the treatment of anxiety and depressive disorders and other diseases.
In particular, the present invention provides compounds of formula (I)
wherein
X is O and Y is CH 2 , X is O and Y is C═O, X is C═O and Y is NR 6 , X—Y is CH═CH, X—Y is CH 2 —CH 2 , X is C═O and Y is O, X is CH 2 and Y is NR 6 , or X is CH 2 and Y is O;
A is selected from the group consisting of
R 1 , R 2 , R 3 and R 4 are each independently
hydrogen, halo, C 1-6 -alkyl, optionally substituted by OH halo-C 1-6 -alkyl, C 1-6 -alkoxy, optionally substituted by OH, or halo-C 1-6 -alkoxy;
R 5 and R 5′ are each independently hydrogen or methyl;
R 6 is hydrogen or C 1-6 -alkyl;
R 7 is hydrogen,
C 1-6 -alkyl, optionally substituted by CN or OH, or —(C 1-6 -alkylene)-C(O)—NR a R b ;
R 8 is hydrogen,
C 1-6 -alkyl, C 1-6 -alkoxy, —(C 1-6 -alkylene)-NR c R d , —(C 1-6 -alkylene)-C(O)R f , benzyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, or phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano;
R 9 is hydrogen, halo, C 1-6 -alkyl, or C 1-6 -alkoxy;
R 10 is hydrogen, halo, C 1-6 -alkyl, halo-C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, or —O—C 2-10 -alkenyl;
R 11 is hydrogen, halo, C 1-6 -alkyl, or C 1-6 -alkoxy;
or R 10 and R 11 are bound together to form a ring with the benzo moiety, wherein
—R 10 —R 11 — is —O—(CH 2 ) n —O— wherein n is 1 or 2;
R 12 is hydrogen,
C 1-6 -alkyl, optionally substituted by CN or OH, —(C 1-6 -alkylene)-NR g R h , —(C 1-6 -alkylene)-C(O)—NR i R j —O-benzyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, nitro, halo, cyano, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, halo-C 1-6 -alkyl, —(C 1-6 -alkylene)-C(O)R f , phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, —(C 1-3 -alkylene)-R m ,
wherein R m is phenyl, a 5- to 6-membered heteroaryl, 4- to 6-membered heterocycloalkyl or 3 to 6-membered cycloalkyl,
each optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, or
—NR n R o ;
or R 11 and R 12 are bound together to form a ring with the benzo moiety, wherein —R 11 —R 12 — is —O—(CH 2 ) n —C(O)—,
—C(O)—(CH 2 ), —O—, or —O—(CH 2 ) n —O— wherein n is 1 or 2;
R a , R b , R i and R j are each independently
hydrogen, C 1-6 -alkyl, —(C 1-6 -alkylene)-NR k R l ,
wherein R k and R l are each independently hydrogen or C 1-6 -alkyl,
or R a and R b , or R i and R j together with the nitrogen to which they are bound form a five or six membered heterocycle comprising one or two heteroatoms selected from the group of nitrogen, oxygen and sulfur;
R c , R d , R g , R h , R n and R o are each independently
hydrogen, C 1-6 -alkyl, —C(O)R e , or —S(O) 2 R e
wherein R e is selected from the group of
hydrogen, C 1-6 -alkyl, and phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano;
or R c and R d , or R n and R o together with the nitrogen to which they are bound form a five or six membered heterocycle comprising one or two heteroatoms selected from the group of nitrogen, oxygen and sulfur;
R f is selected from the group of
hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy; and phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano;
or a pharmaceutically acceptable salt thereof.
The compounds of formula (I) can be manufactured by the methods given below, by the methods given in the examples or by analogous methods. Appropriate reaction conditions for the individual reaction steps are known to a person skilled in the art. Starting materials are either commercially available or can be prepared by methods analogous to the methods given below, by methods described in references cited in the text or in the examples, or by methods known in the art.
The compounds of formula (I) possess pharmaceutical activity, in particular they are modulators of V1a receptor activity. More particular, the compounds are antagonists of the V1a receptor. The present invention provides methods for the treatment of dysmenorrhea, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, obsessive compulsive disorder, anxiety and depressive disorders. The preferred indications with regard to the present invention are the treatment of anxiety and depressive disorders.
DETAILED DESCRIPTION OF THE INVENTION
The following definitions of the general terms used in the present description apply irrespective of whether the terms in question appear alone or in combination. It must be noted that, as used in the specification and the appended claims, the singular forms “a”, “an,” and “the” include plural forms unless the context clearly dictates otherwise.
In the present description, the term “alkyl,” alone or in combination with other groups, refers to a branched or straight-chain monovalent saturated hydrocarbon radical. The term “C 1-6 -alkyl” denotes a saturated straight- or branched-chain hydrocarbon group containing from 1 to 6 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, the isomeric pentyls and the like. A preferred sub-group of C 1-6 -alkyl is C 1-4 -alkyl, i.e. with 1-4 carbon atoms.
In the present invention, the term “alkylene” refers to a linear or branched saturated divalent hydrocarbon radical. In particular, “C 1-6 -alkylene” means a linear saturated divalent hydrocarbon radical of one to six carbon atoms or a branched saturated divalent hydrocarbon radical of three to six carbon atoms, e.g. methylene, ethylene, 2,2-dimethylethylene, n-propylene, 2-methylpropylene, and the like.
In the present description, the terms “alkoxy” and “C 1-6 -alkoxy” refer to the group R′—O—, wherein R′ is alkyl or C 1-6 -alkyl as defined above. Examples of alkoxy groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy and the like. A preferred sub-group of C 1-6 -alkoxy, and still more preferred alkoxy groups are methoxy and/or ethoxy.
In the present description, the terms “thioalkyl” and “C 1-6 -thioalkyl” refer to the group R′—S—, wherein R′ is alkyl or C 1-6 -alkyl as defined above.
The terms “C 1-6 -hydroxyalkyl” and “C 1-6 -alkyl substituted by OH” denote a C 1-6 -alkyl group as defined above wherein at least one of the hydrogen atoms of the alkyl group is replaced by a hydroxyl group.
The terms “C 1-6 -cyanoalkyl” and “C 1-6 -alkyl substituted by CN” denote a C 1-6 -alkyl group as defined above wherein at least one of the hydrogen atoms of the alkyl group is replaced by a CN group.
The terms “halo” and “halogen” refer to fluorine (F), chlorine (Cl), bromine (Br) and iodine (I) with fluorine, chlorine and bromine being preferred.
The term “halo-C 1-6 -alkyl” is synonymous with “C 1-6 -haloalkyl” or “C 1-6 -alkyl substituted by halo” and means a C 1-6 -alkyl group as defined above wherein at least one of the hydrogen atoms of the alkyl group is replaced by a halogen atom, preferably fluoro or chloro, most preferably fluoro. Examples of halo-C 1-6 -alkyl include but are not limited to methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, tert-butyl, pentyl or n-hexyl substituted by one or more Cl, F, Br or I atom(s) as well as those groups specifically illustrated by the examples herein below. Among the preferred halo-C 1-6 -alkyl groups are difluoro- or trifluoro-methyl or -ethyl.
The term “halo-C 1-6 -alkoxy” is synonymous with “C 1-6 -haloalkoxy” or “C 1-6 -alkoxy substituted by halo” and means a C 1-6 -alkoxy group as defined above wherein at least one of the hydrogen atoms of the alkyl group is replaced by a halogen atom, preferably fluoro or chloro, most preferably fluoro. Among the preferred halogenated alkoxy groups are difluoro- or trifluoro-methoxy or -ethoxy.
The term “C 2-12 -alkenyl,” alone or in combination, denotes a straight-chain or branched hydrocarbon residue of 2 to 12 carbon atoms comprising at least one double bond. A preferred sub-group of C 2-12 -alkenyl is C 2-6 -alkyenyl. Examples of the preferred alkenyl groups are ethenyl, propen-1-yl, propen-2-yl(allyl), buten-1-yl, buten-2-yl, buten-3-yl, penten-1-yl, penten-2-yl, penten-3-yl, penten-4-yl, hexen-1-yl, hexen-2-yl, hexen-3-yl, hexen-4-yl and hexen-5-yl, as well as those specifically illustrated by the examples herein below.
The term “5 or 6 membered heteroaryl” means a monovalent aromatic ring of 5 or 6 ring atoms as ring members containing one, two, or three ring heteroatoms selected from N, O, and S, the rest being carbon atoms. 5 or 6 membered heteroaryl can optionally be substituted with one, two, three or four substituents, wherein each substituent may independently be selected from the group consisting of hydroxy, C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -thioalkyl, halo, cyano, nitro, halo-C 1-6 -alkyl, C 1-6 -hydroxyalkyl, C 1-6 -alkoxycarbonyl, amino, C 1-6 -alkylamino, di(C 1-6 )alkylamino, aminocarbonyl, and carbonylamino, unless otherwise specifically indicated. Preferred substituents are halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, hydroxy or cyano. Examples of heteroaryl moieties include, but are not limited to pyrrolyl, pyrazolyl, imidazolyl, furanyl (synonymous to furyl), thiophenyl (synonymous to thienyl), oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, each of which is optionally substituted as described herein.
The term “heterocycloalkyl” means a monovalent saturated ring, consisting of one ring of 3 to 7, preferably from 4 to 6 atoms as ring members, including one, two, or three heteroatoms selected from nitrogen, oxygen and sulfur, the rest being carbon atoms. 3 to 7 membered heterocycloalkyl can optionally be substituted with one, two, three or four substituents, wherein each substituent is independently hydroxy, C 1-6 -alkyl, C 1-6 -alkoxy, C 1-6 -thioalkyl, halo, cyano, nitro, halo-C 1-6 -alkyl, C 1-6 -hydroxyalkyl, C 1-6 -alkoxycarbonyl, amino, C 1-6 -alkylamino, di(C 1-6 )alkylamino, aminocarbonyl, or carbonylamino, unless otherwise specifically indicated. Preferred substituents are halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, hydroxy or cyano. Examples of heterocyclic moieties include, but are not limited to, oxiranyl, thiiranyl, oxetanyl, tetrahydro-furanyl, tetrahydro-thiophenyl (synonymous to tetrahydro-thienyl), pyrrolidinyl, pyrazolidinyl, imidazolidinyl, oxazidinyl, isoxazidinyl, thiazolidinyl, isothiazolidinyl, piperidinyl, piperazidinyl, morpholinyl, or tetrahydropyranyl, each of which is optionally substituted as described herein.
The term “heterocycle” in the definition “R a and R b , R c and R d , R i and R j , or R n and R o , together with the nitrogen to which they are bound form a five- or six-membered heterocycle comprising one or two heteroatoms selected from the group of nitrogen, oxygen and sulfur” means either heterocycloalkyl or heteroaryl in the above-given sense which may optionally be substituted as described above. Preferably, the “heterocycle” may optionally be substituted with one, two or three substituents selected from halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, and cyano. Preferred heterocycles are optionally substituted piperazine, N-methylpiperazine, morpholin, piperidine and pyrrolidine.
The term “C 3-6 -cycloalkyl” denotes a monovalent or divalent saturated carbocyclic moiety consisting of a monocyclic ring. Cycloalkyl can optionally be substituted with one, two, three or four substituents, wherein each substituent is independently hydroxy, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, amino, unless otherwise specifically indicated. Examples of cycloalkyl moieties include optionally substituted cyclopropyl, optionally substituted cyclobutyl, optionally substituted cyclopentyl and optionally substituted cyclohexyl as well as those specifically illustrated by the examples herein below.
The term “one or more” substituents preferably means one, two or three substituents per ring.
“Pharmaceutically acceptable” such as pharmaceutically acceptable carrier, excipient, etc., means pharmacologically acceptable and substantially non-toxic to the subject to which the particular compound is administered.
The term “pharmaceutically acceptable acid addition salts” embraces salts with inorganic and organic acids, such as hydrochloric acid, nitric acid, sulfuric acid, phosphoric acid, citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric acid, methane-sulfonic acid, p-toluenesulfonic acid and the like.
“Therapeutically effective amount” means an amount that is effective to prevent, alleviate or ameliorate symptoms of disease or prolong the survival of the subject being treated.
The invention further comprises individual optical isomers of the compounds herein as well as racemic and non-racemic mixtures thereof.
In detail, the present invention provides compounds of formula (I)
wherein
X is O and Y is CH 2 , or X is O and Y is C═O, or X is C═O and Y is NR 6 , or X—Y is CH═CH, or X—Y is CH 2 —CH 2 , or X is C═O and Y is O, or X is CH 2 and Y is NR 6 , or X is CH 2 and Y is O;
A is selected from the group consisting of
R 1 , R 2 , R 3 and R 4 are each independently
hydrogen, halo, C 1-6 -alkyl, optionally substituted by OH halo-C 1-6 -alkyl, C 1-6 -alkoxy, optionally substituted by OH, or halo-C 1-6 -alkoxy;
R 5 and R 5′ are each independently hydrogen or methyl;
R 6 is hydrogen or C 1-6 -alkyl;
R 7 is hydrogen,
C 1-6 -alkyl, optionally substituted by CN or OH, or —(C 1-6 -alkylene)-C(O)—NR a R b ;
R 8 is hydrogen,
C 1-6 -alkyl, C 1-6 -alkoxy, —(C 1-6 -alkylene)-NR c R d , —(C 1-6 -alkylene)-C(O)R f , benzyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, or phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano;
R 9 is hydrogen, halo, C 1-6 -alkyl, or C 1-6 -alkoxy;
R 10 is hydrogen, halo, C 1-6 -alkyl, halo-C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, or —O—C 2-10 -alkenyl;
R 11 is hydrogen, halo, C 1-6 -alkyl, or C 1-6 -alkoxy;
or R 10 and R 11 are bound together to form a ring with the benzo moiety, wherein —R 10 —R 11 — is —O—(CH 2 ) n —O— wherein n is 1 or 2;
R 12 is hydrogen,
C 1-6 -alkyl, optionally substituted by CN or OH, —(C 1-6 -alkylene)-NR g R h , —(C 1-6 -alkylene)-C(O)—NR i R j —O-benzyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, nitro, halo, cyano, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, halo-C 1-6 -alkyl, —(C 1-6 -alkylene)-C(O)R f , phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, —(C 1-3 -alkylene)-R m ,
wherein R m is phenyl, a 5- to 6-membered heteroaryl, 4- to 6-membered heterocycloalkyl or 3 to 6-membered cycloalkyl,
each optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, or
—NR n R o ;
or R 11 and R 12 are bound together to form a ring with the benzo moiety, wherein —R 11 —R 12 — is —O—(CH 2 ) n —C(O)—,
—C(O)—(CH 2 ) n —O—, or —O—(CH 2 ) n —O— wherein n is 1 or 2;
R a , R b , R i and R j are each independently
hydrogen, C 1-6 -alkyl, —(C 1-6 -alkylene)-NR k R l ,
wherein R k and R l are each independently hydrogen or C 1-6 -alkyl,
or R a and R b , or R i and R j together with the nitrogen to which they are bound form a five or six membered heterocycle comprising one or two heteroatoms selected from the group of nitrogen, oxygen and sulfur;
R c , R d , R g , R h , R n and R o are each independently
hydrogen, C 1-6 -alkyl, —C(O)R e , or —S(O) 2 R e
wherein R e is selected from the group of
hydrogen, C 1-6 -alkyl, and phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano;
or R c and R d , or R n and R o together with the nitrogen to which they are bound form a five or six membered heterocycle comprising one or two heteroatoms selected from the group of nitrogen, oxygen and sulfur;
R f is selected from
hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy; and phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano;
or a pharmaceutically acceptable salt thereof.
In certain embodiments of the invention, R a and R b , R c and R d , R i and R j , or R n and R o together with the nitrogen to which they are bound may form piperazine, 4-(C 1-6 -alkyl)-piperazine, 4-methylpiperazine, morpholine, piperidine or pyrrolidine.
In certain embodiments of the invention, R a and R b , R c and R d , R i and R j , or R n and R o together with the nitrogen to which they are bound may form 4-methylpiperazine, or morpholine, in particular morpholine.
In certain embodiments of the invention, wherein R m is a 5- to 6-membered heteroaryl, the preferred heteroaryl is selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine, imidazole, pyrazole, oxazole, and isoxazole. All these residues are optionally substituted as described herein.
In embodiments of the invention, wherein R m is a 4- to 6-membered heterocycloalkyl, the preferred heterocycloalkyl is selected from the group consisting of pyrrolidine, oxethane, tetrahydropyrane, piperidine, morpholine, and piperazine. All these residues are optionally substituted as described herein.
In certain embodiments of the invention,
R 1 , R 2 , R 3 and R 4 are each independently
hydrogen, halo, or C 1-6 -alkoxy, optionally substituted by OH.
In certain embodiments of the invention, R 1 is hydrogen; R 2 is hydrogen or C 1-6 -alkoxy, R 3 is hydrogen, halo, or C 1-6 -alkoxy, optionally substituted by OH; and R 4 is hydrogen.
In certain embodiments all R 1 to R 4 are hydrogen.
In certain embodiments, one residue of R 1 to R 4 is halo and the others are hydrogen.
In certain embodiments, one residue of R 1 to R 4 is C 1-6 -alkoxy, optionally substituted by OH, preferably methoxy or —O(CH 2 ) 2 OH, and the others are hydrogen.
In certain embodiments of the invention, R 5 and R 5′ are both hydrogen, in other embodiments of the invention, R 5 and R 5′ are both methyl, in other embodiments of the invention, R 5 is hydrogen and R 5′ is methyl.
In certain embodiments of the invention, R 5 is hydrogen, R 5′ is methyl, X is O and Y is C═O.
In certain embodiments of the invention, R 6 is hydrogen or C 1-6 -alkyl, preferably hydrogen.
In certain embodiments of the invention,
R 7 is hydrogen,
C 1-6 -alkyl, optionally substituted by CN or OH, or —(C 1-6 -alkylene)-C(O)—NR a R b ,
wherein R a and R b are each independently hydrogen or C 1-6 -alkyl.
Preferably, R 7 is hydrogen.
In certain embodiments of the invention,
R 8 is hydrogen,
C 1-6 -alkyl, or C 1-6 -alkoxy, —(C 1-6 -alkylene)-NR c R d ,
wherein R c and R d are each independently
hydrogen, —C(O)R e , or —S(O) 2 R e
wherein R e is selected from the group of hydrogen, C 1-6 -alkyl, and phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano,
—(C 1-6 -alkylene)-C(O)R f ,
wherein R f is
hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, or phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano;
benzyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, or phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano.
Preferably, R 8 is hydrogen; C 1-6 -alkyl, preferably methyl; or C 1-6 -alkoxy, preferably methoxy or —O-iso-propyl.
In a certain embodiment of the invention, R 9 is hydrogen, halo or C 1-6 -alkoxy. Preferably, R 9 is hydrogen or C 1-6 -alkoxy.
In certain embodiments of the invention, R 9 is hydrogen; halo, preferably fluoro, chloro or bromo; C 1-6 -alkyl, preferably methyl; C 1-6 -alkoxy, preferably methoxy or —O-iso-propyl; halo-C 1-6 -alkoxy, preferably trifluoromethoxy; or —O—C 2-10 -alkenyl, preferably allyl.
In certain embodiments of the invention, R 10 is hydrogen; halo, preferably bromo or chloro; C 1-6 -alkyl, preferably methyl; or C 1-6 -alkoxy, preferably methoxy.
In certain embodiments of the invention, R 11 is hydrogen; halo, preferably bromo or chloro; C 1-6 -alkyl, preferably methyl; or C 1-6 -alkoxy, preferably methoxy. More preferably, R 11 is hydrogen.
In certain embodiments of the invention
R 12 is hydrogen,
C 1-6 -alkyl, optionally substituted by CN or OH, —(C 1-6 -alkylene)-NR g R h , wherein R g and R h are each independently
hydrogen, C 1-6 -alkyl, —C(O)R e , or —S(O) 2 R e , wherein R e is selected from
hydrogen, C 1-6 -alkyl, and phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano;
—(C 1-16 -alkylene)-C(O)—NR i R j , wherein R i and R j are each independently
hydrogen, C 1-6 -alkyl, —(C 1-6 -alkylene)-NR k R l ,
wherein R k and R l are each independently hydrogen or C 1-6 -alkyl,
or R i and R j together with the nitrogen to which they are bound form a five or six membered heterocycle comprising one or two heteroatoms selected from the group of nitrogen, oxygen and sulfur;
—O-benzyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, nitro, halo, cyano, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, halo-C 1-6 -alkyl, —(C 1-6 -alkylene)-C(O)R f , wherein R f is
C 1-6 -alkyl, C 1-6 -alkoxy, or phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano,
phenyl, optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, —(C 1-3 -alkylene)-R m ,
wherein R m is phenyl, a 5- to 6-membered heteroaryl, 4- to 6-membered heterocycloalkyl or 3 to 6-membered cycloalkyl,
each optionally substituted by one or more halo, halo-C 1-6 -alkyl, C 1-6 -alkyl, C 1-6 -alkoxy, halo-C 1-6 -alkoxy, nitro, or cyano, or
—NR n R o ,
wherein R n and R o are each independently
hydrogen, C 1-6 -alkyl,
or R n and R o together with the nitrogen to which they are bound form a five or six membered heterocycle comprising one or two heteroatoms selected from the group of nitrogen, oxygen and sulfur.
In certain embodiments of the invention,
R 12 is hydrogen,
C 1-6 -alkyl, optionally substituted by CN or OH, C 1-6 -alkoxy, or —NR n R o ,
wherein R n and R o are each independently
hydrogen, C 1-6 -alkyl,
or R n and R o together with the nitrogen to which they are bound form a five or six membered heterocycle comprising one or two heteroatoms selected from the group of nitrogen, oxygen.
In certain embodiments of the invention, namely in combination with any embodiment described herein, R 7 , R 8 , R 9 , R 10 , R 11 and R 12 are not simultaneously hydrogen.
In certain embodiments of the invention, X is O and Y is CH 2 , A is selected from the group consisting of (a), (b), (c), (d) and (e); and R 1 to R 5 and R 7 to R 12 are as defined above.
In certain embodiments of the invention, X is O and Y is C═O, A is (f) or (g), and R 1 to R 5 and R 7 to R 12 are as defined above.
In certain embodiments of the invention, X is C═O and Y is NR 6 , A is (f), and R 1 to R 12 are as defined above.
In certain embodiments of the invention, X—Y is CH═CH, and A is (f) or (g), and R 1 to R 5 and R 7 to R 12 are as defined above.
In one embodiment
X is O and Y is CH 2 , X is O and Y is C═O, X is C═O and Y is O, or X is CH 2 and Y is O.
In another embodiment
X is C═O and Y is NR 6 , or X is CH 2 and Y is NR 6 .
In yet another embodiment
X—Y is CH═CH, or X—Y is CH 2 —CH 2 .
Preferred X and Y are:
X is O and Y is CH 2 , X is O and Y is C═O, X is C═O and Y is NR 6 , X—Y is CH═CH, or X—Y is CH 2 —CH 2 .
Preferred compounds of the invention are:
1′-(1-Benzothien-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidine], 1′-[(7-Methoxy-1-benzothien-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine], 1′-[(3-Isopropoxy-1-benzothien-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine], 1′-[(5-Methoxy-2,3-dihydro-1-benzothien-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine], 1′-[(4-Methoxy-7-morpholin-4-yl-1,3-benzothiazol-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine], 1′-[(5-Bromo-7-ethyl-1-benzofuran-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine], 1′-(1-Benzimidazol-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidine], 1′-[(5-Methyl-1H-benzimidazol-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine], 1′-[(5-Chloro-1H-benzimidazol-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine], (1RS,3′SR)-3′-Methyl-1′-[(3-methyl-1H-inden-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, 6-Methoxy-1′-[(3-methyl-3H-inden-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, 5-Methoxy-1′-[(3-methyl-1H-inden-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, 1′-(1H-Pyrrolo[2,3-b]pyridin-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, 6-Methoxy-1′-(1H-pyrrolo[2,3-b]pyridin-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, 6-(2-Hydroxyethoxy)-1′-(1H-pyrrolo[2,3-b]pyridin-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one, 5-Bromo-1′-[(3-methyl-1H-inden-2-yl)carbonyl]spiro[indole-3,4′-piperidin]-2(1H)-one, 1′-[(3-Methyl-1H-inden-2-yl)carbonyl]spiro[indene-1,4′-piperidine], and 1′-(1H-Pyrrolo[2,3-b]pyridin-2-ylcarbonyl)spiro[indene-1,4′-piperidine].
The invention also encompasses methods for the treatment of dysmenorrhea, hypertension, chronic heart failure, inappropriate secretion of vasopressin, liver cirrhosis, nephrotic syndrome, obsessive compulsive disorder, anxiety and depressive disorders which comprises administering a therapeutically effective amount of a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), or (Ig).
The invention also encompasses a pharmaceutical composition comprising a compound of formula (I), (Ia), (Ib), (Ic), (Id), (Ie), (If), or (Ig) and a pharmaceutically acceptable carrier. The pharmaceutical composition may further comprise at least one pharmaceutically acceptable excipient.
In a certain embodiment, the compound of the invention of general formula (I) can be manufactured according to a process comprising reacting a compound of formula (II):
with a carboxylic acid of the formula III
wherein R 1 to R 5′ , X, Y and A are as defined above.
The synthesis of compounds of general formula (I) will be described in more detail below and in the examples.
General Scheme A
Compounds of formula (I) can be prepared via an amide coupling between a spiropiperidine derivative of formula (II) and a carboxylic acid A-CO 2 H (III), wherein A is defined as hereinabove. The usual reagents and protocols known in the art can be used to effect the amide coupling. Spiropiperine derivatives of formula (II) and carboxylic acids (III) are either commercially available or readily prepared using procedures described hereinafter or using methods known in the art starting from commercially available materials. General scheme A is hereinafter further illustrated with general procedure I.
General Procedure I: Amide Coupling:
To a 0.1 M stirred solution of a carboxylic acid derivative in CH 2 Cl 2 are added EDC (1.3 eq), HOBt (1.3 eq), Et 3 N (1.3 eq) and the spiropiperidine derivative (1 eq). The mixture is stirred over night at RT and then poured onto water and extracted with CH 2 Cl 2 . The combined organic phases are dried over Na 2 SO 4 and concentrated in vacuo. Flash chromatography or preparative HPLC affords the title compound.
The compounds of the present invention exhibit V1a activity, which may be detected as described below:
V1a Activity
Material & Method:
The human V1a receptor was cloned by RT-PCR from total human liver RNA. The coding sequence was subcloned in an expression vector after sequencing to confirm the identity of the amplified sequence. To demonstrate the affinity of the compounds from the present invention to the human V1a receptor binding studies were performed. Cell membranes were prepared from HEK293 cells transiently transfected with the expression vector and grown in 20 liter fermenters with the following protocol.
50 g of cells were resuspended in 30 ml freshly prepared ice cold Lysis buffer (50 mM HEPES, 1 mM EDTA, 10 mM MgCl2 adjusted to pH=7.4+complete cocktail of protease inhibitor (Roche Diagnostics)); homogenized with Polytron for 1 min; and sonicated on ice for 2×2 minutes at 80% intensity (Vibracell sonicator). The preparation was centrifuged 20 min at 500 g at 4° C., the pellet was discarded and the supernatant centrifuged 1 hour at 43,000 g at 4° C. (19,000 rpm). The pellet was resuspended in 12.5 ml Lysis buffer+12.5 ml Sucrose 20% and homogenized using a Polytron for 1-2 min. The protein concentration was determined by the Bradford method and aliquots were stored at −80° C. until use. For binding studies 60 mg Yttrium silicate SPA beads (Amersham) were mixed with an aliquot of membrane in binding buffer (50 mM Tris, 120 mM NaCl, 5 mM KCl, 2 mM CaCl2, 10 mM MgCl2) for 15 minutes with mixing. 50 ul of bead/membrane mixture was then added to each well of a 96 well plate, followed by 50 ul of 4 nM 3H-Vasopressin (American Radiolabeled Chemicals). For total binding measurement 100 ul of binding buffer were added to the respective wells, for non-specific binding 100 ul of 8.4 mM cold vasopressin and for compound testing 100 ul of a serial dilution of each compound in 2% DMSO. The plate was incubated 1 h at room temperature, centrifuged 1 min at 1000 g and counted on a Packard Top-Count. Non-specific binding counts were subtracted from each well and data was normalized to the maximum specific binding set at 100%. To calculate an IC 50 the curve was fitted using a non-linear regression model (XLfit), and the Ki was calculated using the Cheng-Prussoff equation.
Example
pKi hV1a
1
7.6
2
7.3
4
7.2
6
7.3
9
7.5
10
7.2
14
6.7
The present invention also provides pharmaceutical compositions containing compounds of the invention, for example compounds of formula (Ia), (Ib), (Ic), (Id), (Ie), (If), and (g), and their pharmaceutically acceptable acid addition salts, and a pharmaceutically acceptable carrier. Such pharmaceutical compositions can be in the form of tablets, coated tablets, dragées, hard and soft gelatin capsules, solutions, emulsions or suspensions. The pharmaceutical compositions also can be in the form of suppositories or injectable solutions.
The pharmaceutical compounds of the invention, in addition to one or more compounds of the invention, contain a pharmaceutically acceptable carrier. Suitable pharmaceutically acceptable carriers include pharmaceutically inert, inorganic and organic carriers. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts etc can be used as such excipients e.g. for tablets, dragées and hard gelatine capsules. Suitable excipients for soft gelatine capsules are e.g. vegetable oils, waxes, fats, semi-solid and liquid polyols etc. Suitable excipients for the manufacture of solutions and syrups are e.g. water, polyols, saccharose, invert sugar, glucose etc. Suitable excipients for injection solutions are e.g. water, alcohols, polyols, glycerol, vegetable oils etc. Suitable excipients for suppositories are e.g. natural or hardened oils, waxes, fats, semi-liquid or liquid polyols etc.
Moreover, the pharmaceutical compositions can contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances.
The dosage at which the compounds of the invention can be administered can vary within wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, in the case of oral administration a daily dosage of about 10 to 1000 mg per person of a compound of general formula (I) should be appropriate, although the above upper limit can also be exceeded when necessary.
The following Examples illustrate the present invention without limiting it. All temperatures are given in degrees Celsius.
EXAMPLE A
Tablets of the following composition can be manufactured in the usual manner:
mg/tablet
Active substance
5
Lactose
45
Corn starch
15
Microcrystalline cellulose
34
Magnesium stearate
1
Tablet weight
100
EXAMPLE B
Capsules of the following composition can be manufactured:
mg/capsule
Active substance
10
Lactose
155
Corn starch
30
Talc
5
Capsule fill weight
200
The active substance, lactose and corn starch can be firstly mixed in a mixer and then in a comminuting machine. The mixture can be returned to the mixer, the talc can be added thereto and mixed thoroughly. The mixture can be filled by machine into hard gelatine capsules.
EXAMPLE C
Suppositories of the following composition can be manufactured:
mg/supp.
Active substance
15
Suppository mass
1285
Total
1300
The suppository mass can be melted in a glass or steel vessel, mixed thoroughly and cooled to 45° C.
Thereupon, the finely powdered active substance can be added thereto and stirred until it has dispersed completely. The mixture then can be poured into suppository moulds of suitable size, left to cool; the suppositories can then be removed from the moulds and packed individually in wax paper or metal foil.
In the following, the synthesis of compounds of formula (I) is further exemplified: The compounds of formula I may be prepared in accordance with the process variants as described above. The starting materials described in the Example section are either commercially available or are otherwise known or derived from the chemical literature, for instance as cited below, or may be prepared as described in the Examples section.
EXAMPLES
Example 1
1′-(1-Benzothien-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: Benzo[b]thiophene-2-carboxylic acid,
ES-MS m/e (%): 350.2 (M+H + ).
Example 2
1′-[(7-Methoxy-1-benzothien-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: 7-Methoxy-benzo[b]thiophene-2-carboxylic acid,
ES-MS m/e (%): 380.1 (M+H + ).
Example 3
1′-[(3-Isopropoxy-1-benzothien-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: 3-Isopropoxy-benzo[b]thiophene-2-carboxylic acid (described in J. Med. Chem. 1992, 35, 958),
ES-MS m/e (%): 408.2 (M+H + ).
Example 4
1′-[(5-Methoxy-2,3-dihydro-1-benzothien-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: 5-Methoxy-2,3-dihydro-benzo[b]thiophene-2-carboxylic acid
ES-MS m/e (%): 381.0 (M+H + ).
5-Methoxy-2,3-dihydro-benzo[b]thiophene-2-carboxylic acid
From the commercially available 5-methoxy-benzo[b]thiophene-2-carboxylic acid was prepared 5-methoxy-2,3-dihydro-benzo[b]thiophene-2-carboxylic acid by reduction using known procedures. One example is Mg/MeOH.
Example 5
1′-[(4-Methoxy-7-morpholin-4-yl-1,3-benzothiazol-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: 4-Methoxy-7-morpholin-4-yl-benzothiazole-2-carboxylic acid (described in patent WO2003045385)
ES-MS m/e (%): 466.6 (M+H + ).
Example 6
1′-[(5-Bromo-7-ethyl-1-benzofuran-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: 5-Bromo-7-ethyl-benzofuran-2-carboxylic acid
ES-MS m/e (%): 442.0 (M+H + ).
Example 7
1′-(1H-Benzimidazol-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: 1H-Benzoimidazole-2-carboxylic acid,
ES-MS m/e (%): 334.2 (M+H + ).
Example 8
1′-[(5-Methyl-1H-benzimidazol-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: 5-Methyl-1H-benzoimidazole-2-carboxylic acid,
ES-MS m/e (%): 348.1 (M+H + ).
Example 9
1′-[(5-Chloro-1H-benzimidazol-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidine] (described in J. Org. Chem. 1976, 41, 2628), Acid: 5-Chloro-1H-benzoimidazole-2-carboxylic acid,
ES-MS m/e (%): 368.0 (M+H + ).
Example 10
(1RS,3′SR)-3′-Methyl-1′-[(3-methyl-1H-inden-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one
Amide coupling according to general procedure I:
Amine: (1RS,3′SR)-3′-Methyl-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one (prepared according to WO 9929696) Acid: 3-Methyl-1H-indene-2-carboxylic acid,
ES-MS m/e (%): 374.5 (M+H + ).
Example 11
6-Methoxy-1′-[(3-methyl-1H-inden-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one
Amide coupling according to general procedure I:
Amine: 6-Methoxy-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one (prepared according to EP 722941) Acid: 3-Methyl-1H-indene-2-carboxylic acid,
ES-MS m/e (%): 390.5 (M+H + ).
Example 12
5-Methoxy-1′-[(3-methyl-1H-inden-2-yl)carbonyl]-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one
Amide coupling according to general procedure I:
Amine: 5-Methoxy-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one (described in EP 722941) Acid: 3-Methyl-1H-indene-2-carboxylic acid,
ES-MS m/e (%): 390.5 (M+H + ).
Example 13
1′-(1H-Pyrrolo[2,3-b]pyridin-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one
Amide coupling according to general procedure I:
Amine: 3H-Spiro[2-benzofuran-1,4′-piperidin]-3-one (preparation described in Organic Process Research & Development (2006), 10(4), 822-828.) Acid: 1H-Pyrrolo[2,3-b]pyridine-2-carboxylic acid,
ES-MS m/e (%): 348.4 (M+H + ).
Example 14
6-Methoxy-1′-(1H-pyrrolo[2,3-b]pyridin-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one
Amide coupling according to general procedure I:
Amine: 6-Methoxy-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one (preparation described in EP 722941) Acid: 1H-Pyrrolo[2,3-b]pyridine-2-carboxylic acid,
ES-MS m/e (%): 378.4 (M+H + ).
Example 15
6-(2-Hydroxyethoxy)-1′-(1H-pyrrolo[2,3-b]pyridin-2-ylcarbonyl)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one
Amide coupling according to general procedure I:
Amine: 6-(2-Hydroxyethoxy)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one (preparation described in EP 722941) Acid: 1H-Pyrrolo[2,3-b]pyridine-2-carboxylic acid,
ES-MS m/e (%): 408.4 (M+H + ).
6-(2-Hydroxyethoxy)-1′-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one
Preparation of N-Methylated Lactone Intermediate
To a solution of the substituted ortho-bromo benzoic acid (10.9 g, 50 mmol) in dry THF (200 ml) at −78° C. n-butyllithium (1.6 M in hexanes) (100 mmol) was added drop wise (3 h) and the resulting solution was stirred for an additional 2 h at the same temperature. Freshly distilled N-methyl 4-piperidone (7.91 g, 70 mmol) in dry hexane (25 ml) was added over 30 min at the same temperature. The mixture was then allowed to stir at rt and was finally added to ether (200 ml) and water (300 ml). The basic (aqueous) layer was extracted with ether (5×100 ml) and the aqueous layer was acidified with concentrated hydrochloric acid (pH 2-3) and extracted with ether. The aqueous solution was boiled for 1 h and was then cooled to 0-5° C. and made alkaline (pH 9-10) with cold aqueous sodium hydroxide. The cold solution was rapidly extracted with chloroform (5×200 ml). The combined chloroform extracts were washed with water, dried, concentrated to give light yellow solid which was purified over neutral alumina eluting with a gradient of 30-50% ethyl acetate-hexane to obtain 1.75 g (15%) of N-methylated lactone as white solid. 1H-NMR (CDCl3, 400 MHz): δ1.68-1.75 (m, 2H), 2.18-2.19 (m, 1H), 2.38 (s, 3H), 2.44-2.52 (m, 2H), 2.68-2.84 (m, 2H), 2.84-2.85 (m, 1H), 7.02-7.05 (m, 1H), 7.19-7.22 (m, 1H), 7.84-7.87 (m, 1H); FIA-MS: 236 (M+1).
Preparation of Cyano-Piperidine Intermediate
To a solution of the N-methylated lactone from above (1.17 g, 5 mmol) in dry chloroform (10 ml) was added cyanogenbromide (60 nmol) and the resulting solution was refluxed for 36 h. The reaction mixture was extracted with 5% HCl (5 ml) and then with water (2.5 ml). The chloroform solution was dried (anhydrous MgSO4) and concentrated to give a pale yellow solid which was chromatographed over SiO2 eluting with 1% MeOH—CH 2 Cl 2 to give 858 mg (70%) of the desired Cyano-piperidine as white solid. 1H-NMR (CDCl3, 400 MHz): δ1.72-1.76 (m, 2H), 2.22-2.30 (m, 1H), 3.48-3.60 (m, 4H), 7.09-7.11 (m, 1H), 7.11-7.28 (m, 1H), 7.89-7.92 (m, 1H); IR (KBr): 3492, 3043, 2216, 1760, 1602, 1478 cm−1.
Preparation of 6-(2-hydroxyethoxy)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one
The above cyano-piperidine (1.23 g, 5 mmol) was heated with ethylene glycol (5 ml) and sodium hydroxide (0.82 g, 20.5 mmol) for 15-20 min at 130° C. Most of the ethylene glycol was removed by distillation under high vacuum. The residual reaction mixture was diluted with water and extracted repeatedly with chloroform. The combined organics was dried and concentrated to give a semi solid material which was purified over Al2O3 column upon elution with 5-7% MeOH2CI2 containing NH3 (aqueous) to yield 789 mg (60%) of 6-(2-hydroxyethoxy)-3H-spiro[2-benzofuran-1,4′-piperidin]-3-one as pale yellow solid. 1H-NMR (d6-DMSO, 400 MHz): δ1.47-1.50 (m, 2H), 2.03-2.10 (m, 2H0, 2.79-2.85 (m, 2H), 2.95-2.97 (m, 2H), 3.73-3.76 (m, 2H), 4.12-4.14 (m, 2H), 7.09 (d, J=8.4 Hz, 1H), 7.20 (s, 1H), 7.69 (d, J=8.4 Hz, 1H); 13 C-NMR (d6-DMSO, 100 MHz): □□35.9, 42.3, 59.3, 70.4, 84.6, 106.4, 116.6, 117.0, 126.8, 156.9, 163.9, 168.5; FIA-MS: 264.3 (M+1).
Example 16
5-Bromo-1′-[(3-methyl-1H-inden-2-yl)carbonyl]spiro[indole-3,4′-piperidin]-2(1H)-one
Amide coupling according to general procedure I:
Amine: 5-Bromo-spiro[indole-3,4′-piperidin]-2(1H)-one (prepared described herein below) Acid: 3-Methyl-1H-indene-2-carboxylic acid,
ES-MS m/e (%): 437.4 (M+H + ).
5-bromo-spiro[indole-3,4′-piperidin]-2(1H)-one
1,5-Dichloro-3-methyl-3-azapentane hydrochloride 3
Formic acid (10.0 g; 0.2 mol) and 37% formaldehyde (20 ml) were mixed in a 250 ml round-bottom flask equipped with reflux condenser. 1,5-Dichloro-3-azapentane, hydrochloride (17.0 g; 0.1 mol) was added and the solution was heated with magnetic stirring at 100 C. After 3 h the temperature was increased to 120 C for 20 min and finally allowed to cool to room temperature before the solvent was evaporated in vacuo to afford 3 as white solid in quantitative yield. 1HNMR (CD3OD, 400 MHz) δ 3.0 (s, 3H); 3.45 (br s, 2H); 3.62 (br s, 2H); 4.07 (br s, 4H).
1,2-Benzo-8-methyl-3,8-diazaspiro[4,5]decane-4-one 5
A solution of oxindole 4 (6.25 g, 47 mmol) in THF (500 ml) was cooled to −78 C and to it a solution of sodium hexamethyldisilazide (43 g, 235 mmol) in THF (300 ml) was added drop wise under N2 atmosphere. After stirring at −78 C for 45 min, N-methylbis (2-chloromethyl) amine hydrochloride (9 g, 47 mmol) was added, as a solid. The reaction mixture was stirred at −78 C for 1 h and at room temperature for 24 h. After quenching with H2O (90 ml), the mixture was extracted with ethyl acetate (3×100 ml). The organic extracts were washed with brine (25 ml), dried and the solvent removed in vacuo. Silica gel chromatography (5-50% MeOH/CH 2 Cl 2 , gradient) gave 6 g (57%) of 5 as a solid. 1HNMR (CD3OD, 400 MHz) δ 1.84 (m, 2H); 2.51 (m, 2H); 2.62 (s, 3H); 3.02 (m, 2H); 3.37 (m, 2H); 6.82 (d, 1H, J=7.68 Hz); 6.94 (t, 1H, J=7.58 Hz); 7.12 (t, 1H, J=7.7 Hz); 7.26 (d, 1H, J=9 Hz); 9.27 (br s, 1H).
5-Bromo-1,2-dihydro-2-oxospiro[3H-indole-3,4′-piperidine]-1′methyl 6
A solution of 1,2-Benzo-8-methyl-3,8-diazaspiro[4,5]decane-4-one (6.3 g, 29.1 mmol) in CH 3 CN (100 ml) and MeOH (5 ml) was cooled to −5° C. and NBS (7.8 g, 44 mmol) was slowly added with stirring. The reaction mixture was stirred for 3.5 h at 0° C. Solvent was removed by vacuo. The residue was purified by silica gel chromatography (2-20% MeOH/CH 2 Cl 2 ) to give 6 g as a solid. The solid compound was dissolved in ethyl acetate (600 ml) and washed with saturated aqueous NaHCO 3 solution, dried (Na 2 SO 4 ). Evaporation of the solvent in vacuo gave 4.2 g (47%) of 6. 1 HNMR (CD 3 OD, 400 MHz) δ 7.51 (d, J=1.8 Hz, 1H), 7.35 (dd, J=1.9 and 8.2 Hz, 1H), 6.81 (d, J=8.2 Hz, 1H), 2.93 (m, 2H), 2.67 (m, 2H), 2.41 (s, 3H), 1.86 (m, 4H).
5-Bromo-1,2-dihydro-2-oxospiro[3H-indole-3,4′-piperidine]-1′-cyano 7
5-Bromo-1,2-dihydro-2-oxospiro[3H-indole-3,4′-piperidine]-1′-methyl 6 (4.6 g, 15.6 mmol) was dissolved in chloroform (700 ml) and treated with CNBr (22 g, 209.5 mmol) at room temperature. The mixture was heated to reflux for 24 h. The reaction mixture was cooled, diluted with methylene chloride (300 ml) and washed with 10% aqueous K 2 CO 3 solution (2×100 ml). After the mixture was dried (Na 2 SO 4 ) and concentrated, the residue was purified by silica gel chromatography (0-5% MeOH/CH 2 Cl 2 ) to gave 7 as a solid 3.9 g (82%). 1HNMR (CDCl 3 , 400 MHz) δ 7.52 (d, J=1.8 Hz, 1H), 7.37 (dd, J=1.8 and 8.2 Hz, 1H), 6.82 (d, J=8.2 Hz, 1H), 3.83 (m, 2H), 3.41 (m, 2H), 2.00 (m, 2H), 1.86 (m, 2H).
5-Bromo-spiro[indole-3,4′-piperidin]-2(1H)-one 2
5-Bromo-1,2-dihydro-2-oxospiro[3H-indole-3,4′-piperidine]-1′-cyano 7 (3.3 g, 10.8 mmol) was suspended in ethylene glycol (10 ml). The mixture was treated in NaOH (1.8 g, 45 mmol) and heated to 130° C. for 15 min. It was diluted with methylene chloride (500 ml) and washed with 10% aqueous K 2 CO 3 (2×100 m). The organic layer was dried (Na 2 SO 4 ) and concentrated and residue purified by silica gel chromatography (30% MeOH/CH 2 Cl 2 ) to gave 2 as a light ceramic white solid 1.8 g (60%), mp 256-258° C. 1 HNMR (DMSO-d 6 , 400 MHz) δ 10.6 (br s, 1H, NH), 7.57 (d, J=1.84 Hz, 1H), 7.36 (d, J=8.2 Hz, 1H), 6.79 (d, J=8.2 Hz, 1H), 4.05 (br s, 1H, NH), 3.06 (m, 2H), 2.84 (m, 2H), 1.64 (m, 2H), 1.55 (m, 2H), 13 C NMR (DMSO-d 6 , 100 MHz) δ 180.93, 140.64, 137.98, 130.42, 126.75, 113.20, 111.45, 46.24, 40.92, 32.94. Anal. Calcd for C 12 H 13 BrN 2 O: C, 51.26; H, 4.66; N, 9.9. Found: C, 50.87; H, 4.91; N, 9.67.
Example 17
1′-[(3-Methyl-1H-inden-2-yl)carbonyl]spiro[indene-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: Spiro[indene-1,4′-piperidine], Acid: 3-Methyl-1H-indene-2-carboxylic acid,
ES-MS m/e (%): 342.5 (M+H + ).
Example 18
1′-(1H-Pyrrolo[2,3-b]pyridin-2-ylcarbonyl)spiro[indene-1,4′-piperidine]
Amide coupling according to general procedure I:
Amine: Spiro[indene-1,4′-piperidine], Acid: 1H-Pyrrolo[2,3-b]pyridine-2-carboxylic acid,
ES-MS m/e (%): 330.4 (M+H + ).
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The present invention is concerned with novel spiro-piperidine derivatives as V1a receptor antagonists, their manufacture, pharmaceutical compositions containing them and their use as medicaments. The active compounds of the present invention are useful in the prevention and/or treatment of anxiety and depressive disorders and other diseases.
In particular, the present invention is concerned with compounds of the general formula (I)
wherein R 1 to R 5 , R 5 ′, X, Y and A are as defined in the specification.
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FIELD OF THE INVENTION
The present invention relates to novel compounds which have hemoregulatory activities and can be used to inhibit the myelopoietic system of humans and animals.
BACKGROUND OF THE INVENTION
A variety of regulatory messengers and modifiers such as colony stimulating factors, interferons, and different types of peptides are responsible for the regulation of myelopoiesis.
We have now found certain compounds which have an inhibitory effect on myelopoietic cells in vitro. They may be used to prevent quiescent cells from entering into cell division. Cells entering into cell division are susceptible to attack by cytotoxic anti-cancer drugs. In addition to providing a protective function in therapy using cytotoxic drugs, the compounds may also be used to arrest proliferation of cancer cells related to the myelopoietic system, i.e. myeloid leukemia.
SUMMARY OF THE INVENTION
This invention comprises compounds, hereinafter represented as formula (I), which have hemoregulatory activities and can be used to inhibit haematopoiesis.
The compounds are useful in providing a protective function in therapy using irradiation and/or cytotoxic drugs, and may also be used to arrest proliferation of cancer cells related to the myelopoietic system, for example, in the treatment of myeloid leukemia. The compounds may also be used in many clinical situations where it is desirable to alter haematopoiesis.
These compounds may also be used in combination with the dimers of co-pending U.S. application Ser. No.08/001,905, incorporated by reference herein, to provide alternating peaks of high and low activity in the bone marrow cells, thus augmenting the natural circadian rhythm of haematopoiesis. In this way, cytostatic therapy can be given at periods of low bone marrow activity, thus reducing the risk of bone marrow damage, while regeneration will be promoted by the succeeding peak of activity. This invention is also a pharmaceutical composition, which comprises a compound of formula (I) and a pharmaceutically acceptable carrier.
This invention further constitutes a method for inhibiting the myelopoietic system of an animal, including humans, which comprises administering to an animal in need thereof, an effective amount of a compound of formula (I).
DETAILED DESCRIPTION OF THE INVENTION
The compounds of this invention are illustrated by the Formula (I): ##STR1## wherein
R 1 and R 2 are independently hydrogen, C 1-6 alkyl, phenyl, napthyl, benzyl, pyridyl, furyl, oxazolyl or thiazolyl;
R 3 and R 4 are independently hydrogen, --CO 2 H, --(CH 2 ) n OH, --C(O)NH 2 , tetrazole, --CO 2 (C 1-3 alkyl), C(O)C 1-3 alkyl, CSNH 2 , C 1-6 alkyl or --(CH 2 ) n CO 2 H; n is 1, 2 or 3;
provided at least one of R 1 and R 2 and one of R 3 and R 4 is not hydrogen;
or a pharmaceutically acceptable salt thereof.
Also included in this invention are pharmaceutically acceptable salt complexes of the compounds of this invention.
Preferred compounds are:
(4S,5R)-4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole-4-carboxylic acid;
(4S,5S)-4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole-4-carboxylic acid;
(4S,5R)-4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole-4-carboxamide; and
(4R,5R)-4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole-4-carboxylic acid.
The present invention provides compounds of Formula (I) above ##STR2## which can be prepared by a process that comprises:
a) reacting a compound of Formula (2) ##STR3## with a substituted amino-alcohol of Formula (3) ##STR4## wherein R 1 and R 2 are independently selected from H, C 1-6 alkyl, phenyl, napthyl, benzyl, pyridyl, furyl, oxazolyl or thiazolyl. R 3 and R 4 are independently selected from H, CONH 2 , CSNH 2 , (CH 2 ) n OH, (CH 2 ) n CO 2 H, tetrazole, --COO(C 1-3 alkyl), --C(O)C 1-3 alkyl or C 1-6 alkyl in a suitable solvent such as DMF with a coupling reagent such as N-Ethyl-N'(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) and a tertiary amine such as triethyl amine to provide a compound of Formula (4). ##STR5##
Cyclization of compound (4) in the presence of Burgess Reagent (methoxycarbonylsulfamoyl)-triethylammonium hydroxide, inner salt, in refluxing THF provides oxazolines of Formula (5). ##STR6##
The treatment of compounds of Formula (5), wherein R 3 or R 4 is an ester, with a base such as sodium hydroxide in suitable solvent such as aqueous ethanol affords compounds of Formula (I).
The compounds of Formula (I) where either R 3 or R 4 is CONH 2 can be obtained by the aminolysis of compounds of Formula (5) wherein R 3 or R 4 is ester.
In general, in order to exert a inhibitory effect, the compounds of the invention may be administered to human patients by injection in the dose range of about 0.5 ng to about 10 mg, for example about 5-500 ng, or orally in the dose range of about 50 ng to about 5 mg, for example about 0.1 ng to 1 mg per 70 kg body weight per day; if administered by infusion or similar techniques, the dose may be in the range of about 0.005 ng to about 10 mg per 70 kg body weight, for example about 0.03 ng to 1 mg over six days. In principle, it is desirable to produce a concentration of the peptide of about 10 -15 M to about 10 -5 M in the extracellular fluid of the patient.
According to a still further feature of the present invention there are provided pharmaceutical compositions comprising as active ingredient one or more compound of formula (I) as hereinbefore defined or physiologically compatible salts thereof, in association with a pharmaceutical carrier or excipient. The compositions according to the invention may be presented; for example, in a form suitable for oral, nasal, parenteral or rectal administration.
As used herein, the term "pharmaceutical" includes veterinary applications of the invention. These compounds may be encapsulated, tableted or prepared in an emulsion or syrup for oral administration. Pharmaceutically acceptable solid or liquid carriers may be added to enhance or stabilize the composition, or to facilitate preparation of the composition. Liquid carriers include syrup, peanut oil, olive oil, glycerin, saline and water. Solid carriers include starch, lactose, calcium sulfate dihydrate, terra alba, magnesium stearate or stearic acid, talc, pectin, acacia, agar or gelatin. The carrier may also include a sustained release material such a glyceryl monostearate or glyceryl distearate, alone or with a wax. The amount of solid carrier varies but, preferably will be between about 20 mg to about 1 g per dosage unit. The pharmaceutical preparations are made following the conventional techniques of pharmacy involving milling, mixing, granulating, and compressing, when necessary, for tablet forms; or milling, mixing and filling for hard gelatin capsule forms. Capsules containing one or several active ingredients may be produced, for example, by mixing the active ingredients with inert carriers, such as lactose or sorbitol, and filling the mixture into gelatin capsules. When a liquid carrier is used, the preparation will be in the form of a syrup, elixir, emulsion or an aqueous or non-aqueous suspension. Such a liquid formulation may be administered directly p.o. or filled into a soft gelatin capsule. Organ specific carrier systems may also be used.
Alternately pharmaceutical compositions of the compounds of this invention, or derivatives thereof, may be formulated as solutions of lyophilized powders for parenteral administration. Powders may be reconstituted by addition of a suitable diluent or other pharmaceutically acceptable carrier prior to use. The liquid formulation is generally a buffered, isotonic, aqueous solution. Examples of suitable diluents are normal isotonic saline solution, standard 5% dextrose in water or buffered sodium or ammonium acetate solution. Such formulation is especially suitable for parenteral administration, but may also be used for oral administration and contained in a metered dose inhaler or nebulizer for insufflation. It may be desirable to add excipients such as polyvinylpyrrolidone, gelatin, hydroxy cellulose, acacia, polyethylene glycol, mannitol, sodium chloride or sodium citrate.
For rectal administration, a pulverized powder of the compounds of this invention may be combined with excipients such as cocoa butter, glycerin, gelatin or polyethylene glycols and molded into a suppository. The pulverized powders may also be compounded with an oily preparation, gel, cream or emulsion, buffered or unbuffered, and administered through a transdermal patch.
Nasal sprays may be formulated similarly in aqueous solution and packed into spray containers either with an aerosol propellant or provided with means for manual compression.
Dosage units containing the compounds of this invention preferably contain 1 mg-100 mg, for example 0.1-50 mg of the peptide of formula (I) or salt thereof.
According to a still further feature of the present invention there is provided a method of inhibition of myelopoiesis which comprises administering an effective amount of a pharmaceutical composition as hereinbefore defined to a subject.
No unacceptable toxicological effects are expected when compounds of the invention are administered in accordance with the present invention. The myelosuppressive activity of the compounds of Formula (1) was evaluated in either of the following assays:
Inhibition of Murine HPP-CFC (High Proliferative Potential Colony Forming Cells) Colony Formation
The Lin - Scal + (HPP-CFC) cells are isolated from femurs and tibia of normal female C57BL/6J mice. Single cell suspension is obtained by crushing the femurs and tibia then filtering the suspension through a 70 micron filter. Cells are washed and incubated in PBS+1% FBS (fetal bovine serum) at a concentration of 10 8 cells/ml with an optimal concentration of a cocktail of monoclonal antibodies directed against various lineage markers. After 30 minutes on ice, the cells are washed and the Lin marker expressing cells are removed with magnetic beads coated with the sheep anti rat IgG. Cells are washed in PBS+1% FBS buffer and resuspended to a concentration of 10 8 cells/ml. Optimal concentration of Ly6A/E-FITC (from Pharmingen) is added to the suspension and the cells are incubated for 30-45 minutes. The cells positive for Ly6A/E and negative for anti rat IgG are analyzed and sorted in a Coulter Epics Elite Cell Sorter equipped with a 488 nM tuned argon ion laser set to give a power of 15 mW with a rate of 1500-2000 cells/second (Coulter Electronics CA, USA). The final recovery of cells is 0.05-0.1% of the unfractionated bone marrow. The Lin-Scal+ cells are seeded in a double layer semisolid agar colony forming assay.
The compounds of Formula (I) are dissolved in PBS+1% FBS to give concentrations ranging from 1 mg/ml to 0.1 ng/ml. Four hundred Lin-Scal+ cells are seeded in the presence or absence of the compound. The cells are stimulated with a cocktail of Il-1, Il-3 and SCF (stem cell factor). The HPP colonies are defined as colonies larger than 0.5 mm diameter The difference between the colony number observed with the PBS buffer and the target compound solution is the measure of inhibition the compounds of the invention. The compounds of the invention gave activities ranging from 0.1 ng/ml to 10 mg/ml.
SK&F 107647 Antagonism Assay
This assay monitors the capacity of compounds of Formula (I) to inhibit the myelo-stimulatory activity of SK&F 107647: ##STR7##
The murine bone marrow derived stromal cell line, C6.4 are grown in 12 well plates in RPMI 1640 with 10% FBS. Upon reaching confluence, C6.4 cells are washed and media exchanged with fresh RPMI 1640 without FBS. Confluent cell layers of murine C6.4 cells are treated with SK&F 107647 (1 microgram/ml) which results in the production of a soluble hematopoietic synergistic activity measurable in a murine CFU-C assay (described below). The compounds of Formula (I) alone do not induce synergistic activity production from the stromal cell line. The compounds of Formula (I) are added to C6.4 cell cultures immediately prior to the addition of SK&F 107647. Cell-free supernatants are collected 18 hours later. Supernatants are fractionated with a Centricon-30 molecular weight cut-off membrane. C6.4 cell synergistic activity is measured in a murine CFU-C assay.
CFU-C Assay
(Colony Forming Unit in Culture Assay)
Bone marrow cells from C57B 1/6 female mice are cultured in nutrient rich media with 0.3% agar and a source of colony stimulating factor (CSF) for a period of 6-7 days at 37° C. in a humidified atmoshper of 7.5% CO 2 . Cell aggregates >50 cells are counted as collonies (CFU-c).
The Combination of SK&F 107647 treated C6.4 cell 30 K-effluent (30 K-E) with sub optimal levels of CSF results in colony growth greater than CSF alone. Murine bone marrow cells are harvested then suspended in RPMI 1640 with 10% FBS. Bone marrow cells (7.5E+4 cells/ml) are cultured with sub optimal levels of CSF plus dilutions of test C6.4 cell 30 K-E supernatants in a standard murine soft agar CFU-C assay. The SK&F 107647 treated culture 30 K-E represents the stimulated activity level. The combination of compounds of Formula I with SK&F 107647 can result in several different outcomes:
1) synergistic activity equal to SK&F 107647=not active as antagonist
2) synergistic activity significantly less that SK&F 107647=weak antagonist
3) no synergistic activity=antagonist or toxicity (requires separate test in CFU-C assay)
Data analysis: by convention 1 Unit (U) is equal to 1 colony stimulated* above background CSF alone CFU-C number.
Example:
CSF=20 CFU-C colonies
CSF+0.05 ml 30 K-E=50 CFU-C colonies
Calculated activity=30 Units/0.05 ml or 600 U/ml
The compounds of the invention showed activity at concentrations ranging from 10 ng/ml to 1 mg/ml.
The examples which follow serve to illustrate this invention. The Examples are intended to in no way limit the scope of this invention, but are provided to show how to make and use the compounds of this invention.
In the examples, all temperatures are in degrees Centigrade.
EXAMPLE 1
(4S, 5R)-4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole4-carboxylic acid ##STR8## a) N-Picolinyl-allo-threonyl methyl ester (Pic-allo-ThrOMe)
To a suspension of allo-ThrOMeoHCl (3.50 g, 20.4 mmol) in CHCl 3 (5 mL) was added Et 3 N (3.20 mL, 22.5 mmol). The resulting solution was stirred at room temperature for 30 min. The solvent was removed in vacuo and the remaining oil was azeotroped with toluene (3×5 mL). The residue was dissolved in DMF (10 mL) and cooled to 0° C. Picolinic acid (2.80 g, 22.5 mmol), Et 3 N (3.20 mL, 22.5 mmol), EDC (4.70 g, 22.5 mmol) and HOBt (3.31 g, 22.5 mmol) were sequentially added. The reaction was allowed to warm to room temperature and maintained there for 18 h. The bulk of the solvent was removed in vacuo and the crude reaction mixture was partitioned between EtOAc (50 mL) and water (10 mL). The aqueous layer was acidified with 0.1N HCl (pH about 5). The organic layer was separated and dried over MgSO 4 . Concentration afforded crude product which was recrystallized from CHCl 3 /hexanes to give 3.20 g (66%) of the desired product.
b) (4S, 5R)-4-Carboxymethyl-4,5-dihydro-5-methyl-2-(2-pyridinyl)oxazole
To a solution of Pic-allo-ThrOMe (70.0 mg, 0.29 mmol, obtained as above) in THF (5 mL) was added in one portion (methoxycarbonylsulfamoyl)-triethylammonium hydroxide, inner salt (Burgess reagent) (80.0 mg, 0.34 mmol). When the Burgess reagent had dissolved, the reaction was heated to reflux for 18 h. After allowing the reaction to cool, the solvent was removed in vacuo. The crude reaction product was purified by flash chromatography (5% MeOH/EtOAc, silica gel) to give 40.0 mg (62%) of the desired product as a clear oil.
c) (4S, 5R)-4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole-4-carboxylic acid
To a solution of (4S, 5R)-4-carboxymethyl-4,5-dihydro-5-methyl-2-(2-pyridinyl)oxazole (0.22 g, 1.00 mmol, obtained as above) in MeOH (2 mL) was added aq NaOH (44.0 mg, 1.10 mmol in 0.20 mL of H 2 O ). After 1 h at room temperature, the solvent was removed under reduced pressure. The residue was partitioned between EtOAc (5 mL) and 1N HCl (1 mL). The aqueous layer was extracted with further EtOAc (2×10 mL). the combined organic extracts were dried over MgSO 4 and concentrated to give a white residue. Flash chromatography (2% to 10% MeOH/CHCl 3 +1% AcOH, silica gel) gave 80.0 mg (39%) of the desired compound as a white solid.
13 C NMR (100 MHz, CD 3 OD) d 181.9, 178.7, 165.8, 151.0, 146.5, 140.0, 128.4, 125.0, 84.0, 77.0.
MS (ES+) m/z 207.0 (M+H)
EXAMPLE 2
(4S, 5S)-4.5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole4-carboxylic acid ##STR9## a) N-Picolinyl-threonyl methyl ester (Pic-ThrOMe)
In a fashion analogous to Example 1(a), ThrOMeoHCl (3.50 g, 20.4 mmol), Et 3 N (2×3.20 mL, 2×22.5 mmol), picolinic acid (2.80 g, 22.5 mmol), EDC (4.70 g, 22.5 mmol) and HOBt (3.31 g, 22.5 mmol) gave 3.45 g (71%) of the desired product after recrystallization from CHCl 3 /hexanes.
b) (4S, 5S)4-Carboxymethyl4,5-dihydro-5-methyl-2-(2-pyridinyl)oxazole
In a fashion analogous to Example 1(b), Pic-ThrOMe (70.0 mg, 0.29 mmol), and Burgess reagent (80.0 mg, 0.34 mmol) gave 40.0 mg (62%) of the desired product as a clear oil.
c) (4S, 5R)-4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole4-carboxylic acid
In a fashion analogous to Example 1(c), (4S, 5S)4-carboxymethyl-4,5-dihydro-5-methyl-2-(2-pyridinyl)oxazole (0.020 g, 0.09 mmol) and NaOH (4.0 mg, 0.10 mmol in 0.20 mL of H 2 O) gave 8.0 mg (42%) of the desired compound as a white solid.
13 C NMR (100 MHz, CD 3 OD) d 181.9, 178.7, 165.8, 151.0, 146.5, 140.0, 128.4, 125.0, 84.0, 77.0.
MS (ES+) m/z 207.0 (M+H).
EXAMPLE 3
(4S, 5R)4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole4-carboxamide ##STR10##
a) (4S, 5R)-4-Carboxymethyl-4,5-dihydro-5-methyl-2-(2-pyridinyl)oxazole (25 mg; 0.11 mmol obtained as in Example 1(b)) was dissolved in 2.0M NH 3 in MeOH (2 ml, 4.0 mmol). After 18 h at RT, the solvent was removed in vacuo. Purification using a Bond-Elut C18 column gave 4.9 mg (22%) of the desired product.
1 H NMR (400 MHz, CDCl 3 ) d 8.7 (d; 1H); 8.1 (d, 1 H), 7.85 (m, 1 H), 7.45 (m,1 H), 6.8 (broad s;1H); 5.95 (broad s;1H); 5.1 (m, 1 H), 4.45 (d, 1 H), 1.65 (d, 3 H).
EXAMPLE 4
(4R, 5R)-4.5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole-4-carboxylic acid ##STR11## a) N-Picolinyl-d-threonyl methyl ester (Pic-d-ThrOMe)
In a fashion analogous to Example 1(a), d-ThrOMeOHCl (1.75 g, 10.2 mmol), Et 3 N (2×1.60 mL, 2×11.2 mmol), picolinic acid (1.40 g, 11.2 mmol), EDC (2.35 g, 11.2 mmol) and HOBt (1.16 g, 11.2 mmol) gave 1.95 g (73%) of the desired product after recrystallization from CHCl 3 /hexanes.
b) (4R, 5R)-4-Carboxymethyl4,5-dihydro-5-methyl-2-(2-pyridinyl)oxazole
In a fashion analogous to Example 1(b), Pic-d-ThrOMe (0.35 g, 1.47 mmol) and Burgess reagent (0.50 g, 2.10 mmol) gave 0.20 g (63%) of the desired product as a clear oil.
c) (4R, 5R)4,5-Dihydro-5-methyl-2-(2-pyridinyl)oxazole4-carboxylic acid
In a fashion analogous to Example 1(c), (4R, 5R)-4-carboxymethyl-4,5-dihydro-5-methyl-2-(2-pyridinyl)oxazole (0.11 g, 0.50 mmol) and NaOH (22.0 mg, 0.55 mmol in 0.50 mL of H 2 O) gave 8.0 mg (42%) of the desired compound as a white solid.
13 C NMR (100 MHz, CD 3 OD) d 181.9, 178.6, 166.2, 151.0, 146.5, 140.0, 128.4, 125.0, 84.4, 76.6.
MS (ES+) m/z 207.0 (M+H).
EXAMPLE 5
Formulations for pharmaceutical use incorporating compounds of the present invention can be prepared in various forms and with numerous excipients. Examples of such formulations are given below.
______________________________________Tablets/Ingredients______________________________________ Per Tablet1. Active ingredient (Cpd of Form. I) 40 mg2. Corn Starch 20 mg3. Alginic acid 20 mg4. Sodium alginate 20 mg5. Mg stearate 1.3 mg 2.3 mg______________________________________
Procedure for Tablets
Step 1 Blend ingredients No. 1, No. 2, No. 3 and No. 4 in a suitable mixer/blender.
Step 2 Add sufficient water portion-wise to the blend from Step 1 with careful mixing after each addition. Such additions of water and mixing until the mass is of a consistency to permit its converion to wet granules.
Step 3 The wet mass is converted to granules by passing it through an oscillating granulator using a No. 8 mesh (2.38 mm) screen.
Step 4 The wet granules are then dried in an oven at 140° F. (60° C.) until dry.
Step 5 The dry granules are lubricated with ingredient No. 5
Step 6 The lubricated granules are compressed on a suitable tablet press.
Parenteral Formulation
A pharmaceutical composition for parenteral administration is prepared by dissolving an appropriate amount of a compound of formula I in polyethylene glycol with heating. This solution is then diluted with water for injections Ph Eur. (to 100 ml). The solution is then sterilized by filtration through a 0.22 micron membrane filter and sealed in sterile containers.
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The present invention relates to novel compounds which have hemoregulatory activities and can be used to inhibit the myelopoietic system of humans and animals.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the priority, under 35 U.S.C. §119, of German Patent Application DE 10 2006 049 648.5, filed Oct. 20, 2006; the prior application is herewith incorporated by reference in its entirety.
BACKGROUND OF THE INVENTION
Field of the Invention
[0002] The present invention relates to a method of controlling a powder sprayer having a fan jet nozzle configuration in a printing press. The invention also relates to a printing press having a powder sprayer.
[0003] German Published, Non-Prosecuted Patent Application DE 100 01 590 A1 describes a powder sprayer with a fan jet nozzle configuration. That powder sprayer includes nozzle heads disposed in a row. Each nozzle head includes two nozzles, each of which emits a powdered-air jet. A blower tube emitting compressed-air jets is disposed above the nozzle heads. The emission speed of those compressed-air jets is approximately twice as high as the speed of the powdered-air jets. Together, the compressed-air jets form a supportive fan jet that is free of powder and surrounds the powdered-air jets on all sides. The supportive fan jet screens the powdered-air jets off against turbulent flows that are caused by the movement of a gripper conveying the printed sheet. That ensures that the powdered-air jets reach the printed sheet, unaffected by the turbulent flows. However, if printed sheets made of paper are processed, the print quality may suffer as compared to printed sheets made of board. Although the momentum exerted by the supportive fan jet on the printed sheets is suitable for board sheets, it is too strong for paper sheets. The momentum affects the transportation of the paper sheets, which consequently begin to flutter. Problems arise, in particular, when both sides of the paper sheets have just been printed. In many printing presses, a sheet-guiding device is disposed opposite the powder sprayer, which means that the freshly printed upper side of the sheets faces the powder sprayer and the lower side of the sheets, which has also been recently printed, faces the sheet-guiding device. Due to the fluttering, the paper sheets may hit the sheet-guiding device, causing the printed image on the lower side of the sheets to become smeared. That means a considerable loss of print quality.
[0004] German Published, Non-Prosecuted Patent Application DE 199 37 090 A1, corresponding to Patent Abstracts of Japan Publication No. 2001070842 A, describes a method of powdering printed sheets wherein a powdered-air jet is generated by a blown-air generator. During operation, the output of the blown-air generator is varied to adapt the output of the blown-air generator, inter alia, to the conveying speed of the printed sheets or to the machine speed. The pressure of the powdered-air jet is adjustable between 0.1 bar and 0.5 bar (i.e. approximately between 1.5 psi and 7.3 psi).
[0005] German Patent DE 42 37 111 B4 describes a powder sprayer that is controlled by a programmed control unit. The control unit includes a keyboard for inputting basic parameters for an upcoming print job. Those basic parameters include, for example, the format of the sheets to be printed and the conveying speed.
SUMMARY OF THE INVENTION
[0006] It is accordingly an object of the invention to provide a method of controlling a powder sprayer and a printing press having a powder sprayer, which overcome the hereinafore-mentioned disadvantages of the heretofore-known methods and devices of this general type and in which a fan jet nozzle configuration ensures that a high level of print quality is maintained at all times.
[0007] With the foregoing and other objects in view there is provided, in accordance with the invention, a method of controlling a powder sprayer having a fan jet nozzle configuration, which may also be referred to as a surrounding jet nozzle configuration, in a printing press. The method comprises controlling the fan jet nozzle configuration as a function of operating parameters of the printing press.
[0008] As a result of this feature, the air supply to the fan jet nozzle configuration can be varied from print job to print job in order to adapt the air supply during operation to the requirements of the respective print job in an optimum way and to avoid adverse effects on the transportation of the sheets due to the powder sprayer. Thus, for every print job, the print quality remains on the same high level.
[0009] In accordance with another mode of the invention, the operating parameters are different printed sheet grammages, i.e. different specific masses per unit of area of the printed sheets. The printed sheet grammages may differ from print job to print job, for example if light-weight paper sheets are processed in one print job and heavy board sheets are processed in another print job. In this case, the air supply to the fan jet nozzle configuration can be adapted to the different printed sheet grammages.
[0010] In accordance with a further mode of the invention, the operating parameters are settings of the printing press as far as perfecting or double-sided printing and straight printing or one-sided printing are concerned. In this case, the printing press is a perfecting press with a reversing device for reversing the printed sheets. The reversing device may be adjusted in a desired way, in that it reverses the printed sheets in the perfecting mode and transports the printed sheets without reversing them in the straight-printing mode. The fan jet nozzle configuration may be controlled in such a way that the air supply in the perfecting mode differs from the air supply in the straight-printing mode. As a result, the sheets are conveyed smoothly and without disruption caused by the powder sprayer even in the perfecting mode.
[0011] In accordance with an added mode of the invention, the emission speed of supportive fan jets of the fan jet configuration is modified as a function of the operating parameters. If the operating parameters are the varying printed sheet grammages, the emission speed of the supportive fan jets emitted by the fan jet nozzle configuration is modified as a function of the printed sheet grammages, that is to say when the printing press is switched from processing printed sheets of lower grammage to processing printed sheets of higher grammage, the emission speed of the supportive fan jets is increased. In the other case, i.e. if the operating parameters are the settings of the printing press in terms of perfecting or straight printing, the emission speed of the supportive fan jets of the fan jet nozzle configuration is modified as a function of the settings, that is to say when the printing press is switched from the perfecting mode to the straight-printing mode, the emission speed of the supportive fan jets is increased.
[0012] In accordance with an additional mode of the invention, the emission speed of powdered-air core jets of the fan jet nozzle configuration remains unchanged when the emission speed of the supportive fan jets is modified. The supportive fan jets may be generated by a first blown-air generator and the powdered-air core jets may be generated by a second blown-air generator.
[0013] The two developments that have been mentioned in the last two paragraphs are based on the concept that the fan jet nozzle configuration includes a plurality of fan jet nozzles and each of the fan jet nozzles includes a core jet nozzle channel and a fan jet nozzle channel surrounding the core jet nozzle channel. Each fan jet nozzle emits the powdered-air core jet from the core jet nozzle channel, which is a blown-air jet mixed with powder for powdering the printed sheets. The fan jet nozzle channel of each fan jet nozzle emits the supportive fan jet, which is a blown-air jet without powder. As viewed in the flow direction of the supportive fan jet, the latter has a substantially annular profile in the interior of which the powdered-air core jet is located. The fan jet nozzle channels of the fan jet nozzles are connected to the first blown-air generator, which supplies the fan jet nozzle channels with the blown air of relatively high pressure of the supportive fan jets. The core jet nozzle channels are connected to the second blown-air generator, which supplies the blown air of relatively low pressure of the powdered-air core jets to the core jet nozzle channels. The blown air supplied by the second blown-air generator is mixed with powder, for example through the use of an injector, in order to form the powdered-air core jets.
[0014] With the objects of the invention in view, there is concomitantly provided a printing press, for implementing the method, comprising a powder sprayer having a fan jet nozzle configuration. A control unit controls the fan jet nozzle configuration in dependence on operating parameters of the printing press.
[0015] Other features which are considered as characteristic for the invention are set forth in the appended claims.
[0016] Although the invention is illustrated and described herein as embodied in a method of controlling a powder sprayer and a printing press having a powder sprayer, it is nevertheless not intended to be limited to the details shown, since various modifications and structural changes may be made therein without departing from the spirit of the invention and within the scope and range of equivalents of the claims.
[0017] The construction and method of operation of the invention, however, together with additional objects and advantages thereof will be best understood from the following description of specific embodiments when read in connection with the accompanying drawings.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING
[0018] FIG. 1 is a diagrammatic, longitudinal-sectional view of a complete printing press including a sheet delivery and a powder sprayer disposed therein;
[0019] FIG. 2 is a diagrammatic and schematic view of the powder sprayer; and
[0020] FIG. 3 is a sectional view of the powder sprayer taken along a line III-III of FIG. 2 , in the direction of the arrows and representing a nozzle bar and a nozzle head disposed thereon.
DETAILED DESCRIPTION OF THE INVENTION
[0021] Referring now to the figures of the drawings in detail and first, particularly, to FIG. 1 thereof, there is seen a printing press 1 including printing units 2 to 5 and a sheet delivery 6 . The sheet delivery includes a chain conveyor 7 , which deposits printed sheets on a delivery pile 8 . Moreover, the printing press 1 includes a reversing device 9 , which can be switched from a straight-printing mode, in which only one side of the sheets is printed, to a perfecting mode, in which both sides of the sheets are printed. In the straight-printing mode without sheet reversal, both the printing units 2 and 3 located upstream of the reversing device and the printing units 4 and 5 located downstream of the reversing device print on the front side of the printed sheets. In the perfecting mode, the printed sheets are printed on the front side in the upstream printing units 2 and 3 and on the back side in the downstream printing units 4 and 5 . The sheet delivery 6 includes a powder sprayer 10 , which powders the printed sheets as they are conveyed past by the chain conveyor 7 .
[0022] FIG. 2 shows that the powder sprayer includes a nozzle bar 11 that has surrounding jet nozzles or fan jet nozzles 12 disposed thereon. The fan jet nozzles 12 are disposed in a row over the width of the printed sheet. Together, they form a fan jet nozzle configuration 13 . The nozzle bar 11 is connected to a first blown-air generator 21 , and to a second blown-air generator 22 through a metering device 23 . The metering device 23 includes an injector 24 , which introduces the powder into the blown air generated by the second blown-air generator 22 to form a powder/air mixture. The blown-air generators 21 , 22 , which belong to the powder sprayer 10 , may be disposed outside the printing press 1 and are controlled by an electronic control unit 25 .
[0023] FIG. 3 shows that each of the fan jet nozzles 12 is constructed in the form of a nozzle head 14 attached to the nozzle bar 11 . Each fan jet nozzle 12 includes an outer fan jet nozzle channel 15 , which has a substantially annular cross section, and an inner core jet nozzle channel 16 , which is surrounded by the fan jet nozzle channel 15 .
[0024] The outer fan jet nozzle channel 15 is connected to the first blown-air generator 21 through a supportive-air line 17 . The core jet nozzle channel 16 is connected to the second blown-air generator 22 through a powdered-air line 18 . The supportive-air line 17 and the powdered-air line 18 are formed of air channels formed in the nozzle bar 11 and of hose or tube lines connected to the nozzle bar 11 . The outer fan jet nozzle channel 15 emits a supportive-air fan jet 19 from its opening and the core jet nozzle channel 16 emits a powdered-air core jet 20 from its opening.
[0025] In a non-illustrated modified embodiment, the fan jet nozzle configuration is formed of a row of core jet nozzle channels that is disposed between an upstream row of fan jet nozzle channels and a downstream row of fan jet nozzle channels, as viewed in the direction of sheet travel. The core jet nozzle channels emit powdered-air core jets, which are locked in between two blown-air curtains emitted by the two rows of fan jet nozzle channels, to form supportive-air fan jets.
[0026] The powder sprayer 10 operates as follows:
[0027] The second blown-air generator 22 supplies blown air at a pressure of between 0.5 bar and 1.0 bar to the powdered-air line 18 . However, the effect of the second blown-air generator 22 is unavoidably reduced by the injector 24 . As a result, the total of the forces, which result from the differentiation of the momentum of the powdered-air core jets 20 as a function of time, only range between 0.1 Newton and 2.0 Newton, preferably between 0.5 Newton and 1.0 Newton. The forces may be measured at the openings of the core jet nozzle channels 16 , and their number corresponds to the total number of nozzle heads 14 of the nozzle bar 11 . The total of the forces can be said to be the resultant force. The first blown-air generator 21 supplies blown air at a pressure of approximately 0.2 bar to the supportive-air line 17 . This pressure is comparatively low, so that a central blown-air supply of the printing press 1 may be used as the first blown-air generator 21 . The second blown-air generator 22 may be a compressor that is separate from the central blown-air supply. The total of the forces, which results from a differentiation of the momentum of the supportive-air fan jets 19 as a function of time, ranges between 0.5 Newton and 18.0 Newton, preferably between 2.0 Newton and 6.0 Newton. These forces may be measured at the openings of the fan jet nozzle channels 15 , and the number of these forces corresponds to the total number of fan jet nozzles 12 of the nozzle bar 11 , which is 24 in the given example.
[0028] The momentum of the supportive-air fan jets is not only varied in dependence on the machine speed, the format of the printed sheets, the settings of the delivery, and a powder removal by suction, but also in dependence on the grammage of the printed sheets and on whether the printing press 1 is being operated in the straight-printing mode or in the perfecting mode.
[0029] Sheets of higher grammage require a higher supportive-air momentum than sheets of lower grammage. Once the grammage of the printed sheets of the upcoming print job have been input into the electronic control unit 25 , the latter automatically adjusts the output of the first blown-air generator 21 in such a way that the blown-air generator 21 generates the air pressure required for the necessary supportive-air momentum in the supportive-air line 17 .
[0030] A higher supportive-air momentum is needed in the straight-printing mode than in the perfecting mode. Once the mode of operation of the printing press 1 for the upcoming print job has been input at the control unit 25 , for example the straight-printing mode, the electronic control unit 25 adjusts the reversing device 9 and the first blown-air generator 21 in a corresponding way.
[0031] It is an advantage that the powdered air and the supportive air are supplied from separate sources and that it is not the momentum of both air lines that is increased but only the momentum of the supportive-air line 17 . This means that the existing central blown-air supply (first blown-air generator 21 ) of the printing press 1 can be used to increase the momentum. The momentum of the powdered air generated by the second blown-air generator 22 may be maintained at a constant minimum value. The total momentum of the air required to stabilize the powdered-air jet is primarily generated by the outer supportive air rather than by the inner powdered air. This feature reduces cost and saves construction space. Of course, it is possible to adjust the amount of powder introduced into the printing press, which is also referred to as a characteristic powder curve, in a manner corresponding to the respective effectiveness of the powder application.
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A method of controlling a powder sprayer having a fan jet nozzle configuration in a printing press, includes controlling the fan jet nozzle configuration as a function of operating parameters of the printing press. A printing press having a powder sprayer is also provided.
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RELATED APPLICATION/S
[0001] This application is a continuation-in-part (CIP) of PCT Patent Application No. PCT/IL2009/001048 filed Nov. 5, 2009, which claims the benefit of priority of U.S. Provisional Patent Application No. 61/193,204 filed Nov. 5, 2008. The content of both these applications are incorporated herein by reference.
FIELD AND BACKGROUND OF THE INVENTION
[0002] The present invention relates to a device and method for treatment of a dental cavity such as a root canal and, more particularly, but not exclusively to a device for sterilizing a root canal.
[0003] A root canal is the commonly used term for the main canals within the dentine of the tooth. These are part of the natural cavity within a tooth that consists of the dental pulp chamber, the main canals, and sometimes more intricate anatomical branches that may connect the root canals to each other or to the root surface of the tooth. Root canals are filled with a highly vascularized, loose connective tissue, the dental pulp. This sometimes becomes infected and inflamed, generally due to caries or tooth fractures that allow microorganisms, mostly bacteria from the oral flora or their byproducts, access to the pulp chamber or the root canals. The infected tissue is removed by a surgical intervention known as endodontic therapy, more commonly known as root canal treatment.
[0004] Removal and disinfection procedures are not always effective at removing individual bacteria, but it is even more difficult to remove bacterial films. Nevertheless complete removal of bacteria or sterilization of the canal prior to sealing the root canal is a necessary condition for a successful outcome to the treatment.
[0005] Known systems insert cleaning (disinfecting) fluids into the root canal but such fluids are highly toxic. Furthermore they have to be present in the root canal for a relatively large amount of time. In addition the fluid must reach every part of the root canal, something which cannot be guaranteed. In some cases, particularly where infection is already present, the treatment must be repeated several times before the root canal can be sealed. The method takes time and depends very much on the expertise of the dentist carrying out the treatment.
[0006] A further disadvantage of the above system is that bubbles or air pockets tend to occur, especially in the deeper parts of the root canal or where root canal passages are not straight, and the air pockets tend to prevent the cleaning fluid from making contact with all surfaces.
[0007] Other systems place an electrode inside the root canal and another electrode outside the tooth and pass a current between the two, closing the circuit via the human body. The electromagnetic field and in some case the temperature kills bacteria, but the effectiveness is limited because often the conditions in the canal are not ideal. This is particularly the case when the electrode is far from the apical aria. One version uses 500 Watts of power, at a frequency of 300-KHz, in order to create a current path from the apical aria of the root canal to the external electrode, through the patient's flesh. A disadvantage of this system is that much of the power provided goes to setting up the current path and not to carrying out the sterilization. Furthermore the sterilization effect is not uniform over the root canal, and requires exceptional skill on the part of the dentist in order to be successful. Furthermore the resistance provided by the human body varies between individuals, making it impossible to control the power level in given cases. Thus a higher than designed resistance may reduce the output and vice versa. Furthermore the power increases with proximity to the apical aria, due to the reduced distance between the two ends of the probe or electrode and in some cases a current overload may result, causing pain to the patient. Thus it is impossible to control the power and you may either expose the client to sharp, pain or you may fail to provide sufficient power to destroy all the bacteria.
[0008] In particular, efforts to ensure that the effect is evenly distributed over the root canal are complicated by the need to avoid the root canal apex. The apex contains healthy tissue which should not be damaged.
[0009] There is thus a widely recognized need for, and it would be highly advantageous to have, a method of root canal sterilization that is devoid of the above limitations.
SUMMARY OF THE INVENTION
[0010] According to some embodiments of a first aspect of the present invention there is provided a device for disinfecting and/or sterilization of a dental cavity comprising:
an electrode pair adapted to extend into said cavity to provide current along at least a portion of the cavity; and a controller configured for sending controlled electrical energy to said cavity via current flowing between the electrodes when located in said cavity, thereby to provide electrical energy for said disinfection and/or sterilization.
[0013] In an embodiment of the invention a first electrode of said electrode pair forms a central axis and a second electrode of said electrode pair is coiled about said central axis.
[0014] Optionally, said first electrode is controllably extendable along said axial direction, thereby to vary a length of a gap between said first electrode and said second electrode.
[0015] Optionally, said controller is configured to adjust a level of energy released within said cavity.
[0016] In an embodiment of the invention, the level of energy is limited in accordance with a tooth cavity resistance.
[0017] Optionally, the device further comprises a plug for closure of said cavity. Optionally, the plug is movable to define a depth to which said electrode pair extends into said cavity.
[0018] Optionally, the controller configured to detect whether the cavity contains conductive fluid, said detecting comprising measuring conductivity between the electrodes.
[0019] Optionally, the controller is configured to cut off said current if the absence of said fluid is detected in said cavity.
[0020] In an embodiment of the invention, the device is configured with an apex detection unit for detecting the distance of an apex of said cavity from said electrode pair. Optionally, the controller disables pulse generation when the electrode is at the apex.
[0021] Optionally, the controller comprises a pulse generator. Optionally, the device comprises a resistance measurement unit for measuring electrical resistance between said electrode pair. Optionally, the controller is operatively connected to said resistance measurement unit, and shuts off said controlled current whenever said electrical resistance is at a level indicating that said electrodes are not currently located in said cavity or the cavity does not contain a liquid
[0022] There is further provided, in accordance with an embodiment of the invention, a method of treatment of a dental cavity comprising:
inserting a pair of electrodes into said cavity; and generating a controlled energy pulse between said electrodes, in an amount suitable for sterilizing and/or disinfecting said cavity.
[0025] In an embodiment of the invention the method includes filling said cavity with a conductive fluid prior to said generating a controlled energy pulse. Optionally, the method includes providing a pulse to dry tissues within said cavity for removal.
[0026] In an embodiment of the invention, the method includes measuring a location of an apex of said cavity and setting a mechanical limiter to provide insertion of said electrodes a controlled distance into said cavity responsive to said apex location measurement.
[0027] In an embodiment of the invention, the energy is according to a local volume of said cavity.
[0028] In an embodiment of the invention, the method includes locating the electrode pair at a first depth in said cavity and providing an energy pulse thereat and then relocating said electrodes to a second depth and an providing an energy pulse thereat.
[0029] Optionally, conductive fluid comprises a salt solution. Optionally, the salt solution comprises a salt concentration lying between 0.9% and saturation. Optionally the salt concentration comprises any one of the group comprising a 2% solution, a 3% solution, a 4% solution, a 5% solution, a 6% solution, a 7% solution, an 8% solution, a 9% solution, a 10% solution, an 11% solution, a 12% solution, a 13% solution, a 14% solution, a 15% solution, a 16% solution, a 17% solution, an 18% solution, a 19% solution, and a 20% solution.
[0030] Optionally, the conductive fluid comprises one or more of ethylenediaminetetraacetic acid (EDTA hydrogen peroxide, EDTA, chlorhexidine or iodoform (IKI—potassium iodide).
[0031] In an embodiment of the invention, the energy pulse causes a breakdown in the cavity that is limited to the cavity.
[0032] There is further provided, in accordance with an embodiment of the invention, a method of treatment of a cavity comprising:
[0033] inserting a pair of electrodes into said cavity; and
[0034] generating controlled energy between said electrodes, and therewith disinfecting and/or sterilizing said cavity.
[0035] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The materials, methods, and examples provided herein are illustrative only and not intended to be limiting.
BRIEF DESCRIPTION OF THE DRAWINGS
[0036] The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in order to provide what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.
[0037] In the drawings:
[0038] FIG. 1 is a simplified diagram illustrating a first device according to an embodiment of the present invention where electrodes are inserted into a root canal;
[0039] FIG. 2 shows both a detail and an exploded diagram of the electrode assembly of the device of FIG. 1 ;
[0040] FIG. 3A is a simplified cross section of the handle and electrode moving mechanism of the device of FIG. 1 ;
[0041] FIG. 3B is an alternative version of the electrode moving assembly of FIG. 3A allowing for multiple electrode positions;
[0042] FIG. 4 is another simplified diagram showing the cross section compared to the complete assembly and against the various assemblies separated from each other;
[0043] FIG. 5 is a simplified diagram showing the device of FIG. 1 with attachments for apex location, according to another embodiment of the present invention;
[0044] FIG. 6 is a simplified diagram showing in greater detail the electrode assembly of FIG. 1 in the root canal;
[0045] FIG. 7 is a simplified flow chart showing the operation of a device according to an embodiment of the present invention;
[0046] FIG. 8 is a simplified diagram showing the device in the two different positions for the first and second pulse trains respectively according to an embodiment of the present invention; and
[0047] FIG. 9 is a simplified schematic diagram which shows use of attachments for apex location in order to set the position of the electrode in the root canal.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0048] The present embodiments comprise an apparatus and a method for root canal sterilization using electrical energy, where an electrode pair is inserted into the root canal. A discharge is induced between the electrodes of the electrode pair. The current is confined to the root canal, and electrical energy is therefore kept out of surrounding tissues. The result is that several Joules of energy can be released within the root canal to kill the bacteria, without detrimental effect on the human body
[0049] The effect can be enhanced by filling the root canal with either a conductive fluid, such as salt water or an irrigation fluid such as 17% ethylenediaminetetraacetic acid (EDTA), to take two examples. Other fluids with high conductivity and/or sterilizing or disinfecting ability may also be considered. Mixtures of conducting materials and sterilizing or disinfection agents may also be used. In an embodiment of the invention a conductive fluid is placed in the root canal and the electrode pair is dipped or otherwise contacted with a sterilizing or disinfecting fluid. The electrode pair is then inserted into the conducting liquid in the root canal and the current is made to flow between the electrodes. Other sterilizing or disinfecting solutions can be used. Applicants believe that hydrogen peroxide, chlorhexidine, iodoform (IKI—potassium iodide are suitable.
[0050] In an embodiment the electrical energy diffuses into the root canal volume and kills the bacteria. The bacteria are killed by one or more of an electromagnetic wave, a wave of heat provided via the liquid and a pressure wave. Although any one of the above may be useful, two or more are preferred for clinical effectiveness and all three together provide the ideal sterilization, thus providing the sterilization.
[0051] It is believed that an important factor in the sterilization process is aggressive oxidation cause by the break-up of the water in the solution in which one component is atomic oxygen. The resulting oxidation is very strong compared to that resulting from mere high temperatures. The breakdown caused by the pulse gives rise to pressure and thermal waves which force the atomic oxygen particles into side tubules and channels in the interior of the root. It is believed that many of these tubules and channels are not open during normal sterilization.
[0052] Furthermore the electric current generated between the electrodes can be concentrated mainly between the two electrode tips, so the use of energy can be tightly controlled. Thus given precise placing of the electrodes in the root canal it is possible to provide energy at precise locations in the root canal and to vary the energy in accordance with the locations. Furthermore since there is no need to generate an electrical path through the Apex or the tissues of the gums, the energy level can be tailored for the particular location within the canal according to the canal volume and shape.
[0053] The principles and operation of an apparatus and method according to the present invention may be better understood with reference to the drawings and accompanying description.
[0054] Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangement of the components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting. It should also be understood that for simplicity some features are described only with respect to some embodiments. However, combinations of elements from different embodiments are also included in the scope of the invention.
[0055] Reference is now made to FIG. 1 which illustrates a device 10 for sterilization of a dental root cavity 12 , according to an embodiment of the invention. The device comprises an electrode pair 14 for extending into the cavity.
[0056] A controller—control box 16 —comprises a power supply 17 , a controller 18 and an apex locator unit 19 . The power supply includes capacitors to store energy, a voltage supply, a supply limiter and a timer, and provides precise pulses. The controller 18 optionally includes a microprocessor and is able to carry out functions such as measuring apex location within the root canal, measuring conductivity and calculating the pulses needed for the given conditions, in some embodiments of the invention.
[0057] The controller 16 sends a controlled electrical current at high voltage to the cavity via the electrodes. The controlled current is confined within the cavity since both electrodes are located within the cavity. The energy released carries out the disinfection. The energy released can be of the order of magnitude of 1 to 10 or even 40 Joules we aren't yet sure, but it will most likely be between 25-40J, and may be calculated to heat fluid within the cavity within milliseconds to a temperature exceeding 200 or 500 degrees Celsius or at least a temperature exceeding 100 degrees Celsius, to kill any bacteria present. It can be expected that this almost instant heating causes a shock wave within the cavity.
[0058] It is noted that to heat the root canal volume, typically approximately 7 micro liters which has been filled with a water based solution to reach 100 degrees Celsius requires approximately two Joules. To evaporate the same volume an additional 16 Joules is needed.
[0059] The pulse is optionally a pulse modulated high voltage alternating current whose duration defines the necessary energy levels. The high voltage and the distance between the electrodes define whether breakdown will occur, preferably leading to breakdown.
[0060] Reference is now made to FIG. 2 which is a detail of FIG. 1 showing the electrodes of the electrode pair. A first electrode 20 extends axially within a sleeve 22 . Sleeve 22 is an insulator. A tip of the first electrode 20 extends from the sleeve 22 . The second electrode 24 of the pair is coiled around the central axis. The electrode construction is made thin enough and flexible enough to be inserted into a root canal. In particular the end of the assembly comes to a point to allow for penetration into the depths of the canal. The head of the axial electrode, meaning the proximal end, has a larger diameter than the distal end, and the outer electrode is wound around the axial electrode. The two electrodes are isolated from each other.
[0061] In some embodiments of the invention, the first electrode is controllably extendable along the axial direction, so that the tip can be extended or retracted as desired. The result is to vary the length of a gap between the first electrode and the second electrode and thus control the passage of electrical energy within the canal. The mechanism defines at least two specific lengths of the electrode gap, providing two locations or more in the root canal for releasing energy. Pulses of energy often lead to sparks and the location of the spark is generally in the region between the two ends of the electrodes so that adjusting the height of the first electrode is a relatively accurate way of pinpointing the location of the spark and thus providing precise pinpointing of the energy, from which point the energy spreads around the canal to carry out sterilization.
[0062] The controller may alter the current or the voltage or the time or length of the pulses and thus adjust the level of energy released within the cavity. Such an energy level adjustment may be carried out in conjunction with adjustment of the location of the electrode so that greater energy is provided at the outermost end of the root canal and lesser energy at the narrower apex.
[0063] It is further noted that the conical shape of the apex tends to decrease resistance and increase the energy at the narrow parts of the canal, thus naturally providing the energy level adjustment even without artificially intervening.
[0064] Furthermore the number of pulses in a pulse train is limited so as to reduce the possibility of unintentional energy release after the device has been removed from the root canal.
[0065] The construction of the electrode assembly may include a plug 26 which serves to close the cavity, and helps to keep any liquids inside. The plug thus prevents release of fluids heated by the spark. In addition, if any kind of toxic fluid is used then it prevents the release of the toxic fluid into the mouth
[0066] In an embodiment, the plug is movable to define a depth to which the electrode pair extends into said cavity. As shown the plug is located over rotatable element 28 which can be screwed along thread 30 to provide a finely defined length of the electrode assembly. The length can be set to define the distance to the apex of the root canal so as to prevent the electrodes from being extended into the apex.
[0067] In an embodiment the cavity is filled with fluid before insertion of the electrodes, so that the effect of the current is to heat the fluid. The electrodes can be used to measure the resistance in the cavity prior to supply of the current so as to ascertain that the fluid is present. The controller may be set to cut off the current if absence of fluid is detected. In one embodiment there is no separate measurement activity. The first of a train of spark-causing pulses is generated and if the conductivity is too low then it is inferred that the fluid is not present and the remainder of the train is stopped.
[0068] The device may be used together with any kind of fluid injector that injects the conductive fluid into the cavity.
[0069] The conductive fluid may be a salt solution, say between 2 and 20% saline solution. Alternatively, other fluids, such as EDTA or the other sterilizing or disinfecting materials mentioned herein may be used. Alternatively, mixtures of antibacterial and conducting materials or conducting antibacterial solutions are used. In some embodiments, the cavity is filled with a conducting liquid and the electrodes, carrying antibacterial material are inserted into the liquid. The root canal cavity is very small, of the order of about 7 micro liters in volume, so that very little fluid is in fact present. A small amount of energy can thus heat the fluid very quickly.
[0070] As shown in FIG. 2 , the central electrode extends beyond both the sleeve and the tip of the outer electrode. A gap between the electrodes of about 7-10 mm is initially defined, however the central electrode can be retracted from this initial position to define different length gaps during the course of the treatment. As mentioned above, the spark generally begins in the region between the two electrodes and thus retraction of the central electrode moves this region and allows for sparks at different locations in the root canal. Since the initial maximum extent is set not to reach the apex, all further treatment is safely away from the apex as well. The spark location can be safely moved within the canal under complete control. Furthermore the amount of energy can be varied according to the present depth. In the deepest parts of the canal the diameter is much smaller and thus less energy is needed than say at the surface.
[0071] The amount of power may be arrived at by online measurement of the current and voltage during the pulse train. The constricted space of the canal can only accommodate a limited amount of energy, and increasing the amount of energy beyond this value achieves nothing. However, since increased energy causes heating of the tooth, higher energy inputs may not be desirable. The pulse energy level may thus be limited to the lowest value giving such an upper resistance value for any reason.
Controlling according to the upper resistance value provides for greater energy for greater width and less energy for lesser width.
[0073] Overall, a preferred diameter for the central electrode is 0.15 mm. The spiral shape of the second electrode may serve to increase the structural stability of the electrode assembly as a whole.
[0074] The device may include an apex locator detection unit which detects the apex of the root canal. Such an apex detection unit is discussed in applicant's copending US Patent Application Publication No. 2008/0187880 A1, the disclosure of which is incorporated by reference. However, any apex detector, as known in the art, may be used in some embodiments of the invention. Alternatively, no apex measurement is made by system 10 . Plug 26 serves as a mechanical limiter to limit an extension of said electrode pair into the detected apex.
[0075] The controller 16 may comprise a pulse generator and the current may be controlled by varying a size of the pulses generated.
[0076] As mentioned, measurement of the resistance measurement between the electrodes is useful for a number of purposes. Thus the controller may include a resistance measurement unit which measures electrical resistance around the extent of the electrode pair. The controller may shut off the controlled current to the electrodes whenever the electrical resistance is at a level indicating that the electrodes are not currently located in the cavity or are located in an apex of said cavity, or when the fluid does not appear to be present.
[0077] In an embodiment, the controller supports a pre-disinfection stage of cavity clearing, in which pre-treatment pulses from the electrodes clear dead or dying tissue from the root canal or the walls. Such a pre-disinfection stage may be carried out without artificial insertion of fluid, more specifically prior to insertion of the fluid into the root canal. The natural moisture in the canal may be sufficient. As shown in FIG. 1 (and in greater detail in FIG. 6 ), the plug 26 is placed over the tooth being treated. Handle 32 is held by the operator to keep the electrode assembly steady within the root canal and button 34 is pressed both to start a train of pulses and to operate the retraction mechanism of the central electrode, so that the pulses can be spread out over at least two locations over the length of the canal.
[0078] Reference is now made to FIG. 3A , which is a cross section showing the mechanism of device 10 , according to an embodiment of the invention. Parts that are the same as those in figures already described are given corresponding reference numerals and are described further only as necessary for an understanding of the present embodiment. FIG. 3A particularly shows the details of the mechanism for advancing the electrode. Electromagnet 36 is alternatively energized and de-energized to attract or not attract pole 38 . Pole 38 takes with it block 40 which is pulled upwards until it reaches step 41 , where it is stopped. The arrangement provides for two electrode positions, an upper position and a lower position, as illustrated in FIG. 8 below. The length of slot 42 is chosen for optimal location of the spark along the root canal. Spring 43 ensures an electrical connection to the outer electrode irrespective of the position of the electrode. Button 34 allows the user to operate the controller which will operate the control of the electromagnet and thus the position of the electrode.
[0079] Reference is now made to FIG. 3B , which is a simplified cross-section illustrating a variation of the mechanism of FIG. 3A in which a stepper motor allows a larger number of electrode positions to be attained. Parts that are the same as those in figures already described are given corresponding reference numerals and are described further only as necessary for an understanding of the present embodiment. Stepper motor 44 receives commands from the controller and rotates accordingly. Block 45 rotates and via the mutual thread arrangement advances or retracts pole 46 accordingly in a controlled manner.
[0080] Reference is now made to FIG. 4 , which shows that the device may be constructed in three parts, the insertion head 50 , which includes the electrode assembly and the cap, the electrode control unit 52 which includes the cap mechanism and the plunger mechanism, and the handle itself 54 , which is angled for ease of use. The electrode assembly may be removable for sterilization in an autoclave
[0081] FIG. 5 illustrates an embodiment of a working device. The sterilization device 10 is one of three attachments to a main controller 60 and is inserted into the root canal where electrical sparks are used to sterilize the root canal. Hook 62 is looped on the lip and the combination of hook 62 and attachment 64 are used for locating the apex, in conjunction with the apex location unit.
[0082] FIG. 6 is an enlarged diagram showing the electrode assembly inserted into the root canal. Plug 26 both seals liquids within the tooth cavity and acts as a limiter to prevent the electrodes from reaching the root canal apex. The axial electrode 20 has an exposed tip portion 70 . The coiled second electrode 24 has a tip 74 . The distance between the tip 74 and the beginning of the exposed portion 70 defines a spark gap, and it is this distance which is varied by moving the axial electrode so that the precise location of the spark can be varied during the therapy as described above in respect of FIGS. 3A and 3B . The sleeve is fixed with the electrode assembly 50 which is fixed in place by holders 71 .
[0083] A prototype using the above energy levels managed to sterilize a root canal having a high concentration of bacteria, of the order of 10 −6 , which is equivalent to a highly infected root canal.
[0084] A process for use of the device is now described with respect to FIG. 7 . The process begins with stage 80 by locating the apex using the apex locator attachment 19 and hook 62 . Alternatively, the location of the apex (referenced to the top of the tooth) is determined using a separate apex locator. At the same time as the apex is located the moisture level of the root is measured and fed directly into the operating program. In stage 82 , plug 26 is then rotated to define the depth of the apex so as to act as a guard against the electrodes being inserted into the apex. Preferably the plug is set to give a predetermined distance of clearance from the apex, one or two or more millimeters of clearance. For example, initial clearance of 3-4 millimeters appears to be suitable.
[0085] An intermediate stage 84 of providing an initial pulse based on partial penetration of the electrode device into the canal can optionally be carried out in order to dry the tissues of the canal which will need to be removed by the files prior to sterilization. Drying the tissues eases their subsequent removal. The size of pulse needed to dry the tissues may be obtained from the detected moisture level of the canal as detected previously.
[0086] The optional conductive and/or cleaning and/or disinfecting fluid may be injected into the root canal in stage 86 .
[0087] The electrode assembly is now attached to the handle and inserted into the channel until further progress is impeded by the plug, in stage 88 . In some embodiments of the invention, the electrode assembly is dipped in a disinfectant or antibacterial material before being inserted into the liquid in the root canal.
[0088] The dentist then presses on the button 34 , which operates the control program in the controller. The control program issues one or more pulses of defined power depending on the location of the electrode within the canal and the size of the canal—the apical constriction. When the volume of the canal is lower, the power in the pulses will be lower. The voltage level of the pulses is controlled to affect the overall power as is the timing of the pulses. The pulse train may stop when the program is completed. As a safety feature, in an embodiment of the invention, a single push-button operates the system, with a first push of the button causing a set of capacitors to charge and a second push causing the capacitors to discharge into the cavity. As an additional safety feature, a waiting period between pulse trains is preferably required, for example a wait of 45 seconds between pulse trains. A typical number of pulses for the train would not exceed four although it is envisioned that a larger number such as 6 could be used. Between pulse trains, the root canal is preferably rinsed and refilled with liquid.
[0089] Once the control program has completed the train of pulses for the deeper part of the root canal—stage 90 , the plunger is operated to move the electrodes to the higher part of the canal, further from the apex—stage 92 . In stage 94 a further pulse train is produced, and here greater power is used as the size of the canal is larger. If needed additional iquid is added and/or the electrode assembly is dipped in disinfectant or ant-bacterial material before stage 94 . As mentioned the amount of power is arrived at by online measurement of the current and voltage. The pulse energy level may thus be limited to to a value giving a desired energy.
[0090] Finally, in stage 96 , a large pulse is optionally supplied to disable the electrodes and stop further activity. The large pulse is a safety feature intended to ensure that electrical energy is not inadvertently released outside the root canal, say in contact with the jaw or the molars.
[0091] A further safety feature involves the ability to detect inadvertent entry of the electrodes into the apex for whatever reason, say human error in setting the plug. The apex locator mechanism continually operates via a small current through the electrode 20 sent to hook 62 , of the order of 10 mA. A danger area is defined and whenever the electrodes are indicated to be in that danger area the pulse train is automatically shut down.
[0092] An additional safety feature ensures that the actual energy of the pulse does not exceed the calculated energy.
[0093] Reference is now made to FIG. 8 which illustrates the device of the present embodiments in two pulse positions in the root canal The device is initially extended as far as plug 26 will allow, which means that the electrode reaches deep into the root canal, and almost up to the apex. The first pulse or pulse train is issued at this first deep position—position A. Then the electrode is retracted, for example using the mechanism of FIG. 3A above, and the second pulse or pulse train is emitted at position B. Optionally, a single pulse train or multiple pulse trains at a single position (for example, 3-4 mm from the apex) is sufficient to provide sterilization.
[0094] A device according to the present embodiments may have a number of advantages over the existing systems that use electrodes.
[0095] First of all there is no heating of tissues outside the root canal. Rather all the energy is concentrated in the region that requires sterilization. Furthermore there is no nerve stimulation outside the region of treatment. Thirdly there is no need to subject the patient to the psychological trauma of having the other electrode clearly in view and being felt. Furthermore the safety features that are needed are fewer than for the existing devices.
[0096] As a further safety feature, the energy of the pulse is limited by the upper resistance threshold of the cavity.
[0097] FIG. 9 is a simplified schematic diagram which shows use of attachments for apex location in order to set the plug. Parts that are the same as in earlier figures are given the same reference numerals and are only explained again in accordance with the need to understand the present figure. The process of locating the apex is controlled within controller 60 . Hook 62 is placed on the gum to define a ground and then a train of high frequency pulses are released into the canal from apex location attachment 64 . The reflection of the pulses is measured. A second train of pulses is then emitted at a different frequency and the reflection is measured. The two reflections are subjected to signal processing and then applied to a look up table which supplies a number, that number being the length of the canal. The user then sets the plug to give an electrode length according to (in fact slightly less than) that number in millimeters. The preferred process is more fully described in applicant's copending International Patent Application No. PCT/IL2007/000755, the contents of which are hereby incorporated by reference.
[0098] It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.
[0099] Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents, and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.
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A device for disinfecting and/or sterilization of a dental cavity comprising:
an electrode pair adapted to extend into said cavity to provide current along at least a portion of the cavity; and a controller configured for sending controlled electrical energy to said cavity via current flowing between the electrodes when located in said cavity, thereby to provide electrical energy for said disinfection and/or sterilization.
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[0001] This application claims priority from U. S. Provisional Patent application ser. no. 60/937,309, filed Jun. 27, 2007.
[0002] The invention disclosed and claimed herein is a gasifier and gasifier system based on the gasifier, which contains as a major component, a novel feed system for feeding organic materials into the burn pile of the gasifier.
[0003] The invention is useful for gasifying solid organic materials and using such gasified products for conversion to thermal energy.
[0004] Materials that can be gasified using this invention include, among other materials, biomass materials, such as forestry and agricultural residues, industrial waste materials, such as saw mill pulp and paper products, hydrocarbon based products and plastics, and the like.
BACKGROUND OF THE INVENTION
[0005] It has been known in the art for a long time to use industrial and agricultural solid organic by-products, such as forestry an agricultural residue and the like, as potential sources of large amount of chemical energy. Such organic materials are frequently referred to as “biomass” materials. There is a large library of patents and other publications dealing with gasifiers (retorts) and associated systems for creating energy from biomass materials.
[0006] Patents dealing with such systems are for example, U.S. Pat. No. 4,971,599 that issued to Cordell on Nov. 20, 1990; U.S. Pat. No. 4,691,846 that issued to Cordell, et al. on Sep. 8, 1987; U.S. Pat. No. 4,593,629 that issued to Pedersen, et al. on Jun. 10, 1986; U.S. Pat. No. 4,430,948 that issued to Schafer, et al. on Feb. 14, 1984; U.S. Pat. No. 4,321,877 that issued to Schmidt, et al. on Mar. 30, 1982; U.S. Pat. No. 4,312,278 that issued to Smith, et al. on Jan. 26, 1982; U.S. Pat. No. 4,184,436 that issued to Palm, et al. on Jan. 22, 1980, and U.S. Pat. No. 5,138,957 that issued to Morey, et al. on Aug. 18, 1992.
[0007] However, none of these patents deal with a horizontal auger system to deliver feed material to a discharge elbow that discharges directly to a burn pile in the gasifier. The prior art deals with vertical auger units and most of them deal with a double vertical auger system. The disadvantage to the use of vertical augers is that the inside vertical auger cannot be repaired while the system is on-line, and they have a tendency to burn up at the tip when dry fuels are fired, or when there is an upset in the system. This problem has been completely eliminated by the use of a single, horizontal auger firing into a ceramic discharge elbow for discharging directly into the burn pile.
[0008] The gasifier of the instant invention is less costly to build and operate, easier to maintain, has fewer moving parts and contains nearly 100% ceramic internals to prevent warping and contortion of metal parts that are used in the prior art devices.
SUMMARY OF THE INVENTION
[0009] In accordance with the present invention, there is provided a low cost to build, low cost to operate, easier to maintain, and relatively simple gasifier and system. The gasifier is used in a gasification system to provide recovery of energy from feed stock of forestry and agricultural residues, such as industrial waste materials such a pulp and paper products, hydrocarbon based products, such as plastic and the like, by gasification of such materials with the inventive gasifier and employment of the inventive system disclosed herein.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] FIG. 1 is a full side view of a gasifier of this invention.
[0011] FIG. 2 is a partial cross sectional side view of a portion of the gasifier of FIG. 1 , through line 2 - 2 of FIG. 4 .
[0012] FIG. 3 is a cross sectional view of a portion of the gasifier of FIG. 1 , through line 3 - 3 of FIG. 4 .
THE INVENTION
[0013] Thus, in more detail, there is an improved gasifier system for pyrolizing organic material, the gasifier system comprising a gasifier having a cylindrical housing. The cylindrical housing has a steel sidewall and the sidewall is completely lined with a refractory material. The sidewall has a top and a bottom.
[0014] The top of the sidewall is closed and sealed with a monolithic dome, the dome comprising a steel-walled hemi-elliptical section. The hemi-elliptical section comprises a height to diameter ratio of at least 1 to 2 and the dome has a top and is completely lined with a refractory material. The dome has a syngas exit duct centered at the top and the bottom of the sidewall is fixed to a furnace bed.
[0015] There is a refractory lined ash removal system comprised of an air-locked ash removal auger, an ash lift conveyer and, an enclosed ash dumpster.
[0016] There is a refractory lined combustion system comprised of a tuyere plenum, a segmented ceramic combustion hearth contained in a refractory lined hopper, a tuyere manifold, a plurality of tuyeres leading from the tuyere manifold through the tuyere plenum to a burn pile area.
[0017] There is a retractable, all-ceramic lance ignition burner projecting from the outside of the tuyere plenum and through the tuyere plenum and into the segmented ceramic combustion hearth and above the burn pile area.
[0018] There is a refractory lined upper housing comprising the burn pile area and a feed system for feeding organic materials to the burn pile area. The feed system comprises a hopper for organic material, a conveyor for conveying organic materials to the feed hopper, and a horizontal auger contained in an auger housing for conveying organic material through a ceramic discharge elbow and into the burn pile area.
[0019] The auger housing connects the hopper and the discharge ceramic elbow, and the auger housing has a control valve associated with it to control air flow through the auger housing.
[0020] There is an air cooling system for the ceramic elbow and auger housing, and the air cooling system comprises an electrical fan and an air feed system, the air feed system comprising an air feed duct housed in a refractory lined housing.
[0021] The upper housing of the upper segment contains a burn pile height detector.
[0022] In addition to that Supra, there is contemplated within the scope of this invention to use a grate over the air-locked ash removal auger. Preferably this grate is a ceramic grate, and most especially, the ceramic grate is an oscillating ceramic grate system.
[0023] One of the major features of this invention is the gasifier feed system which is a horizontal auger driven feed system that feeds directly into the bottom without having to auger the feed through significant vertical elevations.
DETAILED DESCRIPTION OF THE INVENTION
[0024] Turning now to FIG. 1 wherein there is shown a full front view of a gasifier system 1 of this invention showing a refractory lined combustion chamber 2 having a cylindrical housing 29 wherein the cylindrical housing has sidewalls 30 that are completely lined with a refractory material 27 , a feed hopper 3 , a litter feed conveyor 24 , a tuyere air manifold 4 , an oscillating ceramic grate 5 , an ash auger 6 , an ash lift conveyor 7 , an enclosed ash dumpster 8 , a tuyere plenum 9 , a lance ignition burner 10 , a combustion air fan 11 , a feed tube 12 , a feed tube housing 13 , a pile control detector 14 , a syngas exit duct 15 , and a control valve 16 . The cylindrical housing 29 has a top 31 and a bottom 32 , the top 31 being surmounted by a monolithic dome 33 having the syngas exit duct 15 mounted thereon (See FIG. 1 ).
[0025] The dome 33 has a hemi-elliptical section comprising a height to diameter ratio of at least 1 to 2 and the dome 33 is also completely lined with a refractory material (not shown).
[0026] FIG. 4 is a full top view of the gasifier system 1 of this invention wherein like numbers indicate like components, and FIG. 2 is a full cross sectional view through lines of FIG. 4 .
[0027] The bottom 32 of the sidewall 30 of the cylindrical housing 29 of the combustion chamber 2 is fixed to a furnace bed, generally 34 , the furnace bed 34 comprises an upper segment 35 , a middle segment 36 , and a lower segment 37 .
[0028] As shown in FIG. 4 , the lower segment 37 is a refractory lined ash removal system comprising an air-locked ash removal auger 6 and an ash auger housing 17 for the ash auger 6 and a flange 18 that permits the retention and removal of the auger 6 from the ash auger housing for replacement or repair, an ash lift conveyer 7 , and an enclosed ash dumpster 8 .
[0029] In FIG. 2 , there is shown the components of the middle segment 36 which shows a fixed ceramic hearth 19 constructed of replaceable sections and a plurality of oscillating ceramic ash removal plates 20 located above the fixed ceramic hearth 19 . Situated above the oscillating ceramic ash removal plates 20 is the tuyere plenum 9 having side wall 21 , wherein there is located the retractable ignition burner 10 . Multiple tuyeres 23 are inserted through the side walls 21 and lead to a burn pile area, generally 40 in FIGS. 2 and 3 and the tuyeres 23 are fed air or other gas from the tuyere manifold 4 located on the outside of the furnace 34 . The tuyeres 23 can be changeable inside diameter tuyeres and can be zoned, manifolded or single plenum, as shown herein, to inject air or flue gas into the tuyere plenum 9 as required by pulsing, steady or varying flow of the burning mass described infra.
[0030] The housing for the tuyere plenum 9 the burning chamber 22 is constructed of insulated wear/temperature lining 26 , retained with stainless steel alloy “Y” anchors as shown at 25 and is line with insulated fire brick lining 27 . It should be noted in FIG. 2 that the combustion chamber 2 is constructed such that there is built into the walls thereof, a stabilizing reflective arch 28 . In addition, there is a retractable, all-ceramic lance ignition burner 10 projecting from the outside of the tuyere plenum 9 and through the tuyere plenum 9 and into the segmented ceramic combustion hearth and above the burn pile area 40 .
[0031] The novelty and essence of this invention is the delivery system for the burnable biomass material 41 . The upper segment 35 comprises a refractory lined upper housing 42 containing the burn pile area 40 . The upper housing 42 of the upper segment 35 contains a burn pile height detector 14 .
[0032] The feed system 43 , generally, comprises a system for feeding organic materials (biomass, litter, etc.) to the burn pile area 40 . The system comprises a hopper 3 for the biomass material 41 , a biomass material conveyor 24 for conveying the biomass 41 to the feed hopper 3 , an auger system 38 comprising a horizontal auger 44 contained in an auger housing 39 .
[0033] The auger housing 39 terminates inside of the furnace 34 in a ceramic feed elbow 45 that is directed upwardly from the terminal end of the auger housing 39 and allows the biomass material 41 to overflow and descend to the burn pile area 40 . The horizontal feed system 43 is possible because of the ceramic elbow 45 . It should be noted that the ceramic elbow 45 is preferred to be wider at the top 46 than at the bottom 47 to enhance the flow of biomass material 41 through the ceramic elbow 45 .
[0034] FIG. 3 also shows the accumulation of ash 48 and the general distillates 49 that are generated by the burning pile of biomass material 41 .
[0035] As can be observed from FIG. 1 , in addition to the tuyeres 23 , air is introduced into the furnace 34 through a duct 50 using an auxiliary fan 11 to enhance the burning activity in the furnace 34 . This provide for an air cooling system for the ceramic elbow 45 and auger housing 39 . This system is comprised of an electrical fan and an air feed system that is integrated and controlled by the gasifier.
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A gasifier and gasifier system based on the gasifier, which contains as a major component, a novel feed system for feeding organic materials into the burn pile of the gasifier. The gasifier feed system is a horizontal auger driven feed system that feeds directly through a ceramic elbow into the furnace without having to auger the feed through significant vertical elevations.
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BACKGROUND OF THE INVENTION
[0001] The present invention relates to a process for the optical resolution of a key intermediate for preparing pharmacologically active 2,7-substituted octahydro-1H-pyrido[1,2-a]pyrazine derivatives, such as (7S,trans)-2-(2-pyrimidinyl)-7-(hydroxymethyl)octahydro-2H-pyrido(1,2-a)pyrazine, which are disclosed in U.S. Pat. No. 5,852,031, the contents of which are hereby incorporated by reference. These pyrazine compounds are ligands with specificity for dopamine receptor subtypes, especially the dopamine D4 receptor, within the animal body, and are therefore useful in the treatment of disorders of the dopamine system. The process of the present invention involves resolution of trans-7-(hydroxymethyl)octahydro-2H-pyrido(1,2-a)pyrazine using D-(−) or L-(+)naproxen.
[0002] Previously, the desirable optically resolved pyrazine compounds were obtained by later-stage resolution using D-(−) or L-(+)-tartaric acid, as disclosed in European Patent No. 569387. The present method has the advantage of minimizing material losses incurred by conducting resolutions after a multistep synthetic sequence, and results in a more efficient, higher-yielding process for preparing the (7S,trans)-2-(2-pyrimidinyl)-7-(hydroxymethyl)octahydro-2H-pyrido(1,2-a)pyrazines.
SUMMARY OF THE INVENTION
[0003] The present invention relates to a process for separating a racemic mixture, or an optically enriched mixture, of trans-7-(hydroxymethyl) octahydro-2H-pyrido(1,2-a)pyrazine containing a first enantiomer having the formula:
[0004] and a second enantiomer having the formula:
[0005] the process comprising:
[0006] reacting the racemic mixture, or the optically enriched mixture, with (+)-naproxen or (−)-naproxen to form, respectively, a diastereomeric mixture of the (+)- or (−)-naproxen salts of each of the enantiomers; separating each of the diastereomeric (+)- or (−)-naproxen salts; and if desired, converting the respective naproxen salt of each enantiomer to the free base thereof.
[0007] The present invention further provides a salt of a compound with a substance selected from the group consisting of (+)-naproxen and (−)-naproxen, said compound having the formula
[0008] The present invention also provides a salt of a compound compound with a substance selected from the group consisting of (+)-naproxen and (−)-naproxen, said compound having the formula
BRIEF DESCRIPTION OF DRAWINGS
[0009] FIG. 1 shows a synthetic pathway for preparing key intermediates in the manufacture of biologically active 2,7-substituted octahydro-1H-pyrido[1,2-a]pyrazine derivatives.
DETAILED DESCRIPTION OF THE INVENTION
[0010] As illustrated in the accompanying FIGURE, the present invention provides a process for resolution of a racemic mixture, or an optically enriched mixture, of pyrazines which comprises forming a (+)- or (−)-naproxen salt (2) of the pyrazines (1) and thereafter, in a separating step, converting the respective (+)- or (−)-naproxen salt to the free-base of the associated enantiomer (3). Preferably, in one implementation of the process of the invention, the racemic mixture, or the optically enriched mixture, is reacted with (+)-naproxen. The amount of (+)-naproxen added in the reaction is from about 0.5 equivalent to about 1.0 equivalent, and is preferably about 0.5 equivalent. In the process, the separating step comprises isolating an insoluble (+)-naproxen salt from a soluble (+)-naproxen salt, and the insoluble (+)-naproxen salt is a salt of the first enantiomer.
[0011] Alternatively, the process of the present invention may be performed wherein the racemic mixture, or the optically enriched mixture, of pyrazines is reacted with (−)-naproxen. In such case, the separating step comprises isolating an insoluble (−)-naproxen salt from a soluble (−)-naproxen salt, and the insoluble (−)-naproxen salt is a salt of the second enantiomer. In one embodiment, the process comprises a reacting step which comprises contacting the racemic mixture, or the optically enriched mixture, with (+)-naproxen to form a precipitate in a solution, wherein the precipitate is the (+)-naproxen salt of the first enantiomer; and the process further comprises separating the precipitate from the solution; and further comprising converting the (+)-naproxen salt of the first enantiomer to the free-base thereof.
[0012] The reacting step optionally comprises contacting the racemic mixture, or the optically enriched mixture, with (−)-naproxen to form a precipitate in a solution, the solution comprising the (−)-naproxen salt of the first enantiomer dissolved therein; the separating step comprises separating the precipitate from the solution and evaporating the solution so as to provide the salt of the first enantiomer; and further comprising converting the (−)-naproxen salt of the first enantiomer to the free-base thereof.
[0013] Accordingly, in the process of the present invention, trans-7-(hydroxymethyl)octahydro-2H-pyrido(1,2-a)pyrazine is resolved using (+)-naproxen or (−)-naproxen. The pyrazine is reacted with either (+)-naproxen or (−)-naproxen in an inert polar solvent. Suitable solvents include methanol, ethanol, isopropanol, ethyl acetate, diethyl ether and tetrahydrofuran, or mixtures thereof. Ethanol is a preferred solvent. The temperature of the reaction is not critical. Generally, the reaction mixture will be heated to a temperature sufficient to dissolve the starting material (i.e., about 30 to about 50° C., preferably about 40° C.) and then allowed to cool. Upon cooling, one of the diastereoisomeric (+)-naproxen or (−)-naproxen salts precipitates. When the (+)-naproxen salt is formed, the 7R enantiomer remains in solution and the 7S enantiomer precipitates. When the (−)-naproxen salt is formed, the 7S enantiomer remains in solution and the 7R enantiomer precipitates. If the desired enantiomer remains in solution, it is recovered by evaporating the liquid.
[0014] In order to convert the resulting isolated salt to the free base, any suitable method known in the art may be applied. Preferably, the salt is dissolved in water and the pH is raised to between about 10 to about 14, preferably about pH 12, using a base, such as sodium hydroxide, sodium bicarbonate, sodium carbonate, potassium hydroxide, potassium bicarbonate, potassium carbonate, ammonium hydroxide, and the like. The free base pyrazine is extracted from the aqueous layer using an inert non-polar solvent, such as isopropyl ether, diethyl ether, 1,1,1-trichloroethane, or methylene chloride, preferably the latter.
[0015] Pharmacologically useful pyrazine compounds may be prepared using the optically resolved intermediates as described herein. Among the uses are the amelioration of the symptoms of anxiety and other psychiatric conditions in a human subject. Methods for further synthetic elaboration of the optically resolved pyrazines to the pharmaceutical targets are disclosed in U.S. Pat. No. 5,852,031. The pyrazines prepared thereby are administered in accordance with methods known in the art in an effective amount of about 2 to about 200 mg/day, in single or divided daily doses. In particular cases, dosages outside that range are prescribed at the discretion of the attending physician. The preferred route of administration is generally oral, but parenteral administration (e.g., intramuscular, intravenous, intradermal) will be preferred in special cases, e.g. where oral absorption is impaired as by disease, or the patient is unable to swallow. These compounds are generally administered in the form of pharmaceutical compositions comprising a pharmaceutically acceptable vehicle or diluent. Such are generally formulated in a conventional manner utilizing solid or liquid vehicles or diluents as appropriate to the mode of desired administration: for oral administration, in the form of tablets, hard or soft gelatin capsules, suspensions, granules, powders and the like; and, for parenteral administration, in the form of injectable solutions or suspensions, and the like.
[0016] The present invention is illustrated, but not limited, by the following examples.
EXAMPLE 1
[0017] Diastereomeric Salt 2 of trans-7-(hydroxymeth-yl)octahydro-2H-pyr-ido(1,2-a)pyrazine
[0018] Five grams g (29.2 mmol) of racemic trans-7-(hydroxymethyl)octa-hydro-2H-pyrido(1,2-a)pyrazine (rac-1) were dissolved in 25 ml of ethanol. (+)-Naproxen (3.2 g, 13.9 mmol) was added. Upon stirring, a solid began to precipitate. After stirring at room temperature for 48 hours the reaction was filtered and the solids dried. The diastereomeric salt (2; 3.1 grams) of trans-7-(hydroxymethyl)octahydro-2H-pyrido(1,2-a)pyrazine was thereby obtained (56% yield based on one enantiomer). [α] D =−13.4 (c=1.11, MeOH).
EXAMPLE 2
[0019] (7S,trans)-7-(Hydroxymethyl)octahydro-2H-pyrido(1,2-a)pyrazine (7S-3)
[0020] A solution of 3.0 g of diastereomeric salt (2) of trans-7-(hydroxymeth-yl)octahydro-2H-pyrido(1,2-a)pyrazine (7.49 mmol) in isopropanol was heated to reflux. 4.0 g of Na 2 CO 3 (37.4 mmol) was added and the mixture was refluxed for 17 hr. The reaction was cooled to room temperature and filtered. The solids were washed with isopropanol and the filtrate was concentrated to dryness. The solids thus obtained were treated with hot toluene and filtered to remove insoluble salts. The filtrate was cooled and filtered to yield 0.9 g of a white solid (7S-3; 70%). [α] D =−24.80 (c=0.895, MeOH). An authentic sample of (7S,trans)-7-(hydroxymethyl)octahydro-2H-pyrido(1,2-a)pyrazine showed [α] D =−27.0° (c=0.895, MeOH) indicating that the material produced here was approximately 92% ee.
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The invention provides a process for the optical resolution of a racemic mixture, or an optically enriched mixture, of trans-7-(hydroxymethyl)octa-hydro-2H-pyrido-1,2a)pyrazine, a key intermediate for preparing pharmacologically active 2,7-substituted octahydro-1H-pyrido[1,2-a]pyrazine derivatives useful in the treatment of disorders of the dopamine system. The process of the invention involves use of D-(−) or L-(+)naproxen as a resolving agent.
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[0001] The present invention relates generally to golf and more particularly to training devices or aids for golfers to prevent improper shifting of the golfer's leg and improper swaying of the golfer's hips.
[0002] Golf is a game of balance and skill. During the swing, a golfers weight shifts between the back leg (during the backswing). One problem that may occur is that when the golfer shifts their weight on the backswing, they may lean their body tilting their rear leg or knee. During the forward swing, they may not be able to correct this. This generally results in the face of the club being too open on impact with the ball and results in slicing. The term slicing a golf ball is well known within the art and generally refers to when the ball spins so as to curve in the lateral direction toward which the body faces. For example, the right of a right handed golfer.
[0003] It can be extremely difficult to correct a slice and add distance as golfing can be counterintuitive and go against the golfers natural stride and comfort. Accordingly, many attempts have been made to correct a golfers balance and form. However, none has provided such a lightweight, effective apparatus that may be used by golfers of all shapes and sizes and does not require working parts and adjustment for size or shape.
[0004] Accordingly, the present invention provides an easy to use, lightweight apparatus that can be used for golfers of all shapes, sizes and heights as well as by right and left handed individuals without any adjustment or difficulty.
SUMMARY OF THE INVENTION
[0005] The present invention relates generally to golf training devices.
[0006] According to one embodiment of the present invention, an apparatus to train and prevent golfers from slicing a golf ball is provided, the apparatus comprising: a belt clip; a protrusion in communication with and perpendicular to the belt clip; a soft material having an opening that is the same shape as the protrusion to allow the soft material to attach to the protrusion, wherein said soft foam material protrudes at least two inches from said belt clip.
[0007] According to another embodiment, an apparatus to train and prevent golfers from slicing a golf ball is disclosed, the apparatus comprising: a belt clip having a rounded portion and a clip portion; a protrusion in communication with and perpendicular to said rounded portion, wherein said protrusion is an elongated plus sign; a soft material having an opening that is the same shape as said protrusion to allow said soft material to matedly attach to said protrusion.
[0008] These and other features, aspects and advantages of the present invention will become better understood with reference to the following description and claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 depicts the present invention;
[0010] FIG. 2 depicts an exploded view according to the present invention;
[0011] FIG. 3 depicts an elevational view of the belt clip and protrusion according to the present invention
[0012] FIG. 4 depicts an elevational view of the belt clip and protrusion according to the present invention;
[0013] FIG. 5 depicts a side view according to the present invention;
[0014] FIG. 6 depicts a side view according to the present invention and
[0015] FIG. 7 depicts a schematic according to the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0016] The following detailed description is of the best currently contemplated modes of carrying out the invention. The description is not to be taken in a limiting sense, but is made merely for the purpose of illustrating the general principles of the invention, since the scope of the invention is best defined by the appended claims.
[0017] The present invention provides is a unique golf training apparatus that is useful in developing the proper club swing for golfers. The apparatus ( 10 ) is a geometric design apparatus ( 10 ) that is attached to the golfers belt or waist band by means of a fixed or break away clip. The clip is slipped onto the golfer's belt or waistband and is positioned on or in close proximity of the golfer's hip. Due to the geometry, length and position of the apparatus ( 10 ) the proper swing of a golfer must miss and not contact the apparatus ( 10 ) to maintain the proper club swing and follow through critical to a good golf swing. If the golfer contacts the apparatus ( 10 ) and it is dislodged from the golfer's belt or waistband or if the apparatus ( 10 ) detaches from the belt clip then an improper swing and/or body position has occurred. By the action of the golfer's arm swing and/or hip follow through during an improper swing the apparatus ( 10 ) assembly will be dislodged from the golfer's belt or waistband.
[0018] The present invention is constructive of but not exclusively of the following materials and designs: The belt clip ( 12 ) assembly is an injected molded plastic clip designed in such a manner that it can be affixed to a standard belt worn in standard belt loops of men's or women's trousers. The belt clip ( 12 ) is also designed where it can be slipped over the waist band of the standard men's or women's trousers without the need for a standard belt. The belt clip ( 12 ) can be a of a design permanently affixed or a design such that the belt clip ( 12 ) will disconnect from the apparatus assembly by means of a connecting means such as a mechanical connector, magnetic connector, VELCRO® or other type of apparatus.
[0019] The protruding cylindrical portion of the apparatus is constructed of molded plastic, Styrofoam, or other soft material as deemed necessary by the design. This cylindrical portion of the apparatus can be designed and manufactured in such a manner as to be permanently affixed to the belt clip assembly or can be designed to dislodge from the belt clip assembly by a connecting means such as a mechanical connector, magnetic connector, VELCRO® or other type of apparatus.
[0020] The apparatus can be of cylindrical or other geometric shape and dimension as deemed necessary for the design. As shown in FIGS. 1-3 , the present invention provides an apparatus ( 10 ) to train and prevent golfers from slicing a golf ball, the apparatus ( 10 ) comprising: a belt clip ( 12 ); a protrusion ( 14 ) in communication with and perpendicular to the belt clip ( 12 ); a soft foam material ( 16 ) having an opening ( 18 ) that is the same shape as the protrusion ( 14 ) to allow the soft material ( 16 ) to attach to the protrusion ( 14 ), wherein the soft foam material ( 14 ) protrudes at least two inches from the belt clip. The opening, according to a preferred embodiment is the same shape as the protrusion ( 14 ) to allow the protrusion ( 14 ) to matedly attach to the opening ( 18 ). The foam material forms the opening which is the same shape as the protrusion ( 14 ). It is envisioned that the belt clip may have a rounded portion ( 11 ). The soft foam material ( 16 ) may be any material that is foam or cushion like without departing from the present invention. There may also be an adhesive to fixedly attach the soft foam material ( 16 ) to the protrusion ( 14 ). According to one embodiment, the protrusion may be an elongated plus sign shape ( 14 ). The term an elongated plus sign shape ( 14 ) is intended to refer to that depicted in FIG. 3 . The protrusion may also be a cut cone ( 20 ) with at least two traction ribs ( 22 ) protruding towards the belt clip at angle less than 60 degrees from the cut cone. The traction ribs ( 22 ) should point back towards the belt clip so that the foam material does not come lose with outward or downward pressure. As shown in FIG. 4 , there are four traction ribs placed at the same cone height and separated radially by 90 degrees. As shown in FIG. 5 , the at least two traction ribs may be two sets of two tractions rib placed at two different cone heights and separated radially by 180 degrees. As shown in FIG. 6 , the soft material ( 24 ) may be dome shaped. FIGS. 1-2 depict the soft material ( 16 ) as an elongated cylinder shape. The soft material may also be an elongated rectangular shape. Typically the said soft material is between 4 and 6 inches in length, preferably 5 inches. FIG. 1 depicts the length as “L”. FIG. 7 depicts another embodiment according to the present invention. As shown, the protrusion ( 41 ) is a dome or raised circle. The soft material ( 42 ) is removably attached to the protrusion ( 41 ) by a connecting means, which is a magnet ( 44 ). There is also a keeping means ( 40 ). The keeping means according to the embodiment depicted is a string. However, it may be any variety of items that prevent the soft material ( 42 ) from falling to the ground.
[0021] It should be understood that the foregoing relates to preferred embodiments of the invention and that modifications may be made without departing from the spirit and scope of the invention as set forth in the following claims.
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An apparatus to train and prevent golfers from slicing a golf ball and increases distance by promoting the proper angle of attack when striking a golf ball and creating the proper body motion for maximum performance, the apparatus comprising: a belt clip having a rounded portion and a clip; a protrusion in communication with and perpendicular to rounded portion; a soft material having an opening that is the same shape as protrusion to allow soft material to attach to protrusion.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation application of U.S. patent application Ser. No. 13/014,886 filed on Jan. 27, 2011, the entire disclosure of which is incorporated by reference herein.
FIELD
[0002] The present disclosure relates to imaging a subject, and particularly to an optimal image acquisition procedure for an imaging device.
BACKGROUND
[0003] This section provides background information related to the present disclosure which is not necessarily prior art.
[0004] A subject, such as a human patient, may select or be required to undergo a surgical procedure to correct or augment an anatomy of the patient. The augmentation of the anatomy can include various procedures, such as movement or augmentation of bone, insertion of implantable devices, or other appropriate procedures. A surgeon can perform the procedure on the subject with images of the patient that can be acquired using imaging systems such as a magnetic resonance imaging (MRI) system, computed tomography (CT) system, fluoroscopy (e.g., C-Arm imaging systems), or other appropriate imaging systems.
[0005] Images of a patient can assist a surgeon in performing a procedure including planning the procedure and performing the procedure. A surgeon may select a two dimensional image or a three dimensional image representation of the patient. The images can assist the surgeon in performing a procedure with a less invasive technique by allowing the surgeon to view the anatomy of the patient without removing the overlying tissue (including dermal and muscular tissue) when performing a procedure.
SUMMARY
[0006] This section provides a general summary of the disclosure, and is not a comprehensive disclosure of its full scope or all of its features.
[0007] According to various embodiments, provided is a system for acquiring image data of a subject with an imaging system. The system can include a gantry that completely annularly encompasses at least a portion of the subject. The system can also include a source positioned within and movable relative to the gantry. The source can be responsive to a signal to output at least one pulse. The system can include a detector positioned within and movable relative to the gantry and the source to detect the at least one pulse emitted by the source. The system can also include a detector control module that sets detector data based on the detected at least one pulse, and an image acquisition control module that sets the signal for the source and receives the detector data. The image acquisition control module can be operable to reconstruct image data based on the detector data. The signal can include a signal for the source to output a single pulse or a signal for the source to output two pulses.
[0008] Further provided is a method for acquiring image data of a subject with an imaging system. The method can include positioning a gantry to completely annularly encompass at least a portion of the subject, with a source and a detector positioned within and movable relative to the gantry. The method can also include receiving at least one user input that provides a request for an output for the source, and determining, based on the user input, a type of output for the source. The method can include outputting one pulse with the source or substantially simultaneously outputting two pulses with the source, and receiving the one pulse or two pulses with the detector. The method can also include reconstructing, based on the one pulse or two pulses received by the detector, an image of the subject.
[0009] Also provided is a method for acquiring image data of a subject with an imaging system. The method can include positioning a gantry to completely annularly encompass at least a portion of the subject, with a source and a detector positioned within and movable relative to the gantry. The method can include outputting a first pulse having a first pulse rate with the source, and substantially simultaneously outputting a second pulse with a second pulse rate with the source, the second pulse rate being different than the first pulse rate. The method can include receiving the first pulse and the second pulse with the detector, and reconstructing, based on first pulse and the second pulse received by the detector, an image of the subject.
[0010] Further areas of applicability will become apparent from the description provided herein. The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure.
DRAWINGS
[0011] The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.
[0012] FIG. 1 is an environmental view of an exemplary imaging system in an operating theatre;
[0013] FIG. 2 is a schematic illustration of an exemplary computing system for use with the imaging system of FIG. 1 ;
[0014] FIG. 3 is a simplified block diagram illustrating a system for implementing an image acquisition control module according to various embodiments;
[0015] FIG. 4 is a dataflow diagram illustrating an exemplary control system performed by the image acquisition control module of FIG. 3 ;
[0016] FIG. 5 is a flowchart illustrating a method performed by the image acquisition control module;
[0017] FIG. 6 is a continuation of the flowchart of FIG. 5 at A;
[0018] FIG. 7 is a continuation of the flowchart of FIG. 5 at B;
[0019] FIG. 8 is a continuation of the flowchart of FIG. 5 at C; and
[0020] FIG. 9 is a schematic timing diagram for a dual energy output for the imaging system of FIG. 1 .
DETAILED DESCRIPTION
[0021] The following description is merely exemplary in nature. It should be understood that throughout the drawings, corresponding reference numerals indicate like or corresponding parts and features. As indicated above, the present teachings are directed toward providing optimized image acquisition for an imaging device, such as an O-Arm® imaging system sold by Medtronic Navigation, Inc. having a place of business in Louisville, Colo., USA. It should be noted, however, that the present teachings could be applicable to any appropriate imaging device, such as a C-arm imaging device. Further, as used herein, the term “module” can refer to a computer readable media that can be accessed by a computing device, an application specific integrated circuit (ASIC), an electronic circuit, a processor (shared, dedicated, or group) and memory that executes one or more software or firmware programs, a combinational logic circuit, and/or other suitable software, firmware programs or components that provide the described functionality. In addition, it should be noted that the values provided herein for the pulse rate in kilovolts and width in milliseconds are merely exemplary as both the pulse rate and width can vary based upon the particular patient and clinical scenario, such as in the case of a pediatric patient.
[0022] With reference to FIG. 1 , in an operating theatre or operating room 10 , a user, such as a user 12 , can perform a procedure on a patient 14 . In performing the procedure, the user 12 can use an imaging system 16 to acquire image data of the patient 14 for performing a procedure. The image data acquired of the patient 14 can include two-dimension (2D) projections acquired with an x-ray imaging system, including those disclosed herein. It will be understood, however, that 2D forward projections of a volumetric model can also be generated, also as disclosed herein.
[0023] In one example, a model can be generated using the acquired image data. The model can be a three-dimension (3D) volumetric model generated based on the acquired image data using various techniques, including algebraic iterative techniques, also as discussed further herein. Displayed image data 18 can be displayed on a display device 20 , and additionally, could be displayed on a display device 32 a associated with an imaging computing system 32 , as will be discussed in greater detail herein. The displayed image data 18 can be a 2D image, a 3D image, or a time changing four-dimension image. The displayed image data 18 can also include the acquired image data, the generated image data, both, or a merging of both the types of image data.
[0024] It will be understood that the image data acquired of the patient 14 can be acquired as 2D projections, for example with an x-ray imaging system. The 2D projections can then be used to reconstruct the 3D volumetric image data of the patient 14 . Also, theoretical or forward 2D projections can be generated from the 3D volumetric image data. Accordingly, it will be understood that image data can be either or both of 2D projections or 3D volumetric models.
[0025] The display device 20 can be part of a computing system 22 . The computing system 22 can include a variety of computer-readable media. The computer-readable media can be any available media that can be accessed by the computing system 22 and can include both volatile and non-volatile media, and removable and non-removable media. By way of example, and not limitation, the computer-readable media can comprise computer storage media and communication media. Storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, Digital Versatile Disk (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store computer-readable instructions, software, data structures, program modules, and other data and which can be accessed by the computing system 22 . The computer-readable media may be accessed directly or through a network such as the Internet.
[0026] In one example, the computing system 22 can include an input device 24 , such as a keyboard, and one or more processors 26 (the one or more processors can include multiple-processing core processors, microprocessors, etc.) that can be incorporated with the computing system 22 . The input device 24 can comprise any suitable device to enable a user to interface with the computing system 22 , such as a touchpad, touch pen, touch screen, keyboard, mouse, joystick, trackball, wireless mouse, or a combination thereof. Furthermore, while the computing system 22 is described and illustrated herein as comprising the input device 24 discrete from the display device 20 , the computing system 22 could comprise a touchpad or tablet computing device, and further, that the computing system 22 could be integrated within or be part of the imaging computing system 32 associated with the imaging system 16 .
[0027] A connection 28 can be provided between the computing system 22 and the display device 20 for data communication to allow driving the display device 20 to illustrate the image data 18 .
[0028] The imaging system 16 can include the O-Arm® imaging system sold by Medtronic Navigation, Inc. having a place of business in Louisville, Colo., USA. The imaging system 16 , including the O-Arm® imaging system, or other appropriate imaging systems in use during a selected procedure are also described in U.S. patent application Ser. No. 12/465,206, entitled “System And Method For Automatic Registration Between An Image And A Subject,” filed on May 13, 2009, incorporated herein by reference. Additional description regarding the O-Arm imaging system or other appropriate imaging systems can be found in U.S. Pat. Nos. 7,188,998, 7,108,421, 7,106,825, 7,001,045 and 6,940,941, each of which is incorporated herein by reference.
[0029] The O-Arm® imaging system 16 can include a mobile cart 30 that includes the imaging computing system 32 and an imaging gantry 34 in which is positioned a source unit 36 and a detector 38 . With reference to FIG. 2 , a diagram is provided that illustrates an exemplary embodiment of the imaging computing system 32 , some or all of the components of which can be used in conjunction with the teachings of the present disclosure. The imaging computing system 32 can include a variety of computer-readable media. The computer-readable media can be any available media that can be accessed by the imaging computing system 32 and includes both volatile and non-volatile media, and removable and non-removable media. By way of example, and not limitation, the computer-readable media can comprise computer storage media and communication media. Storage media includes, but is not limited to, RAM, ROM, EEPROM, flash memory or other memory technology, CD-ROM, Digital Versatile Disk (DVD) or other optical disk storage, magnetic cassettes, magnetic tape, magnetic disk storage or other magnetic storage devices, or any other medium which can be used to store computer-readable instructions, software, data structures, program modules, and other data and which can be accessed by the imaging computing system 32 . The computer-readable media may be accessed directly or through a network such as the Internet.
[0030] In one example, the imaging computing system 32 comprises a display device 32 a and a system unit 32 b . As illustrated, the display device 32 a can comprise a computer video screen or monitor. The imaging computing system 32 can also include at least one input device 32 c . The system unit 32 b includes, as shown in an exploded view at 100 , a processor 102 and a memory 104 , which can include software 106 and data 108 .
[0031] In this example, the at least one input device 32 c comprises a keyboard. It should be understood, however, that the at least one user input device 32 c can comprise any suitable device to enable a user to interface with the imaging computing system 32 , such as a touchpad, touch pen, touch screen, keyboard, mouse, joystick, trackball, wireless mouse, or a combination thereof. Furthermore, while the imaging computing system 32 is described and illustrated herein as comprising the system unit 32 b with the display device 32 a , the imaging computing system 32 could comprise a touchpad or tablet computing device.
[0032] As will be discussed with regard to FIGS. 3-9 , the imaging computing system 32 can control the source 36 and the detector 38 to optimize image data acquisition via an image acquisition control module 110 , which can be stored in the memory 104 and accessed by the processor 102 . A connection can be provided between the processor 102 and the display device 32 a for data communication to allow driving the display device 32 a to illustrate the image data 18 .
[0033] With reference to FIG. 1 , the mobile cart 30 can be moved from one operating theater or room to another and the gantry 34 can move relative to the mobile cart 30 , as discussed further herein. This allows the imaging system 16 to be mobile allowing it to be used in multiple locations and with multiple procedures without requiring a capital expenditure or space dedicated to a fixed imaging system.
[0034] The source unit 36 can emit x-rays through the patient 14 to be detected by the detector 38 . As is understood by one skilled in the art, the x-rays emitted by the source 36 can be emitted in a cone and detected by the detector 38 . The source 36 /detector 38 is generally diametrically opposed within the gantry 34 . The detector 38 can move rotationally in a 360° motion around the patient 14 generally in the directions of arrow 39 within the gantry 34 with the source 36 remaining generally 180° from and opposed to the detector 38 . Also, the gantry 34 can isometrically sway or swing (herein also referred to as iso-sway) generally in the direction of arrow 40 , relative to the patient 14 , which can be placed on a patient support or table 15 . The gantry 34 can also tilt relative to the patient 14 illustrated by arrows 42 , move longitudinally along the line 44 relative to the patient 14 and the mobile cart 30 , can move up and down generally along the line 46 relative to the mobile cart 30 and transversely to the patient 14 , and move perpendicularly generally in the direction of arrow 48 relative to the patient 14 to allow for positioning of the source 36 /detector 38 at any desired position relative to the patient 14 .
[0035] The O-Arm® imaging system 16 can be precisely controlled by the imaging computing system 32 to move the source 36 /detector 38 relative to the patient 14 to generate precise image data of the patient 14 . In addition, the imaging system 16 can be connected with the processor 26 via connection 50 which can include a wired or wireless connection or physical media transfer from the imaging system 16 to the processor 26 . Thus, image data collected with the imaging system 16 can also be transferred from the imaging computing system 32 to the computing system 22 for navigation, display, reconstruction, etc.
[0036] Briefly, according to various embodiments, the imaging system 16 can be used with an unnavigated or navigated procedure. In a navigated procedure, a localizer, including either or both of an optical localizer 60 and an electromagnetic localizer 62 can be used to generate a field or receive or send a signal within a navigation domain relative to the patient 14 . The navigated space or navigational domain relative to the patient 14 can be registered to the image data 18 to allow registration of a navigation space defined within the navigational domain and an image space defined by the image data 18 . A patient tracker or a dynamic reference frame 64 can be connected to the patient 14 to allow for a dynamic registration and maintenance of registration of the patient 14 to the image data 18 .
[0037] An instrument 66 can then be tracked relative to the patient 14 to allow for a navigated procedure. The instrument 66 can include an optical tracking device 68 and/or an electromagnetic tracking device 70 to allow for tracking of the instrument 66 with either or both of the optical localizer 60 or the electromagnetic localizer 62 . The instrument 66 can include a communication line 72 with a navigation interface device 74 as can the electromagnetic localizer 62 and/or the optical localizer 60 . Using the communication lines 74 , 78 respectively, the probe interface 74 can then communicate with the processor 26 with a communication line 80 . It will be understood that any of the connections or communication lines 28 , 50 , 76 , 78 , or 80 can be wired, wireless, physical media transmission or movement, or any other appropriate communication. Nevertheless, the appropriate communication systems can be provided with the respective localizers to allow for tracking of the instrument 66 relative to the patient 14 to allow for illustration of the tracked location of the instrument 66 relative to the image data 18 for performing a procedure.
[0038] It will be understood that the instrument 66 can be an interventional instrument and/or an implant. Implants can include a ventricular or vascular stent, a spinal implant, neurological stent or the like. The instrument 66 can be an interventional instrument such as a deep brain or neurological stimulator, an ablation device, or other appropriate instrument. Tracking the instrument 66 allows for viewing the location of the instrument 66 relative to the patient 14 with use of the registered image data 18 and without direct viewing of the instrument 66 within the patient 14 .
[0039] Further, the imaging system 16 can include a tracking device, such as an optical tracking device 82 or an electromagnetic tracking device 84 to be tracked with a respective optical localizer 60 or the electromagnetic localizer 62 . The tracking device can be associated directly with the source 36 , the detector 38 , the gantry 34 , or other appropriate part of the imaging system 16 to determine the location or position of the detector 38 relative to a selected reference frame. As illustrated, the tracking device 82 , 84 can be positioned on the exterior of the housing of the gantry 34 . Accordingly, the imaging system 16 can be tracked relative to the patient 14 as can the instrument 66 to allow for initial registration, automatic registration or continued registration of the patient 14 relative to the image data 18 . Registration and navigated procedures are discussed in the above incorporated U.S. patent application Ser. No. 12/465,206.
[0040] Further, with continued reference to FIG. 1 , the operating theatre 10 can optionally include a gating device or an electrocardiogram or ECG 112 , which is attached to the patient 14 , via skin electrodes, and in communication with the imaging computing system 32 . Respiration and cardiac motion can cause movement of cardiac structures relative to the imaging system 16 . Therefore, images can be acquired from the imaging system 16 based on a time-gated basis triggered by a physiological signal. For example, the ECG or EGM signal may be acquired from the skin electrodes or from a sensing electrode included on the instrument 66 or from a separate reference probe (not shown). A characteristic of this signal, such as an R-wave peak or P-wave peak associated with ventricular or atrial depolarization, respectively, may be used as a triggering event for the imaging computing system 32 to drive the source 36 . By time-gating the acquisition of the image data 18 , the image data 18 can be reconstructed to provide a 3D view of an organ of interest in a particular phase, as will be discussed in greater detail herein.
[0041] It should be noted that in a navigated procedure, the ECG 112 can also be use to time-gate the navigation data. In this regard, the characteristic of the signal, such as the R-wave peak or P-wave peak associated with ventricular or atrial depolarization, respectively, can be used as a triggering event for driving the coils in the electromagnetic localizer 62 . Further detail regarding the time-gating of the navigation data can be found in U.S. Pat. No. 7,599,730, entitled “Navigation System for Cardiac Therapies,” filed Nov. 19, 2002, which is hereby incorporated by reference.
[0042] With reference to FIG. 3 , a simplified block diagram schematically illustrates an exemplary system 114 for implementing the image acquisition control module 110 according to various embodiments. In one example, the image acquisition control module 110 can be implemented by the imaging computing system 32 of the imaging system 16 . The image acquisition control module 110 can receive user input from the input device 32 c . Note that while the display is illustrated and described herein as comprising the display device 32 a , the imaging computing system 32 could output image data 18 to the display device 20 .
[0043] The image acquisition control module 110 can send a source output signal 116 to the source 36 . As will be discussed, the source output signal 116 can comprise a signal for the source 36 to output or emit at least one or more x-ray pulses 118 a . . . 118 n at a particular pulse rate and pulse width.
[0044] The image acquisition control module 110 can also output a move signal 120 to the source 36 to move the position of the source 36 within the gantry 34 , and the image acquisition control module 110 can also output a move signal 122 to the detector 38 to move the position of the detector 38 within the gantry 34 . Generally, the source 36 and the detector 38 can move about 360° around a longitudinal axis 14 L of the patient 14 within the gantry 34 . The movement of the detector 38 and the source 36 relative to the patient 14 can allow the imaging system 16 to acquire image data at a plurality of selected locations and orientations relative to the subject 14 .
[0045] In this regard, the 2D projection image data can be acquired by substantially annular or 360° orientation movement of the source 36 /detector 38 around the patient 14 due to positioning of the source 36 /detector 38 moving around the patient 14 in the optimal movement. Also, due to movements of the gantry 34 , the source 36 /detector 38 need never move in a pure circle, but rather can move in a spiral helix, or other rotary movement about or relative to the patient 14 . Also, the path can be substantially non-symmetrical and/or non-linear based on movements of the imaging system 16 , including the gantry 34 and the source 36 /detector 38 together. In other words, the path need not be continuous in that the source 36 /detector 38 and the gantry 34 can stop, move back from the direction from which it just came (e.g., oscillate), etc. in following the optimal path. Thus, the source 36 /detector 38 need never travel a full 360° around the patient 14 as the gantry 34 may tilt or otherwise move and the source 36 /detector 38 may stop and move back in the direction it has already passed. Further detail regarding the movement of the source 36 and the detector 38 can be found in U.S. Pat. No. 7,108,421, entitled “Systems and Methods for Imaging Large Field-of-View Objects,” filed on Mar. 18, 2003 and incorporated herein by reference.
[0046] With continued reference to FIG. 3 , the pulses 118 a . . . 118 n can be received by the detector 38 . The detector 38 can transmit a signal 120 regarding the received pulses to the image acquisition control module 110 . Based on the signal(s) 120 received from the detector 38 , the image acquisition control module 110 can generate the image data 18 on the display device 32 a or the display device 20 .
[0047] In this regard, the image acquisition control module 110 can perform automatic reconstruction of an initial three dimensional model of the area of interest of the patient 14 . Reconstruction of the three dimensional model can be performed in any appropriate manner, such as using an algebraic techniques for optimization. Appropriate algebraic techniques include Expectation maximization (EM), Ordered Subsets EM (OS-EM), Simultaneous Algebraic Reconstruction Technique (SART) and total variation minimization, as generally understood by those skilled in the art. The application to performing a 3D volumetric reconstruction based on the 2D projections allows for efficient and complete volumetric reconstruction.
[0048] Generally, an algebraic technique can include an iterative process to perform a reconstruction of the patient 14 for display as the image data 18 . For example, a pure or theoretical image data projection, such as those based on or generated from an atlas or stylized model of a “theoretical” patient, can be iteratively changed until the theoretical projection images match the acquired 2D projection image data of the patient 14 . Then, the stylized model can be appropriately altered as the 3D volumetric reconstruction model of the acquired 2D projection image data of the selected patient 14 and can be used in a surgical intervention, such as navigation, diagnosis, or planning. The theoretical model can be associated with theoretical image data to construct the theoretical model. In this way, the model or the image data 18 can be built based upon image data acquired of the patient 14 with the imaging system 16 . The image acquisition control module 110 can output image data 18 to the display device 32 a or the display device 20 .
[0049] With reference to FIG. 4 , a dataflow diagram illustrates various components of an image acquisition control system that can be embedded within the image acquisition control module 110 . The image acquisition control module 110 can control the imaging system 16 to generate the image data 18 for display on the display device 32 a and/or display device 20 . Various embodiments of the image acquisition control system according to the present disclosure can include any number of sub-modules embedded within the image acquisition control module 110 . The sub-modules shown may be combined and/or further partitioned to similarly generate the image data 18 . Further, the image acquisition control module 110 can comprise one or more software modules embodied in non-transitory, machine readable code that runs on the processor 108 . Inputs to the system can be received from the input device 32 c , input device 24 , or even received from other control modules (not shown) within the computing system 22 or imaging computing system 32 , and/or determined by other sub-modules (not shown) within the image acquisition control module 110 (not shown).
[0050] With continuing reference to FIG. 4 , the image acquisition control module 110 can include an image control module 130 , a source control module 132 and a detector control module 134 . The image control module 130 can receive as input user input data 136 . The user input data 136 can comprise input received from the input device 32 c or input device 22 . The user input data 136 can comprise a request for the imaging system 16 to perform a particular form of imaging. For example, the user input data 136 could comprise a request for the imaging system 16 to perform gated imaging. In another example, the user input data 136 could comprise a request for the imaging system 16 to perform dual energy imaging, or single energy imaging. Based on the user input data 136 , the image control module 130 can set source data 138 for the source control module 132 . The source data 138 can comprise a signal to start the imaging system 16 , a signal to power-down the imaging system 16 , a signal to perform gated imaging, a signal to perform dual energy imaging or a signal to perform single energy imaging.
[0051] The image control module 130 can also receive as input detector data 140 . The detector data 140 can comprise the energy from the pulses 118 a - 118 n received by the detector 38 . Based on the detector data 140 , the image control module 130 can set move data 142 for the source control module 132 and the move data 144 for the detector control module 134 . The move data 142 can comprise a signal for the source 36 to be moved to a predetermined angular position within the gantry 34 to acquire additional image data for the patient 14 . The move data 144 can comprise a signal for the detector 38 to be moved to a predetermined angular position within the gantry 34 relative to the source 36 to acquire additional image data for the patient 14 . The image control module 130 can also output the image data 18 based on the detector data 140 . The image data 18 can comprise the reconstructed 3D image of the patient.
[0052] With continued reference to FIG. 4 , the source control module 132 can receive as input the source data 138 and the move data 142 from the image control module 130 . Based on the move data 142 , the source 36 can move within the gantry 34 to a desired location. Based on the source data 138 , the source 36 can output pulse data 146 . The pulse data 146 can comprise at least one x-ray pulse, and in some instances can comprise more than one x-ray pulse, as will be discussed in greater detail herein.
[0053] The detector control module 134 can receive as input the move data 144 and the detector data 140 . Based on the move data 144 , the detector 38 can move within the gantry 34 to a desired location relative to the location of the source 36 . The detector control module 134 can set the detector data 140 for the image control module 130 .
[0054] With reference now to FIG. 5 , a flowchart diagram illustrates an exemplary method performed by the image acquisition control module 110 . It should be noted that the flowchart diagram described herein with regard to FIGS. 5-8 is merely exemplary, as the image acquisition control module 110 could generate the image data 18 in any desired or user requested sequence. With continued reference to FIG. 5 , at decision block 200 , the method determines if a startup request signal has been received via the input device 32 c . If not, the method loops. Otherwise, the method goes to decision block 202 .
[0055] At decision block 202 , the method determines if a type of energy output for the source 36 of the imaging system 16 has been specified. If a type of output for the source 36 has been specified, then the method goes to decision block 204 . Otherwise, the method loops. At decision block 204 , the method determines if the type of output for the source 36 is gated image acquisition. If the type of output for the source 36 is gated image acquisition, the method goes to A on FIG. 6 . Otherwise, the method goes to decision block 206 .
[0056] At decision block 206 , the method determines if the type of output for the source 36 is a single energy output. If the output for the source 36 is single energy imaging output, then the method goes to B on FIG. 7 . Otherwise, the method goes to decision block 208 . At decision block 208 , the method determines if the output for the source 36 is dual energy output. If the output for the source 36 is dual energy output, then the method goes to C on FIG. 8 . Otherwise, the method loops to decision block 202 .
[0057] With reference to FIG. 6 , at block 300 , the method acquires at least one physiological signal. Then, at decision block 302 , the method determines if a triggering event has occurred. If a triggering event has occurred, then the method goes to block 304 . Otherwise, the method loops until a triggering event has occurred. At block 304 , the method outputs a first pulse 118 a at a first pulse rate. Then, at block 306 , the method acquires detector data 140 for the first pulse 118 a . At decision block 308 , the method determines if another triggering event has occurred. If another triggering event has occurred, then the method goes to block 310 . Otherwise, the method loops.
[0058] At block 310 , the method outputs a second pulse 118 b at a second pulse rate, which can have a different pulse width and height. The second pulse rate width and/or height can be greater than, less than or equal to the width and/or height of the first pulse rate. For example, the second pulse rate can have a second kilovolt (kV) value and a second width value in milliseconds (ms) and the first pulse rate can have a first kilovolt (kV) value and a first width value in milliseconds (ms), which may or may not be equal. In one example, the first kilovolt (kV) value can be from about 100 kV to about 120 kV, such as about 110 kV, and the second kilovolt (kV) value can be from about 70 kV to about 90 kV. The first width value can be from about 5 ms to about 15 ms, for example, about 10 ms, and the second current value can be from about 10 ms to about 20 ms, for example about 15 ms.
[0059] At block 312 , the method acquires the detector data 140 for the second pulse 118 b . At block 314 , the method moves the source 36 and the detector 38 . Then, at decision block 316 , the method determines if enough image data has been acquired for the patient 14 . In this regard, the method can determine if the source 36 /detector 38 have gathered a suitable number of frames of image data to enable successful 3D reconstruction of the area of interest. In one example, the source 36 /detector 38 can acquire about 180 to about 240 frames of images, which can be substantially equivalent to gathering about 360° worth of image data, even if the source 36 /detector 38 does not fully circumscribe or travel 360° around the patient 14 . Based on gathered image data, the image acquisition control module 110 can perform automatic reconstruction of the area of interest. Further information regarding image acquisition techniques can be found in U.S. patent application Ser. No. 12/908,186, filed on Oct. 20, 2010, entitled “Selected Image Acquisition Technique to Optimize Patient Model Construction,” and incorporated by reference herein.
[0060] If enough image data has been acquired for reconstruction, then the method goes to block 318 . Otherwise, the method loops to decision block 302 . At block 318 , the method compiles the detector data 140 . At block 320 , the method reconstructs the detector data 140 into the image data 18 using 3D reconstruction. At block 322 , the method outputs the image data 18 to the display device 32 a . At decision block 324 , the method determines if a power down request has been received via the input device 32 c . If a power down request has been received, the method ends. Otherwise, the method goes to D on FIG. 5 .
[0061] With reference to FIG. 7 , at block 400 , the method outputs a pulse 118 . The pulse 118 can comprise a single pulse of energy, which can have a kilovolt (kV) value, which can be from about 80 kV to about 125 kV, The pulse width for this pulse 118 can range from about 5 ms to about 15 ms. Thus, the pulse 118 can have a wider pulse of smaller magnitude of current, which can be used in place of a larger magnitude of current pulse.
[0062] At block 402 , the method acquires the detector data 140 for that pulse 118 . At block 404 , the method moves the source 36 and the detector 38 . At decision block 406 , the method determines if enough image data has been acquired for the patient 14 . If enough image data has been acquired for the patient 14 , then the method goes to block 408 . Otherwise, the method loops to block 400 . At block 408 , the method compiles the detector data 140 . At block 410 , the method reconstructs the detector data 140 into the image data 18 using 3D reconstruction. At block 412 , the method outputs the image data 18 to the display device 32 a . At decision block 414 , the method determines if a power down request has been received via the input device 32 c . If a power down request has been received, then the method ends. Otherwise, the method goes to D on FIG. 5 .
[0063] With reference to FIGS. 8 and 9 , at block 500 , the method outputs a first pulse 118 a at a first pulse rate having a first width and height and outputs a second pulse 118 b at a second pulse rate having a second width and height. The second pulse rate width and/or height can be greater than, less than or equal to the first pulse rate width and/or height. For example, with reference to FIG. 9 , the first pulse 118 a can have a first kilovolt (kV) value 550 and a first width value 554 in milliseconds (ms). The second pulse 118 b can have a second kilovolt (kV) value 556 and a second width value 560 in milliseconds (ms).
[0064] In one example, the first kilovolt (kV) value 550 can be from about 90 kV to about 120 kV such as 110 kV, and the second kilovolt (kV) value 556 can be from about 70 kV to about 90 kV, such as 80 kV. The first pulse width 554 can range from about 5 ms to about 15 ms, for example 10 ms, while the second pulse width 560 can range from about 10 ms to about 20 ms, for example 15 ms.
[0065] With reference back to FIG. 8 , at block 502 , the method can acquire detector data 140 for the first pulse 118 a and the second pulse 118 b . At block 504 , the method can move the source 36 and the detector 38 by a predetermined amount. At decision block 506 , the method can determine if enough image data has been acquired for the patient 14 . In this regard, the method can determine if the source 36 /detector 38 have gathered a suitable number of frames of image data to enable successful 3D reconstruction of the area of interest, as discussed with regard to FIG. 6 .
[0066] If enough image data has been acquired for the patient 14 , then the method goes to block 508 . Otherwise, the method goes to block 510 . At block 510 , the method waits a predetermined time period for the afterglow effects to subside before the method loops to block 500 .
[0067] In this regard, each pulse 118 emitted by the source 36 causes the detector 38 to glow for a period of time after the pulse 118 has been emitted (“afterglow”). In cases where the first pulse 118 a and the second pulse 118 b have the same pulse rate (i.e. same kilovolts and same milliamps for the same period of time), the afterglow associated with each pulse 118 a , 118 b will be approximately the same except for the first pulse 118 a . As the afterglow is the same for each image, the effect of the afterglow can be removed from the image data 18 during processing thereby resulting in substantially undistorted image data 18 . In cases where the first pulse 118 a and the second pulse 118 b have different pulse rates, however, the afterglow associated with each pulse can vary, and thus, the effects of the afterglow cannot be easily removed from the image data 18 . Accordingly, by waiting a predetermined period of time before emitting another first pulse 118 a and second pulse 118 b , the detector 38 can stop glowing, thereby substantially reducing the effects of the afterglow all together. With brief reference to FIG. 9 , the predetermined time period between the emission of another first pulse 118 a and second pulse 118 b is illustrated with reference numeral 562 .
[0068] With reference back to FIG. 8 , at block 508 , the method can compile the detector data 140 . At block 512 , the method can reconstruct the detector data 140 into the image data 18 using 3D reconstruction. At block 514 , the method can output the image data 18 to the display device 32 a . At decision block 516 , the method can determine if a power down request has been received via the input device 32 c . If a power down request has been received, then the method ends. Otherwise, the method goes to D on FIG. 5 .
[0069] Thus, the image acquisition control module 110 can be used to optimize the acquisition of the image data 18 by the imaging system 16 . In addition, by enabling the user to select between gated image acquisition, single energy output and dual energy output from the source 36 , the image acquisition can be tailored to a particular patient 14 . With particular regard to gated image acquisition, the ability to gate the image acquisition to a particular physiological event can enable the user to view a selected organ of interest at a particular phase. The use of single energy output of a low current for a wider pulse width can enable a low-power generator, such as those associated with a mobile cart 30 , to acquire the image data 18 at the same quality and resolution as a high-power stationary generator. The use of dual energy output can optimize the acquisition of the image data 18 by providing high resolution imaging, without increasing the radiation dose received by the patient 14 . In addition, the image acquisition control module 110 can control the source 36 to emit dual energy pulses 118 without requiring a separate source 36 , detector 38 and gantry 34 .
[0070] While specific examples have been described in the specification and illustrated in the drawings, it will be understood by those of ordinary skill in the art that various changes can be made and equivalents can be substituted for elements thereof without departing from the scope of the present teachings. Furthermore, the mixing and matching of features, elements and/or functions between various examples is expressly contemplated herein so that one of ordinary skill in the art would appreciate from the present teachings that features, elements and/or functions of one example can be incorporated into another example as appropriate, unless described otherwise, above. Moreover, many modifications can be made to adapt a particular situation or material to the present teachings without departing from the essential scope thereof. Therefore, it is intended that the present teachings not be limited to the particular examples illustrated by the drawings and described in the specification, but that the scope of the present teachings will include any embodiments falling within the foregoing description.
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A system and a method for acquiring image data of a subject with an imaging system is provided. The system can include a gantry that completely annularly encompasses at least a portion of the subject, with a source positioned within and movable relative to the gantry. The source can be responsive to a signal to output at least one pulse. The system can include a detector positioned within and movable relative to the gantry to detect the pulse emitted by the source. The system can also include a detector control module that sets detector data based on the detected pulse, and an image acquisition control module that sets the signal for the source and receives the detector data. The image acquisition control module can reconstruct image data based on the detector data. The signal can include a signal for the source to output a single pulse or two pulses.
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BACKGROUND OF THE INVENTION
[0001] This invention relates to a method and apparatus for high-speed fluid flow control. More particularly, the invention is directed to a valve formed, at least in part, of an actuating material, such as piezoelectric or anti-ferro-electric material. The valve is used for controlling fluid flow (including air flow) in a variety of devices including imaging devices (e.g. printers, copiers, etc.) for which air flow is used to handle paper. In one embodiment, the subject valve takes advantage of the phenomenon of buckling, resultant bistability and other structural mechanics to efficiently, and in a high-speed manner, open and close to regulate fluid flow. In another embodiment, the valve includes implementation of the actuating material to bend an s-shaped blocking element within the valve. The valve is also advantageously implemented in arrays and formed using batch fabrication techniques.
[0002] While the invention is particularly directed to the art of high-speed valves for regulating fluid flow in certain applications such as paper handling, and will be thus described with specific reference thereto, it will be appreciated that the invention may have usefulness in other fields and applications. For example, the invention may be used for controlling concentrations of chemicals over a volume to regulate chemical reactions, liquids, or for controlling sorting processes such as those known in the food processing and drug fields.
[0003] By way of background, micro-device valves for use in, for example, paper-handling applications are known. In this regard, U.S. Pat. Nos. 5,839,722; 5,897,097; 5,941,501; and, 5,971,355, all commonly assigned and incorporated herein by this reference, disclose various such valves in an exemplary environment of a microdevice support system for a paper handling system 110 . Referring now to FIG. 1, valve and sensor arrays can be used for moving objects, including flexible objects such as papers. As shown, a paper handling system 110 can be optimized for handling sheets of paper 112 without requiring direct physical contact by rollers, belts, or other mechanical transport devices. The paper handling system 110 has a conveyor 120 , divided into a lower section 122 and an upper section 124 . For clarity, the upper section 124 is cut away to better illustrate paper movement, however, it will be appreciated that the I upper section 124 and lower section 122 are substantially coextensive. The sections 122 and 124 are maintained in spaced apart relationship to define a passage 123 therebetween, with the passage sized to accommodate non-contacting passage therethrough of paper 112 . Each section 122 and 124 has a plurality of independently or semi-independently controlled adjustable air jets 126 for dynamically supporting, moving, and guiding paper 112 through the system 110 . The intensity or directionality of air jets 126 can be controlled by microdevice valves in air jets 126 , or even by use of alternative microdevices for directing air flow, such as directional vanes, louvers, or other mechanical air flow redirectors that can be embedded within or adjacent to air jets 126 .
[0004] The conveyor 120 is constructed from multiple laminate layers with embedded microelectromechanical controllers and sensors. As will be appreciated, using opposed and precisely controllable air jets in sections 122 and 124 having multiple angled orientations is one mechanism for advantageously permitting adjustable application of air flow to opposing sides of paper 112 , dynamically holding the paper between sections 122 and 124 , while allowing precise control of paper position, velocity, and orientation through application of vertical, lateral, or longitudinal forces (again by directed air jets). As an added advantage, the use of independent or semi-independent controlled adjustable air jets allows for dynamically increasing or decreasing air flow directed against portions of paper 112 , allowing straightening, flattening, curling, decurling, or other desired modification in paper topography, as well as adjustments to paper position, orientation and velocity. In addition, paper of various weights, sizes, and mechanical characteristics can be easily supported and accelerated by appropriate modification of the airflow applied by air jets 126 . For example, a heavy, thick, and relatively inflexible cardboard type paper may require more air flow from the jets 126 for support and maneuvering, while a lightweight paper sheet may require less overall air flow, but may need quicker and more frequent air flow adjustments directed by the independent or semi-independent air jets 126 to compensate for flutter or edge curling effects. Advantageously, the use of large numbers of independent valve controlled air jets allows diverse paper types and sizes to simultaneously be transported, with appropriate modifications to air flow characteristics being made for each paper in the conveyor 120 .
[0005] Active flexible object guidance (of paper 112 ) to correct for flutter and other dynamic problems of flexible objects is enabled by provision of a sensing unit 140 that is connected to the plurality of sensors embedded in the conveyor 120 . The sensing unit 140 senses the motion state of paper 112 by integrating information received from the embedded sensors, giving spatial and dynamic information to a motion analysis unit 150 capable of calculating relative or absolute movement of paper 112 from the received sensory information, with movement calculations generally providing overall position, orientation, velocity of paper 112 , as well as position, orientation, and velocity of subregions of the paper 112 (due to flexure of the paper 112 ). Typically, the motion analysis unit 150 is a general purpose computer, embedded microprocessor, digital signal processor, or dedicated hardware system capable of high speed image processing calculations necessary for determining object movement. Using this calculated movement information, a motion control unit 152 connected to the motion analysis unit 150 sends control signals to conveyor 120 to appropriately modify movement of paper 112 by selectively increasing or decreasing application of directed air jets to subregions of the paper 112 to reduce flutter, buckling, curling, or other undesired deviations from the desired motion state. As will be appreciated, use of discrete sensors, motion analysis units, and motion control units is not required, with integrated motion analysis and motion control assemblies being contemplated. In fact, it is even possible to provide a plurality of integrated sensors, motion analysis units, and motion control units as integrated microcontroller assemblies on the conveyor, with each air jet being locally or semi-locally controlled in response to locally sensed information.
[0006] Whether the sensing unit 140 is discrete or integrated with microcontrollers, in order to ascertain object position properly the sensing unit 140 must be reliable and accurate, ideally having two dimensional spatial and temporal resolution sufficient for overall tracking of the paper through the paper transport path with submillimeter precision, and three dimensional tracking ability for even small areas of the flexible object (typically at less than about one square centimeter, although lesser resolution is of course possible). Further, in many processes the object is moving quickly, allowing less than about 1 to 100 milliseconds for tracking measurements. Fortunately, optical sensors, video imaging systems, infrared or optical edge detectors, or certain other conventional detectors are capable of providing suitable spatial and temporal resolutions. For best results, two-dimensional optical sensors (such as charge coupled devices (CCD's)), or position sensitive detectors are utilized. However, suitably arranged one-dimensional sensor arrays can also be used. As will also be appreciated, sensors other than optical sensors may be used, including but not limited to pressure sensors, thermal sensors, acoustic sensors, or electrostatic sensors.
[0007] In operation, use of a sensing unit 140 for feedback control of object movement allows for precise micromanipulation of object motion state. For an illustrative example, in FIG. 1 paper 112 is sequentially illustrated in four distinct positions along conveyor 120 , respectively labeled as paper position 108 , paper position 114 , paper position 116 , and paper position 118 . In initial position 108 , the paper 112 moves along a curving path defined by a flexible portion 130 of the conveyor, constructed at least in part from a flexible laminate. In position 114 , the paper 112 becomes slightly misaligned. As paper 112 is moved along conveyor 120 toward position 116 by air jets 126 , the embedded sensors provide information that allows sensor unit 140 to calculate a time series of discrete spatial measurements that correspond to the instantaneous position fo paper 112 . These elements of a time series of spatial measurement information are continuously passed to the motion analysis unit 150 . The motion analysis unit 150 uses the received information (i.e. the sensor measured one, two or three-dimensional spatial information) to accurately determine motion state of paper 112 , including its position, velocity, and internal paper dynamics (e.g. trajectory of areas of the paper undergoing curl or flutter). This information (which may be collectively termed “trajectory”) is passed to the motion control unit 152 , which computes a new desired trajectory and/or corrective response to minimize deviation from the desired trajectory. The motion control unit 152 sends signals to selected air jets 126 to correct the misalignment, bringing the paper 112 closer to a correct alignment as indicated by position 116 . This feedback control process for properly orienting paper 112 by feedback controlled corrections to paper trajectory (the paper 112 now spatially located at position 116 ) is repeated, with the trajectory of paper 112 finally being correctly aligned as shown at position 118 . As will be appreciated, this feedback control process for modifying the trajectory of flexible objects can be quickly repeated, with millisecond cycle times feasible if fast sensor, motion processing, and air jet systems are employed. Faster cycle times are feasible as a function of the processing used, computational load, and particular implementation.
[0008] Advantageously, known systems such as this allow for manipulation and control of a wide variety of objects and processes. In addition to paper handling, other rigid solids such as semiconductor wafers, or flexible articles of manufacture, including extruded plastics, metallic foils, wires, fabrics, or even optical fibers can be moved in accurate three-dimensional alignment. As will be appreciated, modifications in layout of conveyor 120 are contemplated, including but not limited to use of curved conveyors (with curvature either in a process direction or perpendicular to the process direction to allow for vertical or horizontal “switchbacks” or turns), use of cylindrical or other non-linear conveyors, or even use of segmented conveyors separated by regions that do not support air jets. In addition, it may be possible to construct the conveyer 120 from flexible materials, from modular components, or as interlocking segmented portions to allow for quick and convenient layout of the conveyor in a desired materials processing path.
[0009] The valves used in the above referenced systems disclosed in the prior noted patents, however, are electrostatic valves. Such valves have physical and mechanical characteristics that do not render them entirely conducive to certain applications. For example, electrostatic valves tend to be formed with membranes that are flexible and thin, thus lacking robustness. In addition, electrostatic valves typically lack compatibility with liquid that is regulated in liquid fluid flow systems.
[0010] Further, these electrostatic valves do not maintain a physical state or configuration in the absence of power. The valves may be bistable with power applied thereto; however, the devices return to a default state once the power is removed. The significance of this characteristic becomes amplified in circumstances where arrays of valves are formed and individually addressing the valves is desired. If for example, a 1000×1000 array of valves is fabricated, one million wires would be needed to address and power each valve. This excessive amount of wiring is problematic in many applications.
[0011] Bimorph actuators have also been proposed to construct air flow valves. However, these valves are not bistable and are normally closed.
[0012] The present invention contemplates a new and improved high-speed valve that overcomes the above-referenced difficulties and others.
SUMMARY OF THE INVENTION
[0013] A method and apparatus for high-speed fluid flow control are provided.
[0014] In one aspect of the invention, the apparatus comprises a valve body having a base portion and wall portions, at least one aperture defined in the base portion for ingress or egress of the fluid, an actuating element attached between the wall portions—the actuating element comprising a material having a plurality of physical states that varies as a function of applied voltage and being positioned to transition from a first physical state to a second physical state to selectively open and close the aperture, the transition including a buckling of the actuating element, and electrodes positioned to apply the voltage to the actuating element.
[0015] In another aspect of the invention, the actuating element is formed of piezoelectric material.
[0016] In another aspect of the invention, the actuating element is formed of one of anti-ferro-electric material and a ferro-electric material.
[0017] In another aspect of the invention, the actuating element is formed of ferro-electric material.
[0018] In another aspect of the invention, the actuating element is a diaphragm.
[0019] In another aspect of the invention, the actuating element comprises multiple layers.
[0020] In another aspect of the invention, the multiple layers are selectively actuated by the applied voltage.
[0021] In another aspect of the invention, the actuating element maintains the second state in the absence of the applied voltage.
[0022] In another aspect of the invention, the apparatus is adaptable to be addressable in a matrix.
[0023] In another aspect of the invention, the method of actuation is comprised of steps of applying the voltage to the electrodes to actuate the actuating element while the actuating element is in a first physical state, maintaining the application of the voltage to buckle the actuating element into a second physical state, and removing the application of the voltage such that the actuating element remains in the second physical state.
[0024] In another aspect of the invention, the method further comprises selectively applying the voltage to corresponding electrodes of multiple layers of the actuating element.
[0025] In another aspect of the invention, the apparatus comprises a valve body having a base portion and wall portions, an aperture defined in the base portion for ingress and egress of the fluid, a blocking element attached between the base portion and a wall portion—the blocking element having at least one actuating element formed thereon, the actuating element comprising a material having a plurality of physical states that varies as a function of applied voltage and being positioned to transition from a first physical state to a second physical state to selectively open and close the aperture, and electrodes positioned to apply the voltage to the actuating element.
[0026] In another aspect of the invention, the blocking element has a substantially s-shaped configuration.
[0027] In another aspect of the invention, the actuating element is formed of a piezoelectric material In another aspect of the invention, the actuating element is formed of one of an anti-ferro-electric material and a ferro-electric material.
[0028] In another aspect of the invention, the at least one actuating element comprises a plurality of actuating elements positioned such that selective actuation of each of the actuating elements generates bending moments in the actuating elements to move the blocking element to vary the configuration.
[0029] In another aspect of the invention, the at least one actuating element comprises two actuating elements.
[0030] In another aspect of the invention, the method is comprised of steps of selectively actuating a first actuating element by applying the voltage thereto to generate a first bending moment in the actuating element to place the actuating element, and concurrently actuating a second actuating element by applying the voltage thereto to generate a second bending moment in the second actuating element such that the first and second bending moments are of opposite sense to alter the configuration of the blocking element.
[0031] In another aspect of the invention, a system comprises a substrate, a plurality of valves positioned on the substrate in a matrix configuration having rows and columns—each valve including a valve body having a base portion and wall portions, an aperture defined in the base portion for ingress and egress of the fluid, an actuating element attached between the wall portions, the actuating element comprising a material having a plurality of physical states that varies as a function of applied voltage and being positioned to transition from a first physical state to a second physical state to selectively open and close the aperture, the transition including a buckling of the actuating element, and electrodes positioned to apply the voltage to the actuating element—a plurality of row address lines, each row address line corresponding to a row of valves, and a plurality of column address lines, each column address line corresponding to a column of valves.
[0032] In another aspect of the invention, each actuating element maintains the second state in the absence of the applied voltage.
[0033] A primary advantage of the present invention is that it provides a valve that performs at relatively high-speed levels.
[0034] Another advantage of the present invention in certain embodiments is that it provides a valve that is bistable, i.e. stable in two configurations, irrespective of whether the valve is supplied with power at all times because of the employment of the principles of buckling.
[0035] Other advantages of the present invention include low cost, insensitivity to surface roughness, relative strength, low power consumption, compatibility with liquid fluid flow applications and ease of fabrication.
[0036] Further scope of the applicability of the present invention will become apparent from the detailed description provided below. It should be understood, however, that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art.
DESCRIPTION OF THE DRAWINGS
[0037] The present invention exists in the construction, arrangement, and combination of the various parts of the device, and steps of the method, whereby the objects contemplated are attained as hereinafter more fully set forth, specifically pointed out in the claims, and illustrated in the accompanying drawings in which:
[0038] [0038]FIG. 1 is a partial view of a paper handling system having a conveyor with air jets and micro-device sensors;
[0039] FIGS. 2 ( a )-( d ) are cross sectional views of a valve of a first embodiment according to the present invention;
[0040] FIGS. 3 ( a )-( c ) are cross sectional views of a valve of another embodiment according to the present invention;
[0041] [0041]FIG. 4 is a cross sectional view of a valve of still another embodiment of according to the present invention;
[0042] [0042]FIG. 5 illustrates a portion of a matrix of valves according to the present invention; and, FIGS. 6 ( a )-( b ) are cross sectional views of valves according to further embodiments of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0043] The present invention is directed to an improved high-speed valve—advantageously implementing actuating elements formed of, for example, piezoelectric material—for use in the systems described above as well as others. The advantages will become apparent to those skilled in the art upon a reading of the present description. As noted above, such advantages include high-speed performance (10 kHz range and higher), relatively low cost, insensitivity to surface roughness, relative strength when compared to electrostatic valves, low power consumption, bistability (for purposes of being matrix addressable in certain applications), compatibility with liquid fluid applications and ease of fabrication.
[0044] Referring now to the drawings wherein the showings are for purposes of illustrating the preferred embodiments of the invention only and not for purposes of limiting same, FIGS. 2 ( a )-( d ) provide views of a preferred valve according to the present invention. As shown, in FIGS. 2 ( a ) and ( b ), a valve 200 includes a base portion 202 having an aperture 204 defined therein. The valve 200 also includes wall portions 206 that have connected thereto an actuating element 208 . It is to be appreciated that the aperture 204 (as well as other apertures disclosed herein) is only representatively shown and preferably is connected to another volume of fluid from which fluid may flow depending on the state of the valve. It is to be appreciated that the actuating element 208 also has electrodes connected thereto that suitably take the form of layers 208 ′, for example.
[0045] [0045]FIG. 2( a ) shows the valve 200 in a closed position, i.e. where the actuating element 208 is sealed against the aperture 204 . Conversely, FIG. 2( b ) illustrates the valve in an open position, i.e. where the actuating element 208 is buckled upwardly to allow fluid to flow through the aperture 204 . To induce the transition from the configuration shown in FIG. 2( a ) to the configuration shown in FIG. 2( b ), a voltage is applied to the actuating element 208 to elongate the material against fixed ends shown at 210 . Application of the voltage may be accomplished in a variety of manners that are well known to those skilled in the art. Nonetheless, the resulting axial load generated by the application of the voltage results in the buckling of the actuating element.
[0046] Preferably, the actuating element is formed of piezoceramic (e.g. piezoelectric) material or other material that changes strain state upon the application of a voltage. More specifically, these materials have a plurality of physical states and are consequently capable of changing shape due to an applied voltage and are well known in the art. For example, anti-ferro-electric and ferro-electric materials, similar in nature to piezoelectric material, may also be employed for applications according to the present invention. When structures such as 208 are fabricated using piezoceramic, ferro-electric and anti-ferro-electric materials, once such materials are strained to a given point, i.e., buckled from one physical state to another, they remain in that strained state even if the applied voltage is removed. This feature provides various advantages that will be discussed in detail below in connection with, for example, FIG. 5.
[0047] With reference to FIGS. 2 ( c )-( d ), it is to be appreciated that the configurations of the actuating elements implemented to obtain the advantages of the present invention may vary. For example, as shown in FIG. 2( c ), the valve 200 includes an actuating element 208 that is a substantially circular diaphragm with vent holes as shown at 212 . In FIG. 2( d ), the valve 200 includes an actuating element 208 that is flap-like (e.g. substantially rectangular) with notched areas, such as indicated at 214 , for purposes of facilitating buckling by locally reducing the stiffness of the actuating element. Of course, it should be recognized that the notched areas are not necessary.
[0048] Referring now to FIGS. 3 ( a )-( c ), a valve 300 , which may take the general shapes of the configurations illustrated in FIGS. 2 ( c )-( d ) as well as other suitable configurations, is illustrated. The valve 300 includes a base portion 302 having an aperture 304 formed therein. Wall portions 306 have attached therebetween an actuating element 308 . In this embodiment, the actuating element 308 has multiple layers. As shown, actuating layers 310 and 312 are positioned between electrode layers 314 to effect suitable actuation of the layers. The provision of multiple layers in the embodiment shown in FIGS. 3 ( a )-( c ) allow for the actuating element 308 to be buckled in two directions.
[0049] In this regard, FIG. 3( a ) illustrates the valve in an open state. FIG. 3( b ) illustrates the valve in a closed state. In addition, FIG. 3( c ) illustrates the valve 300 in a nominal state, which may also be considered an open state for certain applications.
[0050] Referring now to FIG. 4, a valve 400 is shown. This valve includes a base portion 402 having an aperture 404 defined therein. The valve 400 also includes wall portions 406 with a multi-layer actuating element 408 connected therein and an additional aperture 410 provided in a top wall portion. The embodiment of FIG. 4 illustrates an advantage of implementation of a multi-layered actuating element described in connection with FIGS. 3 ( a )-( c ). As shown, the actuating element 408 may be buckled in either direction to selectively close the apertures 404 and 410 .
[0051] The multi-layer actuating elements 308 and 408 are preferably actuated by the application of a unique series of voltage signals through their respective electrodes to selectively transition the actuating elements from a first physical state to a second physical state. The transition preferably is achieved by providing a mechanical buckling of the material. In this regard, with exemplary reference to FIG. 3( c ) for convenience (although the following discussion is equally applicable to the valve 400 of FIG. 4), a voltage is provided to the layer 310 to initiate the expansion of the layer to cause movement. Once the actuating element 308 is moving in a direction, the layer 312 is similarly actuated to continue to drive the actuating element in the direction of movement and cause the element to buckle. This configuration is illustrated in FIG. 3( a ). Once buckled, the element will remain in that position irrespective of whether power is supplied to the valve.
[0052] To unbuckle the actuating element 308 , the layer 312 is actuated with a voltage of a polarity opposite to the voltage that moved the element in the direction to place it in the position of FIG. 3( a ). Once the actuating element is moving in the direction desired, the layer 310 is actuated with a similarly sensed polarity to return the actuating element to the position of FIG. 3( c ). Of course, it is to be appreciated that the actuating element 308 could be transitioned from the configuration of FIG. 3( c ) to the configuration of FIG. 3( b ) in like manner.
[0053] It should be further recognized that the exemplary valve 300 may not require the nominal state shown in FIG. 3( c ). In this case, the actuating element 308 will preferably toggle between the positions shown in FIGS. 3 ( a ) and ( b ). To effect this toggling, similar sequences of voltage signals should be applied as above except that the actuating element will be driven through the nominal position with the application of suitable voltage signals. The conservation of momentum may be applied in these circumstances to toggle the actuating element from the stable position of FIG. 3( a ) to the stable position of FIG. 3( b ), or vice versa, in a fast and efficient manner. Those skilled in art will further appreciate that the principle of using momentum to drive the actuating element through the nominal position could also be applied to actuating elements of a single layer in appropriate circumstances.
[0054] With reference now to FIG. 5, a matrix or array 500 of the valves positioned on a substrate in a matrix configuration having rows and columns is illustrated. This matrix includes valves 502 that are selectively addressable through row address lines 504 and column address lines 506 . In this configuration, the array of valves is matrix addressable such that any single valve can be addressed by accessing a suitable row address line and a column address line. The valve can thus be opened and closed independent of the surrounding valves. Moreover, the valve array retains its state even if power is removed.
[0055] The primary reason that non-volatile matrix addressability is feasible with the valves of the present invention, but not prior art electrostatic valves, is that the valves take advantage of the principles of buckling. As a consequence, no power is required for any valve to maintain a buckled physical state. Thus, separate lines are not required for each valve. In an array of valves numbering 1000×1000, only 2000 lines are required, not the one million as would be required to individually address a electrostatic array of similar size.
[0056] Referring now to FIG. 6( a ), an alternative embodiment of the present invention is shown. A valve 600 includes a base portion 602 having an aperture 604 formed therein. A top wall portion 606 is also shown. A blocking element 610 is positioned between the base portion 602 and the top wall portion 606 . Significantly, actuating elements such as those shown at 620 and 622 are positioned on a membrane 612 . The actuating element positioned on the membrane can be selectively actuated (through suitably positioned electrodes) to bend (or roll) the s-shaped configuration of the membrane to open and close the aperture 604 . As shown, the s-shape can be moved in the directions indicated by the arrow A. Preferably, the actuating elements on the “comers” of the s-shape are actuated while the other actuating elements are not so actuated.
[0057] Referring now to FIG. 6( b ), a similar device is shown. In this embodiment, a valve 650 includes a base portion 652 having an aperture 654 defined therein. Also shown is a top wall portion 656 . A blocking element 660 includes a membrane 662 having actuating elements 670 and 672 formed thereon. In operation, the actuating elements are actuated to generate bending moments therein to move the s-shaped configuration in the direction of the arrow A as shown to open or close the aperture 654 .
[0058] It is to be appreciated that the valves of the present invention may be constructed of a variety of materials that will be apparent to those skilled in the art, provided that the actuating elements implemented comprise a material that has a plurality of physical states that vary as a function of an applied voltage and, for selected embodiments, are of a mechanical character to allow buckling. For example, lead zirconate titanate (PZT) is the preferred piezoelectric material. However, polyvinylidene difluoride (PVDF or PVF2), zinc oxide (ZnO) and others can be used. In addition, the base and wall portions of the present valves may be formed of metal, plastic or any other rigid material that is advantageously batch fabricated or injection molded. An elastomer material such as Latex or Viton may also be suitably disposed around the aperture for sealing purposes. Further, the membrane for the S-shaped valve may be formed of any suitable flexible material, including Mylar. Similarly, the valves may be constructed in a variety of manners including batch fabrication. In some circumstances, formation processes that take stress and strain forces into account should be implemented.
[0059] The above description merely provides a disclosure of particular embodiments of the invention and is not intended for the purposes of limiting the same thereto. As such, the invention is not limited to only the above-described embodiments. Rather, it is recognized that one skilled in the art could conceive alternative embodiments that fall within the scope of the invention.
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This invention relates to a method and apparatus for high-speed fluid flow control. More particularly, the invention is directed to a valve formed, at least in part, of an actuating material, such as piezoelectric or anti-ferro-electric material. The valve is used for controlling fluid flow (including air flow) in a variety of devices including imaging devices (e.g. printers, copiers, etc.) for which air flow is used to handle paper. In one embodiment, the subject valve takes advantage of the phenomenon of buckling, resultant bistability and other structural mechanics to efficiently, and in a high-speed manner, open and close to regulate fluid flow. In another embodiment, the valve includes implementation of the actuating material to bend an s-shaped blocking element within the valve. The valve is also advantageously implemented in matrices and formed using batch fabrication techniques.
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TECHNICAL FIELD OF THE INVENTION
This invention relates generally to lawn care and more particularly to devices for aerating the soil of a lawn to cultivate thick and healthy grass.
BACKGROUND OF THE INVENTION
Modern lawns require a great deal of care and attention in order to nurture a thick green carpet of grass. Such care includes consistent mowing, watering, and thatching as well as periodic overseeding and fertilization. In addition, it is imperative that a healthy lawn be aerated at least twice a year and, preferably, even more often. Aeration usually entails creating a multitude of closely spaced small holes in the surface of the ground to permit air and oxygen to be absorbed into the soil. The holes also tend to increase moisture penetration into the soil and serve as receptacles for grass seed to prevent the seed from being washed away and to promote germination and growth.
Numerous lawn aeration devices have been available. One such device comprises a large cylindrical drum studded about its periphery with a plurality of short radially extending spikes. The drum is rolled or pulled over the ground and, as it rolls, the spikes are driven into the soil to create shallow holes. While this device is widely used and has proven somewhat successful, it is nevertheless plagued with numerous problems and shortcomings inherent in its design. For example, since the spikes necessarily engage the ground at an angle and are rotated laterally through the soil, significant force is required to penetrate the ground and move the spikes through the dirt. As a result, the drums of these devices generally are relatively large and usually are filled with water or sand or have large cement blocks or other weights to provide sufficient weight to drive the spikes into and through the soil. In addition, the density of spikes on the drum and thus the density of holes the aerator can make in the soil is severely limited since the weight of the device is inherently inadequate to drive more than a few of the spikes at a time into and through the soil. Finally, as each of the spikes of this device is forcibly driven into the soil, it pushes aside the dirt to make room for the spike. This is the action that actually creates the hole; however, it also necessarily compacts and hardens the soil all around the sides of the hole. As a result, penetration of air from within the hole into surrounding soil is reduced as is the penetration of moisture. Consequently, the efficiency and advantages of the aeration are reduced.
Another lawn aeration device seeks to address the soil compaction problems of drum and spike aerators by providing hollow spikes that actually pierce the ground and remove a plug of soil to create a hole. During each penetration of the ground, another soil plug is forced upwardly through the hollow spike and the plugs are simply ejected from the spike at its upper extent. While these types of devices, commonly known as pluggers, tend to reduce the compaction of soil around the sides of the holes, they nevertheless do not eliminate it, This is because the soil must still be parted to accommodate the thickness of the walls of the hollow spikes as they pierce the soil. In addition, such hollow spike aerators still require significant force to drive them into and through the soil and thus still require large heavy and cumbersome structures for proper operation. This is because sliding friction of the soil plug through hole in the spike is relatively high requiring extra force to drive plug through the soil.
Slicer styled aerators also exist. These aerators generally have thin star shaped blades that rotate over the ground to slice a narrow furrow or slot in the soil. Such aerators have many of the same problems as other types of aerators and also create furrows that tend to close up quickly when stepped upon. Further, the slots are so narrow that seeds and fertilizer cannot easily get into the narrow slot and its water retention is very small.
Because of their weight, many lawn aerators are motorized. This not only makes them expensive but also renders them difficult to use. When the heavy spiked drums are driven over the ground by their motors, they naturally bump, bounce, and shake about as the spikes are driven into and through the soil. This can create significant fatigue for users of these aerators. Further, the unitary drum construction of these devices renders them very difficult to turn at the end of an aerating run and the drum often must be manually scraped about in an arc to achieve the turn. This is not only cumbersome, it also tends to destroy healthy grass already growing in the lawn and can create an unsightly mess, particularly in moist or wet soil.
Thus, there exists a need for a simple compact aerator that is light, small, and easily pulled or pushed manually across the ground. Such an aerator should require minimum force for piercing and aerating the soil, thus eliminating the need for heavy drums and the like. The spikes of the aerator should be designed to eliminate the compaction of soil common with prior art devices and, in fact, should insure that the soil is actually loosened in the vicinity of each hole to insure maximum aeration and moisture penetration. The device should be easy to use by the common homeowner, inexpensive to purchase, and sufficiently small, light, and easy to roll that it can be attached and pulled behind a standard walk behind awn mower so that a lawn can be aerated as it is mowed. It is to the provision of such a lawn aerator that the present invention is primarily directed.
SUMMARY OF THE INVENTION
Briefly described, the present invention, in one preferred embodiment thereof, is an improved lawn aerator that is small, lightweight, and pullable behind a standard walk behind or self propelled mower to aerate a lawn as the lawn is mowed. The aerator comprises a frame having a tongue that can be attached to the back of a mower for pulling or can be attached to a handle for manual operation. An axle is mounted to the bottom of the frame and a set of aerator wheels are mounted at spaced intervals along the axle. Each of the aerator wheels has a disc-shaped hub from which a set of four curved spikes outwardly extend. The aerator wheels are oriented to roll across the ground. The spikes initially project from their hubs along a radius but have shanks that are curved generally in the direction of rotation of the wheels. Each of the spikes is tapered to a relatively sharpened ground piercing end.
In the ideal embodiment, the curve of each spike is critically determined to insure that the sharpened end of the spike engages and pierces the surface of the soil at a substantially right angle as the aerator wheel rolls across the ground. The curve further insures that, as the aerator wheel continues to roll, the shank of the curved spike which is shaped like a flat knife-like blade or tine, progressively follows the end of the spike into the soil through the opening initially formed by the sharpened end. Accordingly, as the aerator wheel rolls across the ground, each of its spikes in turn pierces the soil like the tip end of a knife and slices cleanly through the pierce point until the spike is fully submerged in the soil, which occurs when the center of the wheel is aligned with the pierce point on the ground.
As the wheel continues to roll past the pierce point, the curved spike begins to be rotated back up out of the ground on the trailing side of the wheel. Since it is moving in the direction of its curve, the spike functions as a cup-shaped spade that loosens, pulls, and lifts a loose clump of soil from the ground leaving a small hole. The loose clump of dirt removed from the hole is simply tossed aside on the surface leaving behind porous loose dirt on the walls of the hole. This loose dirt allows air and oxygen to penetrate freely through the walls of the hole and into the surrounding soil resulting in greatly improved oxygenization of the soil over prior art aerators, which, as discussed above, tend to leave holes with compacted soil sides. Further, since a loose clump of soil is lifted and laid on the ground, the clump tends to break up and disburse more readily than the hard dowel-like plugs produced by prior art aerators.
In addition to the forgoing advantages of easy penetration and the creation of porous hole sides that enhance aeration, the present invention also addresses the bulk and weight problems associated with prior art aerators. First, as discussed above, the curved spikes are formed to insure that their sharpened ends pierce the ground cleanly and easily and that their shanks slip into the soil substantially through the pierce point as the wheels rotate. This alone greatly reduces the force required to drive the spikes into the ground such that only a fraction of the weight required to drive in the spikes of prior art devices is needed. In addition to this, however, the spikes are positioned about their hubs so that one spike is being rotated out of the ground and, in the process, dislodging and pulling a plug of dirt from the soil as the next successive spike is piercing and slipping into the soil. The dislodging and pulling of the soil creates significant downward force on the aerator wheel. This force, in turn, is transferred to the piercing spike helping to drive it into the soil. It will thus be seen that the action of the spikes being extracted from the soil as the aerator wheels roll provides a significant portion of the downward force needed to drive successive spikes into the soil. As a matter of fact, the device of this invention virtually grips and digs into the soil like the talons of a hawk under the influence of its own action. As a result, an even further significant reduction in the extra unit weight needed to drive the spikes into the soil is realized.
The configuration and operation of the aerator wheels and spikes of this invention allows, for the first time, a practical lawn aerator that can be made small, light, and economical enough to become a common tool of the homeowner that can simply be hitched to a standard push mower and towed as a lawn is mowed. In such a configuration, the mower cuts the grass and the aerator follows behind to aerate the soil. A handle can also be attached as an alternative to towing for manual operation of the aerator alone. Numerous configurations of the invention are possible, including large commercial versions for golf courses and the like and small hand versions for aerating a flower bed or herb garden. All of these as well as other objects, features, and advantages of this invention will become more apparent upon review of the detailed description set forth below when taken in conjunction with the accompanying drawings, which are briefly described as follows.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is and overhead perspective view of a lawn aerator that embodies principles of the present invention in a preferred form.
FIG. 2 is a perspective view of the lawn aerator of FIG. 1 as seen from the bottom side thereof and illustrating the spiked aerator wheels of the device.
FIGS. 3A-3F show sequentially the operation of the wheels and curved aerator spikes of the present invention as the device is pulled or pushed across the ground.
FIG. 4 illustrates the empirical determination of the spike shape for the ideal embodiment thereof.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now in more detail to the drawings in which like numerals refer to like parts throughout the several views, FIGS. 1 and 2 illustrate a compact aerator that embodies principals of the present invention in a preferred form. The aerator 11 comprises a metal frame 12 formed of side bars 13, a back bar 14, and angled front bars 16 and 17. The front bars 16 and 17 terminate in a tongue assembly 18. The tongue assembly 18 includes a coupler 19 adapted to couple to a hitch 21. The hitch 21, in turn, is adapted to be mounted on the back panel of a standard or self-propelled walk behind mower, garden tractor, or other appropriate lawn vehicle for pulling the aerator of the present invention.
A pair of support bars 22 extend between the rear bar 14 and respective ones of the front bars 16 and 17 and are firmly welded or otherwise affixed thereto. A pair of axle mounting brackets 23 are fixed to the underside of the frame 12 and extend downwardly therefrom. More specifically, each of the brackets 23 is welded to the rear bar 14 at one end and is welded to a respective one of the support bars 22 adjacent the front portion of the frame 12. An elongated axle 24 is secured to the bottoms of the axle mounting brackets by a pair of U-bolts 26 and associated nuts 27. The axle 24 extends across the width of the frame 12 approximately in the center portion thereof. A set of aerator wheels 28 each having a hub 39 and curved spikes 42 are rotatably mounted at spaced intervals along the length of the axle 24. The details of the aerator wheel construction and operation will be described in more detail herein below.
A pair of rollers 29 are each rotatably secured to the end of a pivot arm 31. The pivot arms 31 are welded or otherwise fixed to the ends of a pivot axle 32 that is rotatably journaled within a pair of spaced bearing brackets 33 that are fixed to the side bars 13. With this arrangement, the rollers 29 can be pivoted on their pivot arms 31 in the directions indicated by arrow 34 between a raised position as shown in FIGS. 1 and 2 and a lowered position (not shown) wherein the pivot arms 31 extend downwardly from the frame. This last position of the rollers 29 provides for easy transportation of the aerator 11 to and from storage sites and to and from areas that are to be aerated. A handle 36 is fixed to one of the pivot bars 31 for manually raising and lowering the rollers 29. A latch 35 is provided on the frame 12 for locking the handle 36 in its down position and thus locking the wheels 29 in their up positions. Similarly, a spring bar 37 and associated latch 38 are provided for releasibly locking the handle 36 in its up position and thus the rollers in their down positions.
As best seen in FIG. 2, each of the aerator wheels 28 comprises a generally disc-shaped central hub 39 that is rotatably journaled on the axle 24 by means of appropriate bearings 41. Extending outwardly from each of the hubs 39 is a set of four aerator spikes 42, which actually pierce and penetrate the ground to achieve aeration. A set of four equally spaced radial holes is drilled through the edge of each hub 39 and one of the spikes 32 is releasibly secured in each hole by means of a corresponding set screw 43.
Each of the aerator spikes 42 initially extends from its hub 39 along a radius thereof but immediately begins to curve generally in the direction of rotation of the hub. In addition, each of the spikes is tapered to a relatively sharp point at its free end. As discussed in more detail below, in the ideal emobiment the curve of each spike 42 is critically determined so that as the aerator wheels 28 rotate in the directions indicated by arrows in FIG. 2, each spike pierces the ground at its sharpened end whereupon the shank of the spike progressively follows the end into the ground through the initial pierce point. This configuration greatly reduces the force needed to drive the spikes into the ground and thus reduces significantly the size, bulk, and weight of the aeration device. As a matter of fact, it has been found that a simple four inch cement block 44 (FIG. 2) nestled within the cradle formed by the frame and its support bars provides more than sufficient weight to drive the spikes of all three aerator wheels cleanly and smoothly into the ground.
FIGS. 3A-3F illustrate the sequential operation of each aerator wheel as it moves across the surface of the ground. In these illustrations, the wheels are seen to be moving across the ground in the direction of arrows 46 and rotating in the direction of arrows 47. Throughout these illustrations, dashed line 48 is positioned at a substantially fixed point on the ground to illustrate relative motions of the components of the wheel. In addition, the designations I, J, and K indicate three of the aerator spikes on the wheel as it moves across the ground.
In FIG. 3A, aerator spike I is seen to be inserted almost fully into the ground beneath the rolling hub 39. The tip of aerator spike J is poised above the ground in position for penetration at point P. In FIG. 3B, the hub 39 has rotated in the direction 47 and translated across the ground in direction 46 until the point of aerator spike J has engaged the ground at point P. At the same time, aerator spike I has begun to be rotated up behind the hub 39 and out of the ground. As spike I moves in this fashion, its curved shape functions as a spade that begins to dig and pull a clump of soil S from the ground. In its wake, the aerator spike I begins to leave a hole H in the ground. It will be understood that since the aerator spike I is shoveling the clump of dirt S from the hole H and moving it up out of the hole, the sides of the holes will naturally be comprised of loose dirt and soil from which the clump S has been broken and pulled away.
In FIG. 3C, the hub 39 has been rotated a bit further. It is seen from this figure that the sharpened tip of the aerator spike J has pierced the surface of the ground at point P and is being driven by the motion of the aerator wheel deeper into the soil. The curve of spike J, and all of the spikes for that matter, is predetermined so that as the hub 39 moves in direction 46 across the ground, the shank of spike J progressively slips into the ground through the original puncture point P made by the tip of the spike. Thus, the spike is not moved laterally across its length through the soil as with spikes on prior art devices but rather is slipped slowly and cleanly into the ground in a fashion reminiscent of a knife being stuck into the soil. This configuration of the spikes and their resulting functionality reduces by a great amount the force required to drive the spike J into the soil. In fact, this force has been found to be very small indeed when the spikes are appropriately sharpened and the ground is of average compaction.
At the same time that spike J is being driven progressively into the ground through point P, spike I which previously was driven into the ground, begins to move further out of the ground shoveling the small clump of soil S along with it as it goes. As the spike I shovels out the clump of soil S, a corresponding downward force equal to the force required to break out the clump of soil, pull and break away any roots, and extract the clump from the ground is imparted to the hub 39. This force, in turn, is transferred to the entering spike J. As a result, the shoveling action of spike I actually provides some of the downward force necessary to drive the next succeeding spike J into the ground behind spike I. In practice, it has been found that this shoveling action indeed provides a significant fraction of the necessary force for driving successive spikes into the ground. In fact, as the device of this invention is pushed or pulled across the ground, its spikes tend to grab and grip the ground like the talons of a hawk and hug the ground closely as the device is moved across the surface. In FIG. 3C, the clump of soil S is beginning to be dislodged and broken away from the soil and is being carried above the surface of the ground.
In FIG. 3D, the hub 39 has rotated a bit further and the aerator wheel has moved laterally in the direction 46. The aerator spike J has slipped further into the ground through puncture point P and aerator spike I has almost been completely extracted from the ground, carrying with it the clump of soil S and leaving behind it the ragged hole H.
In FIG. 3E, spike I has been rotated completely out of the ground and the center of the hub 39 is aligned over the puncture point P on the ground. At this point, the spike J is completely inserted into the ground beneath the hub 39 and is just beginning to be rotated up out of the ground behind the moving hub. In the meantime, the prior action of spike I has left a hole H in the ground and the clump of soil S that was removed from the hole has been laid atop the ground. It can be seen that the aerator of this invention allows for closely spaced aeration holes, which are highly desirable for proper soil aeration.
In FIG. 3F, the hub 39 has been moved across the ground in direction 46 until spike K has engaged the surface of the ground and is beginning to be pushed into the soil. Spike J is now moving up around behind the hub 39, bringing with it a clump of soil S and leaving behind it a hole H as did spike I in the previous cycle. Thus, in FIGS. 3A-3F, the aerator wheel is shown to complete a cycle and begin another cycle. It will be appreciated that as the wheel moves across the ground, it leaves behind it a series of spaced rough-edged holes from which dirt has been removed and deposited onto the ground.
The ideal curve of the spikes as illustrated in FIGS. 3A through 3F can be determined empirically through the following mathematical solution. The solution yields a formula to determine the X and Y coordinates of a point B, which lies along the inside edge of a curved spike meeting the conditions described above. The point B is the point on the spike that enters the ground through point A when the hub is rolled through a corresponding arbitrary angle θ in the x direction. In the cartesian coordinate system in which the solution is presented, the X axis is horizontal, the Y axis is vertical, and the point X=0, Y=0 coincides with point H directly below the center of a circular hub. Point C has coordinates X=r, Y=r when the hub is in its initial position as shown in FIG. 4, where r is the radius of the hub.
From geometry and trigonometry, we know that the following relationships are true: ##EQU1##
ED=rSinθ
EB=AH-EH
EG=Cos(θ)×EB
BG=Sin(θ)×EB
and
DH=FH-(Cos(θ)×FH)
We also know that the X and Y coordinates of point B are:
X=EG+ED
Y=BG+DH
By substitution, we have the following final equations: ##EQU2##
In order to determine a set of X,Y points that define the desired curve, one need only select a radius r for the hub and solve the above equations for a plurality of θ's between 0 and degrees, The result is a set of points B that define the curve AC depicted in FIG. 4.
The invention has thus far been described in terms of the ideal shape of the spikes to insure that each spike pierces the ground normal to its surface and slices into the soil through a single point. While this configuration has indeed been found to be ideal and preferred for aerator hubs that are driven to pull themselves across the ground, a slightly modified variant is preferred for an aerator that is pulled or pushed across the ground. In this later situation, the spikes can tend to ride up and walk over the surface of the ground, particularly in dense or hard soil. In addition, the ideal spike as determined from the above equations inherently limits the depth to which the spike can penetrate for a hub of a given radius.
To address these problems for pushed or pulled aerators, it has been found advantageous to rotate the curved spikes slightly outwardly from their ideal positions. With this modification, the spikes extend further outwardly from the hub and thus can penetrate the ground further to create deeper aeration holes. In addition, the modified spikes do not pierce the ground vertically but rather at a slight acute angle. This configuration in conjunction with the forwardly and downwardly directed composite force imparted by the vector sum of gravity and the pulling force eases penetration and prevents the spikes from "walking" on top of the ground. An additional advantage is that the modified spikes do not slice into the soil through precisely one point but rather tend to pierce at a point and then move slightly rearwardly toward the hub as the hub rolls. This insures that there is no compacting of the soil in front of the path of the spike and thus insures that the resulting aeration hole has loose dirt sides all around for maximum aeration.
Accordingly, the present invention should not be interpreted as being limited by the illustrated embodiment exhibiting the ideal shaped spike. Rather, the invention contemplates and encompasses the above described and other variations of the ideal embodiment with the ideal spike shape representing only a preferred starting place.
With the just described mechanism, it has been found that effective and efficient aeration can be accomplished with a mechanism that is substantially smaller and many times lighter than prior art aeration devices. In addition, the apparatus of this invention can be made inexpensively so that the average home owner can afford one and use it periodically to aerate his lawn. When not in use, the apparatus is light enough simply to be hung on a wall. During use, it can be hitched to the back panel of a standard walk behind mower, riding mower, or other lawn implement and pulled along behind. As an additional advantage, the present invention provides aeration holes that are superior to those provided by prior art devices. This is because the dirt is pulled out of the holes rather than compacted against the sides of the holes. As a result, the sides of the holes comprise loose dirt through which moisture and oxygen can freely migrate into surrounding soil. Thus, the present invention represents a significant advance in the lawn-care art in a number of critical aspects.
The invention has been described herein in terms of preferred embodiments and methodologies. It will be obvious to those of skill in this art, however, that various modifications might well be made to the illustrated embodiments within the scope of the invention. For example, while the aerator wheels have been shown with four spikes, fewer or more than four might also be employed. In addition, the aerator wheels themselves might well be simply molded from a single piece of metal rather than formed of a hub with detachable spikes. The invention has been illustrated in terms of a multi-wheel pull-along device for use with lawn mowers. However, single wheel, hand-held aerators for use with small flower gardens or herb gardens might also be employed within the scope of this invention. On the other side of the spectrum, large commercial versions of the aerator might also be produced to aerate golf courses, farms, and other large plots of land. These and many other possible additions, deletions, and modifications are possible and may be made to the illustrated embodiments without departing from the spirit and scope of this invention as set forth in the claims.
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A compact lawn aerator comprises a rigid frame having a hitch for releasibly fastening the frame to the back of a self-propelled mower. An elongated axle is secured to the under side of the frame and a set of aerator wheels are rotatably mounted at spaced intervals along the axle. Each of the aerator wheels has a generally disk-shaped hub from the periphery of which four spikes radiate. Each spike initially projects from the hub along a radius but curves along its length in the direction of rotation of the wheel. The spikes are tapered to a sharpened point and their curve is determined so that, as the wheel rotates, the ends of the spikes pierce the soil at substantially right angles and the shank of the spikes slip into the ground progressively through the pierce point. This greatly reduces the force needed to drive the spikes into the ground, thus reducing the weight and size of the device. Further, as the spikes continue to rotate out of the soil, their curved shape functions as a cupped spade that tears and pulls a soil plug from the ground, leaving a loosely packed hole through which air can freely migrate into surrounding soil. The downward force imparted by the pulling out of the soil plug helps drive the successive plug into the ground, further significantly reducing the required weight of the device.
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CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. application Ser. No. 12/504,033, filed Jul. 16, 2009, which claims priority to U.S. Provisional Application No. 61/018,441, filed Jul. 17, 2008, entitled “ARTIFICIAL INTERVERTEBRAL DISC PLACEMENT SYSTEM” the full disclosures of which are incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to medical devices and methods. More specifically, the present invention relates to intervertebral disc prostheses.
[0003] Back pain takes an enormous toll on the health and productivity of people around the world. According to the American Academy of Orthopedic Surgeons, approximately 80 percent of Americans will experience back pain at some time in their life. On any one day, it is estimated that 5% of the working population in America is disabled by back pain.
[0004] One common cause of back pain is injury, degeneration and/or dysfunction of one or more intervertebral discs. Intervertebral discs are the soft tissue structures located between each of the thirty-three vertebral bones that make up the vertebral (spinal) column. Essentially, the discs allow the vertebrae to move relative to one another. The vertebral column and discs are vital anatomical structures, in that they form a central axis that supports the head and torso, allow for movement of the back, and protect the spinal cord, which passes through the vertebrae in proximity to the discs.
[0005] Discs often become damaged due to wear and tear or acute injury. For example, discs may bulge (herniate), tear, rupture, degenerate or the like. A bulging disc may press against the spinal cord or a nerve exiting the spinal cord, causing “radicular” pain (pain in one or more extremities caused by impingement of a nerve root). Degeneration or other damage to a disc may cause a loss of “disc height,” meaning that the natural space between two vertebrae decreases. Decreased disc height may cause a disc to bulge, facet loads to increase, two vertebrae to rub together in an unnatural way and/or increased pressure on certain parts of the vertebrae and/or nerve roots, thus causing pain. In general, chronic and acute damage to intervertebral discs is a common source of back related pain and loss of mobility.
[0006] When one or more damaged intervertebral discs cause a patient pain and discomfort, surgery is often required. Traditionally, surgical procedures for treating intervertebral discs have involved discectomy (partial or total removal of a disc), with or without fusion of the two vertebrae adjacent to the disc. Fusion of the two vertebrae is achieved by inserting bone graft material between the two vertebrae such that the two vertebrae and the graft material grow together. Oftentimes, pins, rods, screws, cages and/or the like are inserted between the vertebrae to act as support structures to hold the vertebrae and graft material in place while they permanently fuse together. Although fusion often treats the back pain, it reduces the patient's ability to move, because the back cannot bend or twist at the fused area. In addition, fusion increases stresses at adjacent levels of the spine, potentially accelerating degeneration of the adjacent discs.
[0007] In an attempt to treat disc related pain without fusion, an alternative approach has been developed, in which a movable, implantable, artificial intervertebral disc (or “disc prosthesis”) is inserted between two vertebrae. A number of different artificial intervertebral discs are currently being developed. For example, U.S. Patent Application Publication Nos. 2005-0021146, 2005-0021145, and 2006-0025862, which are hereby incorporated by reference in their entirety, describe artificial intervertebral discs. This type of intervertebral disc has upper and lower plates positioned against the vertebrae and a mobile core positioned between the two plates to allow articulation, translation and rotational motion between the vertebrae.
[0008] Another example of an intervertebral disc prostheses having a movable core is the CHARITE artificial disc (provided by DePuy Spine, Inc.) and described in U.S. Pat. No. 5,401,269. Other examples of intervertebral disc prostheses include MOBIDISC (provided by LDR Medical), the BRYAN Cervical Disc (provided by Medtronic Sofamor Danek, Inc.), and the PRODISC (from Synthes Stratec, Inc.) and described in U.S. Pat. No. 6,936,071. Some of these intervertebral discs are mobile core discs while others have a ball and socket type two piece design. Although existing disc prostheses provide advantages over traditional treatment methods, improvements are ongoing.
[0009] These known artificial intervertebral discs generally include upper and lower plates which locate against and engage the adjacent vertebral bodies, and a core for providing motion between the plates. The core may be movable or fixed, metallic, ceramic or polymer and generally has at least one convex outer articulation surface which mates with a concave articulation recess on one of the plates in a fixed core device. In a movable core device two sets of articulation surfaces are provided. In order to implant these intervertebral discs, the natural disc is removed and the vertebrae are distracted or forced apart in order to fit the artificial disc in place. The plates may be inserted individually or together and with or without a core. It is desirable to reduce the duration of the artificial disc procedure by implanting the disc in an assembled configuration. However, when holding the disc for implantation it is desirable to prevent contact of the placement tool with the bone integration surface of the disc to avoid damage to any bone integration structures or coatings thereon.
[0010] Currently available artificial intervertebral discs are held and delivered with a variety of different instruments and techniques. It would be desirable to provide a disc system with a simple placement instrument which easily and securely grasps the implant for insertion.
[0011] In addition, it would be desirable to hold the disc in the implantation instrument in an articulated or angled insertion configuration to prevent the need for over distraction of the disc space.
[0012] Therefore, a need exists for an improved artificial intervertebral disc placement system which securely and easily holds the articulating plates of the disc in a fixed arrangement suitable for placement of the disc.
BRIEF SUMMARY OF THE INVENTION
[0013] According to the invention there is provided an artificial disc placement system including a placement instrument with a quick and easy assembly mechanism and quick deployment.
[0014] In accordance with one aspect of the invention, an intervertebral disc placement system includes an artificial disc and a placement instrument. The artificial disc comprises an upper plate having an upper vertebra contacting surface and a lower surface having a bearing surface thereon; a lower plate having a lower vertebra contacting surface and an upper surface having a bearing surface thereon, wherein the upper and lower plates are configured to articulate with respect to one another; and a first notch in the lower surface of the upper plate and a second notch in the upper surface of the lower plate, wherein the first and second notches are aligned with one another. The placement instrument includes a handle and a rotatable key, wherein the key is configured to fit into the first and second notches.
[0015] In accordance with another embodiment of the invention, an intervertebral disc placement system includes an upper plate having an upper vertebra contacting surface and a lower surface having a bearing surface thereon; a lower plate having a lower vertebra contacting surface and an upper surface arranged to articulate with respect to the bearing surface of the upper plate; a first notch in the lower surface of the upper plate and a second notch in the upper surface of the lower plate, wherein the first and second notches are aligned with one another and face one another; and a placement instrument. The placement instrument has a handle and at least one movable key and the at least one key is configured to move into the first and second notches and retract toward the handle to secure the upper and lower plates to the placement instrument.
[0016] In accordance with a further embodiment of the invention, an intervertebral disc placement system includes an artificial disc and a placement instrument. The artificial disc comprises an upper plate having an upper vertebra contacting surface, a lower surface having an articulating surface thereon, anterior, posterior and two lateral edges; and a lower plate having a lower vertebra contacting surface, an upper articulating surface arranged to articulate with respect to the upper plate, anterior, posterior and two lateral edges. The placement instrument includes a handle and a disc receiving portion configured to receive the upper and lower plates of the artificial disc in the placement instrument in a locked configuration where the upper surface of the upper plate and the lower surface of the lower plate are angled such that the upper surface of the upper plate and the lower surface of the lower plate are closer together at an end of the disc remote from the placement instrument.
[0017] In accordance with an additional embodiment of the invention, an method of inserting an artificial disc into a space between two adjacent vertebrae includes the steps of: positioning the artificial disc on a placement instrument with upper and lower vertebrae contacting surfaces of the artificial disc positioned at an angle with respect to one another such that the vertebrae contacting surfaces are closer together at an end of the disc remote from the placement instrument; inserting the artificial disc partway into the space under constraint to prevent endplates of the prosthesis from articulating; releasing the prosthesis from constraint; and inserting the unconstrained prosthesis farther into the space.
[0018] Other features of the invention are set forth in the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] FIG. 1 is a bottom perspective view of a superior plate of an artificial disc;
[0020] FIG. 2 is a top perspective view of the plate of FIG. 1 ;
[0021] FIG. 3 is a side cross sectional view of the superior plate taken along line 3 - 3 of FIG. 1 ;
[0022] FIG. 4 is a top perspective view of an inferior plate of an artificial disc;
[0023] FIG. 5 is a bottom perspective view of the plate of FIG. 2 ;
[0024] FIG. 6 is a side cross sectional view of the inferior plate taken along line 6 - 6 of FIG. 4 ;
[0025] FIG. 7 is a perspective view of a core for use with the superior and inferior plates of FIGS. 1 and 4 ;
[0026] FIG. 8 is a perspective view of the assembled intervertebral disc held by an placement instrument;
[0027] FIG. 9 is a perspective view of the placement instrument of FIG. 8 ;
[0028] FIG. 10 is a top view of the placement instrument of FIG. 9 ;
[0029] FIG. 11 is a side cross sectional view of the placement instrument taken along line 11 - 11 of FIG. 10 ;
[0030] FIG. 12 is a top view of the placement instrument with a disc locking key in the unlocked position; and
[0031] FIG. 13 is a top view of the placement instrument with the key in the locked position.
DETAILED DESCRIPTION OF THE INVENTION
[0032] An intervertebral disc placement system according to the present invention includes a multi part disc and an associated placement instrument. The placement instrument holds the disc securely for placement into an intervertebral disc space and quickly releases the implant within the disc space.
[0033] FIGS. 1-3 illustrate a superior or upper plate 10 of an intervertebral disc. FIGS. 4-6 illustrate a corresponding inferior or lower plate 20 and FIG. 7 illustrates a core 30 positionable between the plates to form a complete articulating intervertebral disc. The upper and lower plates 10 , 20 include outer vertebral body contacting surfaces which are provided with attachment enhancing features to ensure bone integration. The attachment enhancing features shown include one or more fins and an array of serrations. In the embodiment shown the upper plate includes two fins 12 and the lower plate includes one fin 22 . The fins 12 , 22 can be an elongate fins pierced by one or more transverse holes 14 for bone ingrowth. The fins 12 , 22 can have one or both ends formed at an angle, such as a 45 degree angle to aid in insertion of the fins into corresponding slots cut into the vertebral body. Particularly, the leading end of the fins 12 , 22 should have an angled end surface.
[0034] The disc can be inserted laterally, from an anterior side, or from a posterior side. In the embodiment shown, the disc is designed for insertion laterally into an intervertebral space from either side. The lateral insertion of the disc is particularly useful in the lumbar spine where an anterior approach involves passing through the abdominal cavity and the posterior approach involve removal of a portion of the vertebra, such as the facets. Although the disc will be described herein as inserted laterally and is shown in a size appropriate for the lumbar spine, the system can be modified to accommodate other locations in the spine and other implantation approaches.
[0035] In the embodiment shown, two spaced apart superior fins 12 and a single central inferior fin 22 are provided on the upper and lower plates, respectively, extending in a lateral direction. Alternatively, one, two or more fins can be provided on either plate. In the example shown, the single fin is provided on one plate while the double fins are provided on the other plate to achieve a staggered arrangement particularly useful for multi-level disc implant procedures or in case an additional disc implant is required at a later time. The locations of the one and two fin plates can also be reversed so that the two fins are provided on the inferior plate. The orientation of the fin(s) 12 , 22 can also be modified depending on the insertion direction for the intervertebral disc.
[0036] The fins 12 , 22 are configured to be placed in slots in the vertebral bodies. The transverse holes 14 may be formed in any shape and may extend partially or all the way through the fins 12 , 22 . Preferably, the fins 12 , 22 each have a height greater than a width and have a length greater than the height. The fin length is preferably greater than one half of a dimension of the plate in the corresponding direction.
[0037] The fins 12 , 22 provide improved attachment to the bone and prevent rotation of the plates in the bone. In some embodiments, the fins 12 , 22 may extend from the surface of the plates 10 , 20 at an angle other than 90.degree. For example on one or more of the plates 10 , 20 where multiple fins 12 , 22 are attached to the surface the fins may be canted away from one another with the bases slightly closer together than their edges at an angle such as about 80-88 degrees. The fins 12 , 22 may have any other suitable configuration including various numbers, angles, serrated edges, and curvatures, in various embodiments. In some embodiments, the fins 12 , 22 may be omitted altogether.
[0038] The intervertebral body contacting surfaces of the plates 10 , 20 also can include other geometries of bone integration structures including serrations, teeth, grooves, ridges, pins, barbs or the like. When the bone integration structures are ridges, teeth, barbs or similar structures, they may be angled to ease insertion and prevent migration. These bone integration structures can be used to precisely cut the bone during implantation to cause bleeding bone and encourage bone integration. Additionally, the outer surfaces of the plates 10 , 12 may be provided with a rough microfinish formed by blasting with aluminum oxide microparticles or the like to improve bone integration. In some embodiments, the outer surface may also be titanium plasma sprayed or HA (hydroxylapatite) coated to further enhance attachment of the outer surface to vertebral bone.
[0039] The intervertebral body contacting surfaces shown include a plurality of serrations 16 . The serrations 16 as shown are pyramid shaped serrations extending in mutually orthogonal directions, however, other shapes may also be used. The serrations have a height of about 0.5-1 mm and a width about equal to their height. With passage of time, firm connection between the plates 10 , 20 and the vertebrae will be achieved as bone tissue grows over the serrated finish. Bone tissue growth will also take place about the fins 12 , 22 and through the holes 14 therein, further enhancing the connection which is achieved.
[0040] Opposite the serrated vertebral body contacting surfaces of the plates 10 , 20 , the plates have concave bearing surfaces 18 , 28 . These concave bearing surfaces are shaped to accommodate and retain a mobile core. The particular shape and curvature of the bearing surfaces 18 , 28 can vary to accommodate different shaped cores or different applications. Surrounding the bearing surfaces 18 , 28 are angled surfaces 19 , 29 which limit the articulation of the disc. The angle at which the surfaces 19 , 29 are formed can be varied to form a disc with a selected maximum articulation. The maximum articulation can be different in each direction including the anterior, posterior and lateral directions. In one example, the disc is designed to allow angulations between the upper and lower plates of a maximum of .+−.12 degrees in the lateral direction, .+−.12 degrees in the anterior/posterior direction, and unlimited rotation.
[0041] The core 30 , as shown in FIG. 7 , can be formed as a circular disc shaped member with upper and lower bearing surfaces 32 which match the curvature of the concave bearing surfaces 18 , 28 of the plates. The core 30 also has one or more annular rims 34 which cooperate with a retention feature 40 on at least one of the plates 10 , 20 to retain the core between the plates when the intervertebral disc is implanted between the vertebrae of a patient. The core 30 is moveable with respect to both the upper and lower plates 10 , 20 to allow articulation, translation and rotation of the upper and lower plates with respect to one another. The core bearing surfaces 32 and concave bearing surfaces 18 , 28 of the plates have the same radius of curvature which may vary depending on the size of the intervertebral disc.
[0042] The retention feature 40 in the illustrated embodiment comprises a retention ring 42 on the lower plate 20 , shown most clearly in FIG. 6 . The retention ring 42 protrudes inwardly from an edge of the bearing surface 28 . Although a circumferential core retaining feature is shown, other core retaining features may also be used including at least those shown in U.S. Patent Publication Nos. 2005/0251262, 2005/0021146, and 2005/0021145, which are incorporated herein by reference in their entirety.
[0043] Although the core 30 has been shown as circular in cross section with spherically shaped bearing surfaces 32 , other shapes may be used including oval, elliptical, or kidney bean shaped. These non-circular shaped cores can be used to limit rotational motion between the upper and lower plates 10 , 20 . The bearing surfaces 18 , 28 , 32 of the plates and core are shown as spherical, however flat, cylindrical, tab and groove, stepped or other shaped bearing surfaces may also be used.
[0044] Although the core 30 and plates 10 , 20 have been shown as solid members, the core and plates may be made in multiple parts and/or of multiple materials. The core can be made of low friction materials, such as titanium, titanium nitrides, other titanium based alloys, tantalum, nickel titanium alloys, stainless steel, cobalt chrome alloys, ceramics, or biologically compatible polymer materials including PEEK, UHMWPE, PLA or fiber reinforced polymers. High friction coating materials can also be used.
[0045] The present invention has been illustrated as a three piece articulating disc with a mobile core. The invention may also be embodied in a two piece or ball and socket type disc which can be held by a placement instrument in the same manner described below with respect to the three piece disc.
[0046] The intervertebral disc according to the present invention provides articulation in two directions as well as translation and rotation. The plates 10 , 20 are provided with notches 44 at one lateral end of each plate for use in grasping the disc by a placement instrument 50 shown in FIG. 8 . The placement instrument facilitates holding and manipulation of the disc for insertion or removal of the disc in an intervertebral disc space. The notches 44 allow the plates 10 , 20 to be grasped and inserted simultaneously in a locked orientation with or without a core 30 there between. The lateral edges of the plates 10 , 20 also include a stepped surface 46 . On the end of the plates with the notches 22 , the stepped surfaces 46 engage a corresponding abutment surface on the placement instrument to further secure the plates in the placement instrument.
[0047] The upper and lower plates 10 , 20 may be formed from titanium, titanium nitrides, other titanium based alloys, tantalum, nickel titanium alloys, stainless steel, cobalt chrome alloys, ceramics, or biologically compatible polymer materials including PEEK, UHMWPE, PLA or fiber reinforced polymers. The bearing surfaces or recesses 18 , 28 are concavely, spherically curved and can have a hard coating such as a titanium nitride finish. The plates 10 , 20 may be treated with aluminum oxide blasting followed by a titanium plasma spray to improve bone integration. Other materials and coatings can also be used such as titanium coated with titanium nitride, aluminum oxide blasting, HA (hydroxylapatite) coating, micro HA coating, and/or bone integration promoting coatings. Any other suitable metals or combinations of metals may be used as well as ceramic or polymer materials, and combinations thereof to optimize imaging characteristics. Any suitable technique may be used to couple materials together, such as snap fitting, slip fitting, lamination, interference fitting, use of adhesives, welding and/or the like.
[0048] FIG. 8 illustrates the plates 10 , 20 secured in the placement instrument 50 and arranged with the upper plate at an angle with respect to the lower plate for placement of the disk. The angled placement orientation allows the plates 10 , 20 to be inserted more easily into the intervertebral space with a narrow leading end formed by the angle of the plates. An angle between the upper vertebral body contacting surface of the upper plate 10 and the lower vertebral body contacting surface of the lower plate is at least 5 degrees. Preferably, the angle is about 15-30 degrees, and more preferably about 25 degrees.
[0049] FIG. 9 illustrates the disc holding end of the placement instrument 50 is mounted on a shaft 60 . The instrument 50 includes a pair of arms 52 having flat surfaces on opposite top and bottom sides for supporting the plates interior surfaces. An abutment surface 54 overhangs a groove 56 which is configured to receive the protruding stepped surface at the ends of the 46 of the plates. A rotatable key 58 functions as a locking mechanism and is received in the notches 44 of the plates. The engagement of the rotatable key 58 in the notches 44 allows the plates 10 , 20 to be made without any outwardly extending engagement features. This can provide an advantage of a lower profile over many of the know devices having exterior rims or grooves for engagement by a placement instrument. The key engagement system of the placement instrument also provides the advantage of a narrower placement profile than those placement instruments which grasp the side surfaces of a disc.
[0050] FIGS. 12 and 13 show the operation of the handle end of the placement instrument 50 which includes the handle 62 , a rotatable knob 64 , and a movable lever 66 . The movable lever 66 is connected through a central shaft 68 of the handle (shown in FIG. 11 ) to the key 58 and functions as a key rotating mechanism to move the key from an unlocked position shown in FIG. 12 to a locked position shown in FIG. 13 . The rotatable knob 64 functions as a retraction mechanism to retract the key 58 toward the handle 62 to secure the plates against the abutment surfaces 54 . In operation, the plates 10 , 20 are place in the disc holding end of the placement instrument with the notches 44 aligned over the key 58 and the key in the unlocked position of FIG. 12 . The key 58 is then rotated 90 degrees by moving the lever 66 90 degrees causing the ends of the key to enter the notches 44 . The plates 10 , 20 are then pulled tight against the abutment surfaces 54 of the instrument by rotating the knob 64 to retract the key toward the handle. This pulls the key 58 against the side of the notches 44 to lock the plates tightly in place.
[0051] The disc holding end of the placement instrument 50 can be marked, such as by markers 70 which include either two dots or one dot indicating that the position for either a two fin or one fin plate. Other marking or indicia can also be used to identify the correct location and/or orientation of the plates, such as labeling (superior, inferior), color coding, or other insignia.
[0052] The artificial intervertebral disc is surgically implanted between adjacent spinal vertebrae in place of a damaged disc. Those skilled in the art will understand that the damaged disc is partially or totally removed according to known procedures and the adjacent vertebrae are forcibly separated from one another to provide the necessary space for insertion of the disc. The plates 10 , 20 are slipped into place between the vertebrae with their fins 12 , 22 entering slots cut in the opposing vertebral surfaces to receive them. The plates 10 , 20 may be inserted simultaneously with or without the core 30 . The disc may be inserted all the way to a final resting place with the placement instrument 50 , or after partial insertion of the disc, the individual plates 10 , 20 can be further advanced independently or together to a final position. The insertion of the disc partway into the intervertebral space while connected to the placement instrument and then the further insertion of the plates while they are free to move with respect to one another allows the disc to moved to a final position while it is free to take on the angulation or lordosis of the space. This reduces the problem of overdistraction of the disc space.
[0053] Once the disc has been partially or completely inserted, the placement instrument 50 is removed from the plates 10 , 20 by simply rotating the lever 66 90 degrees back to the unlocked position of the key 58 . Once the disc has been inserted, the vertebra move together to hold the assembled disc in place.
[0054] The vertebral contacting surfaces of the plates 10 , 20 including the serrations 16 locate against the opposing vertebrae and, with passage of time, firm connection between the plates and the vertebrae will be achieved as bone tissue grows over the serrated finish. Bone tissue growth will also take place about the fins 12 , 22 and through the holes 14 therein, further enhancing the connection which is achieved.
[0055] While the exemplary embodiments have been described in some detail, by way of example and for clarity of understanding, those of skill in the art will recognize that a variety of modifications, adaptations, and changes may be employed. Hence, the scope of the present invention should be limited solely by the appended claims.
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An intervertebral disc placement system includes a multi part intervertebral disc, such as a mobile core disc, and an associated placement instrument. The placement instrument holds the disc securely with the disc endplates angled for ease of placement of the disc into an intervertebral disc space and quickly releases the implant within the disc space. The disc includes upper and lower plates having notches in inner surfaces for engagement of the placement instrument. The placement instrument has a rotatable key configured to fit into the first and second notches to grasp the disc from the interior and eliminate the need for an external grasping mechanism which could interfere with disc placement.
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CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This is a Division of co-pending U.S. patent application Ser. No. 09/735,810, filed Dec. 14, 2000, which is a Continuation of International Application PCT/EP00/00404, filed Jan. 19, 2000 which in turn claims priority of German applications DE 199 17 324.9, filed Apr. 16, 1999 and DE 199 30 564.1, filed Jul. 2, 1999, the priorities of which are hereby claimed, said International Application having been published in German, but not in English, as WO 00/62705 Oct. 26, 2000.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The invention relates to an assembly for the manufacture of shaped parts from ceramics, in particular for medical or dental-medical purposes.
[0004] 2. Description of the Related Art
[0005] In medical engineering, dental medicine or dental engineering, prosthetic parts have hitherto been manufactured mainly from high-quality precious metal alloys, cobalt chromium alloys and partially also from titanium. Due to the necessary bio-compatibility of such medical products, the metal surfaces of these prosthetic parts are usually coated with ceramic substrates. In dental medicine and dental engineering a veneering with dental porcelains, in particular in the anterior tooth region, often takes place for mainly aesthetic reasons.
[0006] For a fairly long time, efforts have been made to substitute these metal alloys with completely ceramic systems. However, this requires the use of high-performance ceramics, as are used in industrial ceramics partially with industrially manufactured serial products. In contrast with the industrially manufactured ceramic parts, however, the prosthetic workpieces manufactured in medical engineering or dental engineering are in each case unique, which is why, for economical, material-technical and industrial reasons, the known industrial production methods cannot be used. A further known problem of such high-performance ceramics is the partially great contraction of the ceramic pastes during sintering, which can amount to up to 20%. However, such dimensional changes cannot be tolerated with dental-technical shaped parts, because, for example with bridgework, the distances between the columns (stumps) or the height of the contact points to the antagonist, must be kept within the micrometer range.
[0007] For this reason, several attempts have been made to machine prosthetic parts from solid ceramic blocks, the sintering of which is complete (semifinished material), directly by way of machining with geometrically defined cutting edges, machining with geometrically undefined cutting edges or by way of erosion by means of ultrasound erosion or lasers.
[0008] The grinding-out or milling of ceramic parts with the aid of diamond tools, for example with the so-called CAD-CAM method, has become generally accepted in practice—although only to a limited extent. With this method, first of all a measurement is taken of the tooth stump, and subsequently of the crown provided thereon, which is available, for example, as a wax model. The data is then entered into a CAD program which controls a milling machine. This milling machine then automatically machines the sintered and high-strength ceramic block. However, expenditure for this is extremely high because the ceramic block which is already sintered is extremely hard. If, for example, high-performance ceramics such as aluminum oxide (Al 2 O 3 ) or zirconium oxide (ZrO 2 ) are ground, the diamond tools wear out very quickly, resulting in geometry tolerances on the workpiece because the geometry and the diameter of the tools change during the machining. Moreover, at critical points of the prosthesis parts, for example at crown edges, material eruptions or micro-tears can arise. A further problem is represented by the long grinding time, because work can only be done at low eroding rates and at reduced rate of feed, because otherwise great stresses in the material can arise, which can lead in turn to hairline cracks and the like. Moreover, a separating step is necessary, where, at the end of the machining, the milled-out crown is separated from the rest of the ceramic block. With this manual separating and grinding procedure, both geometry errors and material eruptions can arise, with the result that the expensively manufactured part can possibly no longer be used. Finally, the machining of high-performance ceramics requires expensive and automatically operating grinding or milling machines because the dental technician or machine operator can no longer manually control the machining parameters (feed, delivery) at all. Alternatively to the high-performance ceramics, modified dental ceramics can, admittedly, also be used, which permit a still economical grinding machining, but these modified ceramics then also only have reduced strength values.
[0009] Alternatively to the machining of ceramic blocks which are already sintered and which are high-strength, methods have therefore been developed, where the ceramic shaped parts are manufactured from a ceramic raw material which is not yet sintered or from presintered material. With two known methods, first of all an impression is made of the machined tooth stump and then a positive is formed, which for its part consists of fire-proof material, in particular ceramics. A tooth crown of wax is formed on to this positive stump, the tooth crown of wax simulating the final shape of the crown. Subsequently, the positive stump, with the wax crown located thereon, is placed upon a rubber base which forms the floor for a rubber ring, with this rubber ring surrounding the positive stump with the wax crown with clearance. A liquid or plastic embedding mass is then introduced into the muffle form formed in this way, the embedding mass surrounding the positive stump with the wax crown apart from a pouring channel. This pouring channel is formed, for example, by a wax cone which is connected to the wax crown.
[0010] After the hardening of the embedding mass, the rubber foundation and the rubber ring are removed, so that the hardened embedding mass with the filling wax cone is freely available. This unit is then put into an out-waxing and preheating furnace so that the wax of the wax crown is expelled by way of the filling vent. In this way a cavity corresponding to the wax crown is formed in the embedding mass.
[0011] The embedding mass with the cavity located therein and a sintered porcelain blank are then introduced together into a preheating furnace and heated to about 800° C. At this temperature the sintered porcelain blank becomes plastic, whereas the embedding mass itself hardens. After the removal of the embedding mass and the plastic porcelain blank from the furnace, the now plastic porcelain is introduced by way of the filling opening into the cavity by means of a pressing device. This pressing-in itself takes place in a special pressing-in furnace. After the cooling of the porcelain mass, the embedding mass is then destroyed so that the crown with the filling vent located therein becomes free. As a concluding step, finally the separation of the crown from the filling vent, which has arisen in the pouring channel, and a final external machining take place.
[0012] With this method also there is the danger that tears can arise in the crown upon separation of the porcelain crown from the filling vent. The use of an already sintered porcelain blank guarantees that no more shrinkage occurs with the crown if it is subsequently fired again in the baking oven. In contrast with ceramics, porcelain which is already sintered can again be plasticized upon heating to about 800° C., this no longer being possible with ceramics even at extremely high temperatures. However, compared with porcelain, ceramics have considerably greater bending strength. The manufacture of two or more crowns which are connected to each other by way of a connecting bar, is, for example, not possible with porcelain, because this connecting bar would break. Such complicated dental-technical shaped parts can therefore only be manufactured with ceramic material. This is the reason why porcelain is usually only used for inlays, onlays or single crowns.
[0013] The method currently most widespread in dental engineering for the manufacture of ceramic crowns is the so-called slip method. In this respect, an impression is first of all made of the machined tooth stump and then a metal frame, in particular of gold, titanium or the like, is prepared. This metal frame consists of a thin layer fitting the tooth stump and finally produces a cup-shaped part. Ceramic material is then applied to this frame in plastic form (slip) in several layers, with a firing of the metal frame with the applied ceramic slip taking place in each case after the application of a layer. In this way the crown is coated unevenly on the outside and is adapted to the teeth. In this respect, the ceramic slip is applied to the metal frame with a brush, but has the disadvantage that it contains a high content of liquid, in particular water, which leads to a shrinkage of the material during firing. This shrinkage can only be calculated with difficulty, for which reason the ceramic mass must also be applied in several layers.
[0014] A further method for the manufacture of dental ceramic parts, where the shrinkage of the ceramic material is considered, is described in EP 0 389 461 B1. Here it is suggested to first of all prepare by way of an impression a negative copy of the surface of the machined tooth stump and subsequently to machine an isostatically compressed ceramic green compact by means of copy-milling. During the copy-milling, the sinter shrinkage is considered, in that the surface of the machined green compact is enlarged somewhat in order to offset the subsequent shrinkage again. In the process, however, by way of the copy-milling only the underside of the ceramic green compact is machined, the upper side of the shaped part also being covered after the sintering with a porcelain layer and being brought into the final shape. In a similar manner it is also suggested in EP 0 375 647 B1 to machine a ceramic green compact before the sintering by way of milling.
[0015] However, the machining of such a green compact turns out to be quite difficult because the compressed material is very brittle. The two publications named previously give no information as to how these difficulties can be overcome. In a further development, therefore, in EP 0 580 565 A2 it is suggested to compress the powdery ceramic raw material against the surface of a positive copy of the machined tooth stump. In this respect, in turn the positive copy is enlarged compared with the tooth stump in order to compensate for the shrinkage. Here also the surface of the ceramic shaped part is covered with a porcelain layer.
[0016] In order to avoid this shrinkage of the ceramics during sintering, the shrinkage being difficult to calculate, in EP 0 030 850 the use of a shrinkage-free ceramic material is suggested. In this respect, the raw material is pressed or poured in powdery or in liquid form into a prefabricated casting mold, the structure of which corresponds substantially with the shape of the ceramic part to be manufactured, or is in turn pressed against a stamp which is an exact copy of the tooth stump. As with the other methods, here also therefore, first of all a very costly manufacture of an appropriate casting mold is necessary.
SUMMARY OF THE INVENTION
[0017] It is therefore the object of the present invention to provide a simple and economical assembly for the manufacture of shaped parts of ceramics, which can be carried out, for example, by a dentist or dental technician directly in a medical laboratory, practice laboratory or commercial laboratory.
[0018] The object is achieved by an assembly which includes a powdery ceramic raw material compressed into a ceramic green compact, an embedding mass of an easily machinable material that does not damage or chemically react with the material of the ceramic green compact, the ceramic green material being embedded in the embedding mass, and a holder which holds the embedding mass in a manner to allow the ceramic green compact to be machined while being embedded in the embedding mass.
[0019] In the assembly in accordance with the invention, first of all the powdery ceramic raw material is compressed to form a ceramic green compact, this ceramic green compact is then machined by means of eroding methods and is subsequently sintered to form a high-strength ceramic shaped part, with the green compact being embedded before the machining into a workpiece receiver by means of an embedding mass, which neither damages nor reacts chemically with the green compact. The initially powdery ceramic raw material is only put by the compressing into a state where it can be machined at all. The state of the ceramic green compact is then similar to that of chalk, that is to say, in comparison with already sintered ceramic blocks it can be machined substantially more easily, more quickly and with little abrasion of the tools and accordingly much more accurately. By way of the embedding in accordance with the invention, the ceramic green compact is both fixed and supported during the machining, so that no erupting of thin walls or other damage is to be feared and it can therefore be effectively and accurately machined. A further advantage of this consists in that excess raw material, which is removed by milling during machining of the ceramic green compact, can be recovered again and reused, with the material expenditure being clearly reduced as a result. As the machining tools are also stressed less and therefore achieve a longer service life, the method in accordance with the invention is to be regarded as substantially more economical compared with the known methods, where ceramic blocks which are already sintered are machined. According to the invention, in medicine, dental medicine and dental engineering, bio-compatible implant parts, inlays, partial crowns, crowns, bridges, prosthesis bases or auxiliary parts can be economically manufactured accurately and with high mechanical strength adapted to the purpose of use. In particular, with this invention there is the possibility of bringing a ceramic green compact, the original shape of which has nothing in common with the final structure of the ceramic shaped part to be manufactured, exclusively by way of machining by means of eroding methods, into the desired final shape, without compressing the material as in the known methods—into a casting mold or against a stamp.
[0020] Further developments of the invention are described in detail hereinafter. An essential aspect of this invention lies in the selection of the ceramic raw material. This should shrink as little as possible during the sintering, and in the ideal case should be almost shrinkage-free. A ceramic material which fulfils these conditions is, for example, zirconium (ZrSiO 4 ), the properties of which will be described in more detail. However, it would also be conceivable to use the already known and frequently used ceramics zirconium oxide (ZrO 2 ) or aluminum oxide (Al 2 O 3 ). These shrink to a certain degree during the sintering. However, the ceramic green compact usually compressed to form a cube or to be box-shaped, has an extremely even material density, so that it is to be expected that the material shrinks evenly and therefore foreseeably during the sintering. In contrast with the known methods, where, for example, the powder is pressed into a casting mold or is poured in under pressure, and where, therefore, an uneven density distribution of the raw material is often not to be avoided, with the method in accordance with the invention the shrinkage process can be taken into account very easily and can be compensated for by manufacturing larger shaped parts before the sintering.
[0021] Also described herein are advantageous embodiments for facilitating the machining of the ceramic green compact. The ceramic green compact is preferably machined with the aid of an eroding machine—for example a milling, turning, drilling or grinding machine, with the machining being able to take place automatically. The corresponding control commands for the eroding machine can then be contained in a special erosion program which is prepared, for example, on the basis of a three-dimensionally measured positive model of the tooth stump and the tooth crown. In this respect, when preparing the erosion program, parameters such as, for example, a desired cement gap width or a possible shrinkage factor of the raw ceramic material can be considered. A suitable milling wax, for example, can be used as embedding mass. The machining of the green compact can take place in several steps in which, in each case, certain areas of the green compact are machined, with the areas of the green compact, which have already been machined previously, being surrounded again with the embedding mass and thereby being stabilized. In this way the very thin side walls of ceramic crowns can therefore be protected during the machining. By melting the milling wax, after the machining the ceramic green compact can then be carefully extracted again. This milling wax and the embedding mass can also be collected during the machining of the green compact and reused.
[0022] The properties of three preferably used ceramic materials are now to be discussed.
[0023] The very frequently used aluminum oxide (Al 2 O 3 ) is also known by the name corundum. In addition to many and diverse possibilities of using this material in industry (for example as abrasives, grinding materials, fire-proof materials), aluminum oxide is a very frequently used oxide in most varied clay minerals and ceramics which are used in the case of ceramic tooth replacement, but also in flower vases or coffee-cups. Aluminum oxide is in particular a material suitable for tooth replacement because it has a tooth-colored appearance, high resistance to abrasion, chemical resistance, biological compatibility and a pleasant contact feeling with pickled or polished ceramic surfaces. A further advantage is also to be seen in that aluminum oxide is X-ray translucent and tooth crowns consisting of it do not cause any artefacts during X-ray examinations, which could lead to misinterpretations of the X-ray image.
[0024] Zirconium oxide (ZrO 2 ) can occur in several different crystal modifications. As zirconium oxides have, among the known ceramic materials, the highest bending strength and tensile strength values, high resistance to wear and resistance to corrosion and low thermal conductivity, in recent years they have become increasingly significant in the technical and medical field. As a result of their excellent properties, zirconium oxide ceramics are preferably used for components which can be greatly mechanically loaded. Moreover, zirconium oxide displays only relatively little contraction during the sintering.
[0025] On the basis of zirconium oxide (ZrO 2 ), with the aid of a reaction sintering method, ZrSiO 4 ceramics, which are almost shrinkage-free, can be manufactured. This is achieved in that a reactive component contained in the raw ceramic green compact enlarges its volume during the sintering and therefore compensates for the shrinkage of the remaining components. A method of this kind which is suitable for zirconium oxides is described, for example, in the article “Verfahren zur Herstellung schrumpffreier ZrSiO 4 -Keramiken” (“Method for the manufacture of shrinkage-free ZrSiO 4 -ceramics”) of the Keramische Zeitschrift (Ceramics Journal) 50 (4) 1998. In this case an intermetallic compound (zirconium disilicide, ZrSi 2 ) is used as reactive component. In addition, polysiloxane, a so-called low-loss binder, is used as pressing aid, which reacts during the sintering with the zirconium disilicide and the zirconium oxide to form the desired ceramics (ZrSiO 4 ). The essential advantage of this reaction sintering method consists in that the sinter shrinkage to be expected, which is a function of the portion of the various reaction components, can be estimated with the aid of a simple calculation. The required content of the reactive component, that is to say of the zirconium disilicide (ZrSi 2 ), can then be calculated, where a shrinkage of almost 0% occurs.
[0026] As a result of the properties just described, with these ZrSiO 4 -ceramics micro-structured components can be manufactured, the dimensions of which are identical before and after the sintering. A mechanical finishing, which is often not at all possible with very small detail structures without damaging the workpiece, is then no longer necessary. For the same reasons, these ceramics are therefore also excellently suitable for the manufacture of dental-medical or dental-technical parts, in particular of tooth crowns with thin walls.
[0027] As a result of their properties, the three ceramic materials just named are particularly well suited for use in the dental-medical field. Nevertheless, the method in accordance with the invention is not restricted to these materials, but can also be used with other ceramic materials, for example with magnesium oxide (MgO), aluminum titanate (ATi) or piezo-ceramics (PZT), not only in medical, but also in technical fields. In this respect, the use of a shrinkage-free ceramic material is indeed particularly advantageous, but in no way absolutely necessary because—as already noted—by way of the even compression of the material to form a green compact, a homogeneous density distribution, and accordingly an even and therefore controllable shrinking of the shaped part during the sintering, is achieved.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] The invention will be explained in more detail in the following with reference to the enclosed drawings which show the individual steps of a method in accordance with the invention for the manufacture of a tooth crown.
[0029] [0029]FIG. 1 shows a green compact inserted into a workpiece receiver.
[0030] [0030]FIG. 2 shows the manufacture of the inside of the crown.
[0031] [0031]FIG. 3 shows the manufacture of the first area of the outside of the crown.
[0032] [0032]FIG. 4 shows the re-embedding of the side already machined.
[0033] [0033]FIG. 5 shows the workpiece receiver rotated by 180°.
[0034] [0034]FIG. 6 shows the manufacture of the second area of the outside of the crown.
[0035] [0035]FIG. 7 shows the extraction of the green compact.
[0036] An advantage of the method described in the following consists in that in principle it is very similar to the hitherto known methods for the manufacture of tooth crowns and can therefore be carried out very easily by a dental technician.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
[0037] In this respect, first of all, for example on the basis of an impression, the dental technician makes a positive model of the machined tooth stump from gypsum or another suitable modeling material as the foundation of his prosthetic work. This positive model is then measured three-dimensionally in a measuring device mechanically, optically or according to another method. By way of special software, a milling or erosion program for machining the inside of the crown, the structure of which corresponds to the shape of the tooth stump, is then generated and loaded into the control of an automatic milling machine. In the process, the dental technician can enter additional parameters, for example a necessary cement gap width, which are considered by the software during the preparation of the milling program. Moreover, for ceramics which contract during sintering, corresponding correction factors can be considered, in order to compensate for the contraction by preparing slightly enlarged shaped parts.
[0038] As shown in FIG. 1, the dental technician then inserts an isostatically compressed ceramic green compact 4 , for example of a shrinkage-free ceramic material, of aluminum oxide (Al 2 O 3 ), zirconium oxide (ZrO 2 ) or another high-performance ceramic, into a workpiece receiver 1 provided with an axis of rotation 2 . In this respect, the securing of the green compact 4 in the workpiece receiver 1 takes place by way of its embedding with a preferably pourable embedding material 3 , which fixes the green compact 4 mechanically, but, in the process, does not damage the ceramic compressed composite or change the ceramic raw material by way of any chemical reactions. For example a special milling wax can be used as a reasonably-priced, easily millable embedding material 3 which is suitable as supporting body.
[0039] In the next step, which is shown in FIG. 2, the workpiece receiver 1 is inserted into the holding device of a milling machine and the milling procedure is started, whereby in the present case first of all the milling-out of the inside of the crown of the workpiece 6 takes place. The control of the miller 5 preferably takes place fully automatically with the aid of the milling and erosion program. However, with the use of shrinkage-free ceramics it would also be conceivable to carry out the milling manually, for example by way of a direct copying of the positive model of the stump. However, in this case the positive model would then have to be coated with a spacing lacquer or provided with a foil cap in order to take into account the necessary cement gap width.
[0040] If the milling procedure takes place fully automatically, the dental technician can in the mean time, as usual, model the crown or another dental-technical work in wax. This work, the modeling of which is complete—disposed on the work foundation (the tooth stump or the positive model)—is again measured three-dimensionally in the measuring device in order to ascertain the required structure of the finished tooth crown.
[0041] As previously, with the aid of the software a milling program for the machining of the outside of the crown is then generated and loaded into the control of the milling machine. In the example shown, the milling program is then divided into two steps, in which in each case the areas going as far as the equator of the crown (from the crown edge to the equator or from the occlusal surface as far as the equator) are machined. The first step of this milling program, in which the outside of the crown is machined from the lower crown part as far as the equator, is shown in FIG. 3. The side of the crown 6 which is not yet machined at this instant is, in this respect, as before, supported by the embedding mass 3 and the green compact 4 is therefore prevented from falling out of the workpiece receiver 1 . After the machining of the underside of the workpiece 6 is completed, the embedding mass 3 is subsequently once again poured into it (FIG. 4). It would also be possible to fill up the previously milled-out inside of the crown with the milling wax 3 again already before the machining of this first area of the outside of the crown, in order to support the side walls of the crown. Subsequently, by rotating the workpiece receiver 1 by 180°, the upper side of the crown which is still to be machined is repositioned into a position suitable for the milling (FIG. 5).
[0042] According to the representation in FIG. 6, in the second step of the milling program the outer upper part of the crown is then milled from the occlusal surface as far as the equator. The underside of the workpiece, which is unstable and slightly fragile in this state, is also held securely during this machining step by way of further embedding into the milling wax 3 and is supported at the critical points (the partially very thin side walls of the workpiece 6 ), so that no material eruptions of or damage to the workpiece 6 are to be feared. Moreover, by way of the embedding mass 3 being poured once again into the primary side of the green compact, the workpiece 6 is prevented from falling out.
[0043] During the entire work, the milled-off green compact and embedding material can be drawn off by suction. In an appropriately constructed dust extraction system the loose and powdery green compact material can then be separated from the milling wax 3 and recovered again. The dental technician can then, in turn, press new green compacts from this recovered material in a suitable device, so that an optimum yield of ceramic shaped parts can be achieved from the ceramic base material.
[0044] After the end of the milling procedure, the green compact workpiece 6 is extracted. With the use of milling wax, this working step takes place, for example, by means of a hot-air drier, in a heating furnace or a special waxing-out device shown in FIG. 7. In this respect, the workpiece receiver 1 with the green compact workpiece 6 , which is still supported in a remaining portion of the embedding mass 3 , is placed on to a fluid mat 7 which forms the upper side of a collecting dish 8 . During the supply of heat, the milling wax then melts and drips through the fluid mat 7 into the collecting dish 8 , so that finally the green compact workpiece 6 lies fully extracted on the fluid mat 7 . The molten milling wax collected in the collecting dish can then be reused in exactly the same way as the powdery ceramic raw material already recovered previously.
[0045] In the laboratory, the sintering of the milled-out workpiece 6 to form the high-strength prosthetic part then finally takes place in a suitable ceramic furnace.
[0046] The method just described represents a particularly advantageous use of the invention. In this respect, the individual steps are designed in such a way that the green compact is machined as carefully as possible in order to avoid the occurrence of material eruptions or tears. However, modifications are also conceivable. For example, the sequence of the machining of the inside of the crown and the outside of the crown could also be reversed. Moreover, it would be conceivable to prepare only the inner or outer contours of the workpieces and then also to machine them in another way. However, the shape of the green compact, the machining of which is complete, preferably already corresponds to the desired end shape of the ceramic shaped part (in particular with shrinkage-free ceramics) or, with ceramics which shrink to a certain degree, this shrinkage factor is considered in such a way that during the sintering the green compact shrinks in such a way that the finished shaped part has the desired end shape, so that a costly finishing, which is unprofitable from the commercial point of view, is omitted. However, if it is desired for aesthetic reasons or if it is necessary, only the partial contours of the final shape can be prepared, with the final contours then being prepared by way of veneering by means of porcelain or another suitable material. Finally, according to the shape of the ceramic shaped part to be manufactured, in place of the milling machine, or in addition to it, other eroding machines, for example turning, drilling or grinding machines, can also be used.
[0047] The essential advantage of the invention lies in that by way of the machining of a workpiece from a green compact which can be machined easily and reliably, the hitherto known great machining problems—the high level of tool wear, accuracy and demands on the milling machine and therefore also the manufacturing costs—are considerably reduced. This is in particular of advantage if medical-technical or dental-medical prosthetic workpieces are to be manufactured, where they are unique and therefore cannot be manufactured in large piece numbers. Nevertheless, the invention also offers great advantages in the manufacture of technical parts, because very small parts can also be manufactured with an accuracy which has hitherto not been achieved.
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For the manufacture of shaped parts ( 6 ) from ceramics, for example for dental-technical purposes, an assembly is provided which comprises a powdery ceramic raw material compressed to form a ceramic green compact ( 4 ), an embedding mass ( 3 ) which neither damages nor reacts chemically with the ceramic green compact ( 4 ), and a holder or workpiece receiver ( 1 ) which holds the embedding mass ( 3 ) in a manner to allow the ceramic green compact ( 4 ) to be machined while being embedded in the embedding mass.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application is a C.I.P. of U.S. application Ser. No. 12/283,698, filed Sep. 14, 2008 (scheduled to issue Sep. 25, 2012 as U.S. Pat. No. 8,274,735) and therevia claims benefit of U.S. Provisional Application Ser. Nos. 60/993,795 and 61/134,136 filed on Sep. 14, 2007 and Jul. 7, 2008, respectively. Said application Ser. No. 12/283,698 and said U.S. Provisional Applications No. 60/993,795 and 61/134,136 are hereby incorporated by reference.
FIELD OF THE INVENTION
This invention relates to 1.) improved optical viewing of ultraviolet (hereafter “UV”) laser ablation processes involving solid materials, and to 2.) high sensitivity analysis of solid materials by analytical UV laser ablation, and to 3.) large spot bulk analysis of solid materials by analytical UV laser ablation, and to 4.) automated (mechanized) sample changing for analytical laser ablation, and to 5.) laser micro-machining, and to 6.) large depth-of-focus laser ablation for ablating rough, uneven or non-level surfaces, and to 7.) wide-range, variable demagnification ratio laser ablation, and to 8.) rad-hardened analytical UV laser ablation for analysis of high activity solid nuclear waste (e.g. vitrified as radioactive glass) in a radiation “hot cell”,
in which a focused UV laser beam removes (by optical ablation at focused laser energy densities (more precisely, irradiance) exceeding the surface damage threshold of said solid material) a portion from the surface of said solid materials, for purposes of altering the shape or topography of said solid materials, or for purposes of obtaining vapors, or smoke, or a particulate aerosol from a laser ablation event occurring on the surface of said solid material, or obtaining a mixture of vapors, smoke, and/or particulate aerosol from a laser ablation event occurring on the surface of said solid material, which vapors, smoke, or particulate aerosol, or which mixture of vapors, smoke, and/or particulate
aerosol may then be directed to an external analytical instrument (e.g. inductively coupled plasma (ICP) emission, ICP mass spectrometer (ICP-MS), or flowing after-glow (FAG) mass spectrometer (FAG-MS), said external analytical instrument being capable of providing chemical and/or elemental analysis of said vapors, or smoke, or particulate aerosol, or said mixture of vapors, smoke, and/or particulate aerosol, said chemical and/or elemental analysis being indicative and representative of the chemical or elemental content and/or composition of the original said solid sample materials.
The invention therefore relates to UV laser ablation micro-machining (e.g. in an industrial setting), and/or to analytical UV laser ablation in a general solid sample analysis laboratory or a radiation “hot cell” environment,
and more specifically, the invention relates to 1.) improved optical viewing (by an observer or camera) of the solid material surface to be ablated, and/or during ablation, and/or post-ablation in UV laser ablation, via a reduction of chromatic aberration to allow an observer (or camera) to view (more clearly) the area to be ablated, to view (more clearly) the process of ablation, and/or view (more clearly) the result of ablation, in such a way as to allow an observer to better identify and/or pre-select the area to be ablated, to more clearly view and video-record the ablation event in order to assess ablation process characteristics, and/or to more clearly view the result of ablation on the solid material surface to assess ablation effectiveness and ablation crater or trench morphology and compare that with previous or future ablation experiments in same or other materials under same or varied ablation conditions, said observation being typically optically magnified and then viewed by direct human visual inspection through a magnified optical eyepiece, or a video-camera, or CCD array camera which may be used to capture and/or record images for immediate (real-time) display on a monitor screen, and/or for storage in a computer file,
and further, the invention specifically relates to 2.) high sensitivity analytical UV laser ablation, 3.) large spot bulk analysis in analytical UV laser ablation, and 4.) laser micro-machining, respectively in which substantially larger (than normal) invention UV lasers may be employed in an invention stable multimode resonator (SMR) lasing condition coupled with an invention external optical configuration for larger SMR lasers which results in an inherently homogenized near field invention laser beam profile being efficiently transferred without homogeneity loss to a far field sample surface, which results in external substantially larger invention material ablation rates in these three areas (enumerated above) without increasing the average particle size of smoke or aerosol resulting from the ablation, and creating a more homogeneous focused high powered laser spot capable of ablating more flat bottomed craters and trenches, without deteriorating the “quality” of ablation craters and/or trenches produced (in terms of crater (and/or trench) edge cut (sharp, clean edges without cracking, chipping, or shattering) and/or bottom shape (e.g. bottom flatness)),
and further, the invention specifically relates to 5.) exceptionally large depth-of-focus laser ablation in focusing a laser-light image of a laser illuminated aperture (hereafter laser spot) onto the surface of a target solid sample or target material for ablating rough, non-flat, non-parallel, non-level, or otherwise uneven target surfaces to facilitate tolerance of surface variations (from flat and level) as large as 1-2 mm for either stationary laser spot ablation or line scan ablation and/or raster pattern ablation without refocusing, re-leveling, or resurfacing (e.g. grinding flat) the target sample or material.
and further, the invention specifically relates to 6.) wide-range variable demagnification invention laser ablation, in which large changes in invention optical demagnification of the laser spot may be made on an operational basis in a single invention laser ablation system to optimize ablation rates, aerosol quality, and or crater and/or trench size and quality within the ideal irradiance range (IIR) of each material and for a wide variety of different solid materials,
and further, the invention specifically relates to 7.) automatic (mechanized) solid sample changing for analytical laser ablation,
and finally, the invention specifically relates to 8.) rad-hardened invention analytical laser ablation of solid sample materials in a radiation “hot cell” containing radioactive sample material such as nuclear waste, in which optical components (of the invention laser ablation system) that may otherwise be prone to radiation damage are eliminated from the invention design, or are located outside the hot cell (but in adjacent proximity to the hot cell), or are shielded within the hot cell, or are located within the hot cell at greater distance from radioactive material (and hence receive reduced radiation levels by the “inverse square” law).
BACKGROUND OF THE INVENTION
A description of laser ablation in the publication of Arrowsmith and Hughes, APPLIED SPECTROSCOPY, 42, 7, 1988 (1231-1239) is commonly cited as the beginning of modern analytical laser ablation for inductively coupled plasma (ICP) emission and inductively coupled plasma mass spectrometry (ICP-MS) analysis of solid samples. More recently, the July 2008 issue of Gases & Instruments features an article by Hughes, Brady, and Fry which reviews the use of UV lasers and analytical laser ablation in general, with illustration of how white light illumination and viewing is normally done for UV laser ablation and discussion of parameters affecting ablation quality, ablation morphology, ablation rate, and related aerosol particle size from an ablation event. From the G&I article it should be noted that an opto-mechanical (OM) ablation is desired for analytical laser ablation, rather than a thermal process. It should also be noted from the G&I article that a small particle size is desired in the aerosol resulting from an ablation event, to ensure efficient aerosol mass transport (to the external analytical instrument) and to minimize overall system calibration difficulty and variability.
FIGS. 1A , 1 B illustrate that a dichroic mirror ( 6 ) is normally used in prior art analytical UV laser ablation, to allow a view camera ( 22 ) to view a solid material ( 11 , 24 ) coaxially ( 18 , 19 , 20 ) with a final segment of the UV laser beam ( 7 , 10 , 24 ) which is also focused to ablate the surface of the solid material ( 11 , 24 ). The prior art dichroic mirror ( 6 ) has a very thin film mirror coating which is highly reflective only to light of a specific UV laser wavelength, which is the specific “design” wavelength of the particular (dichroic) laser mirror in question, and which is based on selective constructive interference (in the reflection mode) of light at that design wavelength, exclusively. All other wavelengths (shorter and longer than the specific UV design wavelength) are not reflected. Instead, the thin mirror coating is transparent to the other wavelengths (e.g. visible light) and passes them like a window (even if angled). FIGS. 1A , 1 B thereby illustrate that the prior art UV laser beam ( 5 , 7 ) may be efficiently reflected from the angled side of an appropriately designed UV dichroic mirror ( 6 ) towards a solid sample surface ( 11 , 24 ), while an overhead visible “white light” camera ( 20 , 22 ) view may be taken through the same prior art angled UV dichroic laser mirror ( 6 ) from the top, since the UV dichroic laser mirror ( 6 ) is transparent to visible (e.g. “white”) light.
The prior art objective lens ( 8 ) performs two functions. First it focuses the UV laser beam ( 7 , 10 ) downward onto the solid sample material surface ( 24 ); second, it simultaneously operates (in reverse) to coaxially focus a visible, white light image of the solid sample surface ( 24 ) upward ( 18 , 19 , 20 ) to the camera ( 22 ) focal plane. (It should be noted that an auxiliary visible, white light source, e.g. ring illuminator ( 16 ) is typically also provided to coaxially illuminate ( 17 ) a relatively wide area (e.g. 1-10 mm) of the solid sample surface ( 11 , 24 ) continuously (to light the “subject” for the camera view), while the pulsed, Q-switched UV laser fires (flashes) intermittently ( 10 ), but repetitively to ablate a smaller spot ( 24 , e.g. 0.02-0.2 mm) on the solid sample surface.)
The disadvantage of the prior art coaxial camera view of laser ablation in FIGS. 1A , 1 B is that both the laser beam ( 7 , 10 ) and the camera view ( 18 , 19 , 20 , 22 ) must pass through the same short focal length prior art objective lens ( 8 ), albeit in opposite directions, so the two prior art optical paths are (undesirably) coupled. The prior art objective lens ( 8 ) must be designed to efficiently pass ( 7 , 10 ) UV laser radiation (e.g. 193 nm, 213 nm, and 266 nm) with high transparency at UV wavelengths. The available optical materials (for doing that) do not simultaneously allow an ideally achromatic focused visible (e.g. 400 nm-700 nm) “white light” view for the prior art camera path ( 18 , 19 , 20 , 22 ). The prior art UV laser objective lens ( 8 ) can produce a good quality monochromatic UV laser image ( 24 ), but then it is not achromatic for longer wavelength visible light and therefore cannot focus both ends of the white light spectrum (red and blue) simultaneously in the same prior art camera plane ( 22 ). Undesirable chromatic aberration thus arises for the prior art “white light” on-axis view, in order to ensure a good UV laser ablation experiment. A poorly focused prior art “white light” (camera) image ( 22 ) therefore adversely affects many analytical UV laser ablation systems today, and there remains a need to decouple the visible white light camera view ( 22 ) from the chromatic aberration of a UV laser objective lens ( 8 ).
A second disadvantage of prior art UV analytical laser ablation is that low ablation rates and poor sensitivity for bulk solid analysis typically result under conditions where a high quality opto-mechanical (hereafter OM) ablation occurs with prior art UV analytical laser ablation systems. The basic problem arises from a situation where UV analytical laser ablation (for ICP and ICP-MS) is a relatively new field, with complete (integrated) prior art analytical systems becoming commercially available for the first time in 1995. With UV analytical laser ablation still in its “infancy” (a relatively small number of installations as of this writing), prior art commercial analytical laser ablation manufacturers are both small in size and few in number. Thus far (1995-present), the small group of prior art analytical laser ablation manufacturers have primarily been designing prior art products tailored to the needs of a narrowly focused group of customers working in Geology.
Geologists have certainly done the infant analytical laser ablation field a significant service by purchasing prior art commercial units early in its manufacturing development cycle, thereby making the infant field of analytical laser ablation commercially viable (albeit on a relatively small commercial scale). Through effective lobbying, they (geologists) have influenced the small group of prior art analytical laser ablation manufacturers and successfully imposed their own particular (geologic) biases onto the features and characteristics of commercially available prior art system configurations. The few existing prior art analytical laser ablation manufacturers have therefore catered primarily to the (prior art) geologic “configuration bias” (hereafter, “geo-bias”), rather than designing flexible, general purpose analytical laser ablation systems of the type that would be needed for widespread usage for bulk analysis of solid materials in general, for a wider variety of laboratories.
The prior art geo-bias typically dictates a small, homogeneous focused spot diameter, since geologists are typically interested in elemental analysis of small inclusions and other small heterogeneities in rocks and minerals. Consequently, focused laser spot diameters as small as 2 micron are desired in the geo-bias, and prior art excimer and SMR analytical UV laser ablation systems are not sold with a homogeneous focused spot diameter larger than 200 microns. Prior art SMR analytical UV laser ablation objective lenses ( 8 , FIG. 1A-1B ) to produce such small homogeneous spot diameters typically exhibit short focal length (e.g. F=18-38 mm) and their working distance (to the sample surface) is only slightly more than that. This prior art geo-bias for short focal length objective lenses and small spot diameters is ideal for geologists interested in analyzing small isolated features in heterogeneous rocks and minerals, but it is not ideal for high sensitivity bulk solids analysis or more homogeneous sample materials in other fields.
The short focal length objective lens and small spot diameters characteristic of the geo-bias in prior art SMR analytical laser ablation, actually preclude using high laser power to enhance sensitivity. In fact, there is a certain maximum laser power that can be optimally employed for prior art focused laser spots of 200 microns diameter and less, which is the largest homogeneous focused spot available in commercial prior art excimer and SMR analytical laser ablation systems. In prior art analytical laser ablation manufacturing, the geo-bias therefore leads to use of relatively small excimer and SMR UV lasers (less than 12 mJ at 266 nm) and short laser path lengths. This keeps the system size and price down, but it also limits the sensitivity which can be obtained in bulk solids analysis with a prior art system.
At ETH-Zurich, Guenther, Horn, and Guillong employed larger prior art Gaussian beam (TEM 00) lasers with external prior art beam homogenizing optics, and a large excimer laser was substituted in a commercial prior art system (Geo-Lase by Coherent, distributed for several years by CETAC), but in both cases, the external beam homogenizers were inefficient (subject to significant light transmission loss), the firing frequency reduced to 10 Hz maximum for the TEM 00 Nd-YAG laser, and the objective lenses were characterized by the short geo-bias focal length (F<40 mm) and relatively small maximum focused spot diameter in both cases, so the actual final output (relating to ablation rate) of these prior art systems was only slightly more than the smaller, more efficient, prior art frequency-multiplied SMR Nd-YAG analytical UV laser ablation systems, and sensitivity for bulk analysis wasn't appreciably enhanced with either of these two larger prior art lasers and their associated ablation systems.
One larger (40 mJ) prior art commercial Nd-YAG laser ablation system operating at 266 nm, 10 Hz was coupled to a maximum focused spot size of 780 μm (0.78 mm), but this prior art laser ablation system (MACRO by New Wave, Inc.) wasn't designed for operation in the SMR mode to produce a homogenized beam profile. It was instead an unstable multimode resonator (UMR) with a gradient reflectance mirror (GRM), by design. The prior art GRM unstable resonator is actually designed for small spot focusing (low divergence rate, compared to SMR) and it is well known that the GRM unstable multimode resonator (UMR) does not produce the desirable homogenized beam profile for large spots, and is instead characterized by a “donut with hole” or “scooped” beam profile. Initial laser ablation testing with this prior art GRM unstable resonator (UMR) analytical laser ablation system determined that it was not a reliable configuration at high power (40 mJ, 266 nm). This prior art unstable resonator (UMR) deteriorated rapidly in terms of power output and ablation crater quality. In summary, the GRM unstable multimode resonator (UMR) beam profile is not homogeneous like an SMR, and the limited prior art firing frequency of 10 Hz further reduces the sensitivity of a MACRO system relative to 20 Hz SMR system. Finally, the energy output of this unstable resonator has been reported to be erratic and frequently dropping to 20 mJ instead of the 40 mJ UMR rating.
There remains a need for high sensitivity analytical UV laser ablation based on a stable, reliable, high powered (e.g >12 mJ @ 266 nm, with similar higher powered 213 nm and 193 nm systems) homogenous beam SMR (stable multimode resonator) laser with a firing frequency higher than 10 Hz and a laser objective lens with focal length greater than F=40 mm with reduced demagnification to produce larger homogeneous focused spot diameters (>200 um) commensurate with higher laser power to achieve high analytical sensitivity within the ideal irradiance range (IIR) of solid sample materials.
The referenced G&I article indicated that each different solid sample material has a relatively narrow range of focused laser irradiance (joules/cm 2 /ns) which is ideal for producing the best OM ablation characteristics. Operating within the ideal irradiance range (IIR) for a given material minimizes thermal ablation effects (which otherwise make calibration more difficult and unreliable) and yields the smallest aerosol particle size. If the focused laser ablation irradiance is lower than the IIR for a given material, then thermal ablation predominates, ablation rates are low, calibration is difficult and unreliable, and analytical sensitivity is poor. If the focused laser irradiance is higher that the IIR of a material, then that sample is “over powered” and undesirable sample shattering and cracking occurs, destabilizing the analytical instrument response without significantly improving the sensitivity. In this case, ablation is too violent (rough) and too many large particles are blown out of the ablation crater, the large particles being too large for efficient transport to the external instrument. They wind up splattered throughout the ablation cell, settling out on various cell and tubing wall surfaces without transporting to the plasma or contributing appreciably to the analysis. In such an overpowered situation, the signal in the external instrument becomes temporally unstable. The ideal irradiance range (IRR) should therefore be maintained for each material and should not be exceeded.
For small focused spot diameters (<200 urn) characteristic of the geo-bias, the IIR is matched with relatively small, low powered SMR UV lasers and relatively short prior art laser paths and short focal length prior art objective lenses. For example, for a 266 nm (4 th harmonic) pulsed, Q-switched, Nd-YAG laser, SMR systems in the range of 9-12 mJ are about the limit of useful laser size, in prior art commercial systems where the geo-bias prevails to limit the maximum focused prior art spot diameter to 200 microns or less. Larger lasers of 30 mJ, 40 mJ, 50 mJ, 60 mJ, 90 mJ, and 230 mJ are available at 266 nm and the desired SMR mode, but these have typically not been used for prior art analytical laser ablation, simply because the geo-bias prevailing in that industry precludes their usage in prior art short path applications with a focused spot size range 2-200 microns, where they would simply over-power the ideal irradiance range (IIR) of virtually all solid samples.
The overall result of favoring smaller lasers, shorter path lengths, and limited spot diameter (geo-bias in the prior art analytical laser ablation industry) is that prior art system sizes and prices are “contained”, but analytical sensitivities in this prior art configuration are limited to the part-per-million (ppm) range for ICP and ICP-MS analysis of solids. There is no reported prior art high sensitivity (part-per-billion, ppb) analytical UV laser ablation system based on a stable multi-mode resonator (SRM) and which produces homogeneous focused spot diameters up to 1.5 mm (in a preferred embodiment) and allows use of pulsed SMR 266 nm lasers as large as 50 mJ-230 mJ in a long path length configuration, or other equivalently oversized UV lasers at even shorter wavelength, while still operating within the optimized IIR of solid materials.
An invention is therefore needed for analytical UV laser ablation in which the ppm (part-per-million) sensitivity limitations of the prior art short laser path, short objective focal length, high demagnification ratio and small spot geo-bias would be removed via replacement with a more sensitive analytical laser ablation invention employing longer laser path lengths and longer focal length objective lenses in a ratio favoring lower demagnification ratios and larger spot diameters from larger SMR lasers operating at full power, coupling most of their energy into the sample without exceeding IIR values of solid materials to be analyzed. This would enhance the sensitivity of bulk analysis by analytical laser ablation and lead to a new era of high sensitivity (ppb (part-per-billion)) bulk analysis in the solid phase. It would be further desirable if this were achieved simultaneously with the aforementioned invention decoupling of laser focusing from white light focusing.
Since the ideal irradiance range (IIR) varies widely in solid materials, but is a relatively narrow range for each material, it is apparent that conventional systems with fixed demagnification ratio have a limited ability to maintain the IIR of each material in a wide range of solid materials, while simultaneously running the system at 100% laser power and using the full laser beam to maximize ablation rates. If a larger laser were selected, optical attenuation or power attenuation could be employed to “throttle it back” and keep all samples within their respective IIR's, but if the demagnification ratio is fixed as with prior art systems, ablation rates will not be kept at the maximum possible ablation rate for that laser over a wide range of solid sample materials.
There remains a need for an invention which would allow wide range, operationally variable demagnification ratio (operationally variable maximum spot diameter), so that the laser may be operated at 100% power output while the ablation proceeds within the IIR of each solid material by simply having the spot diameter adjusted so that 100% of the laser power is delivered within the IIR of that material. This could theoretically be done to a limited extent with a turret holding 2 to 4 different interchangeable objective lenses to yield several different demagnification ratios, but the number and range of focal lengths which may be accommodated in a single turret (for a fixed turret-to-laser head “object” distance and a limited range of turret-to-sample image distance variation) is limited to about 3 or 4 lenses whose focal lengths are not widely varying (one from the other). The IIR of solid materials varies more widely than an objective lens turret could cover by itself. In order to accommodate a wider range of IIR, an invention with an operationally variable laser “object” distance (over wide range) and an operationally variable laser “image” distance (over wide range) is also needed (or needed instead). Essentially, there remains a need for a laser ablation system with operationally variable path (over a large range of path length) to create a larger range of demagnification ratios for each objective lens. Such an invention would benefit both analytical laser ablation and laser micro-machining applications.
A third disadvantage of prior art analytical laser ablation is that the currently prevailing geo-bias involving relatively short prior art laser path lengths and short prior art laser objective focal lengths yields a shallow depth-of-focus (in the focused prior art laser spot) of only about 0.25 mm or less. If the sample surface roughness, topography, flatness, or deviation from parallel (to ablation cell horizontal translation axis when mounted in cell) varies by more than this, different locations on the sample surface must be refocused upon changing location in a prior art system. For a laser ablation line scan or raster pattern involving controlled (motorized, FIG. 1B , items 47 - 52 ) horizontal sample motion (during ablation), it is obvious that the sample flatness (and degree to which the sample surface is held parallel to the axis of motion) must be less than the depth-of-focus of the laser spot doing the ablation, otherwise the spot will lose focus and the ablation rate will change during the horizontal motion scan or raster on the sample surface. This typically means that the sample must be flat and parallel to the motion axis, within 0.25 mm (250 μm) or less in a prior art system, and it often requires that solid samples with surface roughness or uneven topography (greater than this) must be cut or ground flat, prior to ablation.
As one of the principal advantages of laser ablation (compared to acid dissolution of solid samples prior to ICP or ICP-MS analysis with nebulizer introduction of the resulting liquid) is supposed to be “elimination of sample preparation”, the oft-required cutting, grinding, or pelletizing of irregular surfaced solid samples for conventional prior art laser ablation is clearly counter-productive. There remains a need for an analytical laser ablation invention with increased depth-of-focus (in the focused laser spot) from the current prior art range of 0.25 mm (or less) to a much larger invention depth-of-focus such as 1 mm or even 2 mm, to accommodate greater surface roughness and larger variation in surface topography for laser ablation analysis without prior sample preparation or resurfacing by cutting, grinding, or pelletizing.
A fourth disadvantage to prior art laser ablation is the lack of an automated sample changer, which (lack) prevents automated sequential analysis of a large group of samples, or even a small group of samples if they are too large for more than one of them to fit into the ablation cell at any one time. Many reasons preclude the use of an auto-sampler in prior art analytical laser ablation. For one example, the short focal length prior art objective lenses (geo-bias) typically do not allow room for the sample cell to be automatically opened while positioned under the objective lens. There remains a need for development of an automatic (mechanized) sample changer for analytical laser ablation.
A fifth disadvantage of prior art analytical laser ablation is that, in the field of high activity nuclear waste analysis, prior art analytical UV laser ablation has heretofore not been well suited to a radiation “hot cell” environment, due to rapid prior art laser ablation component failure upon exposure to high level radioactivity. Typical key conventional prior art laser ablation component failures occur within 500-1,000 rads total accumulated exposure. With high activity nuclear waste samples in a hot cell, exposure rates of 1,000-2,000 rads/hour are to be expected. This means key conventional prior art laser ablation components would fail within 1 hour or less, and sometimes within 15 minutes. This is true of prior art small motors, optical coatings, electronic circuits—especially integrated circuits, laser heads, power supplies, sensors, and video cameras. Additional prior art components subject to failure on a somewhat longer time scale (still problematic) include cables, connectors, insulation on wires, o-rings, lubricants, adhesives, and a variety of plastic or polymer parts, as well as conventional optics. Laser mirrors (thin film dichroic) are particularly susceptible to radiation damage. Conventional prior art analytical UV laser ablation systems can't even withstand 1 day in the hot cell with high activity nuclear waste samples which nevertheless require analysis.
In a March 2007 government report (07-DESIGN-042, U.S. DOE Office of River Protection, contract DE-ACO5-76RL01830), the US DOE has designated laser ablation as a critical technology element (CTE) necessary for the $12.3B nuclear waste processing (vitrification) plant now under construction at the DOE Hanford, WA site. It would therefore be desirable if an invention comprehensively rad-hardened laser ablation system could be developed to withstand 1,000-2,000 rads per hour for an expected useful life of 7-12 years in that environment, instead of failing within less than a day, or less than 1 hour. A total radiation tolerance of 100 million rads total accumulated exposure is therefore desired for an invention comprehensively rad-hardened laser ablation system for nuclear waste analysis. With prior art UV laser ablation systems failing within 500-1,000 rads total accumulated exposure, it is clear that there remains a need for a new invention to meet DOE radiation hot cell needs.
SUMMARY OF THE INVENTION
The invention laser ablation system of FIGS. 2A , 2 B replaces a conventional prior art dichroic mirror beam combiner ((( 6 )— FIG. 1 ) coaxially combining the final segment of the laser optical path with the initial segment of a white light viewing system) with an invention angled mirror-with-hole ( 25 , 26 )— FIGS. 2A , 2 B, 9 A, 9 B. This allows an invention focused UV laser beam ( 7 , 10 ) to pass (unaltered) through the hole ( 26 ) forming a focused spot on the solid material surface ( 11 , 24 ) below, while the invention observer “white light view” ( 18 - 20 , 22 ) of said solid material surface is obtained with the invention angled mirror perimeter ( 33 ) concentrically surrounding the hole ( 26 ) and said UV laser beam ( 7 , 10 ) passing through said hole ( 26 ), and said white light view obtained in an area encompassing and concentrically surrounding said focused laser spot. The advantage of this invention is optical “decoupling” of the UV laser beam ( 7 , 10 ) from the “white light” observer view ( 18 , 20 , 22 , 28 ), even though the two invention light paths coaxially share a superimposed path segment ( 10 , 18 ).
Invention optical decoupling of the two paths is desirable for UV laser ablation to allow separate optical optimization of the invention laser path and the invention white light camera view. (A prior art “coupled path” does not permit this). The invention UV laser objective lens ( 8 ) focuses only the UV laser light, and does not affect the invention white light camera view which may then be separately focused with an invention high quality achromatic visible lens ( 21 ), optimized separately for the invention camera ( 22 ), and thereby eliminating chromatic aberration from the camera view ( 22 , 28 ). This invention allows the best laser ablation characteristics to occur ( 24 ) simultaneously with the best quality observer (camera) image ( 22 ).
The “mirror-with-hole” invention laser ablation viewing system depends on a second aspect of the generalized laser ablation invention which is the use of substantially longer-than-normal focal lengths (greater than F=40 mm, and preferably greater than F=100 mm) in the invention laser objective focusing lens ( 8 ) and substantially longer-than-normal invention laser object distances ( 4 → 8 ). The substantially longer-than-normal invention focal lengths “F”, and substantially longer-than-normal invention laser object distances “0” of the invention give rise to a substantially longer-than-normal invention laser spot image distance “I” ( 8 → 24 ) according to the laser objective lens formula:
1/ F= 1/ O+ 1/ I
where F is the focal length, O is the object distance ( 4 → 8 ) and I is the image distance ( 8 → 24 ), and this increased invention laser spot image distance (I) allows enough room between the invention objective lens ( 8 ) and the solid sample surface ( 11 , 24 ) and sample cell ( 9 , 23 ) to fit (in) the invention “mirror-with-hole” ( 25 , 26 ), which could otherwise not be fitted in (not enough room) below the FIG. 1 conventional prior art analytical laser ablation objective lens ( 8 ) which is limited by the prior art short focal length geo-bias.
A third preferred invention aspect, namely that of large focused spot analysis in SRM analytical laser ablation is also facilitated by the larger-than-normal focal length invention laser objective lens ( 8 ) which allows a reduction in demagnification ratio, yielding larger invention SMR homogeneous laser spot diameters—e.g. >0.2 mm and up to 1.5 mm or more, and this, in turn, permits the use of much larger invention pulsed UV excimer or SRM (frequency multiplied) Nd-YAG lasers ( 1 ) greater than 12 mJ (@ 266 nm) and, in a non-limiting example, up to 300 mJ at 266 nm without exceeding the IIR of solid samples. Up to 25× higher invention ablation rates are thereby enabled, compared to conventional (geo-biased) prior art UV analytical laser ablation, without exceeding the sample HR. Substantially enhanced invention analytical laser ablation sensitivity in the ppb range may thereby be achieved, compared to reduced (ppm range) sensitivity of prior art analytical laser ablation. Embodiments with excimer and 213 nm or 193 nm (frequency multiplied) Nd-YAG lasers may also be envisioned and these are within the scope of the invention, as well as diode pumped lasers, longer wavelength lasers and femto-second lasers. Additional invention embodiments using a long focal length mirror objective focusing element may also be envisioned and are within the scope of this invention.
The longer focal length invention laser ablation objective lens ( 8 ) exhibits advantage in providing an opportunity for greater invention laser ablation bulk analysis sensitivity of a solid surface, since an invention longer focal length lens (e.g. F>40 mm, and especially F=150 to 400 mm in a nonlimiting example) is naturally accompanied by less demagnification in the final SMR focused laser spot size ( 24 ), yielding significantly larger invention SMR laser spot diameters (>0.2 mm, and preferably 0.4-1.6 mm in a nonlimiting example), and therefore allowing use of more powerful invention excimer and SMR lasers ( 1 ) without exceeding the IIR and overpowering (e.g. shattering, cracking, large particle expulsion, etc.) the sample. Essentially, the same energy density (joules/cm 2 ) within the sample IIR may be used from a larger invention laser, but also focused into a larger invention spot diameter ( 24 ) to ablate more material, under (desirable) IIR conditions. The result is a larger solid sample area is ablated at the same (optimized) energy density by the invention.
The final result is that substantially more sample vapor, smoke, and/or particulate aerosol is produced within the sample IIR during ablation with the preferred embodiment large homogeneous spot, high powered, excimer or SMR based Nd-YAG laser ablation invention. Invention ablation rates are therefore desirably stable and consistently higher for the same sample material and energy density. This gives rise to higher invention signals in the external analytical instruments ( 15 ) to which the vapor, smoke, and/or particulate aerosol from the invention are directed for analysis. The higher signal produced from large area IIR invention ablation gives rise to enhanced invention analysis sensitivity, and the combined invention and external analytical instrument ( 15 ) are capable of 10-25 fold more analytical sensitivity, depending on how much bigger the invention laser ( 1 ) and correspondingly selected invention laser spot diameter (facilitating ablation within the sample IIR) are chosen to be.
Essentially, the invention employs substantially longer focal length laser objective lenses ( 8 ) yielding an option for larger spot diameters in invention excimer and SMR analytical UV laser ablation. Instead of limiting to 0.2 mm maximum spot diameter, which is the largest focused spot normally available in conventional prior art excimer and SMR analytical laser ablation, the invention will allow spot diameters of up to 1.5 mm or more in a nonlimiting example, if a sufficiently large excimer or SMR invention laser ( 1 ) is substituted to “make up” the former prior art energy density in the invention larger spot diameters. This will easily allow invention laser ablation analysis in the ppb (parts per billion) or sub-ppb range instead of conventional (part per million) sensitivity limits of prior art analytical laser ablation.
Referring to FIG. 2A , a preferred embodiment invention excimer or SMR Nd-YAG laser ( 1 ) is substantially more powerful than corresponding lasers used in prior art analytical laser ablation. This aspect of the FIG. 2A invention analytical laser ablation invention is enabled by the unusually long focal length of invention laser objective lens ( 8 ) which has focal length greater than F=40 mm (and preferably F=150 mm or more in a nonlimiting example) and is about 4× longer focal length (in a nonlimiting example) than prior art excimer or SMR Nd-YAG analytical laser ablation, and which enables nominally 4× less demagnification and nominally 4× larger focused invention laser spot diameter ( 24 ) according to the parametric equations (using earlier defined terms):
1/ F= 1/ O+ 1/ I and m −1 =O/I
With nominally 4× larger (nonlimiting example) invention excimer or SMR Nd-YAG focused spot diameter ( 24 ), the FIG. 2A preferred invention embodiment can employ a 16× larger SMR invention laser ( 1 ) without exceeding the ideal irradiance range (IIR in J/cm 2 /ns) of solid samples. The prior art laser ablation system of FIG. 1A cannot do this, owing to a 4× (or more) shorter focal length prior art objective lens ( 8 ) which does not facilitate focused laser spot diameters above 0.2 mm in prior art analytical laser ablation systems using excimer or SMR Nd-YAG lasers.
Further manipulation of invention object and image distances according to the above listed parametric equations would actually allow up to a 1.5 mm invention spot diameter and a 30× larger invention laser without exceeding the IIR of solid samples. The combination of an invention 4-30× larger laser with oversized invention spot diameters in the range of 0.4-1.5 mm will yield substantially higher ablation rates at typical sample IIR's and more bulk analysis sensitivity (e.g. 4-30× more) than prior art excimer or SMR Nd-YAG analytical laser ablation systems. Ultra-trace bulk solids analysis in the parts-per-billion (ppb) range may thereby be achieved by a preferred invention embodiment.
By wide range operational repositioning of at least two laser “steering” mirrors (e.g. mirrors 30 , 31 in FIG. 2A being moved to alternate positions in FIGS. 3A-B , 4 A, and 5 ) in a preferred invention folded detour laser path coupled with wide range operational repositioning of a laser objective lens ( 8 ), a preferred embodiment of the invention further provides for wide range, operationally variable demagnification ratio in the focused invention laser spot size ( 24 ). The at least two preferred invention laser steering mirrors ( 30 , 31 ) may be manually relocated to alter the length of a preferred invention folded detour laser object path ( FIGS. 2A , 4 A, and 5 or FIGS. 3A-3B ), or they may be mounted on a preferred embodiment invention precision motorized track ( 41 ) with a lead-screw drive ( 42 ) as in FIG. 6 for motorized alteration of the preferred invention embodiment folded laser object path length. The invention laser objective lens (to be repositioned) may be manually repositioned or in a preferred FIG. 2B embodiment, it may be mounted on a gantry ( 35 ) coupled to a motorized track ( 36 ) with a lead-screw for motorized alteration of the overall invention focused laser spot demagnification ratio in combination with a FIG. 6 motorized repositioning or a FIGS. 3A-C manual repositioning of the invention mirrors 30 , 31 .
It has been noted that movement of laser steering mirrors 30 , 31 in a direction parallel to the beam path from 29 - 30 in FIGS. 3A-C and in FIGS. 2A , 4 A, and 5 . In a second embodiment which may function alone, or in combination with parallel movement of mirrors 30 , 31 , FIGS. 4B-J illustrate that at least one folded optical detour path may be created which is perpendicular to the original FIG. 2A laser path segment between 31 and 6 . By inserting various mirrors 126 - 128 with a perpendicular motion of wedge mount 125 , various folded optical detour paths including 128 → 129 → 134 → 135 ( FIG. 4C ), 127 → 130 → 133 → 136 ( FIG. 4D ), and 126 → 131 → 132 → 137 ( FIG. 4E ) are enabled which lengthen the path segment between 31 and 6 by varied optical detour amounts, while still directing it coincidentally (coaxially) with path 7 through the objective focusing optic 8 focusing (with demagnification) to solid target sample 11 . In a third embodiment, FIGS. 4G-J illustrate that a pair of single larger mirrors 138 , 139 can replace the illustrated six individual mirrors 126 - 128 and 135 - 137 on the movable wedge mount 125 and accomplish essentially the same set of optical detour path elongations.
Speaking broadly, relocation of the movable wedge mount 125 or relocation of the at least two invention laser steering mirrors ( 30 , 31 ) varies the invention object distance, O. Relocation of either the sample ( 11 ) or the invention objective lens ( 8 ) varies the invention image distance I according to the lens formula given earlier. The resulting changes in O and I then give rise to an alteration of the invention demagnification ratio m −1 , such that:
m −1 =O/I
The greatest sensitivity for laser ablation analysis for a given material and a given laser size will occur with the laser operating at 100% output power and the full laser beam focused into a spot diameter yielding the ideal irradiance range (IIR) for that sample material and laser wavelength. Since sample materials vary widely in values of IIR, it would be desirable to have a wide range of full power irradiance values available for a single analytical laser ablation system. This is not possible with prior art laser ablation systems which have a fixed object distance (O). The lens formula dictates that for a fixed prior art object distance (O) and a fixed prior art focal length (F), the prior art image distance (I) and therefore the prior art demagnification ratio (m −1 =O/I) will also be fixed. With a fixed prior art demagnification value, the irradiance at 100% laser power output will not vary, and so variations in IIR for different samples may not be matched at full power with a prior art system having fixed O and fixed F (yielding fixed I and fixed m −1 ). Some samples may fall into the fixed IIR of a given prior art system at full power, but many others will fall outside of their IIR, thus limiting the sensitivity of prior art analysis, and the reliability of prior art calibration.
Preferred invention embodiments shown in FIGS. 2A-6 solve this problem by allowing substantial practical variation of object distance (O) by as much as a full meter or more of path length. Such a large practical variation of invention object distance (O) produces a correspondingly large variation in invention image distance (I) and invention demagnification ratio (m −1 ), thus enabling the FIGS. 2A-6 preferred invention embodiments to serve as the first known wide range, variable demagnification ratio analytical laser ablation system, capable of ablating any solid material within its IIR, and at 100% laser power output, thus achieving maximum sensitivity and calibration reliability for bulk analysis of all materials which is possible for a given laser. To achieve the required large variation in invention object distance, the dichroic mirror pair ( 30 , 31 ) may be moved right or left in the FIGS. 2A , 4 A, 5 and 6 diagrams, thus shortening or lengthening the object distance in the invention folded detour path or movable wedge mount 125 may be moved up or down in the FIGS. 4B-J diagrams, or a combination of mirror 30 , 31 movement and wedge 125 movement may be employed. A corresponding vertical relocation of sample 11 or invention objective lens ( 8 ) (or a combination of the two) is needed to satisfy the lens formula (1/F=1/O+1/I) and keep the laser spot image ( 24 ) focused at sample surface ( 11 ). Invention mirrors 30 , 31 and/or wedge 125 and sample 11 and/or objective lens 8 are thus positioned to maintain a focused laser spot image (of aperture 4 ) on the sample surface ( 11 , 24 ). In one preferred invention embodiment, the mirrors 30 , 31 and/or wedge 125 and objective lens ( 8 ) are moved in such a way that the lens formula (1/F=1/O+1/I) is always kept satisfied as the focal plane ( 24 ) remains fixed. The demagnification ratio (m′=OA) and the irradiance are however greatly altered with these invention mirror and lens movements, and a wide variety of sample IIR may thereby be ideally matched by the invention.
If desired, the repositioning of invention mirrors ( 30 , 31 ) and/or wedge 125 and invention objective lens ( 8 ) may be done manually through use of invention kinematic mounts to allow a variety of pre-set invention demagnification ratios. If the invention components are kinematically mounted ( 39 ) then a separate set of pre-aligned kinematically mounted invention mirrors (e.g. 30 , 31 , 39 in FIGS. 3-5 ) may be provided for each different invention path length configuration of an invention multi-position (multi-configuration) folded laser path and may be quickly interchanged to effect rapid and convenient operational change of the invention demagnification ratio, without a system realignment.
It should be noted that vertical motion of lens 8 on a precision motion stage or gantry (see 35 , 36 in FIG. 2B ) may or may not require invention laser system realignment, however motion of the mirror pair 30 , 31 will most certainly require invention laser system realignment to keep the focused laser spot exactly centered on sample position 24 , taken as a reference position.
To achieve operational invention laser system realignment upon substantial relocation of mirrors 30 , 31 and/or lens 8 , mirrors 30 , 31 may be mounted on a plate ( 39 ) and plate ( 39 ) may be kinematically mounted to the invention optical platform ( 40 ). Pre-alignment of invention mirrors 30 , 31 for a given plate ( 39 ) position on the invention optical platform ( 40 ) will then assure that overall invention alignment is maintained whenever plate ( 39 ) is in it's pre-aligned optical platform position. A key feature of this preferred invention embodiment is that plate ( 39 ) is only used in one position, so each time it is installed in position, its kinematic mount ensures that the pre-aligned mirror ( 30 , 31 ) condition is maintained. To change plate positions (relocation), a different invention plate with a separate invention mirror pair must then be substituted, with the new mirror pair being pre-aligned for the new plate position (also kinematically mounted to the new position). Essentially, this embodiment of the invention uses a new pre-aligned mirror pair and kinematically mounted plate for each available mirror position. To operationally relocate the mirrors, a new mirror pair (and plate) is selected for each position, and each separate mirror pair is pre-aligned to its own location on the optical platform ( 40 ). The required number of mirror pairs must equal the required number of different mirror positions. Operational relocation is achieved simply by demounting the previous mirror pair (and plate) from its quick-release kinematic mount, selecting a new mirror pair (pre-aligned for the new position), and quickly clamping it into its designated (new) position. The pre-alignment characteristic of the newly selected mirror pair makes it unnecessary to re-align the system upon installation of the new pair.
Alternatively, a preferred motorized FIG. 6 embodiment of invention mirror and objective lens reconfiguration (repositioning) to effect invention variable demagnification ratio may be computer controlled if the motors are precision digital stepping motors. In this case a single pair of the at least two invention laser steering mirrors ( 30 , 31 ) would be moved to effect object distance variation in the invention folded laser path.
Path length variation by the folded path detours of FIGS. 4B-J have the special benefit of having fixed, pre-aligned mirror settings on a precision gimbaling mount for each mirror in the series 129 - 134 which automatically maintain alignment of image 24 at a preselected reference location on sample 11 as wedge 125 is relocated to its various positions which are preferred to be kinematically stabilized at each location. Kinematic stabilization ensures that wedge 125 is consistent in its locations, such that the pre-aligned, preset mirrors 129 - 134 always ensure that image 24 remains centered at the preselected reference location on sample 11 as wedge 125 is relocated.
This level of invention system adjustability allows users of an invention analytical laser ablation system to operationally adjust the maximum focused laser spot size to keep invention focused laser energy and irradiance within the IIR of each and every sample type without need of realignment, regardless of how narrow an individual IIR range may be and how widely the IIR may vary from one material to the next. When coupled with the use of larger invention lasers, this invention operationally adjustable maximum spot size feature provides for the maximum possible ablation rate, sensitivity and calibration accuracy (and reliability) possible for each sample type, without shattering the sample or exceeding its IIR, even in the face of different materials with widely varying IIR. Such a characteristic has never before been available in a prior art laser ablation system, and it allows the full invention laser power to be 100% utilized in an optimized way on an operation basis for each sample analysis, and provides for part-per-billion (ppb) analysis of solid samples by invention UV analytical laser ablation, instead of the conventional ppm sensitivity limits of prior art systems.
A further characteristic of a preferred embodiment invention laser ablation system operationally variable demagnification ratio feature is automatic realignment of the invention laser beam following a change of invention demagnification ratio. Normally, if folding mirrors were repositioned to vary the laser path length, a realignment of the laser mirror system would be required. This would normally have to be painstakingly performed using precision angular adjustment controls for the mirrors and also using alignment targets and bore sight tooling. Mirror alignments made in one folded path configuration will not hold when the folded path is reconfigured (to change its length) by relocating one or more mirrors.
For a manually reconfigured ( FIGS. 2A , 3 A-C, 4 A, and 5 ) embodiment of the invention variable demagnification feature, the aforementioned pre-aligned mirrors ( 30 , 31 ) on kinematic mounts ( 39 , FIGS. 3A-C ) will suffice to maintain invention laser beam alignment following a change of path length, if a different (separate) invention pre-aligned mirror pair ( 30 , 31 ) is devoted to each pre-set location in the invention variable folded detour path. In one non-limiting example, if there are to be 8 different invention preset demagnification ratios involving 8 different mirror pair locations, then 8 different pre-aligned mirror pairs ( 30 , 31 ) would be needed, one (pre-aligned) pair ( 30 , 31 ) for each demagnification ratio to be operationally selected. This requires extra mirrors—more than a prior art fixed demagnification system, but the invention mirror pairs are each pre-aligned, operationally demountable, and kinematically stabilized for precise, quick interchange, so the operational change of invention demagnification ratio is relatively easy to perform, and requires no system realignment after changing the demagnification.
An even more convenient (more highly preferred yet) embodiment of the invention may be envisioned without extra mirrors, if a further modification to the preferred FIG. 6 motorized invention embodiment is considered. In the preferred FIG. 6 motorized embodiment, the invention laser ablation system rapidly achieves automatic laser beam realignment through the folded detour path mirror system, when the at least two invention mirrors ( 30 , 31 ) are relocated to alter the invention folded path length, by virtue of invention small precision digitally controlled stepping motors ( 43 ) mounted on the precision gimbaling mirror mounts controlling the invention mirror angles. Preset stepper motor addresses may be pre-determined (through a pre-alignment exercise) for each different invention folded detour path length for the laser. Each time the invention folded path length and demagnification ratio are changed by repositioning the at least two invention mirrors ( 30 , 31 ), stored values of (pre-aligned) invention stepper motor ( 43 ) address may be retrieved by the invention computer that correspond exactly to the new alignment angles of the at least two invention mirrors ( 30 , 31 ) for the new position, and the invention mirror angles may thus be quickly reset to their new pre-determined alignment for each invention demagnification ratio.
A preferred embodiment of the invention involves actual relocation of the same mirror pair 30 , 31 to one or more preset locations along a precision linear track. Precision micrometer settings on the gimbaling mirror angle adjustments of one or both of the two mirrors may be pre-determined to maintain overall system alignment for each preset location on the linear track. Pre-determination of mirror gimbal micrometer settings would be done in a preliminary setup alignment exercise performed for each preset location on the track. Once a full set of micrometer settings has been determined (separate settings for each preset track location), then those micrometer settings simply have to be replicated (for that track position) each time the mirror pair is moved to a new location. This may be done manually with precision micrometer settings, or digital stepping motors may be attached to the gimbaling adjustments and then the pre-determined stepper motor addresses set for the gimbaling adjustments on the mirrors corresponding to a given track location selected. Separate stepper motor addresses (mirror gimbaling adjustments) would be predetermined for each preset track location. A computer may store these stepper motor addresses and then recall them (and reload them to the stepper motors) each time the mirror pair is moved between preset locations.
Invention mirror pair motion to any location between two preset locations on the linear track may be dealt with by computer interpolation between the gimbaling stepper motor addresses for the bracketing preset locations. In this way a full range of continuously variable demagnification ratios may be operationally obtained with automatic system realignment. An invention operator need only enter the desired magnification ratio into the system computer and a digital stepping motor will automatically relocate the mirror pair along the linear track and additional stepping motors will automatically realign the mirrors to a preset or interpolated alignment corresponding to the selected track position.
In addition, the invention laser objective lens may be positioned on a focus track and controlled by the computer to keep the lens formula (1/F=1/O+1/I) satisfied (image focused) for a fixed sample position, as the mirrors move. Essentially, when a new demagnification ratio is specified by the invention user, the computer will solve the parametric equations (1/F=1/O+1/I and m −1 =O/I) for a fixed value of F and the specified m −1 to yield corresponding values of O and I which determine the mirror and lens placements for that m −1 . Then the computer will look up (or interpolate) new pre-determined pre-alignment values of mirror gimbaling (angle) adjustments to restore system alignment. This invention feature is completely new to analytical laser ablation and it will facilitate operational selection of a wide variety of demagnification ratios to meet the application-specific IIR requirements of virtually any solid sample, while allowing the full available laser power to be used for each analysis. This will maximize invention sensitivity and also maximize overall analytical instrument calibration precision, accuracy, consistency, and reliability.
A further preferred embodiment to extend the range of usable spot diameters and demagnification ratios would include variable focal length in the invention objective lens. To facilitate this, interchangeable invention objective lenses of varying focal length may be employed, including (in one preferred embodiment) a rotary turret containing at least two invention objective lenses of different focal length. Invention zoom laser objective lenses and variable focus laser objective lenses may also be envisioned in other embodiments, either alone, or in combination with other lenses (individually interchangeable or on a turret) so long as they have the requisite UV transmission properties.
In one preferred embodiment, the invention objective lens (or turret) may be mounted on a precision motion stage for repositioning (as invention laser mirrors are relocated). In another FIG. 6 embodiment (see especially FIG. 2B , items 8 , 25 , 26 , 21 , 27 , 22 ), the invention objective lens, mirror-with-hole, and visible “white light” achromatic lens and camera may all be mounted on a gantry ( 35 , 66 ), such that the entire gantry moves to reposition these optics, as invention laser mirrors are relocated.
In one preferred embodiment, the invention gantry may also be precisely moved (up and down) to focus the laser spot image and camera object planes (if coincident) onto the solid sample surface. In another embodiment the invention camera ( 22 ) may be relocated to shift the white light object plane to keep coincident with the laser spot image plane which may move upon invention laser mirror and laser objective lens repositioning to achieve varied invention demagnification ratios.
In another preferred embodiment, the solid sample (and/or sample cell) may be moved on a precision vertical motion stage to achieve focus of the laser spot image and camera object planes to the sample surface.
Invention modularity may accommodate lasers of widely differing size and power on a single “flex” platform, without repositioning or reconfiguring the remaining optics.
A final advantage of the “mirror-with-hole” invention laser ablation viewing system is that a prior art thin-film coated dichroic mirror (( 6 ) in FIG. 1 ) is replaced by the invention mirror-with-hole ( 25 , 26 in FIGS. 2A-B , 9 A-B) at an invention optical convergence point of the two (laser and camera) paths, and eliminating the (radiation damage prone) thin-film coating of a prior art dichroic mirror, allows a preferred embodiment invention UV laser ablation mirror-with-hole to function undamaged for at least 100,000 rads total accumulated radiation exposure (in a nonlimiting example, and e.g. for 100 million rads in a preferred embodiment) in a radiation “hot cell” for analysis of high activity nuclear waste, if the invention laser beam ( 5 , 7 ) originates outside of the “hot cell”. (See FIGS. 7A-B , in which the entire FIGS. 7A-B invention upper module apparatus is located on top of the hot cell and the emergent FIGS. 7A-B laser beam ( 7 ) proceeds downward into the hot cell through a small opening in the hot cell ceiling), and the invention final line-of-sight mirror ( 6 )—line of sight to a radioactive solid sample in ablation cell ( 23 ) of the invention lower module (See FIG. 8A ) and also the invention camera ( 22 , See FIGS. 8A-B ) are rad-hardened and/or shielded, respectively. To rad-harden invention line-of-sight mirror 6 ( FIGS. 7A-B ), it cannot be a prior art thin film dichroic laser mirror (subject to rapid radiation damage), and a fully aluminized invention line-of-sight mirror would have to be substituted instead. (Conventional prior art thin film dichroic mirror coatings are rapidly destroyed by radiation damage at 1,000 rads/hour exposure in an activated radiation “hot cell”.) The invention aluminized final line-of-sight laser steering mirror has a reduced reflectance of about 96% R when new, compared with a new (non-irradiated) prior art dichroic mirror (99.7% R), but after a short time (e.g. within a few minutes or hours) of exposure to high activity nuclear waste (e.g. 1000 rads/hr), the prior art dichroic mirror will be destroyed and the invention aluminized final line-of-sight steering mirror will still be 96% R. A small percentage reduction (e.g. 3-4%) of initial reflectance in the invention line-of-sight steering mirror thus extends the invention useful lifetime to about 6-12 years, rather than 6-12 minutes (or hours) lifetime for a prior art system. A preferred FIG. 7A-B , 8 A-B, 9 A-D rad-hardened embodiment of the invention analytical UV laser ablation system is thereby enabled for the analysis of solid nuclear waste, or a witness coupon of the nuclear waste which has been vitrified into radioactive glass, with a small witness coupon to the vitrification process being presented for analysis in ablation cell 23 ( 11 , 24 ).
One preferred invention embodiment therefore employs a split architecture invention laser ablation system for a radiation hot cell as in FIGS. 7A-B , 8 A-B, in which an invention laser ( 1 , FIGS. 7A-B ) and invention laser steering mirrors ( 29 , 30 , 31 , 6 ) are located outside of the hot cell with a beam ( 7 ) from the invention laser entering the hot cell through a window in the hot cell, and in which the invention FIGS. 8A-B and 9 A-D “lower module” comprising an invention long focal length (uncoated) laser objective lens ( 8 ), mirror-with-hole ( 25 , 26 ), invention uncoated view camera lens (module 66 in FIG. 8A , similar to module 66 of FIG. 2B except achromatic lenses ( 21 ) are uncoated), invention shielded view camera ( 67 , 22 ), invention ablation cell ( 23 ), invention automated sample changer ( 44 - 46 , 81 - 84 ), invention ablation cell translational motion stages (( 44 - 46 , 89 , 47 - 49 , 50 - 52 ) facilitating sample focus, line scan ablation, and raster pattern ablation), and invention energy meter ( 90 ) is located inside the hot cell,
In a preferred FIGS. 8A-B embodiment, all hot cell components (key components and subsystems) are modularized for quick dismount and replacement by a hot cell manipulator arm and gripper claw. Kinematic mounting of invention hot cell laser ablation components and subsystems is an invention feature which facilitates replacement by manipulator with optically pre-aligned replacement components and subsystems, thereby eliminating the need for “manned entry” (along with eliminating the need for difficult and expensive hot cell decontamination associated with “manned entry”) for the service replacement exercise.
In one preferred embodiment, said invention FIGS. 8A-B “lower module” components in the hot cell are rad-hardened and/or radiation shielded and/or exhibit placement “at distance” from radioactive samples, to permit each said invention lower module component and the overall invention lower module to withstand at least 100,000 rads and preferably up to 100 million rads total lifetime radiation exposure prior to a radiation damage failure point,
and in which additional invention laser ablation components receiving “line of sight” radiation outside the hot cell, such as a final invention laser beam steering mirror ( 6 ) directing the external invention laser beam ( 7 ) into the hot cell is rad-hardened to withstand radiation exposure,
and in which an invention valve module, directing the flow of carrier gas and/or purge gas to the invention ablation cell, is a rad-hardened valve module capable of withstanding radiation exposure.
In the various radiation hot cell embodiments so far listed, rad hardening is accomplished by the components being manufactured materials selected from a list prepared and published by nuclear testing groups such as CERN, said list being comprised of materials tested and found not to deteriorate under accumulated radiation exposure to at least 100,000 rads and preferably up to 100 million rads in CERN agency reports and testing programs.
This includes construction materials, wiring insulation, connectors, cables, motors, lubricants, seals, and optics. The invention uses CERN approved rad-hardened materials throughout all of its components installed in the hot cell installation. No prior art laser ablation system has done this. Cements and glues are not tolerated. Certain polymers (e.g. Teflon) are not recommended. Electronics (especially integrated circuit chips) must be outside the hot cell (or heavily shielded), with only control voltage and current lines entering. Laser ablation video cameras and energy meters must be rad-hardened and/or heavily shielded from line-of-sight radiation in the hot cell. All of these properties are claimed for the invention laser ablation system, as no prior art laser ablation system employs them, and the invention laser ablation system does employ them and an invention prototype has been built and successfully installed in a radiation hot cell at DOE Hanford site, with radiation damage immunity designed to withstand 100 million rads total lifetime accumulated exposure. At 1000-2000 rads/h, and normal work shifts, the invention prototype is expected to last 6-12 years before failure due to radiation damage. (Prior art laser ablation systems would last maybe 6-12 minutes, or maybe an hour at most in this environment). Higher or lower levels of rad-hardening may be incorporated and still be included in the scope of this invention.
A final advantage of the “mirror-with-hole” invention laser ablation viewing system is that a conventional prior art thin-film coated dichroic mirror (( 6 ) in FIG. 1 ) is replaced by the invention mirror-with-hole ( 25 , 26 in FIG. 9A-B ) at an invention optical convergence point of the two paths, and eliminating the thin-film coating of a prior art dichroic mirror allows a preferred embodiment invention UV laser ablation to function in a radiation “hot cell” for analysis of high activity nuclear waste, if the invention laser beam ( 7 ) originates outside of the “hot cell” (see FIGS. 7A-B ), and the invention final line-of-sight mirror ( 6 )—line of sight to a radioactive solid sample ( 11 , 24 ) and also the invention camera ( 22 ) are rad-hardened and/or shielded ( 67 ), respectively. To rad-harden invention line-of-sight mirror ( 6 ), it cannot be a conventional prior art dichroic laser mirror (subject to rapid radiation damage), and a fully aluminized invention line-of-sight mirror is substituted by the invention instead. (Conventional prior art thin film dichroic mirror coatings are rapidly destroyed by radiation damage at 1,000 rads/hour exposure in an activated radiation “hot cell”.) The invention aluminized final line-of-sight laser steering mirror has a reduced reflectance of about 96% R when new, compared with a new (non-irradiated) prior art dichroic mirror (99.7% R), but after a short time (e.g. within a few minutes or hours) of exposure to high activity nuclear waste (e.g. 1000 rads/hr), the prior art dichroic mirror will be destroyed and the invention aluminized final line-of-sight steering mirror will still be 96% R. A small percentage reduction of initial reflectance in the invention line-of-sight steering mirror thus extends the invention useful lifetime to about 6-12 years, rather than 6-12 minutes (or hours) lifetime for a prior art system. A preferred FIG. 7A-B , 8 A-B rad-hardened embodiment of the invention analytical UV laser ablation system is thereby enabled for the analysis of solid nuclear waste ( 11 , 24 ).
One preferred invention embodiment employs a split architecture invention laser ablation system for a radiation hot cell as in FIGS. 7A-B , 8 A-B in which an invention laser and invention laser steering mirrors are located outside of the hot cell with a beam from the invention laser entering the hot cell through a window in the hot cell, and in which the invention “lower module” comprising an invention long focal length (uncoated) laser objective lens, mirror-with-hole, invention uncoated view camera lens, invention shielded view camera, invention ablation cell, invention automated sample changer, invention ablation cell translational motion stages (facilitating sample focus, line scan ablation, and raster pattern ablation), and invention energy meter are located inside the hot cell,
and in which said invention “lower module” components in the hot cell are rad-hardened and/or radiation shielded and/or exhibit placement “at greater than normal distance” from radioactive samples, to permit each said invention lower module component and the overall invention lower module to withstand at least 100,000 rads and preferably up to 100 million rads total lifetime radiation exposure prior to a radiation damage failure point,
and in which additional invention laser ablation components receiving “line of sight” radiation outside the hot cell, such as a final invention laser beam steering mirror directing the external invention laser beam into the hot cell is rad-hardened to withstand radiation exposure,
and in which an invention valve module, directing the flow of carrier gas and/or purge gas to and from the invention ablation cell, is a rad-hardened valve module capable of withstanding radiation exposure. The invention prototype laser ablation system installed in the hot cell at DOE Hanford site exhibits all of the above embodiment characteristics and is fully functional.
In preferred FIGS. 9B , 8 A-B embodiments of the invention (either “cold” or rad-hardened) laser ablation system, a demountable sample ablation cell for laser ablation analysis is employed in which the ablation cell components assemble and seal by vertically stacking (mating) components, without using fasteners, tie downs, latches, clamps, snaps, bolts or any other fastener or clamping means. Assembly and low pressure sealing is simply by stacking the mated components vertically, and demounting is simply by unstacking the components (with simple “lift off” means), without need to remove or release any fastener, latch, or clamp. In a preferred embodiment invention demountable sample ablation cell, gas seals are achieved by a weight compression factor, with upper cell components having sufficient weight to deliver a gas sealing force to mating lower cell components. The seals or a combination of seals are selected from among a group comprising tapered seals, gaskets, and o-rings and in which the selected seals are compressed to their sealing points solely by the weight of stacked overhead cell components.
If the weight of stacked overhead cell components becomes excessive, a preferred FIG. 8A-B embodiment of the invention employs a demountable sample ablation cell ( 23 , 76 , 80 ) in which a counterbalancing force ( 95 - 102 ) is applied in compound linkages and levers to offset the combined weight of stacked ablation cell components ( 23 ) and FIG. 9B (all) without diminishing sealing forces below their gas sealing points, in order to allow “light duty” X, Y, Z translational stages to control the combined stacked cell positioning. The counterbalancing force may involve a spring loaded plate or platform, or it may involve at least one counterbalancing weight.
In a preferred invention embodiment, an invention sample changer for laser ablation analysis may cause samples or sample holders (containing samples) to be sequentially placed in proximity to an ablation cell to effect sequential laser ablation events and sample analysis by an external ICP, ICP-MS, or FAG-MS instrument, in which a sample changing means places at least a first sample in proximity to an ablation cell, and in which said sample changing means removes said first sample after laser ablation analysis, and in which said sample changing means then places at least a second sample in proximity to said ablation cell.
In a preferred embodiment sample changer, samples may be sequentially lifted out of a counter bore in a movable platform ( 83 , see FIG. 9A ) selected from a movable platform group comprising a rotary carousel, an R-Theta rotating/sliding tray, an X, Y sliding tray, or a linear feed-through tray or conveyor, said samples or sample holders (containing samples) being lifted out of said movable platform by a mechanized push rod ( 81 , 106 ) which pushes upward through a through-hole (( 124 )— FIG. 9C , ( 24 )— FIG. 8A ) contained within the counterbore, and lifts the samples ( 11 ) or sample holders ( 82 , containing samples 11 ) up and out of the movable platform 83 , and in which the lifting action further places the samples or sample holders in proximity to a laser ablation sample cell as in FIG. 9C .
In a preferred embodiment a segment ( 81 ) of the push rod o.d. diameter is less than the i.d. of the through hole ( 124 ) in the movable platform, to an extent which allows horizontal motion of the push rod to effect a line scan, or x, y raster scan, or R-Theta raster scan of the sample horizontally in the laser beam. The invention sample changer's movable platform sequentially presents the samples or sample holders (containing samples) of a group “one at a time” for the push rod to sequentially lift into proximity to the laser ablation sample cell, so that each sample may be analyzed sequentially (in turn) by laser ablation analysis. Referring to FIGS. 9A-C , the sample changer lifting action seals the sample or sample holder ( 82 ) (containing a sample ( 11 )) against or into a sample ablation cell ( 23 ) via weight-stacked matching tapers (an o.d. taper ( 82 ) on the sample holder mating to an identical i.d. taper ( 108 ) in the base of the sample cell).
The sample changer may continue push rod ( 81 ) lifting action after sealing to further lift the sample cell and sample or sample holder (containing a sample) as a stack, said lift proceeding upward to lift the stack out of a stationary sample ablation cell holding platform ( 75 ) and further continues the lift until the upper surface of the sample reaches a laser ablation focal plane ( 24 ) or a specified defocused laser ablation plane. The mechanized push rod and lift stage is further mounted atop an X, Y ( 47 - 49 , 50 - 52 ) or R-Theta translational stage capable of offsetting the push rod with stacked sample holder, sample, and sample ablation cell in a linear horizontal motion (see FIG. 9D offset ( 24 , 11 , 75 - 76 , 47 - 48 ) or an X, Y horizontal raster pattern, or an arc motion or an R-Theta raster pattern for laser ablation or to selected stationary horizontal offset positions for laser ablation after lifting and focusing.
In another FIG. 10 preferred embodiment, the invention sample changer may keep the support rod ( 81 ) vertically stationary and employ the movable platform ( 83 ) to position a sample over the support rod and then lower the sample or sample holder (containing sample) onto the support rod and the platform continues to lower after the sample holder engages the top of the support rod, such that the platform lowers itself to clear the bottom edge of the sample or sample holder. In this embodiment it is preferred that invention laser focusing is be performed by vertical rise or fall of an invention overhead gantry ( 66 ) containing at least the laser objective lens ( 8 ). In a preferred embodiment, the invention gantry would also support the invention visible white light viewing system and mirror-with-hole ( 25 , 26 —see FIG. 2B ). In a preferred FIG. 10 embodiment, the gantry also functions to raise or lower the sample ablation cell enclosure ( 23 ) over the stationary sample or sample holder (containing sample).
In another embodiment, an invention sample cell for laser ablation has the sample cell closed on the top and open on the bottom, and in which the open bottom is positioned in proximity to a sample surface, and in which carrier gas enters the cell via the annular space between the bottom of the sample cell and the top of the sample surface, and in which an outer concentric “skirt” affixed to the sample cell o.d. provides a compliant seal to the sample, and in which carrier gas is entered into the annular space from the skirt. In this embodiment, the sample cell is horizontally stationary, but the compliant seal is a sliding seal which allows the sample to move horizontally without breaking the seal. In one embodiment, the i.d. of the bottom of the invention sample cell and skirt are both smaller than the perimeter of the sample, such that the compliant seal is formed to the sample surface. In another embodiment, the i.d. of at least the skirt is larger than the perimeter of the sample, such that the compliant seal is formed to the sample holder.
In an alternate embodiment, the compliant seal is an inflatable and deflatable bladder which may be deflated for change of sample and inflated to re-establish perimeter seal around the sample. In this embodiment, the samples are presented sequentially in an x, y sliding tray or rotary platter, or R-theta platter during inflate/deflate cycles to effect an inexpensive automatic sample changer.
BRIEF DESCRIPTION OF THE DRAWINGS
The Foregoing and other aspects, benefits and advantages of the invention will be better understood from the following detailed description of preferred embodiments of the invention with reference to the drawings, in which:
FIG. 1A is an unscaled 2-dimensional block diagram of a prior art analytical laser ablation system.
FIG. 1B . is a truncated block diagram section of FIG. 1A , enlarged to show greater detail and a clearer view of prior art items 8 - 13 , 16 - 19 , 23 and 24 which appear in both figures, with addition of a set of X, Y, Z motorized translational stages ( 44 - 53 ).
FIG. 2A is an unscaled 2-dimensional diagram of an embodiment of the invention laser ablation large laser ( 1 ), mirror-with-hole ( 25 , 26 ), and long objective focal length system ( 8 ).
FIG. 2B is a 3-D front view (at slightly elevated vertical perspective) preferred invention embodiment drawing showing a mirror-with-hole ( 25 , 26 ) and an optical gantry ( 35 , 36 , 66 ) containing objective lens ( 8 ), mirror-with-hole ( 25 , 26 ), sample cell lift hooks ( 121 ), and achromatic white light path ( 33 , 21 , 27 , 20 ) with camera ( 22 ). Gantry ( 35 , 36 , 66 ) raises and lowers to stack or unstack the stackable sample ablation cell ( 23 ) onto post (( 38 )—same as ( 81 ) in FIG. 10 ) by means of tabs ( 54 ) and lift hooks ( 121 ).
FIGS. 3A-C are rear view block diagrams of FIG. 2B front view preferred invention embodiment drawing showing invention variable laser path length ( 5 ).
FIG. 4A is an unscaled block diagram similar to FIG. 2A , with laser path ( 4 - 7 ) variation by moving 2 mirrors ( 30 - 31 ).
FIG. 4B is the same as FIG. 2A with addition of movable wedge mount ( 125 ) on which are is mounted six beam steering laser mirrors ( 126 - 128 and 135 - 137 ) which do not intercept the laser beam segment between 31 and 6 in this figure. Six more laser beam steering mirrors ( 129 - 134 ) are illustrated in fixed locations along paths at right angles to the laser beam segment between 31 and 6 in this figure. None of the twelve added laser beam steering mirrors are active in this figure and the laser beam segment length from 31 to 6 is unaffected.
FIG. 4C is the same as FIG. 4B except for the wedge mount ( 125 ) having moved upward in the figure, inserting mirror 128 into the laser beam, which reflects the beam 90 degrees upward to mirror 129 which receives the beam and reflects it over to mirror 134 which reflects it down again to mirror 135 which restores the beam to a path coincident with its original path leading into mirror 6 . The path length from 31 to 6 has been increased by an optical detour path from 128 → 129 → 34 → 135 with the increased path increment essentially equal to twice the offset of mirror 129 from 128 , but the final laser beam segment emerging from the optical detour continues on the normal trajectory into mirror 6 .
FIG. 4D is the same as FIG. 4C except for the wedge mount 125 having moved further upward in the figure, removing mirrors 128 , 129 , 134 , and 135 from the laser beam path and replacing them in the laser beam path with mirrors 127 , 130 , 133 , and 136 enabling a longer optical detour path from 127 → 130 → 133 → 136 with the optical detour path increment essentially equal to twice the offset of mirror 130 from 127 , but the final laser beam segment emerging from the optical detour continues on the normal trajectory into mirror 6 .
FIG. 4E is the same as FIG. 4D except for the wedge mount 125 having moved further yet upward in the figure, removing mirrors 127 , 130 , 133 , and 136 from the laser beam path and replacing them in the laser beam path with mirrors 126 , 131 , 132 , and 137 enabling a longer optical detour path yet from 126 → 131 → 132 → 137 with the optical detour path increment essentially equal to twice the offset of mirror 131 from 126 , but the final laser beam segment emerging from the optical detour continues on the normal trajectory into mirror 6 .
FIG. 4F is the same as FIG. 4E except that mirrors 30 and 31 have moved substantially to the right in the figure, shortening the basic optical path segment from 31 to 6 and making another four optical path lengths from 31 to 6 possible with four-position relocation of wedge mount 125 as earlier illustrated in FIGS. 4B-E but using the new positions of mirrors 31 and 32 . FIGS. 4B-F have thus illustrated eight different optical path lengths obtainable within a single laser ablation system, simply by moving either wedge mount 125 ( FIGS. 4B-E ) or mirrors 31 , 30 .
FIG. 4G is the same as FIG. 4E except that individual mirrors 126 - 128 have been replaced with a single larger mirror 138 , and individual mirrors 135 - 137 have been replaced with a single larger mirror 139 .
FIG. 4H is the same as FIG. 4G except that movable wedge mount has been relocated somewhat lower in the figure so that the incident laser beam (from 31 ) intercepts mirror 138 at a different location on the mirror, causing it to reflect to mirrors 130 , 133 , and 139 instead of mirrors 131 , 132 , and 139 . The FIG. 4H optical detour path has been decreased accordingly from what it was in FIG. 4G .
FIG. 4I is the same as FIG. 4H except that movable wedge mount has been relocated somewhat lower yet in the figure so that the incident laser beam (from 31 ) intercepts mirror 138 at a different location yet on the mirror, causing it to reflect to mirrors 129 , 134 , and 139 instead of mirrors 130 , 133 , and 139 . The FIG. 4I optical detour path has been decreased accordingly from what it was in FIG. 4H .
FIG. 4J is the same as FIG. 4I except that movable wedge mount has been relocated even lower yet in the figure so that the incident laser beam (from 31 ) no longer encounters an optical detour path and it proceeds without detour to mirror 6 .
FIG. 5 is the same as FIG. 4A , but with greater movement of the mirror pair 30 , 31 and shorter overall optical path length.
FIG. 6 is a motorized version of FIGS. 2A , 4 A, and 5 .
FIG. 7A is a 3-D angled perspective view of an upper module (outside of radiation hot cell) of a rad-hardened laser ablation invention.
FIG. 7B is a shorter path version of FIG. 7A with fewer mirrors and 2 energy meters ( 58 ).
FIG. 8A is a lower module (inside radiation hot cell) of rad-hardened laser ablation invention.
FIG. 8B is the same as 8 A but with shield ( 67 ) removed, and with addition of a counterbalancing force ( 95 ) to offset weight of the ablation cell ( 23 ).
FIG. 9A . is another invention version of the FIG. 8A preferred embodiment.
FIG. 9B . is an exploded view of a stacking ablation cell ( 23 ) from FIG. 9A .
FIG. 9C shows the sample holder lifted out of its platform ( 83 ) engaging the ablation cell and lifting it out of its platform ( 75 ), focusing sample 11 at objective lens focal plane ( 24 ).
FIG. 9D is the same as 9 C except platform 47 has motor scanned to the right, effecting a line scan of the laser beam to the left on sample 11 , 24 .
FIG. 10 illustrates a laser ablation autosampler added to a FIG. 2B laser ablation system with platter 83 lowering over stationary support rod 81 and gantry 66 having already lowered stacking ablation cell ( 23 ) onto stationary support rod ( 81 ) and tapered plug ( 106 ) (see FIG. 9A .). The FIG. 10 autosampler is an R-Theta type, in which rotary carousel 83 also translates linearly on track 123 to select among the three concentric rings containing sample holders 82 .
DETAILED DESCRIPTION OF THE INVENTION
Referring to FIGS. 2A-B , a preferred embodiment of the invention involves a mirror-with-hole ( 25 , 26 ) positioned below long focal length invention laser objective lens ( 8 ). The invention mirror-with-hole ( 25 , 26 ) allows a focused invention UV laser beam ( 7 , 10 ) to pass (unaltered) through the hole ( 26 ) to the solid material surface ( 11 ) while the invention observer ( 22 ) visible “white light view” ( 28 ) of said solid material surface is obtained off axis with the invention mirror perimeter ( 33 ) essentially concentrically surrounding the hole ( 26 ) and said UV laser beam ( 7 , 10 ) passing through said hole ( 26 ). The advantage of this invention is that a final delivery segment (to the solid sample surface ( 11 )) of the invention UV laser beam ( 10 ) is coaxially superimposed with an initial segment ( 18 ) of the invention visible “white light” observer view ( 22 ) with both invention paths sharing a single coincident focal plane ( 24 ), which is the “image” plane of the invention laser objective lens ( 8 ) and is also the “object” plane of the invention achromatic white light camera lens doublets ( 21 ), but without the two invention paths sharing any common steering or focusing optic, thus effecting optical “decoupling” of the invention UV laser beam ( 10 ) from the invention visible “white light” observer view ( 18 , 20 , 22 ), even though the two invention light paths coaxially share a superimposed path segment ( 10 , 18 ). The focal length of invention UV laser ablation objective lens ( 8 ) is longer than conventional prior art analytical laser ablation objective lens focal lengths and the invention longer objective lens focal length creates “working room” under said invention laser objective lens ( 8 ) which allows room for the invention “mirror with hole” ( 25 , 26 ) to fit in under said invention objective lens, without interfering with the invention sample ablation cell ( 23 ) or its window ( 9 ).
Invention optical decoupling of the two paths is desirable for UV laser ablation because a UV laser focusing lens (( 8 ) if refractive, and regardless of quality) is not an ideal, aberration-free viewing optic for visible “white light” observer or camera viewing ( 22 ). Conversely, an achromatic lens ( 21 ) designed for high quality “white light” viewing by an observer (or camera ( 22 )) is not suited to UV laser focusing (a high quality visible white light achromatic lens being typically made of glass (or plastic) and therefore opaque to UV laser light). The mirror-with-hole ( 25 , 26 ) invention optically decouples the laser path ( 10 ) from the observer (or camera) path (( 18 , 20 , 22 ) no shared optical steering or focusing elements), and allows completely separate (individually optimized) focusing optics ( 8 versus 21 ) to be used for each invention path, though an invention path segment ( 10 , 18 ) is traversed by both invention beams, and it specifically provides a higher quality achromatic “white light” view ( 22 ) of the solid material surface before, during, and after an invention UV laser ablation event. Sharper invention white light images of the sample surface ( 11 , 24 ) are therefore seen by the observer or camera ( 22 ), while a high quality invention UV laser objective lens ( 8 ) produces a high quality laser spot on the sample ( 11 ), to effect the best ablation characteristics with the invention. The best UV ablation is thus obtained by the invention, while simultaneously yielding the best quality white light view of the event.
Referring to FIG. 2A , a preferred embodiment invention excimer or SMR Nd-YAG laser ( 1 ) is substantially more powerful than corresponding lasers used in prior art analytical laser ablation. This aspect of the FIG. 2A invention analytical laser ablation invention is enabled by the unusually long focal length of invention laser objective lens ( 8 ) which has focal length greater than F=40 mm (and preferably F=150 mm or more in a nonlimiting example) and is about 4× longer focal length (in a nonlimiting example) than prior art excimer or SMR Nd-YAG analytical laser ablation, and which enables nominally 4× less demagnification and nominally 4× larger focused invention laser spot diameter ( 24 ) according to the parametric equations (using earlier defined terms):
1/ F= 1/ O+ 1/ I and m −1 =O/I
With nominally 4× larger (nonlimiting example) invention excimer or SMR Nd-YAG focused spot diameter ( 24 ), the FIG. 2A preferred invention embodiment can employ a 16× larger SMR invention laser ( 1 ) without exceeding the ideal irradiance range (IIR in J/cm 2 /ns) of solid samples. The prior art laser ablation system of FIG. 1A cannot do this, owing to a 4× (or more) shorter focal length prior art objective lens ( 8 ) which does not facilitate focused laser spot diameters above 0.2 mm in prior art commercially available analytical laser ablation systems using excimer or SMR Nd-YAG lasers.
Further manipulation of invention object and image distances according to the above listed parametric equations would actually allow up to a 1.5 mm invention spot diameter and a 30× larger invention laser without exceeding the IIR of solid samples in a nonlimiting example. The (nonlimiting) combination of an invention 4-30× larger laser with oversized invention spot diameters in the (nonlimiting) range of 0.4-1.5 mm will yield substantially higher ablation rates at typical sample IIR's and more bulk analysis sensitivity (e.g. 4-30× more) than prior art excimer or SMR Nd-YAG analytical laser ablation system. Ultra-trace bulk solids analysis in the parts-per-billion (ppb) range may thereby be achieved by a preferred invention embodiment.
The greatest sensitivity for laser ablation analysis for a given material and a given laser size will occur with the laser operating at 100% output power and the full laser beam focused into a spot diameter yielding the ideal irradiance range (IIR) for that sample material and laser wavelength. Since sample materials vary widely in values of IIR, it would be desirable to have a wide range of full power irradiance values available for a single analytical laser ablation system. This is not possible with prior art laser ablation systems which have a fixed object distance (O). The lens formula dictates that for a fixed prior art object distance (O) and a fixed prior art focal length (F), the prior art image distance (I) and therefore the prior art demagnification ratio (m −1 =O/I) will also be fixed. With a fixed prior art demagnification value, the irradiance at 100% laser power output will not vary, and so variations in IIR for different samples may not be matched at full power with a prior art system having fixed O and fixed F (yielding fixed I and fixed m −1 ). Some samples may fall into the fixed IIR of a given prior art system at full power, but many others will fall outside of their IIR, thus limiting the scope and sensitivity of prior art analysis, and the reliability of prior art calibration.
A first preferred invention embodiment shown in FIGS. 2A , 3 A-C, 4 A, 5 and 6 , a second preferred embodiment shown in FIGS. 4B-J , and/or a third preferred embodiment combining the first and second preferred embodiments solves this problem by allowing substantial practical variation of object distance (O) by as much as a full meter or more of path length. Such a large practical variation of invention object distance (O) produces a correspondingly large variation in invention image distance (I) and invention demagnification ratio (m −1 ), thus enabling the FIGS. 2A , 3 A-C, 4 A, 5 , and 6 first preferred invention embodiment and the FIGS. 4B-J second preferred embodiment and/or a third preferred embodiment combining the first and second embodiments to serve as the first known wide range, variable demagnification ratio analytical laser ablation system, capable of ablating any solid material within its IIR, and at 100% laser power output, thus simultaneously achieving maximum sensitivity and calibration reliability for bulk analysis all materials which is possible for a given laser. To achieve the required large variation in invention object distance, the dichroic mirror pair ( 30 , 31 ) may be moved right or left in the FIGS. 2A , 4 A, 5 and 6 diagrams, thus shortening or lengthening the object distance in the illustrated invention folded detour path.
It has been noted that movement of laser steering mirrors 30 , 31 in a direction parallel to the beam path from 29 - 30 in FIGS. 3A-C and in FIGS. 2A , 4 A, and 5 . In a second embodiment which may function alone, or in combination with parallel movement of mirrors 30 , 31 , FIGS. 4B-J illustrate that at least one folded optical detour path may be created which is perpendicular to the original FIG. 2A laser path segment between 31 and 6 . By inserting various mirrors 126 - 128 with a perpendicular motion of wedge mount 125 , various folded optical detour paths including 128 → 129 → 134 → 135 ( FIG. 4C ), 127 → 130 → 133 → 136 ( FIG. 4D ), and 126 → 131 → 132 → 137 ( FIG. 4E ) are enabled which lengthen the path segment between 31 and 6 by varied optical detour amounts, while still directing it coincidentally (coaxially) with path 7 through the objective focusing optic 8 focusing (with demagnification) to solid target sample 11 . In a third embodiment, FIGS. 4G-J illustrate that a pair of single larger mirrors 138 , 139 can replace the illustrated six individual mirrors 126 - 128 and 135 - 137 on the movable wedge mount 125 and accomplish essentially the same set of optical detour path elongations.
In summary, to achieve the required large variation in invention object distance, the dichroic mirror pair ( 30 , 31 ) may be moved right or left in the FIGS. 2A , 4 A, 5 and 6 diagrams, thus shortening or lengthening the object distance in the illustrated invention folded detour path. Alternatively the movable wedge mount ( 125 ) may be moved up or down in the FIGS. 4B-J diagrams, or a combination of right/left movement of the dichroic mirror pair ( 30 - 31 ) and the up/down movement of the movable wedge ( 125 ) may be employed.
A corresponding vertical relocation of invention objective lens ( 8 ) and/or the solid target sample 11 is needed to satisfy the lens formula (1/F=1/O+1/I) and keep the laser spot image ( 24 ) focused at sample surface ( 11 ). Invention mirrors ( 30 , 31 ) and objective lens ( 8 ) are thus positioned to maintain a focused laser spot image ( 24 ) (of aperture 4 ) on the sample surface ( 11 ). In a preferred invention embodiment, the mirrors ( 30 , 31 ) and objective lens ( 8 ) are moved in such a way that the lens formula (1/F=1/O+1/I) is always kept satisfied as the focal plane ( 24 ) remains fixed. The demagnification ratio (m −1 =O/I) and the irradiance are however greatly altered with these invention mirror and lens movements, and a wide variety of sample IIR may thereby be ideally matched by the invention.
It should be noted that vertical motion of lens 8 on a precision motion stage may or may not require invention laser system realignment, however motion of the mirror pair 30 , 31 will most certainly require invention laser system realignment to keep the focused laser spot ( 24 ) exactly centered on sample position ( 11 ), taken as a reference position.
To achieve operational invention laser system realignment upon substantial relocation of mirrors ( 30 , 31 ), they may be mounted on a plate ( 39 ) and plate ( 39 ) may be kinematically mounted to the invention optical platform ( 40 ). Pre-alignment of invention mirrors ( 30 , 31 ) for a given plate ( 39 ) position on the invention optical platform ( 40 ) will then assure that overall invention alignment is maintained whenever plate ( 39 ) is in the given pre-aligned optical platform ( 40 ) position. A key feature of this preferred invention embodiment is that a given plate ( 39 ) is only used in one position, so each time it is installed in the one position, its kinematic mount ensures that the pre-aligned mirror ( 30 , 31 ) condition is maintained. To change plate positions (relocation), a different invention plate with a separate invention mirror pair must then be substituted, with the new mirror pair being pre-aligned for the new plate position (also kinematically mounted to the new position). Essentially, this embodiment of the invention uses a new pre-aligned mirror pair and kinematically mounted plate for each available mirror position. To operationally relocate the mirrors, a new mirror pair (and plate) is selected for each position, with each separate mirror pair having been pre-aligned to its own location on the optical platform ( 40 ). The required number of mirror pairs must equal the required number of different mirror positions. Operational relocation is achieved simply by demounting the previous mirror pair (and plate) from its quick-release kinematic mount, selecting a new mirror pair (pre-aligned for the new position), and quickly clamping it into its designated (new) position. The pre-alignment characteristic of the newly selected mirror pair makes it unnecessary to re-align the system upon installation of the new pair. An alternate embodiment would have each prealigned mirror of the selected pair on separate kinematic mounts instead of on plate ( 39 ).
A preferred embodiment of the invention involves actual relocation of the same mirror pair 30 , 31 to one or more preset locations along a precision linear track ( FIG. 6 ). Precision micrometer settings on the gimbaling mirror angle adjustments ( 43 ) of one or both of the two mirrors may be pre-determined to maintain overall system alignment for each preset location on the linear track. Pre-determination of mirror gimbal micrometer settings would be done in a preliminary setup alignment exercise performed for each preset location on the track. Once a full set of micrometer settings has been determined (separate settings for each preset track location), then those micrometer settings simply have to be replicated (for that track position) each time the mirror pair is moved to a new location. This may be done manually with precision micrometer settings, or digital stepping motors may be attached to the gimbaling adjustments and then the pre-determined stepper motor addresses set for the gimbaling adjustments on the mirrors corresponding to a given track location selected. Separate stepper motor addresses (mirror gimbaling adjustments) would be predetermined for each preset track location.
In a preferred embodiment, a computer may store these stepper motor addresses and then recall them (and reload them to the stepper motors) each time the mirror pair is moved between preset locations.
Invention mirror pair motion to any location between two preset locations on the linear track may be dealt with by computer interpolation between the gimbaling stepper motor addresses for the bracketing preset locations. In this way a full range of continuously variable demagnification ratios may be operationally obtained with automatic system realignment. An invention operator need only enter the desired magnification ratio into the system computer and a digital stepping motor will automatically relocate the mirror pair along the linear track and additional stepping motors will automatically realign the mirrors to a preset or interpolated alignment corresponding to the selected track position.
In addition, the invention laser objective lens ( 8 ) may be positioned on a focus track and controlled by the computer to keep the lens formula (1/F=1/O+1/I) satisfied (image focused) for a fixed sample position, as the mirrors move. Essentially, when a new demagnification ratio is specified by the invention user, the computer will solve the parametric equations (1/F=1/O+1/I and m −1 =O/I) for a fixed value of F and the specified m −1 to yield corresponding values of O and I which determine the mirror ( 30 , 31 ) and lens ( 8 ) placements for that m −1 . Then the computer will look up (or interpolate) new pre-determined pre-alignment values of mirror gimbaling (angle) adjustments ( 43 ) to restore system alignment. This invention feature is completely new to analytical laser ablation and it will facilitate operational selection of a wide variety of demagnification ratios to meet the application-specific IIR requirements of virtually any solid sample, while allowing the full available laser power to be used for each analysis. This will maximize invention sensitivity and also maximize overall analytical instrument calibration precision, accuracy, consistency, and reliability.
Path length variation by the folded path detours of FIGS. 4B-J have the special benefit of having fixed, pre-aligned mirror settings on a precision gimbaling mount for each mirror in the series 129 - 134 which automatically maintain alignment of image 24 at a preselected reference location on sample 11 as wedge 125 is relocated to its various positions which are preferred to be kinematically stabilized at each location. Kinematic stabilization ensures that wedge 125 is consistent in its locations, such that the fixed, pre-aligned, preset mirrors 129 - 134 always ensure that image 24 remains centered at the preselected reference location on sample 11 as wedge 125 is relocated.
A further preferred embodiment to extend the range of usable spot diameters and demagnification ratios would include variable focal length in the invention objective lens. To facilitate this, interchangeable invention objective lenses of varying focal length may be employed, including (in one preferred embodiment) a rotary turret containing at least two invention objective lenses of different focal length. Invention zoom laser objective lenses and variable focus laser objective lenses may also be envisioned in other embodiments, either alone, or in combination with other lenses (individually interchangeable or on a turret) so long as they have the requisite UV transmission properties.
In one preferred embodiment, the invention objective lens (or turret) may be mounted on a precision motion stage for repositioning (as invention mirrors are relocated). In another embodiment, the invention objective lens ( 8 ), mirror-with-hole ( 25 , 26 ), and visible “white light” achromatic lens ( 21 ) and camera ( 22 ) may all be mounted on a FIG. 2B gantry, such that the entire gantry ( 66 , 35 , 36 ) moves to reposition these optics, as invention laser mirrors ( 30 , 31 ) are relocated as in FIGS. 2A , 3 A-C, and FIGS. 4A , 5 and 6 and/or as the movable wedge mount ( 125 ) is relocated as in FIGS. 4B-J .
In one preferred embodiment, the invention gantry may also be precisely moved (up and down) to focus the laser spot image and camera object planes (if coincident) onto the solid sample surface. In another embodiment the invention camera may be relocated to shift the white light object plane to keep coincident with the laser spot image plane which may move upon invention laser mirror and laser objective lens repositioning to achieve varied invention demagnification ratios.
In another preferred embodiment, the solid sample ( 11 ) and/or sample ablation cell ( 23 ) may be moved on a precision vertical motion stage to achieve focus of the laser spot image ( 24 ) and camera object planes ( 28 ) to the sample surface ( 11 ).
Invention modularity may accommodate lasers of widely differing size and power on a single “flex” platform, without repositioning or reconfiguring the remaining optics.
A final advantage of the “mirror-with-hole” invention laser ablation viewing system is that a conventional prior art thin-film coated dichroic mirror (( 6 ) in FIG. 1A-B ) is replaced by the invention mirror-with-hole ( 25 , 26 ) at an invention optical convergence point of the two paths (see FIGS. 2A-B , FIGS. 9A-B ), and eliminating the thin-film coating of a prior art dichroic mirror allows a preferred embodiment invention UV laser ablation ( FIGS. 7A-B , 8 A-B) to function in a radiation “hot cell” for analysis of high activity nuclear waste, if the invention laser beam ( 7 ) originates outside of the “hot cell” (see FIGS. 7A-B ), and the FIG. 7A-B invention final line-of-sight mirror ( 6 )—line of sight to a FIG. 9A (also FIG. 8A-B ) radioactive solid sample ( 11 , 24 ) and also the invention camera ( 22 ) are rad-hardened and/or shielded, respectively. To rad-harden invention line-of-sight mirror ( 6 ), it cannot be a conventional prior art dichroic laser mirror (subject to rapid radiation damage), and a fully aluminized invention line-of-sight mirror would have to be substituted instead. (Conventional prior art thin film dichroic mirror coatings are rapidly destroyed by radiation damage at 1,000 rads/hour exposure in an activated radiation “hot cell”.) The FIG. 7A-B invention aluminized final line-of-sight laser steering mirror ( 6 ) has a reduced reflectance of about 96% R when new, compared with a new (non-irradiated) prior art dichroic mirror (99.7% R), but after a short time (e.g. within a few minutes or hours) of exposure to high activity nuclear waste (e.g. 1000 rads/hr), the prior art dichroic mirror will be destroyed, but the invention aluminized final line-of-sight steering mirror will still be 96% R. A small percentage reduction of initial reflectance in the invention line-of-sight steering mirror ( 6 ) thus extends the invention useful lifetime to about 6-12 years, rather than 6-12 minutes (or hours) lifetime for a prior art system. A preferred FIGS. 7A-B , 8 A-B, FIGS. 9A-D rad-hardened embodiment of the invention analytical UV laser ablation system is thereby enabled for the analysis of solid nuclear waste ( 11 , 24 ).
One preferred invention embodiment employs a split architecture invention laser ablation system for a radiation hot cell as in FIGS. 7A-B , 8 A-B, in which FIGS. 7A-B invention laser, invention upper energy meters ( 58 ) and invention laser steering mirrors are located outside of the hot cell with a beam from the invention laser entering the hot cell through a window in the hot cell, and in which the FIGS. 8A-B invention “lower module” comprising an invention long focal length (uncoated) laser objective lens, mirror-with-hole, invention uncoated view camera lens, invention shielded view camera, invention ablation cell, invention automated sample changer, invention ablation cell translational motion stages (facilitating sample focus, line scan ablation, and raster pattern ablation), and invention lower energy meter ( 90 ) is located inside the hot cell,
and in which said FIGS. 8A-B invention “lower module” components in the hot cell are rad-hardened and/or radiation shielded and/or exhibit placement “at greater than normal distance” from radioactive samples, to permit each said invention lower module component and the overall invention lower module to withstand at least 100,000 rads and preferably up to 100 million rads total lifetime radiation exposure prior to a radiation damage failure point,
and in which additional invention laser ablation components receiving “line of sight” radiation outside the hot cell, such as a final invention laser beam steering mirror directing the external invention laser beam into the hot cell is rad-hardened to withstand radiation exposure,
and in which an invention valve module, directing the flow of carrier gas and/or purge gas to and from the invention ablation cell, is a rad-hardened valve module capable of withstanding radiation exposure.
In preferred embodiments of the invention (either “cold” or rad-hardened) laser ablation system, a demountable sample ablation cell for laser ablation analysis is employed in which the ablation cell components assemble and seal by vertically stacking (mating) components, without using fasteners, tie downs, latches, clamps, snaps, bolts or any other fastener or clamping means. Assembly and sealing is simply by stacking the mated components vertically, and demounting is simply by unstacking the components (with simple “lift off” means), without need to remove or release any fastener, latch, or clamp. In a preferred embodiment invention demountable sample cell, gas seals are achieved by a weight compression factor, with upper cell components having sufficient weight to deliver a sealing force to mating lower cell components. The seals or a combination of seals are selected from among a group comprising tapered seals, gaskets, and o-rings and in which the selected seals are compressed to their gas sealing points solely by the weight of stacked overhead cell components.
If the weight of stacked overhead cell components becomes excessive, a FIG. 8B preferred embodiment of the invention employs a demountable sample cell in which a counterbalancing force ( 95 ) is applied to offset the combined weight of stacked cell ( 23 ) components without diminishing sealing forces below their gas sealing points, in order to allow “light duty” X, Y, Z translational stages to control the combined stacked cell positioning. The counterbalancing force may involve a spring loaded plate or platform, or it may involve at least one counterbalancing weight ( 95 ).
In a preferred invention embodiment, an invention sample changer for laser ablation analysis may cause samples or sample holders (containing samples) to be lifted out of a counter bore in a movable platform selected from a movable platform group comprising a rotary carousel, an R-Theta rotating/sliding tray, an X, Y sliding tray, or a linear feed-through tray or conveyor, said samples or sample holders (containing samples) being lifted out of said movable platform by a mechanized push rod which pushes upward through a through-hole (or other opening) contained within the counterbore, and lifts the samples or sample holders (containing samples) up and out of the movable platform, and in which the lifting action further places the samples or sample holders in proximity to a laser ablation sample cell.
In a preferred embodiment a segment of the push rod o.d. diameter is less than the i.d. of the through-hole (or opening) in the movable platform, to an extent which allows horizontal motion of the push rod to effect a line scan, or X, Y raster scan, or R-Theta raster scan of the sample horizontally in the laser beam. The invention sample changer's movable platform sequentially presents the samples or sample holders (containing samples) of a group “one at a time” for the push rod to sequentially lift into proximity to the laser ablation sample cell, so that each sample may be analyzed sequentially (in turn) by laser ablation analysis. In one embodiment, the sample changer lifting action seals the sample or sample holder (containing a sample) against or into a sample cell via weight stacked matching tapers (an o.d. inserting taper on the sample holder mating to an identical i.d. receiving taper in the base of the sample cell).
The sample changer may continue push rod lifting action after sealing to further lift the sample ablation cell and sample or sample holder (containing a sample) as a stack, said lift proceeding upward to lift the stack out of a stationary sample cell holding platform and further continues the lift until the upper surface of the sample reaches a laser ablation focal plane or a specified defocused laser ablation plane. The mechanized push rod and lift stage is further mounted atop an X, Y or R-Theta translational stage capable of offsetting the push rod with stacked sample holder, sample, and sample ablation cell in a limited linear horizontal motion or a limited X, Y horizontal raster pattern, or a limited arc motion or a limited R-Theta raster pattern during repetitively firing laser ablation events or to selected stationary horizontal offset positions for laser ablation after lifting and focusing.
In another FIG. 10 preferred embodiment, the invention sample changer may keep the push rod ( 81 ) vertically stationary and employ the movable platform ( 83 ) to position a sample over the push rod and then lower the sample or sample holder ( 82 ) (containing sample) onto the push rod and the platform continues to lower after the sample engages the top of the push rod, such that the platform lowers itself to clear the bottom edge of the sample or sample holder. In this embodiment it is preferred that invention laser focusing is be performed by vertical rise or fall of an invention overhead gantry ( 66 ) containing at least the laser objective lens. In a preferred embodiment, the invention gantry would also support the invention visible white light viewing system and mirror-with-hole. In a preferred embodiment, the gantry also functions to raise or lower the sample ablation cell enclosure ( 23 ) over the stationary sample by means of lifting/lowering hooks ( 121 ) engaging/disengaging lift tabs ( 54 ) on the ablation cell ( 23 ).
In another embodiment, an invention sample ablation cell for laser ablation has the sample ablation cell closed on the top and open on the bottom, and in which the open bottom is positioned in proximity to a sample surface, and in which carrier gas enters the ablation cell via the annular space between the bottom of the sample ablation cell and the top of the sample surface, and in which an outer concentric “skirt” affixed to the sample ablation cell o.d. provides a compliant seal to the sample, and in which carrier gas is entered into the annular space from the skirt. In this embodiment, the sample ablation cell is horizontally stationary, but the compliant seal is a sliding seal which allows the sample to move horizontally without breaking the seal. In one embodiment, the i.d. of the bottom of the invention sample ablation cell and skirt are both smaller than the perimeter of the sample, such that the compliant seal is formed to the sample surface. In another embodiment, the i.d. of at least the skirt is larger than the perimeter of the sample, such that the compliant seal is formed to the sample holder.
In yet another alternate embodiment, the compliant seal is an inflatable and deflatable bladder which may be deflated for change of sample and inflated to re-establish perimeter seal around the sample. In this embodiment, the samples are presented sequentially in an x, y sliding tray or rotary platter, or R-theta platter during inflate/deflate cycles to effect an inexpensive automatic sample changer.
The figures and description are of nonlimiting examples, and the laser ablation invention may be envisioned beyond the scope of specific embodiments described herein, and the scope of the invention must therefore be considered to be limited only by the claims. While the invention has been described in terms of its preferred embodiments, those skilled in the art will recognize that the invention can be practiced with modification within the spirit and scope of the appended claims.
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This invention is improved laser ablation of solid samples analyzed by inductively coupled plasma (ICP), ICP mass spectrometry, or flowing afterglow mass spectrometry. A mirror-with-hole eliminates chromatic aberration in sample viewing and allows rad-hardening for radiation hot cell analysis of nuclear waste. Other attributes facilitate comprehensively rad-hardened laser ablation. Additional improvements include large, homogeneous laser spots, long-focus objective lenses, variable laser path length with built-in re-alignment, variable demagnification ratio, higher powered SMR lasers with larger spots enabling sensitive bulk solids analysis, demountable gravitationally self sealing stack assembly sample ablation cells, and laser ablation sample changers.
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FIELD OF THE INVENTION
The invention relates to a process for the synthesis of compounds of the formula I ##STR2## as further defined herein. The compounds are useful as cardiotonic and vasodilating agents and as inhibitors of phosphodiesterase fraction III and platelet aggregation. In addition, the compounds are active as smooth muscle relaxants and bronchodilators.
BACKGROUND OF THE INVENTION
U.S. Pat. Nos. 4,766,118 and 4,721,784 relate to benzoxazinyl-pyridazinone compounds, their uses and methods for making the compounds. Each of these patents discloses two reaction schemes for making 6-(3,4-dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydropyridazin-3-ones.
In one scheme, the initial starting material is a 5-alkanoyl-2-aminophenol. The use of that starting material, which has the alkanoyl group at the 5-position, is required since the group is converted to the tetrahydropyridazin-3-one moiety in the final product and since the carbonyl carbon of the alkanoyl group becomes the carbon that is bonded to the 7-position of the benzoxazine moiety in the final product. This scheme, however, does not teach a method for preparing a 5-alkanoyl-2-aminophenol from a 2-aminophenol precursor. The use of such a precursor as the starting material would be advantageous over the use of the disclosed starting material since it would be less costly to prepare the final product from a simpler (i.e., less functionalized) starting material.
In the other scheme, the formation of the tetrahydropyridazin-3-one moiety's bond to the 7-position of the benzoxazine moiety is effected by acylating a benzoxazine intermediate. That intermediate, however, must be substituted at its 6-position since the acylation only takes place at the 6-position if the 6-position of the benzoxazine is unsubstituted. Consequently this scheme provides no means for synthesizing a compound having a tetrahydropyridazin-3-one moiety linked to the 7-position of a benzoxazine moiety without the latter moiety also being substituted at its 6-position. In addition, this scheme only discloses that the reaction for introducing the alkanoyl (acyl) group, which is ultimately converted to the pyridazinone moiety in the final product, takes place at a later step in the reaction scheme (i.e., after the formation of the benzoxazine intermediate).
SUMMARY OF THE INVENTION
The present invention is directed to a novel method for synthesizing 6-(3,4-dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydropyridazin-3-ones of the general formula I: ##STR3## wherein R 1 is selected from the group consisting of H,
C 1-6 straight-chain or branched-chain alkyl, C 3-6 cycloalkyl and C 3-6 alkenyl; and
R 2 , R 3 , R 4 and R 5 each is selected from the group consisting of H, C 1-6 straight-chain or branched-chain alkyl and C 3-6 cycloalkyl, and
provided that where R 1 is other than H, the 2-nitrogen of the pyridazinone moiety is bonded to a carbon in R 1 other than an unsaturated carbon.
DETAILED DESCRIPTION OF THE INVENTION
The invention in its broadest aspects relates to the preparation of pyridazinone compounds which exhibit cardiotonic activity, vasodilating activity, platelet aggregating inhibitory activity and phosphodiesterase fraction III inhibitory activity. The benzoxazinylpyridazinone compounds demonstrating these activities are shown by the compound of formula I above, wherein C-6 of the pyridazinone moiety is attached at the C-7 of the benzoxazine moiety.
The preferred compounds made by the present invention are those wherein R 1 and R 5 are hydrogen, R 2 , R 3 and R 4 are each independently H or CH 3 .
The C 1-6 straight-chain or branched-chain alkyl moiety includes such groups as methyl, ethyl, isopropyl or tert-butyl; the C 3-6 cycloalkyl moiety includes such groups as cyclopropyl, cyclohexyl or methylcyclopentyl; and the C 3-6 alkenyl moiety includes such groups as propenyl, methylpropenyl or butenyl.
The process for preparing the compounds is shown in scheme I. ##STR4##
in the first step of Scheme I, 2-benzoxazolinone 1 (a carbamate), is acylated with an alkanoic anhydride of the formula (R 2 CH 2 CO) 2 O, wherein R 2 is as defined above (e.g., propionic anhydride or acetic anhydride), to form an acylated carbamate 2. The method of Bonte et al. (Eur. J. Med. Chem., 9, 491 (1974)) is employed in this reaction except that Eaton's reagent (J. Org. Chem., 38, 4071 (1973)) is used instead of polyphosphoric acid. The method is essentially described in British Patent 1,425,430.
In particular, the Eaton's reagent is prepared by heating a mixture of phosphorous pentoxide and a lower (C 1-6 ) alkanesulfonic acid (e.g., methanesulfonic acid) from about 50° C. to about 70° C. until all the solid dissolves. To this reagent solution is added the 2-benzoxazolinone, and the resultant mixture is stirred for about 30 minutes before it is cooled to about 22° C. To this cold solution is added the alkanoic anhydride of the formula (R 2 CH 2 CO) 2 O (e g , acetic or propionic anhydride), and this resultant mixture is stirred at about 22° C. for about 20 hours to about 30 hours. The mixture is then quenched by pouring it into cold water whereupon the temperature is allowed to rise to between about 50° C. to about 60° C. During this quenching, ice is added to keep the temperature around that range. The temperature of the quenched mixture is then allowed to drop to about 40° C. before the mixture is cooled to about 15° C. thereby effecting the precipitation of the product.
Without isolating 2, it is then reacted by applying the general two-step method of Moussavi et al., (Eur. J. Med. Chem.. 14. 55 (1989) to give a 7-alkanoyl-3,4-dihydro-3-oxo-1,4(2H)-benzoxazine 3.
In the first step of a two-step method, the carbamate (--N--C(O)--O--) moiety in compound 2 is hydrolyzed under basic conditions to yield the corresponding acylated aminophenol. The removal of the carbonyl takes place in water to which a base such as an alkali carbonate (e.g., Na 2 CO 3 or K 2 CO 3 ), an alkali hydroxide (e.g., NaOH or KOH) or an alkaline earth hydroxide (e.g., Mg(OH) 2 or Ca(OH) 2 ) is added. The hydrolyis is effected by heating the solution to about reflux for about 6 hours to about 30 hours.
The second step of the two-step method which involves both an alkylation reaction and an acylation reaction of the resultant aminophenol, is also described by Shridhar et al. (Org. Prep. Int., 14, 195 (1982)) and in U.S. Pat. No. 4,358,455 to J. G. Atkinson et al. The reaction is carried out in an aqueous solvent, an organic solvent, or a mixed solvent (i.e., aqueous-organic solvent) wherein the organic solvent is a ketone (e.g., acetone or methyl isobutyl ketone). This reaction mixture is also basified by using a base such as an alkali alkoxide (e.g., sodium ethoxide or potassium tert-butoxide), an alkali carbonate, an alkali hydroxide or an alkaline earth hydroxide.
In particular, the basified solution containing the acylated aminophenol is cooled to about 0° C. and a 2-haloalkanoyl halide of the formula XR 3 R 4 CCOX, wherein R 3 and R 4 are as defined above and X is the same or different species selected from the group consisting of chloro, bromo and iodo, is added slowly thereto. Following the addition of the 2-haloalkanoyl halide, the mixture is heated to about reflux for about 9 hours to about 16 hours to yield compound 3. The preferred reaction solvent mixture is a water-methyl isobutyl ketone solution and the preferred haloalkanoyl halides are 2-chloroacetyl chloride, 2-chloropropionyl chloride or 2-chloro-2-methylpropionyl chloride.
Compound 3 is then converted to compound 4 employing the three-step method of McEvoy and Allen (J. Org. Chem., 38, 4044 (1973)).
Compound 3 is reacted in a Mannich reaction with a secondary amine or preferably with its hydrohalide (e.g. HCl) or acetate salt and an aldehyde (e.g., formaldehyde or paraformaldehyde) to yield the corresponding substituted aminomethyl compound. The secondary amine is of the formula HN(R') 2 wherein R' is the same or different group and is a lower (C 1-6 ) alkyl, lower (C 1-6 ) hydroxyalkyl, lower ) alkenyl, phenyl lower alkyl and lower ) cycloalkyl lower alkyl. The secondary amine also includes cyclic secondary amines formed by the covalent bonding of the R's together with the nitrogen. Examples of the secondary amines include diethylamine, morpholine, dimethylamine, tetrahydroisoquinoline, diethanolamine, diallylamine, dibenzylamine, piperidine and isopropylmethylamine. This reaction takes place in water or in an organic solvent such as cycloethers (e.g., tetrahydrofuran or dioxane), C 1-4 alcohols (e.g., methanol or ethanol) and alkanoic acid anhydrides (e.g., acetic or propionic anhydride). The reaction mixture is heated to about reflux for about 2 hours to about 4 hours. This reaction is preferentially carried out using dimethylamine hydrochloride and formaldehyde in acetic anhydride.
The product from the Mannich reaction is then reacted with an alkylating reagent of the formula RL wherein L is a displaceable group to yield the corresponding quaternary ammonium compound. R is C 1-6 straight-chain or branched alkyl and C 3-6 cycloalkyl; L is halo (e.g., chloro, bromo or iodo), --OS(O)Cl or --OSO 3 R wherein R is as defined above. Examples of RL include methyl iodide, 2-chloropropane, diethyl sulfate, dimethyl sulfate, methyl chlorosulfite, and propyl chlorosulfite. Suitable solvents for this reation include water or organic solvents such as C 1-4 alcohols (e.g., methanol or ethanol) and ketones (e.g., acetone or 2-butanone). The reaction is effected from about 10° C. to about the reflux temperature. The reaction takes about 3 days to about 5 days at lower temperatures whereas it takes about 3 hours to about 8 hours at higher temperatures. It is preferably effected by heating the mixture to about reflux for about 5 hours to about 8 hours.
That quaternary ammonium salt is then converted to the corresponding nitrile by treating the salt with an alkali metal cyanide such as potassium or sodium cyanide. This reaction takes place in an aqueous solution, an aqueous alcoholic solution, an anhydrous alcoholic solution or an inert solvent (e.g., dimethylformamide or dimethylsulfoxide) wherein the alcohols are C 1-4 alcohols (e.g., methanol or ethanol). The reaction is effected at about 22° C. to the reflux temperature for about 20 hours to about 30 hours. It is preferably effected by reacting the mixture at about 22° C. for about 22 hours to about 30 hours.
Finally, that nitrile is subjected to acid hydrolysis to yield the corresponding acid compound 4. This reaction takes place under acidic conditions in water wherein a mineral acid such as hydrochloric acid or sulfuric acid is employed. In particular, the normality of the hydrolysis solution is adjusted from about 5.0N to about 8.0N and the mixture is heated to about reflux for about 0.5 hours to about 2.5 hours.
The compounds of formulae Ia or Ib are then prepared by heating a solution of 4 to about reflux temperature for about 1 hour to about 8 hours with a hydrazine derivative of the formula R 1 HN-NH2, wherein R 1 is as defined above and where the hydrazine nitrogen is bonded to a carbon in R 1 other than an unsaturated carbon.
It is preferred to use at least an equivalent amount of the aforesaid hydrazine to the amount of 4. This reaction is carried out in an aqueous or an alcohol solution, wherein an alcohol such as methanol, ethanol or isopropanol is employed.
Compounds of formulae Ia or Ib are prepared alternatively by first esterifying compound 4 and then treating the corresponding ester 5 with the aforesaid hydrazine as noted above.
The esterification is accomplished under acidic reaction conditions by suspending 4 in a C 1-3 alcohol (e.g., R"OH, wherein R" is a C 1-3 alkyl) such as methanol or ethanol and then adding thereto an alkanoyl halide such as acetyl chloride. The reaction is effected at about room temperature in about 1 day to about 3 days or at about reflux temperature in about 0.5 hour to about 4 hours.
Alternatively, compound 4 is esterified under acidic reaction conditions by adding an acid such as hydrochloric, sulfuric or p-toluenesulfonic acid to a C 1-3 alcohol, R"OH, (e.g., methanol or ethanol) containing compound 4. The acid is used in about 5 to about 10 weight % to 4. Alternatively, a strong acid ion exchange resin is used in place of the aforesaid acid, and the resin is used in about 10 to about 30 weight % to 4. The reaction itself is effected at about reflux temperature in about 1.5 hours to about 4 hours.
In order to shift the equilibrium in favor of the formation of 5 under acidic conditions, the water that is formed during the esterification process is removed by adding to the esterification reaction mixture another organic liquid such as benzene or toluene to form an azeotrope; from which water is removed during reflux in an apparatus such as a Dean Stark trap or a Soxhlet extractor containing a drying agent (e.g., molecular sieves).
Compound 4 is also esterified to prepare 5 by treating 4 with an alkali or an alkaline earth base as described above to form the alkali or alkaline earth salt of 4, and then treating the salt with an alkylating agent of the formula R"L wherein R" is C 1-3 alkyl; L is halo (e.g., chloro, bromo or iodo), --OS(O)Cl or --OSO 3 R" wherein R" is as defined above. The alkylation takes place in an organic solvent such as a ketone (e.g., acetone), a lower alcohol (e.g., methanol or isopropanol), xylene, benzene dimethylformamide or dimethylsulfoxide, at about 0° C. to about reflux temperature from about 0.5 hour to about 24 hours.
The compounds of formula Ib are alternatively prepared by alkylating Ia under an inert atmosphere or dry conditions (e.g., nitrogen atmosphere) at the 2-position of the pyridazinone moiety. This alkylation is carried out by treating compounds of formula Ia with an alkali metal base such as sodium hydride in an inert solvent, e.g., dimethylformamide or dimethyl sulfoxide) to yield the corresponding salt of Ia and then adding to the resultant salt an alkylating agent of the formula R 1 L 1 wherein R 1 is as defined above except for H (i.e., C 1-6 straight-chain or branched alkyl, C 3-6 cycloalkyl and C 3-6 alkenyl); L 1 is halo (e.g., chloro, bromo or iodo), --OS(O)Cl or --OSO 3 R 1 wherein R 1 is as defined above except for H and L 1 is bonded to a carbon in R 1 other than an unsaturated carbon. The reaction occurs at about 0° C. to about reflux temperature for about 0.5 hour to about 24 hours to give the N-alkylated compounds of the formula Ib.
Alternatively, the compound of the formula I which is alkylated at the 2-position of the pyridazinone moiety is formed by reacting a hydrazine derivative of the formula R 1 HN--NH 2 , wherein R 1 is as defined above except for H and where the hydrazine nitrogen is bonded to a carbon in R 1 other than an unsaturated carbon, with compound 4 under the same reaction conditions as when 4 is reacted with hydrazine.
The preparation of compounds of formulae Ic or Id, which are alkylated at the 4-position of the benzoxazinyl moiety, was carried out by treating compound 4 under an inert atmosphere or under dry conditions with about two equivalents of an alkali metal base such as sodium hydride in an inert solvent (e.g., dimethylformamide or dimethyl sulfoxide) and then adding to the resultant salt an alkylating agent of the formula R 5 L 2 to the solvent wherein R 5 is as defined above except for H (i.e., C 1-6 straight-chain or branched alkyl and C 3-6 cycloalkyl); L 2 is halo (e.g., chloro, bromo or iodo), --OS(O)Cl or --OSO wherein R 5 is as defined above except for H. The reaction occurs at about 0° C. to about 40° C. for about 0.5 hour to about 8 hours to give the N-(alkylated) ester compound, 6, which then reacted with the aforesaid hydrazine derivative of the formula R 1 HN--NH 2 , wherein R 1 is as defined above to produce compounds of formulae Ic or Id.
In addition, although the compounds of the formula I, i.e., where R 2 is other than H or where R 3 and R 4 are not the same group, are obtained as racemic mixtures, however, these mixtures are resolvable to enantiomers. Standard methods are applicable in resolving the mixtures, and, in particular, chiral (enantiomeric) HPLC methods are employed in effecting the enantiomeric separations.
The following examples describe the invention in greater particularity and are intended to be a way of illustrating but not limiting the invention.
EXAMPLES
Example 1:Preparation of 6-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpryidazin-3-one
Step a: 6-Propionyl-2-benzoxazolinone
Phosphorous pentoxide (300 g, 2.10 moles) was added to methanesulfonic acid (3000 g) in a 5-liter three-neck round bottom flask fitted with an overhead mechanical stirrer, thermometer and 500 ml addition funnel. The mixture was heated to 50° C. for one hour or until all of the solid was dissolved. While still at 50° C. 2-benzoxazolinone (270 g, 2.0 moles) was added in one portion and the blue mixture stirred for 30 minutes before cooling to room temperature in an ice-water bath. Propionic anhydride (136 ml, 1.0 moles) was added dropwise to the solution over 20 minutes. After stirring at room temperature for 24 hours, the mixture was poured into 5 liters of cold water and the temperature allowed to climb to about 60° C. Ice was added to keep the temperature between 50° C. and 60° C. during the quenching. The temperature was allowed to drop to 40° C. before the mixture was cooled in an ice bath to 15° C. and the precipitate collected by suction filtration. The filter cake was washed with water then with a minimum amount of cold methanol, and dried to yield 152 g, 40%. mp 203-204.
Step b: 3.4-Dihydro-7-(1-oxopropyl)-3-oxo-1,4(2H)-benzoxazine
6-Propionyl-2-benzoxazolinone (147 g, 0.77 moles) was placed in a 5-liter three-neck round bottom flask with an overhead mechanical stirrer and a reflux condenser. Aqueous 10% sodium carbonate solution (1.5 liters) was added and the mixture heated at reflux for 24 hours.
Sodium bicarbonate (84 g, 1.0 mole) was added to the cooled reaction mixture followed by methyl isobutyl ketone (900 ml). Chloroacetyl chloride (75 ml, 0.94 moles) was added slowly to the vigorously stirred two phase system. When addition was complete the ice bath was replaced with a heating mantle and the reaction heated at reflux for 12 hours. Upon cooling in ice, crystals of the product formed and were collected by filtration and washed with water followed by a minimum amount of diethyl ether (yield 75 g, 50%). A second crop was obtained by separation of the two layers of the filtrate and extracting the water layer with ethyl acetate. The combined organic layers were evaporated to dryness and the residue triturated with diethyl ether. The product was collected by filtration and washed with ether to give an additional 30 g of product. Total yield 70%, mp 170°-172° C.
The following compounds were made by the above procedure, using the appropriate starting materials: 3,4-dihydro-2-methyl-7-(1-oxopropyl)-3-oxo-1,4(2H)-benzoxazine, mp 179°-179.5° C.; and 3,4-dihydro-2,2-dimethyl-7-(1-oxopropyl)-3-oxo-1,4(2H)-benzoxazine, mp 153°-155° C.
Step c: 3,4-Dihydro-7-(3-dimethylamino-2-methyl-1-oxopropyl-3-oxo-1,4(2H)-benzoxazine
3,4-Dihydro-7-(1-oxopropyl)-3-oxo-1,4(2H)-benzoxazine (75 g) was added to a mixture of 37% formalin (36 ml, dimethylamine hydrochloride (44 g) and acetic anhydride (118 ml) which had been heated to give a homogeneous solution. The resultant mixture was heated at reflux for 2.5 hours, then cooled and acetone (100 ml) added. Volatiles were removed by evaporation and the residue taken up in 0.5N HCl (700 ml) and washed with ethyl acetate (2×250 ml). The aqueous layer was chilled in ice and 50% NaOH added until pH 10.5 was achieved. A white precipitate was collected and washed with water. Drying gave 76 g (75%) of a tan powder which was used in the next step without further purification.
Step d: 3.4-Dihydro-7-(3-dimethylamino-1-oxopropyl)-3-oxo-1,4(2H)-benzoxazine methiodide
3,4-Dihydro-7-(2-methyl-3-dimethylamino-1-oxopropyl)-3-oxo-1,4(2H)-benzoxazine (76 g) was dissolved in acetone (750 ml) and iodomethane (45 ml) was added. The mixture was heated at reflux with stirring for 3 hours and then cooled in ice. The crystals that formed were collected by filtration and washed with acetone. Drying gave 110 g (99%) of a light tan solid, mp 223°-224° C.
Step e: 4-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyronitrile
3,4-Dihydro-7-(2-methyl-3-dimethylamino-1-oxopropyl)-3-oxo-1,4(2H)-benzoxazine methiodide (110 g) was dissolved in methanol (400 ml) and water (1000 ml). Potassium cyanide (80 g) dissolved in water (200 ml) was added and the mixture stirred at room temperature for 24 hours. The white precipitate was collected by filtration and washed with water to give 65.7 g (99%) of the titled nitrile, mp 183°-184° C.
Step f: 4-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyric acid
4-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyronitrile (65 g) was heated at reflux for 1.5 hours in 6N HCl (600 ml). The solution was poured into ice water (600 ml) and the resulting solid was collected by filtration, washed with water and recrystallized from acetic acid. After washing with ethanol and then with ethyl ether the product was dried to give 31.6 g of pure white 4-(3,4-dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyric acid, mp 170°-172° C.
The following compounds were made by the above procedures (steps 1(a-f)), using the appropriate starting materials:
4-(3,4-dihydro-2-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyric acid, mp 186°-188° C.; and
4-(3,4-dihydro-2,2-dimethyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyric acid, mp 174°-175.5° C.
Step g: Methyl 4-(3,4-dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyrate
4-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-Oxo-3-methylbutyric acid (5 g) was suspended in methanol (50 ml) and acetyl chloride (0.5 ml) added. The mixture was heated on a steam bath until all of the solid dissolved. The solvent was evaporated at reduced pressure providing the ester as a white foam which was recrystallized from ethyl acetate-methanol to give the product as white crystals, yield 5 g, mp 95°-98° C.
C 14 H 15 NO 5 , Theor.: C, 60.63; H, 5.46; N, 5.05. Found: C, 60.72; H, 5.52; N, 5.17.
Step h: 6-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one
4-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyric acid (31 g, 0.12 moles) was dissolved in ethanol (300 ml) and anhydrous hydrazine (4.7 ml, 0.15 moles) was added. The mixture was heated at reflux overnight. White crystals formed after the mixture was cooled. The crystals were collected by filtration and washed well with ethanol. The solid was dried under vacuum giving 28.5 g (93%) of the titled compound, mp 299°-302° C.
The following compounds were made by the above procedure, using the appropriate starting materials (e.g., of steps 1(f) or 1(g):
6-(3,4-dihydro-2-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one, mp 269°-270° C.; and 6-(3,4-dihydro-2,2-dimethyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one, mp 289.5°-290° C.
Example 2: Preparation of 6-(3,4-dihydro-4-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpryidazin-3-one
Step a: Methyl 4-(3,4-dihydro-4-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyrate
4-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyric acid (3.3g) was dissolved in dimethylformamide. Two equivalents of 60% sodium hydride in an oil suspension (0.489 moles) were added. After 0.5 hour, two equivalents of methyliodide were added. The mixture was allowed to stir under nitrogen for 12 hours, and then poured into water. The product was collected by filtration, or by extraction into ethyl acetate and the subsequent evaporation of the extraction solvent. The resultant brown oil (66%) was used in the next step without further purification.
The following compounds were made by the above procedure, using the appropriate starting materials: methyl 4-(3,4-dihydro-2,4-dimethyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyrate (oil); and methyl 4-(3,4-dihydro-2,2,4-trimethyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyrate (oil).
Step b: 6-(3,4-Dihydro-4-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one
Methyl 4-(3,4-dihydro-4-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyrate was treated with hydrazine as in example 1 to give the title compound, mp 188°-190° C.
The following compounds were made by the above procedure, using the appropriate starting materials:
6-(3,4-dihydro-2,4-dimethyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one, partial melting 222°-224° C. and then from 240°-242° C.; and
6-(3,4-dihydro-2,2,4-trimethyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one, mp 240°-242° C.
Example 3: Preparation of 6-(3,4-dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,5-dimethyl-2,3,4,5-tetrahydropyridazin-3-one
Step a: 6-(3,4-dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,5-dimethyl-2,3,4,5-tetrahydropyridazin-3-one
4-(3,4-Dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-4-oxo-3-methylbutyric acid (1.56 g, 6.0 mmoles) was dissolved in ethanol (300 ml) and methylhydrazine (0.33 ml, 6.0 mmoles) was added. The mixture was heated at reflux for 2 hours, and then cooled to yield to yield the titled compound. The crystals were collected by filtration, recrystallized from ethanol, and recollected by filtration. The solid was dried under vacuum to yield 1.0 g of the titled compound, mp 204°-206° C.
C 14 H 15 N 3 O 3 , Theor.: C, 61.53; H, 5.53; N, 15.38. Found: C, 61.32; H, 5.55; N, 15.68.
Example 4: Preparation of 6-(3,4-dihydro-4-methyl-3-oxo-1,4(2H)-benzoxazin-7yl)-2,5-dimethyl-2,3,4,5-tetrahydropyridazin-3-one
Step a: 6-(3,9-Dihydro-4-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,5-dimethyl-2,3,4,5-tetrahydropyridazin-3-one
6-(3,4-dihydro-4-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,3,4,5-tetrahydro-5-methylpyridazin-3-one (3 g) is suspended in 50 ml of dimethylformamide and one equivalent of 60% sodium hydride in oil is added. When gas evolution ceases, one equivalent of methyl iodide is added and the mixture is allowed to stand for 1.5 hours and then for one hour at 40° C. The mixture is cooled and then poured into 200 ml of ice water, to yield a precipitate that is collected by filtration, washed with water and recrystallized from ethanol. The material is further purified by chromatography on silica gel.
The following compounds are produced as a mixture and separated by chromatography by the above procedure, using the appropriate starting material:
6-(3,4-dihydro-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,5-dimethyl-2,3,4,5-tetrahydropyridazin-3-one, mp 204°-206° C.;
and 6-(3,4-dihydro-4-methyl-3-oxo-1,4(2H)-benzoxazin-7-yl)-2,5-dimethyl-2,3,4,5-tetrahydropyridazin-3-one, mp 188°-190° C.
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The invention relates to a process for the synthesis of compounds of the formula I ##STR1## wherein R 1 -R 5 are as defined herein. The process is a multistep process which comprises acylating a 2-benzoxazolinone with an alkanoic anhydride to form an acylated carbamate, hydrolyzing the carbamate, reacting the resultant aminophenol with haloalkanoyl halide to form a substituted benzoxazine, reacting the benzoxazine with an aldehyde, alkylating the resultant aminomethyl compound with an alkylating agent to form a quaternary ammonium salt, reacting the salt with an alkali metal cyanide to form a nitrile, hydrolyzing the nitrile and reacting the resultant carboxylic acid with hydrazine.
The compounds are useful as cardiotonic and vasodilating agents and as inhibitors of phosphodiesterase fraction III and platelet aggregation. In addition, the compounds are active as smooth muscle relaxants and bronchodilators.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application Ser. No. 11/199,555, filed Aug. 8, 2005, which claims the benefit under 35 U.S.C. § 119 of Provisional U.S. Patent Application Ser. No. 60/600,419, filed Aug. 10, 2004; U.S. patent application Ser. No. 11/199,555 is also a continuation-in-part of each of the following: U.S. patent application Ser. No. 10/032,867, filed Oct. 22, 2001; U.S. patent application Ser. No. 10/351,449, filed Jan. 22, 2003; U.S. patent application Ser. No. 10/441,519, filed May 20, 2003; and U.S. patent application Ser. No. 10/643,787, filed Aug. 19, 2003. All of the above applications are incorporated herein by reference and made a part of this specification.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention pertains to methods and devices for endovascular surgery, and more particularly to devices and methods for treating varicose veins.
[0004] 2. Description of the Related Art
[0005] Varicose veins are distended, visible superficial veins on the legs, and are almost always the result of problems with valves within the venous system of the leg. All leg veins contain one-way flap valves which are designed to help the flow of blood in the veins in an upward direction on its return to the heart. When one or more of these valves fails to function correctly and leaks, some blood is able to flow back down into the leg in the wrong direction and tends to distend branches of superficial veins under the skin. Over a period of time, this additional pressure of blood causes the veins to stretch, bulge and become visible. At the same time, tiny capillary branches of the veins are also overfilled with blood, producing multiple spider veins and often a purple discoloration. Leaky venous valves can occur at any site in the leg but the great majority of varicose veins are caused by faulty valves in the groin or behind the knee. At both these sites there is a major junction at which superficial veins (those subject to varicose veins) flow into the important deep veins of the leg, with a one-way valve to control flow at the junction. Numerous surgical treatments of varicose veins have been developed such surgical stripping and surgical vein removal. Also, radiofrequency (Rf) ablation catheters and laser catheters are used to shrink and ablate varicose veins.
SUMMARY OF THE INVENTION
[0006] In general, the apparatus of the invention comprises a catheter member with a working end having an electrosurgical energy delivery surface for translating along a vessel lumen to shrink and occlude the lumen. The working end comprises a resilient polymer sleeve that is moveable from a first reduced cross-section for introduction to a second expanded cross-section for engaging the vessel wall. In one embodiment, the working end is a resilient sleeve of a polymer having a memory expanded shape that is dimensioned to slide over a guidewire wherein the guidewire is capable of acting as a substantially rigid member to maintain the sleeve in a linear pre-deployed configuration.
[0007] Of particular interest, the working end of the sleeve has exposed electrodes that have a PTCR (positive temperature coefficient of resistance) coating that can modulate Rf current flow to the vessel lumen without thermocouples and controller feedback circuitry. The PTCR material consists of a conductively doped polymer such as silicone. The electrodes are embedded in the catheter sleeve and can operate in bi-polar or mono-polar mode. The PTCR material maintains a low base resistance over a selected temperature range with a dramatically increasing resistance above a selected narrow temperature range as Rf energy is delivered to tissue through the PTCR material. In operation, it can be understood that current flow through the PTCR material will apply active Rf energy (ohmic heating) to the engaged tissue until the point in time that any portion of the material is heated to a range that substantially reduces its conductance. This effect will occur across the PTCR surface thus allowing portions thereof to deliver an independent level of power therethrough. This localized limiting of Rf current can be relied on to prevent any arcing in or about the electrosurgical surface. The system thus eliminates the possibility of tissue char and the potential of emboli. Further, when the PTCR material is elevated in temperature to the selected thermal treatment range, the retained heat of the material volume can also apply thermal energy to the engaged vessel lumen. In one embodiment, the working end will modulate the application of energy to the vessel wall between active Rf ohmic heating and passive conductive heating to maintain a selected temperature level to shrink and occlude the vessel.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] FIG. 1 is a side view of the distal end of a Type “A” catheter-like sleeve and guidewire of the invention in a first linear shape for endoluminal navigation.
[0009] FIG. 2 is a side view of the Type “A” catheter sleeve of FIG. 1 with the guidewire withdrawn and the sleeve in a second expanded shape for treating a varicose vein.
[0010] FIG. 3 is a cut-away view of a small portion of the Type “A” sleeve of FIG. 1 taken along line 3 - 3 of FIG. 2 .
[0011] FIG. 4 is a sectional view of the Type “A” sleeve of FIGS. 1-2 engaging tissue.
[0012] FIG. 5 is a sectional view of the Type “B” sleeve similar to that of FIG. 4 .
DETAILED DESCRIPTION OF THE INVENTION
[0013] 1. Catheter Sleeve Including PTCR Electrosurgical Surface for Treating Varicose Veins.
[0014] FIGS. 1 and 2 illustrate the distal working end 102 of a Type “A” elongated catheter that includes a distal region that includes a distal sleeve end 110 that comprises an electrosurgical surface 112 corresponding to the invention that is adapted for controllably applying energy to the lumen of a blood vessel or other tubular body structure. The sleeve 110 can be any suitable length along axis 115 for endoluminal navigation to a targeted site. The cross-section of the sleeve can be a suitable dimension, for example, 4 French with a 2 French lumen indicated at 116 . The lumen 116 is dimensioned to slide over a guidewire 120 with the guidewire capable of acting as a substantially rigid member to straighten the sleeve 110 to allow endoluminal navigation.
[0015] In the exemplary embodiment of FIGS. 1 and 2 , it can be seen that sleeve 110 has a first untensioned condition in FIG. 2 that has an expanded cross-sectional shape for engaging the walls of a vessel lumen. In FIG. 1 , the sleeve 110 is in a second tensioned linear condition with a lesser cross-section when the guidewire 120 extends therethrough as in FIG. 1 . The untensioned, expanded cross-sectional shape of the sleeve 110 in FIG. 2 is provided by the memory shape of the polymer of the sleeve, and/or by at least one resilient spring element (not shown) molded into the wall 122 of sleeve 110 . Preferably, as can be seen in FIG. 3 , electrode elements 125 A and 125 B in sleeve wall 122 can also provide resilient spring properties to maintain a thin sleeve 110 in an open condition. In use, the working end 102 of sleeve 110 is navigated to the targeted site in the tensioned, linear configuration of FIG. 1 . Thereafter, the guidewire is withdrawn partly (see FIG. 2 ) to allow the sleeve 110 to expand to its untensioned position as in FIG. 2 .
[0016] The sleeve 110 is fabricated of a suitable polymer such as a silicone that is easily deformable between its linear and expanded cross-sectional shapes ( FIGS. 1 and 2 ) after release from its constraint by the guidewire 120 . It should be appreciated that the sleeve member 110 also can be a rod-like member and constrained by, and released from, a bore in a more rigid catheter (not shown). The expanded cross-section of sleeve 110 in FIG. 2 can define an outer diameter of any dimension, for example 2 mm. to 2 cm. and will thus gently push outward to engage the vessel wall as the working end is pulled along the vessel lumen.
[0017] In one embodiment, the sleeve 110 provides a distal working end including an electrosurgical energy delivery surface 112 that comprises helical windings or conductors 125 A and 125 B that function as mono-polar or bi-polar electrodes wherein the conductors 125 A and 125 B have a surface coating of a positive temperature coefficient of resistance (PTCR) polymeric material 126 that functions to control and limit Rf current flows and ohmic heating in the engaged tissue. In the exemplary embodiment of FIG. 1 , shown in cut-away views in FIGS. 3 and 4 , it can be seen that the conductors or electrodes 125 A and 125 B are coupled to, but exposed, in a surface of sleeve wall 122 which is fabricated of a non-conductive polymer. The polymeric PTCR material 126 thus is exposed to provide the electrosurgical energy delivery surface 112 that is adapted to interface with the vessel lumen. More in particular, the PTCR material comprises a non-conductive polymer that is doped with conductive particles. Suitable PTCR materials corresponding to the invention are described in co-pending U.S. Patent Applications listed in the Section above titled CROSS-REFERENCE TO RELATED APPLICATIONS. The polymer portion of the PTCR material can have any thermal conductivity property, but preferably has a low thermal conductivity. The conductive particles can be carbon, gold, platinum, silver, or a stainless steel coated with gold, platinum, silver or the like. In one embodiment, the ration by weight of the polymer-to-conductive particles can range from about 10/90 to about 70/30 (polymer/carbon particles) to provide the selected range at which the sleeve wall will function to substantially limit electrical conductance therethrough at a selected switching range between about 80° C. and 120° C. The non-conductive base polymer 160 a can comprise silicone, high density polyethylene or polypropylene.
[0018] As can be seen in FIGS. 3 and 4 , the polymer of sleeve wall 122 can be formed partly around the conductive elements or electrodes 125 A and 125 B and maintain a selected spacing therebetween. The conductive elements 125 A and 125 B are coupled to a voltage (Rf) source 180 and controller 182 by a connector cable that is detachable from a proximal handle end of sleeve 110 . Thus, the Rf source 180 can apply electrical potential of a first and second polarities (+) and (−) to the conductors 125 A and 125 B and PTCR surfaces 126 and thereafter to the engaged vessel lumen L.
[0019] In the embodiment of FIG. 3 , the conductive elements 125 A and 125 B comprise spaced apart helical coils that are indicated as having opposing polarities, or the conductors 125 A and/or 125 B can have a common polarity to allow operation in a mono-polar manner in cooperation with a ground pad 185 . In one embodiment, the voltage source 180 and controller 182 are configured to switch energy delivery by means of a multiplexer between bi-polar and mono-polar modes. As also can be seen in FIG. 3 , the inner wall surface 184 of wall 122 comprises a portion of the insulative material of sleeve wall 122 that prevents any contact of the electrical components of the sleeve (i.e., PTCR material and electrodes 125 A and 125 B) with the guidewire 120 or blood in the sleeve's lumen during operation (see FIGS. 1-2 ).
[0020] In one method of the invention, the sleeve 110 and electrosurgical surface 112 can limit current flows in tissue and modulate the delivery of energy through electrosurgical surface 112 to the vessel lumen L (see FIGS. 4 and 5 ). The distal end of the sleeve 110 is advanced distally through a targeted varicose vein. The working end is then expanded (see FIG. 2 ) and energized as it is pulled retrograde through the vein. Rf energy application to the vessel lumen will shrink and damage the vessel wall to thereby occlude the vein. When operating in a mono-polar mode as described above, the PTCR material 126 illustrated in FIGS. 3 and 4 will cause current flow in the engaged tissue until the vessel wall reaches a selected switching temperature and thereafter heat is conducted back from the tissue to the PTCR material 126 . Local regions of the PTCR material will then switch off Rf current delivery therethrough which will prevent arcing, charring and tissue desiccation at the interface of the electrosurgical surface 112 and the tissue. This effect will about the surface of each electrode to provide spatially localized modulation of ohmic heating in the engaged tissue. The PTCR material 126 thus senses the tissue temperature that results from ohmic heating and limits current flows to maintain the temperature of the engaged tissue at or about the targeted treatment range.
[0021] Referring again to FIG. 4 , the conductive elements 125 A and 125 B are shown operating in a bi-polar mode and wherein the current flows in tissue a selected distance C (not-to-scale; electrode center-to-center dimension) which in turn controls the depth of ohmic heating in tissue. The electrosurgical surface delivers Rf current flows to the endoluminal tissue wherein the Rf current flows are limited by changes in temperature in at least portions of the PTCR material 126 resulting in the denaturing of proteins within the engaged tissue while substantially preventing desiccation and charring of the tissue. The protein denaturation causes tissue effects that include shrinkage, ablation, occlusion and vessel closure. The sleeve 110 assembly can be manufactured in a number of manners such as extruding an inner portion of the insulative sleeve 110 then using precision windings systems to wind at least one coil of fine wire (with PTCR coating) about the inner sleeve portion. Thereafter, and additional polymeric material can be deposited to partly embed the PTCR coated coils in the sleeve surface. The spacing of the electrodes 125 A and 125 B and temperature resistance profile of the PTCR material 126 are selected to cause the desired Rf current depth and switching temperature.
[0022] In another mode of operation, still referring to FIG. 4 , electrical potential of opposing polarities is applied between conductors 125 A and 125 B which results in current flow through the PTCR material 126 and the engaged tissue T—depending on center-to-center spacing and the conductivity of the PTCR material 126 which is in constant flux as its temperature changes from its conductive heating from engaged ohmically heated tissue. By this means, as described above, the surface 112 acts as a continuously localized temperature control mechanism without the thermocouples and feedback circuitry that are common in many prior art electrosurgical devices. The entire working end assembly can be pulled proximally within the lumen of the blood vessel to cause ohmic heating of a selected length of the blood vessel. The PTCR material 126 will prevent any blood from coagulating about the surface 112 due to its ability to prevent hot-spots or charring as described in previous disclosures referenced above. The method as described above will shrink and occlude the blood vessel to thereby treat varicose veins.
[0023] FIG. 5 illustrates the distal working end of another embodiment of sleeve and electrosurgical surface 112 that is substantially the same as the previously described embodiment. This system is provided with a controller 182 that allows selection of the center-to-center distance between groups of two or more helical conductors operating in a bi-polar mode, in addition to singly paired electrodes as shown in FIG. 4 . The system also can be provided with a multiplexer to automatically switch between different single and multiple arrangements of electrode windings. In this embodiment, at least 4 separate helical coils, or as many as about 24 coils, are independently connected to the electrical source and controller. In operation, the progressively more widely spaced apart bi-polar electrode groups can cause ohmic heating to a greater selected depth in the engaged tissue. Thus, a single diameter sleeve 110 can be adapted for optimal ohmic heating depth no matter the diameter and wall thickness of the blood vessel, whether the blood vessel in 2 mm. or 10 mm.
[0024] In another embodiment, the sleeve can be similar in all respects to the embodiments of FIGS. 1-5 except that the coating on the electrodes can be a pressure sensitive resistive material as disclosed in Ser. No. 10/032,867 filed Oct. 22, 2001; and U.S. patent application Ser. No. 10/351,449 filed Jan. 22, 2003; and U.S. patent application Ser. No. 10/441,519 filed May 20, 2002.
[0025] It should be appreciated that the scope of the invention includes any catheter sleeve 110 that is adapted to provide a first contracted shape for endoluminal navigation and a second expanded shape for engaging the vessel walls, wherein the electrosurgical surface 112 of the sleeve includes at least one electrode and a PTCR polymer 126 having a positive temperature coefficient of resistance. For example, the member be articulatable with pull-wires or the like, or the member may have a core of a shape memory material such as a Nitinol wire or tube.
[0026] Although particular embodiments of the present invention have been described above in detail, it will be understood that this description is merely for purposes of illustration. Specific features of the invention are shown in some drawings and not in others, and this is for convenience only and any feature may be combined with another in accordance with the invention. Further variations will be apparent to one skilled in the art in light of this disclosure and are intended to fall within the scope of the appended claims.
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An electrosurgical instrument and method for treating varicose veins. In one embodiment, an elongate catheter has a distal working end that carries an electrosurgical energy delivery surface comprising at least one electrode with a positive temperature coefficient of resistance (PTCR) surface and/or an electrode with a pressure sensitive variable resistance to provide a smart surface for controlling Rf current flow at the interface of electrosurgical surface and the tissue. The electrode surface then can limit or modulate Rf energy delivery through the surface in response to the temperature of the surface or the engagement pressure of the surface against the engaged tissue. In operation, the smart electrosurgical surface prevents arcing at the electrode-tissue interface, and thus controls ohmic heating to prevent tissue desiccation, charring and emboli formation.
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CROSS-REFERENCE TO RELATED APPLICATIONS
The present utility patent application claims the advantage of provisional application No. 61/248,191 filed Oct. 2, 2009.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
Not Applicable.
THE NAMES OF THE PARTIES TO A JOINT RESEARCH OR DEVELOPMENT
Not Applicable.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to sexual aids and particularly to a dildo sleeve harness which is attached to and worn on the foot of the user to allow for attachment of any strap-on compatible dildo to the bottom of the foot or to the back of the heel, the foot-worn dildo device comprising an elasticized foot-worn sleeve and an attached dildo harness through openings in which the dildo may be held or upon which the base of the dildo may rest and a strap and O-ring assembly used for holding the dildo in place against the dildo harness; the strap and O-ring assembly comprising an O-ring for surrounding the shaft of the dildo and straps attached to the dildo harness at the bottom of the foot and alternately the back of the heel together with straps that attach adjustably around the foot to hold the O-ring in place.
2. Description of Related Art Including Information Disclosed Under 37 CFR 1.97 and 1.98
Sexual satisfaction is an important aspect of a normal natural healthy life. While there are many hand-held devices for sexual self-satisfaction and body mounted devices for mutual sexual satisfaction, there is a lack of foot-mounted sexual satisfaction devices to permit hands-free sexual self-satisfaction and mutual satisfaction.
U.S. Pat. No. 6,899,671, issued May 31, 2005 to Fontenot, describes an intravaginal stimulation apparatus comprising a “Y” shaped tubular device with each of the three arms of the apparatus containing a flexible member. The apparatus is both extendable in width and length with each arm rotatably adjustable and affixed at two ends with adjustable cuffs for securing the apparatus to the user at the ankles. One end of the extendable arm is capable of quick adaptation to a variety of intravaginal appliances. In use, the apparatus is attached to the user's ankles via the adjustable cuffs, and is adjusted to the most comfortable position in a sitting or prone position. The user may then attach the intravaginal appliance of choice. Once insertion of the appliance is made, the user manipulates the apparatus by movement of the user's hips and buttocks in a natural rhythmic manner without the use of hands.
U.S. Pat. No. 6,540,667, issued Apr. 1, 2003 to Hickman, indicates a sexual assistance device and methods which may be used as a marital aid are disclosed which include two elongate members secured by a pivotal connection. A biasing element, such as a spring coil, is disposed at or adjacent the pivotal connection for biasing the opposite ends of the two elongate members away from each other. Respective supports are provided at the two opposite ends of the two elongate members which are engageable with the operator's legs. A sexually stimulating element, such as a vibrator or the like, is preferably removably attached to the pivotal connection. Thus, the operator may produce reciprocal longitudinal movement inwardly and outwardly, relative to the operator's body, by compressing and uncompressing the two elongate members with the legs of the operator thereby fully controlling movement of the sexually stimulating element by the legs of the operator. The biasing force is preferably relatively weak so as to permit easy closing of the operator's legs while still providing a suitable force to permit the legs to securely contact the ends of the two elongate members.
U.S. Pat. No. 6,849,041, issued Feb. 1, 2005 to Astin, is for a phallus retention harness for retaining a phallus with a base portion and an elongate body portion relative to a wearer with a pocket member for receiving and retaining the phallus wherein the pocket member has a first panel and a second panel with an inner volume between the front panel and the rear panel, an aperture in the front panel of the pocket member for enabling the elongate body portion of the phallus to extend therethrough, and an arrangement for retaining the pocket member relative to the wearer's body.
U.S. Pat. No. 4,989,592, issued Feb. 5, 1991 to Chang, puts forth a type of device to improve male sexual potency; a penis protecting pad made of flexible material; on the upper edge of the penis protecting pad are two adjusting pads, and on its lower edges are left and right adjusting belts respectively pulled through the slots on the waist band. On the lower part of the penis protecting pad is a threaded tube joint to accommodate an inside threaded tube body. One end of the tube body is jointed and adhered to a flexible glans penis to form a penis-shaped structure to be worn onto a real penis.
U.S. Pat. No. 6,547,717, issued Apr. 15, 2003 to Green et al, provides a multi-facet sexual aid device for increasing the level of sexual enjoyment between partners which includes a waist belt having a first, second and third belt portion. The first belt portion has a substantially planar portion and a first and second attachment end. The planar portion is a parabolic shaped front element which include a spring-loaded attachment mechanism within a substantially central portion of the planar portion for attaching at least one prosthetic phallic element thereto, as a quick release and quickly deployed element. A couple connector is also used to couple a plurality of different prosthetic phallic elements as either a convex or concave connection to the spring-loaded mechanism. The free ends of each second and third belt portions are fixedly secured at opposing internal first and second internal surface portions via hook and loop fasteners.
U.S. Pat. No. 5,103,810, issued Apr. 14, 1992 to Chang, claims a sexual aid which has a tubular body with a connection piece, two bands sewn or adhered to a lower end of the connection piece and a guard sewn to an upper end of the connection piece. For adjustment of the tightness of the device, a waistband adhered to the guard by adhesive tapes defines slots through which pass ends of the two bands. The tubular body has a number of peaks and valleys running along spiral lines which, with a ring element, stimulate the woman in order to make her reach orgasmic phase more quickly. The tubular body is a hollow structure with a hole at the front end to allow sperm to flow therethrough.
U.S. Patent Application #20090131744, published May 21, 2009 by Pattenden, illustrates a hip-worn sexual aid device comprising an inner region, and an outer region, wherein at least the outer region is fabricated of a molded, lofted foam material that is non-porous, wherein the outer region is configured for use with at least one of an orifice, genitalia and erogenous zone of at least one user.
U.S. Patent Application #20090229617, published Sep. 17, 2009 by Bowman, provides a primarily movement-based, biomechanically advanced interactive apparatus, that can be operated via simultaneous hand and feet action to encourage participation of all major joints/muscles of the body and which is designed to work with the body in motion. The interactive apparatus is designed as a carrier for a wide range of prosthesis of an adult nature and can provide user-controlled multi-plane movement patterns for the same.
What is needed is a foot-mounted sexual satisfaction device to permit hands-free sexual self-satisfaction and mutual satisfaction.
BRIEF SUMMARY OF THE INVENTION
An object of the present invention is to provide a foot-mounted sexual satisfaction device to permit hands-free sexual self-satisfaction and mutual satisfaction.
In brief, the present invention is a dildo harness attached to a foot-sleeve, therefore making the entire entity a foot-sleeve dildo harness. The foot-sleeve dildo harness allows the user to insert a dildo vaginally or anally in the wearer or in a sexual partner, therefore allowing for hands-free vaginal and/or anal stimulation.
The dildo sleeve harness allows for attachment of any strap-on compatible dildo to the bottom of the foot or to the back of the heel. The foot-worn dildo device comprising an elasticized (preferably neoprene) foot-worn sleeve and an attached dildo harness through openings in which the dildo may be held or upon which the base of the dildo may rest and a strap and O-ring assembly used for holding the dildo in place against the dildo harness. The strap and O-ring assembly comprises an O-ring for surrounding the shaft of the dildo and straps attached to the dildo harness at the bottom of the foot and the back of the heel together with straps that attach adjustably around the foot to hold the O-ring in place.
The advantages of the present invention include, without limitation, that it easily allows for hands-free vaginal and anal stimulation. The device can easily slide on the wearer's foot with a dildo extending from the heel and can be used by either sitting on the back of the wearer's heel (having the dildo enter the vagina or anus), or a wearer lying on the wearer's back and bending the wearer's knee may insert the dildo vaginally. The invention can also be used simultaneously by two women sitting across from each other and sliding the dildo to the bottom of the foot-sleeve dildo harness where they can insert the dildo into each other's vaginas, while using their toes for further clitoral stimulation.
In broad embodiment, the present invention is a foot-sleeve dildo harness that mounts a dildo onto the rear or bottom of the harness allowing the wearer to stimulate a vagina or anus on the wearer or on another person.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
These and other details of my invention will be described in connection with the accompanying drawings, which are furnished only by way of illustration and not in limitation of the invention, and in which drawings:
FIG. 1 is a perspective view of the preferred embodiment of the foot sleeve dildo harness of the present invention showing one dildo attached to the heel and another dildo attached to the bottom of the foot using strap and O-ring assemblies;
FIG. 2 is a perspective view of an alternate embodiment of the foot sleeve dildo harness of the present invention showing one dildo attached to the heel and another dildo attached to the bottom of the foot each through a separate opening in the dildo harness;
FIG. 3 is a perspective view of the foot sleeve of the present invention showing the toe and heel openings.
DETAILED DESCRIPTION OF THE INVENTION
In FIGS. 1A , 1 B, 2 A, 2 B and 3 , a foot sleeve dildo harness device 8 comprising a foot sleeve 10 and attached dildo harness 12 having straps 25 and 27 and O-rings 26 forming assemblies for securing any type of body attachable dildo 16 to a heel or a bottom of the foot of a wearer, as shown in FIGS. 1A and 1B , or having openings 14 and 18 in the dildo harness for receiving a dildo 16 inserted therethrough, as shown in FIGS. 2A and 2B , for vaginal and anal stimulation of the wearer or a sexual partner.
The foot sleeve 10 is worn on a foot of a wearer encircling at least a front portion including a portion of the foot bottom and further encircling an ankle and a heel portion of the foot with a heel opening 22 and a toe opening 24 to allow ventilation and toe stimulation.
The dildo harness 12 comprises a dildo receiving strip 13 , extending down the back of the heel and along the bottom of the foot, attached to the foot sleeve 10 by stitching, adhesive, mechanical fasteners, mating hook and loop fasteners or other attaching means and may extend in one strip of dildo receiving material 13 down the back of the foot, around the heel, and along the bottom of the foot or may be in two separate components, one on the heel and the other on the bottom of the foot. The dildo harness 12 further comprises strap 25 and 27 and O-ring 26 means for attaching any of a variety of dildos 16 to the device on a bottom of the foot so that any type of body attachable dildo 16 extends orthogonally downward from the bottom of the foot and on a heel of the foot so that the dildo 16 extends orthogonally rearward from the heel of the foot for vaginal or anal insertion in the body of the wearer or the body of a sex partner.
In FIGS. 1A and 1B , the means for attaching any of a variety of dildos 16 comprises as least one dildo harness 12 having a dildo receiving strip 13 for receiving a base 15 of each of the dildos 16 resting on the strip and an O-ring 26 for encircling the base 15 of each of the dildos 16 and at least one adjustable strap 25 extending from the O-ring 26 to encircle the foot of the wearer to secure the dildo 16 to the sleeve 10 . The foot encircling strap 25 has a clamp 21 for securing the strap and an adjustable buckle 23 to adjust the length of the strap. The first strap 25 encircles the front of the foot to secure the dildo 16 on the bottom of the foot and encircles the ankle and heel of the foot to secure the dildo 16 at the back of the foot. It is preferred that a pair of harness strip attaching straps 27 attach each of the O-rings 16 to the harness strip 13 preferably by a snap 28 A attached to a mating snap 28 B on the harness strip 13 and an overlapping portion of the strap which encircles the O-ring and attaches to itself adjustably by mating hook and loop fasteners 29 A and 29 B attached to facing sides of the straps 27 .
In FIGS. 2A and 2B , the dildo receiving strip 13 has one opening 14 and 18 for a dildo 16 therethrough to receive the dildo 16 inserted through the at least one opening. The bottom opening 18 receives the bottom dildo 16 inserted therethrough with the base 15 of the dildo retained between the dildo receiving strip 13 and the sleeve 10 . The back heel opening 14 receives the back heel dildo 16 inserted therethrough with the base 15 of the dildo retained between the dildo receiving strip 13 and the sleeve 10 .
In FIG. 3 , the sleeve 10 has a top opening 20 to receive the foot of the wearer inserted therein and a heel opening 22 for ventilation and a toe opening 24 for ventilation and to allow stimulation by the toes of the wearer.
The foot sleeve 10 can come in multiple sizes (small, medium and large) to fit multiple foot sizes and can range from 4 to 5 inches deep and 4 to 5 inches in height. The dildo harness 12 may be between 3 to 3.5 inches in diameter and 4.5 to 5.5 inches in length. In FIG. 2 , the rear hole 14 may be 0.5 to 1 inch in diameter and the bottom hole 18 may be 0.5 to 1 inch in diameter. The O-rings of FIG. 1 may come in different sizes to accommodate different sizes of dildos.
The construction details of the invention are that the foot-sleeve 10 and dildo harness 12 may be made of a flexible yet supportive material such as neoprene, or any other sufficiently flexible and stretchy material. Further, the various components of foot-sleeve 10 can be made of different materials.
While it is likely that different manufacturers may produce the same type of dildos 16 with differing shapes and sizes, it is also likely that one particular manufacturer may produce a model of the same type of dildos 16 which is comprised of a similar design and dimensions that would fit through the dildo harness 12 . This dildo 16 would then be used for vaginal and/or anal stimulation.
The hook and loop fastener straps 27 are removable and are adhered by a simple snap. The female end of the plastic buckle straps 25 A and 25 B are sewn onto the foot-sleeve permanently. The male end of the plastic buckle straps may have a metal snap that allows you to remove them for attaching to different sized O-rings for dildos with different girths.
The dildo receiving strip 13 may be just another piece of neoprene sewn to the foot sleeve 10 for extra durability and comfort. This is what the dildo's base actually rests on in FIGS. 1A and 1B .
In use, the wearer will slide their foot through top opening 20 of the foot-sleeve 10 . Once the foot-sleeve 10 is on their foot, the user's heel is exposed through heel opening 22 and toes are exposed through toe opening 24 , as seen in FIG. 3 , for proper support and ventilation.
The present invention easily allows for hands-free vaginal and anal stimulation. The device can easily slide on the wearer's foot with a dildo extending from the heel and can be used by either sitting on the back of the wearer's heel (having the dildo enter the vagina or anus), or a wearer lying on the wearer's back and bending the wearer's knee may insert the dildo vaginally. The invention can also be used simultaneously by two women sitting across from each other and sliding the dildo to the bottom of the foot-sleeve dildo harness where they can insert the dildo into each other's vaginas, while using their toes for further clitoral stimulation.
In broad embodiment, the present invention is a foot-sleeve dildo harness that mounts a dildo onto the rear or bottom of the harness allowing the wearer to stimulate a vagina or anus of the wearer or of another person.
It is understood that the preceding description is given merely by way of illustration and not in limitation of the invention and that various modifications may be made thereto without departing from the spirit of the invention as claimed.
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A foot-sleeve dildo harness uses any of a variety of dildo devices secured in position on a bottom or heel of the foot and extending perpendicularly therefrom. The dildos provide vaginal or anal hands-free stimulation performed on a wearer or on a sexual partner.
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This is a continuation of application Ser. No. 08/755,461, filed Nov. 22, 1996, now abandoned, which is a divisional of application Ser. No. 08/570,599, filed Dec. 11, 1995, now U.S. Pat. No. 5,603,974.
FIELD OF THE INVENTION
The invention relates to thermoplastic polymeric compositions used as packaging materials with barrier properties. The thermoplastic barrier material can take the form of a barrier coating, a flexible film, a semirigid or rigid sheet or a rigid structure. The thermoplastic barrier materials can also take the form of a coating manufactured from an aqueous or solvent based solution or suspension of thermoplastic film forming components containing as one component, the barrier forming materials. Such a film sheet or coating material can act as a barrier to a variety of permeants including water vapor; organics such as aliphatic and aromatic hydrocarbons, aliphatic and aromatic halides, heterocyclic hydrocarbons, alcohols, aldehydes, amines, carboxylic acids, ketones, ethers, esters, sulfides, thiols, monomers, etc.; off flavors and off odors, etc. The thermoplastic barrier compositions of the invention can be extruded, laminated or molded into a variety of useful films, sheets, structures or shapes using conventional processing technology. Further, the monolayer, bilayer or multilayer films can be coated, printed or embossed.
BACGROUND OF THE INVENTION
Much attention has been directed to the development of packaging materials in a film, a semi-rigid or rigid sheet and a rigid container made of a thermoplastic composition. In such applications, the polymeric composition preferably acts as a barrier to the passage of a variety of permeant compositions to prevent contact between ,e.g., the contents of a package and the permeant. Improving barrier properties is an important goal for manufacturers of film and thermoplastic resins.
Barrier properties arise from both the structure and the composition of the material. The order of the structure (i.e.,), the crystallinity or the amorphous nature of the material, the existence of layers or coatings can affect barrier properties. The barrier property of many materials can be increased by using liquid crystal or self-ordering molecular technology, by axially orienting materials such as an ethylene vinyl alcohol film, or by biaxially orienting nylon films and by using other useful structures. Internal polymeric structure can be crystallized or ordered in a way to increase the resistance to permeation of a permeant. A material can be selected, for the thermoplastic or packaging coating, which prevents absorption of a permeant onto the barrier surface. The material can also be selected to prevent the transport of the permeant through the barrier. Permeation that corresponds to Fick's law and non-Fickian diffusion has been observed. Generally, permeation is concentration and temperature dependent regarding mode of transport.
The permeation process can be described as a multistep event. First, collision of the permeant molecule with the polymer is followed by sorption into the polymer. Next, migration through the polymer matrix by random hops occurs and finally the desorption of the penetrant from the polymer completes the process. The process occurs to eliminate an existing chemical concentration difference between the outside of the film and the inside of the package. Permeability of an organic molecule through a packaging film consists of two component parts, the diffusion rate and solubility of the molecule in the film. The diffusion rate measures how fast molecule transport occurs through through film. It affects the ease with which a permeant molecule moves within a polymer. Solubility is a measure of the concentration of the permeant molecule that will be in position to migrate through the film. Diffusion and solubility are important measurements of a barrier film's performance. There are two types of mechanisms of mass transfer for organic vapors permeating through packaging films: capillary flow and activated diffusion. Capillary flow involves small molecules permeating through pinholes or highly porous media. This is of course an undesirable feature in a high barrier film. The second, called activated diffusion, consists of solubilization of the penetrants into an effectively non-porous film at the inflow surface, diffusion through the film under a concentration gradient (high concentration to low concentration), and release from the outflow'surface at a lower concentration. In non-porous polymeric films, therefore, the mass transport of a penetrant includes three steps--sorption, diffusion, and desorption. Sorption and desorption depend upon the solubility of the penetrant in the film. The process of sorption of a vapor by a polymer can be considered to involve two stages: condensation of the vapor onto the polymer followed by solution of the condensed vapor into the polymer. For a thin-film polymer, permeation is the flow of a substance through a film under a permeant concentration gradient. The driving force for permeation is given as the pressure difference of the permeant across the film. Several factors determine the ability of a permeant molecule to permeate through a membrane: size, shape, and chemical nature of the permeant, physical and chemical properties of the polymer, and interactions between the permeant and the polymer.
A permeant for this application means a material that can exist in the atmosphere at a substantial detectable concentration and can be transmitted through a known polymer material. A large variety of permeants are known. Such permeants include water vapor, aromatic and aliphatic hydrocarbons, monomer compositions and residues, off odors, off flavors, perfumes, smoke, pesticides, toxic materials, etc. A typical barrier material comprises a single layer of polymer, a two layer coextruded or laminated polymer film, a coated monolayer, bilayer or multilayer film having one or more coatings on a surface or both surfaces of the film or sheet.
The two most widely used barrier polymers for food packaging are ethylene-vinyl alcohol copolymers (EVOH) ethylene vinyl acetate copolymers (EVA) and polyvinylidene chloride (PVDC). Other useful thermoplastics include ethylene acrylic materials including ethylene acrylic acid, ethylene methacrylic acid, etc. Such polymers are available commercially and offer some resistance to permeation of gases, flavors, aromas, solvents and most chemicals. PVDC is also an excellent barrier to moisture while EVOH offers very good processability and permits substantial use of regrind materials. EVOH copolymer resins are commonly used in a wide variety of grades having varying ethylene concentrations. As the ethylene content is reduced, the barrier properties to gases, flavors and solvents increase. EVOH resins are commonly used in coextrusions with polyolefins, nylon or polyethylene terephthalate (PET) as a structural layer. Commercially, amorphous nylon resins are being promoted for monolayer bottles and films. Moderate barrier polymer materials such as monolayer polyethylene terephthalate, polymethyl pentene or polyvinyl chloride films are available.
Substantial attention is now directed to a variety of. technologies for the improvement of barrier properties. The use of both physical barriers and active chemical barriers or traps in packaging materials are under active investigation. In particular, attention has focused on use of specific copolymer and terpolymer materials, the use of specific polymer alloys, the use of-improved coatings for barrier material such as silica metals, organometallics, and other strategies.
Another important barrier technology involves the use of oxygen absorbers or scavengers that are used in polymeric coatings or in bulk polymer materials. Metallic reducing agents such as ferrous compounds, powdered oxide or metallic platinum can be incorporated into barrier systems. These systems scavenge oxygen by converting it into a stable oxide within the film. Non-metallic oxygen scavengers have also been developed and are intended to alleviate problems associated with metal or metallic tastes or odors. Such systems include compounds including ascorbic acid (vitamin C) and salts. A recent introduction involves organometallic molecules that have a natural affinity for oxygen. Such molecules absorb oxygen molecules into the interior polymer chemical structure removing oxygen from the internal or enclosed space of packaging materials.
Packaging scientists are continuing to develop new polymeric films, coated films, polymeric alloys, etc. using blends of materials to attain higher barrier properties. Many of these systems have attained some degree of utility but have failed to achieve substantial commercial success due to a variety of factors including obtaining barrier performance at low cost.
One problem that arises when searching for polymer blends or compounded polymeric materials, relates to the physical properties of the film. Films must retain substantial clarity, tensile strength, resistance to penetration, tear resistance, etc. to remain useful in packaging materials. Blending unlike materials into a thermoplastic before film extrusion often results in a substantial reduction of film properties. Finding compatible polymer materials for polymer alloys, and compatible additives for polymeric materials typically require empirical demonstation of compatibility and does not follow a clearly developed theory. However compatibility can be demonstrated by showing that the compounded material obtains an improved barrier quality with little reduction in clarity, processability, or structural properties using conventional test methods. Accordingly, a substantial need exists for development of materials that can be incorporated into polymeric material to form a packaging thermoplastic having excellent barrier properties without any substantial reduction in structural properties.
BRIEF DISCUSSION OF THE INVENTION
I have found that the barrier properties of a thermoplastic polymer can be improved, without any important reduction in clarity, processability or structural properties, by forming a barrier layer with a dispersed compatible cyclodextrin derivative in the polymer. I have developed two embodiments. The first comprises a barrier made using the thermoplastic technology containing the cyclodextrin derivative. The second, a coating made by casting a solution or suspension of a film forming polymer or polymer forming material combined with the cyclodextrin derivative to form a barrier layer. The cyclodextrin molecule without a compatible substituent group is not sufficiently compatible in the bulk material to result in a clear useful barrier layer or packaging material. The compatible cyclodextrin derivative is a compound substantially free of an inclusion complex. For this invention the term "substantially free of an inclusion complex" means that the quantity of the dispersed cyclodextrin derivative in the film contains a large fraction having cyclodextrin rings free of a permeant in the interior of the cyclodextrin molecule. The cyclodextrin compound will be added without complex, but some complexing can occur during manufacture from polymer degradation or from inks or coatings compqnents. The internal cavity of the cyclodextrin remains unoccupied by any complexed molecule.
The cyclodextrin derivative has a substituent group bonded to the cyclodextrin molecule that is compatible with the polymeric material. Cyclodextrin is a cyclic dextran molecule having six or more glucose moieties in the molecule. Preferably,-the cyclodextrin is an α-cyclodextrin (αCD), a β-cyclodextrin (γPCD), a γ-cyclodextrin (γCD) or mixtures thereof. We have found that the derivatization of the cyclodextrin molecule is essential for forming a cyclodextrin material that can be effectively blended into the thermoplastic bulk polymer material with no loss in clarity, processability or structural or packaging properties. The substituents on the cyclodextrin molecule are selected to possess a composition, structure and polarity to match that of the polymer to ensure that the cyclodextrin is sufficiently compatible in the polymer material. Further, a derivatized cyclodextrin is selected that can be blended into the thermoplastic polymer, formed into film, semirigid or rigid sheet or other rigid structural materials using conventional thermoplastic manufacturing techniques. Lastly, we have found that the cyclodextrin material can be used in forming such thermoplastic barrier structures without any substantial reduction in structural properties.
The film can provide a trap or barrier to contaminant materials from the polymer matrix and from the product storage and use environment. Thermoplastic polymers used in manufacturing packaging film materials are typically products made by polymerizing monomers resulting from refinery processes. Any refinery stream used in polymerization chemistry, contains residual monomer, trace level refinery hydrocarbons, catalyst and catalyst byproducts as impurities in the polymer matrix. Further, the environment in which materials are packaged after production, stored and used, often contain substantial proportions of contaminants that can permeate through a barrier film or sheet and can contaminate food or other packaged items. Residual polymer volatiles are complexed by dispersing cyclodextrin into molten film polymer using an extruder. The residents time or mixing time of CD and molten polymer in the barrel of the extruder initiates the complexation of residual polymer volatiles. With environmental contamiriants diffusing through the polymer, uncomplexed cyclodextrin dispersed in the polymer is believed to reside, not only between the polymer molecule chains, but in vaguely defined cavities between the polymer chains. As the permeant diffuses through the polymer on a tortuous path, the uncomplexed cyclodextrin is available to complex permeant molecules as they diffuse through the film. Some continual complexation and release of the same guest between cyclodextrin molecules in the film is possible. In other words, the cyclodextrin dispersed in the film is complexing and releasing. The diffusion rate may increase due to the number and size of the cavities caused by the presence of cyclodextrin. The modified cyclodextrin preferably has chemical properties that are compatible with the polymer and are of a size and shape that does not adversely affect the film's barrier property.
The beneficial effect of cyclodextrin over other high-barrier film technologies is twofold. First, cyclodextrin has the ability to complex residual organic volatile contaminants inherent in all polyethylene and polypropylene packaging films. Secondly, cyclodextrin offers the unique ability to complex permeants that may otherwise diffuse through the package film-improving product quality and. safety.
Since all packaging films are permeable to organic vapors, measuring the amount that permeates through the film over time is an important performance measurement of a particular packaging film. The permeation process described above is fast for low-water-activity packaged food products (crackers, cookies, cereals). The process of permeation can be faster or slower depending on the relative humidity outside the package and the product's storage temperature. As the relative humidity outside the package increase, the pressure differential between the outside and inside the package is greater. The greater the differential and/or the higher the temperature, the faster the organic permeants will diffuse through the film. The method used to test the film samples in this research used the worst case (60% relative humidity outside the package and 0.25 water activity inside the package) shelf-life storage conditions to accelerate the outcome of the testing. The organic permeant concentration used has been obtained from food products contaminated by inks used in printing on packaging materials, adhesive systems used in polymer or paper or foil laminations, or numerous environmental contaminants originating from gasoline, diesel fuel, paint solvent, cleaning materials, product fragrance, food products, etc. The relative humidity, water activity and permeant concentration have been used to test numerous high-barrier films presently. used in the industry today. The testing has effectively demonstrated performance differences between various high-barrier films. Four test parameters are important in the performance of the high barrier film. First is the time it takes the permeant to begin diffusing through the package wall known as "lag-time", second, the rate the permeant diffuses through the film, third, the total amount of permeant that can pass through the film over a given time, and fourth, the effectiveness of the barrier to the permeant challenge.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a graphical representation of the dimensions of the cyclodextrin molecule without derivatization. The α, β and γ cyclodextrins are shown.
FIG. 2 is a schematic diagram of the extruder used to form the films set forth in Table I.
FIG. 3 is a diagram of a test device used in measuring the permeability of the films of the inventions.
We have also found that inclusion of the cyclodextrin derivatives in the thermoplastic materials of the invention can improve. other properties of the film such as surface tension, static charge properties and other properties that improve the adaptability of this barrier material to coating and printing. The cyclodextrin derivative materials can be included in a variety of a thermoplastic film and sheet.
DETAILED DESCRIPTION OF THE INVENTION
Film
A film or a sheet is a flat unsupported section of a thermoplastic resin whose thickness is much smaller than its width or length. Films are generally regarded as being 0.25 millimeters (mm) or less, typically 0.01 to 20 mm thick. Sheet may range from about 0.25 mm to several centimeters (cm), typically 0.3 to 3 mm in thickness. Film gor sheet can be used alone or in combination with other sheet, fabric or structural units through lamination, coextrusion or coating. For the invention the term "web" includes film, sheet, semi-rigid and rigid sheet and formed rigid units. Important properties include tensile strength, elongation, stiffness, tear strength and resistance; optical properties including haze, transparency; chemical resistance such as water absorption and transmission of a variety of permeant materials including water vapor and other permeants; electrical properties such as dielectric constant; and permanence properties including shrinkage, cracking, weatherability, etc.
Thermoplastic materials can be formed into barrier film using a variety of processes including blown thermoplastic extrusion, linear biaxially oriented film extrusion and by casting from molten thermoplastic resin, monomer or polymer (aqueous or organic solvent) dispersion. These methods are well known manufacturing procedures. The characteristics in the polymer thermoplastics that lead to successful barrier film formation are as follows. Skilled artisans manufacturing thermoplastic polymers have learned to tailor the polymer material for thermoplastic processing and particular end use application by controlling molecular weight (the melt index has been selected by the thermoplastic industry as a measure of molecular weight--melt index is inversely proportional to molecular weight, density and crystallinity). For blown thermoplastic extrusion polyolefins (LDPE, LLDPE, HDPE) are the most frequently used thermoplastic polymers, although polypropylene, nylon, nitrites, PETG and polycarbonate are sometimes used to make blown film. Polyolefins typically have a melt index from 0.2 to 3 grams/10 mins., a density of about 0.910 to about 0.940 grams/cc, and a molecular weight that can range from about 200,000 to 500,000. For biaxially oriented film extrusion the polymer most often used are olefin based--chiefly polyethylene and polypropylene (melt index from about 0.4 to 4 grams/10 mins. and a molecular weight of about 200,000 to 600,000). Polyesters and nylons can also be used. For casting, molten thermoplastic resin or monomer dispersion are typically produced from polyethylene or polypropylene. Occasionally, nylon, polyester and PVC are cast. For roll coating of aqueous based acrylic urethane and PVDC, etc. dispersions are polymerized to an optimum crystallinity and molecular weight before coating.
A variety of thermoplastic materials are used in making film and sheet products. Such materials include poly(acrylonitrile-co-butadiene-co-styrene) polymers, acrylic polymers such as the polymethylmethacrylate, polyn-butyl acrylate, poly(ethylene-co-acrylic acid), poly(ethylene-co-methacrylate), etc.; cellophane, cellulosics including cellulose acetate, cellulose acetate propionate, cellulose acetate butyrate and cellulose triacetate, etc.; fluoropolymers including polytetrafluoroethylene (teflon), poly(ethylene-cotetrafluoroethylene) copolymers, (tetrafluoroethylene-copropylene) copolymers, polyvinyl fluoride polymers, etc., polyamides such as nylon 6, nylon 6,6, etc.; polycarbonates; polyesters such as poly(ethylene-coterephthalate),. poly(ethylene-co-1,4-naphthalene dicarboxylate), poly(butylene-co-terephthalate); polyimide materials; polyethylene materials including low density polyethylene; linear low density polyethylene, high density polyethylene high Molecular weight high density plyethylene, etc.; polypropylene, biaxially oriented polypropylene; polystyrene, biaxially oriented polystyrene; vinyl films including polyvinyl chloride, (vinyl chlorideco-vinyl acetate) copolymers, polyvinylidene chloride, polyvinyl alcohol, (vinyl chloride-co-vinylidene dichloride) copolymers, specialty films including polysulfone, polyphenylene sulfide, polyphenylene oxide, liquid crystal polyesters, polyether ketones, polyvinylbutyrl, etc.
Film and sheet materials are commonly manufactured using thermoplastic techniques including melt extrusion, calendaring, solution casting, and chemical regeneration processes. In many manufacturing steps an axial or a biaxial orientation step is used. The majority of film and sheet manufactured using melt extrusion techniques. In melt extrusion, the material is heated above its melting point in an extruder typically having an introduction section 27, a melt region 28 and an extruder section 29. The melt is introduced to a slot die resulting in a thin flat profile that is rapidly quenched to solid state and oriented. Typically the hot polymer film after extrusion is rapidly chilled on a roll or drum or using an air stream. Ultimately, a quenching bath can be used. Thermoplastic materials can also be blown. The hot melt polymer is extruded in FIG. 2 in an annular die 22 in a tube form 21. The tube is inflated with air (see air inlet 26) to a diameter determined by the desired film properties and by practical handling considerations. As the hot melt polymer emerges from the annular die, the extruded hot tube is expanded by air to 1.2 or four (4) times its initial die diameter. At the same time the cooling air (see air flow 20) chills the web forming a solid extruded with a hollow circular cross section 21. The film tube is collapsed within a V-shaped frame 23 and is nipped at the end of the frame (nip rolls 24) to trap air within the thus formed bubble. Rolls 24 and 25 draw the film from the die maintaining a continuous production of the extruded tube.
We have found that in the preparation of biaxially oriented film and in the production of blown thermoplastic film that the melt temperature and the die temperature are important in obtaining the permeability or permeant transmission rates preferred for films of the invention, to reduce melt fracture and to improve film uniformity (reduce surface defects). Referring to FIG. 2, the temperature of the melt at the melt region 28 should range from about 390-420° F, preferably 395-415° F. The temperature of the extrusion die 29 should range from about 400-435° F, preferably 410-430° F. The extruded polymer can be cooled using ambient water baths or ambient air. The extruder can be operated at through put such that production rates can be maintained but the polymer can be sufficiently heated to achieve the melt and die temperatures required. Production of the films of the invention at these temperatures ensures that the cyclodextrin material is fully compatible in the thermoplastic melt, is not degraded by the high temperatures and a clear compatible useful barrier film is produced.
Often two thermoplastic materials are joined in a coextrusion process to produce tailored film or sheet products adapted to a particular end use. One or more polymer types in two or more layers of melt are coextruded in a coextrusion die to have a film with versatile properties dried from both layers. Layers of the different polymers or resins are combined by either blending the materials in melt before extrusion or by parallel extrusion of the different thermoplastics. The melt flows laminarly through the die and onto a quenched drum. The film is processed conventionally and may be oriented after cooling. Films can contain a variety of additives such as antioxidants, heat stabilizers, UV stabilizers, slip agents, fillers, and anti-block agents.
The barrier layer of the invention can be made by casting an aqueous dispersion or solvent dispersion or solution of a film forming polymer and the cyclodextrin derivative. The aqueous or solvent based material can be formed by commonly available aqueous or solvent based processing of commercially available polymers, polymer dispersions, polymer solutions or both polymer and common aqueous or solvent processing technology. The cyclodextrin derivative material can be combined with such aqueous or solvent based dispersions or solutions to form a film forming or readily formed coating material. Such barrier layers or barrier coatings can be formed using commonly available coating technology including roller coating, doctor blade coating, spin coating, etc. While the coatings can be made and removed from a preparative surface, commonly coatings are formed on a thermoplastic or thermosetting polymer web, and remain in place to act as a barrier layer on a polymeric web used in a packaging. The typical coatings can be made from the same thermoplastic polymer materials used in film sheet or other structural layers using substantially similar loadings of the cyclodextrin derivative material. The barrier layer or barrier coatings formed using the film forming polymer and the cyclodextrin derivative can be used as a single coating layer or can be used in a multiple coating structure having a barrier layer or coating on one or both sides of a structural film or sheet which can be used with other coating layers including printing layers, clear coating layers and other layers conventional in packaging, food packaging, consumer product packaging, etc.
Cyclodextrin
The thermoplastic films of the invention contain a cyclodextrin having pendent moieties or substituents that render the cyclodextrin material compatible with the thermoplastic polymer. For this invention, compatible means that the cyclodextrin material can be uniformly dispersed into the melt polymer, can retain the ability to trap or complex permeant materials or polymer impurity, and can reside in the polymer without substantial reductions in polymer film characteristics. Compatibility can be determined by measuring polymer characteristics such as tensile strength, tear resistance, etc., permeability or transmission rates for permeants, surface smoothness, clarity, etc. Non-compatible derivatives will result in substantial reduced polymer properties, very high permeability or transmission rates and rough dull film. Qualitative compatibility screening can be obtained by preparing small batches (100 grams-one kilogram of thermoplastic and substituted cyclodextrin). The blended material is extruded at production temperatures as a linear strand extrudate having a diameter of about one to five mm. Incompatible cyclodextrin materials will not disperse uniformly in the melt and can be seen in the transparent melt polymer immediately upon extrusion from the extrusion head. We have found the incompatible cyclodextrin.can degrade at extrusion temperatures and produce a characteristic "burnt flour" odor in an extrusion. Further, we have found that incompatible cyclodextrin can cause substantial melt fracture in the extrudate which can be detected by visual inspection. Lastly, the extrudate can be cut into small pieces, cross-sectioned and examined using an optical microscope to find incompatible cyclodextrin clearly visible in the thermoplastic matrix.
Cyclodextrin is a cyclic oligosaccharide consisting of at least six glucopyranose units joined by α(1"4) linkages. Although cyclodextrin with up to twelve glucose residues are known, the three most common homologs (a cyclodextrin, β cyclodextrin and γ cyclodextrin) having 6, 7 and 8 residues have been used.
Cyclodextrin is produced by a highly selective enzymatic synthesis. They consist of six, seven, or eight glucose monomers arranged in a donut shaped ring, which are denoted α, β, or γ cyclodextrin respectively (See FIG. 1). The specific coupling of the glucose monomers gives the cyclodextrin a rigid, truncated conical molecular structure with a hollow interior of a specific volume. This internal cavity, which is lipophilic (i.e.,) is attractive to hydrocarbon materials (in aqueous systems is hydrophobic) when compared to the exterior, is a key structural feature of the cyclodextrin, providing the ability to complex molecules (e.g., aromatics, alcohols, halides and hydrogen halides, carboxylic acids and their esters, etc.). The complexed molecule must satisfy the size criterion of fitting at least partially into the cyclodextrin internal cavity, resulting in an inclusion complex.
______________________________________CYCLODEXTRIN TYPICAL PROPERTIESPROPERTIES CD α-CD β-CD γ-CD______________________________________Degree of 6 7 8Polymerization(n = )Molecular Size (A°)inside diameter 5.7 7.8 9.5outside diameter 13.7 15.3 16.9height 7.0 7.0 7.0Specific Rotation α!.sub.D.sup.25 +150.5 +162.5 +177.4Color of iodine Blue Yellow Yellowishcomplex BrownSolubility in water(g/100 ml) 25° C.Distilled Water 14.50 1.85 23.20______________________________________
The oligosaccharide ring forms a torus, as a truncated cone, with primary hydroxyl groups of each glucose residue lying on a narrow end of the torus. The secondary glucopyranose hydroxyl groups are located on the wide end. The,parent cyclodextrin molecule, and useful derivatives, can be represented by the following formula (the ring carbons show conventional numbering) in which the vacant bonds represent the balance of the cyclic molecule: ##STR1## wherein R 1 and R 2 are primary or secondary hydroxyl as shown.
Cyclodextrin molecules have available for reaction with a chemical reagent the primary hydroxyl at the six position, of the glucose moiety, and at the secondary hydroxyl in the two and three position. Because of the geometry of the cyclodextrin molecule, and the chemistry of the ring substituents, all hydroxyl groups are not equal in reactivity. However, with care and effective reaction conditions, the cyclodextrin molecule can be reacted to obtain a derivatized molecule having all hydroxyl groups derivatized with a single substituent type. Such a derivative is a persubstituted cyclodextrin. Cyclodextrin with selected substituents (i.e.) substituted only on the primary hydroxyl or selectively substituted only at one or both the secondary hydroxyl groups can also be synthesized if desired. Further directed synthesis of a derivatized molecule with two different substituents or three different substituents is also possible. These substituents can be placed at random or directed to a specific hydroxyl. For the purposes of this invention, the cyclodextrin molecule needs to contain sufficient thermoplastic compatible substituent groups on the molecule to insure that the cyclodextrin material can be uniformly dispersed into the thermoplastic and when formed into a clear film, sheet or rigid structure, does not detract from the polymer physical properties.
Apart from the introduction of substituent groups on the CD hydroxyl other molecule modifications can be used. Other carbohydrate molecules can be incorporated into the cyclic backbone of the cyclodextrin molecule. The primary hydroxyl can be replaced using SN 2 displacement, oxidized dialdehyde or acid groups can be formed for further reaction with derivatizing groups, etc. The secondary hydroxyls can be reacted and removed leaving an unsaturated group to which can be added a variety of known reagents. that can add or cross a double bond to form a derivatized molecule.
Further, one or more ring oxygen of the glycan moiety can be opened to produce a reactive site. These techniques and others can be used to introduce compatibilizing substituent groups on the cyclodextrin molecule.
The preferred preparatory scheme for producing a derivatized cyclodextrin material having a functional group compatible with the thermoplastic polymer involves reactions at the primary or secondary hydroxyls of the cyclodextrin molecule. Broadly we have found that a broad range of pendant substituent moieties can be used on the molecule. These derivatized cyclodextrin molecules can include acylated cyclodextrin, alkylated cyclodextrin, cyclodextrin esters such as tosylates, mesylate and other related sulfo derivatives, hydrocarbyl-amino cyclodextrin, alkyl phosphono and alkyl phosphato cyclodextrin, imidazoyl substituted cyclodextrin, pyridine substituted cyclodextrin, hydrocarbyl sulphur containing functional grouβ cyclodextrin, silicon-containing functional group substituted cyclodextrin, carbonate and carbonate substituted cyclodextrin, carboxylic acid and related substituted cyclodextrin and others. The substituent moiety must include a region that provides compatibility to the derivatized material.
Acyl groups that can be used as compatibilizing functional groups include acetyl, propionyl, butyryl, trifluoroacetyl, benzoyl, acryloyl and other well known groups. The formation of such groups on either the primary or secondary ring hydroxyls of the cyclodextrin molecule involve well known reactions. The acylation reaction can be conducted using the appropriate acid anhydride, acid chloride, and well known synthetic protocols. Peracylated cyclodextrin can be made. Further, cyclodextrin having less than all of available hydroxyls substituted with such groups can be made with one or more of the balance of the available hydroxyls substituted with other functional groups.
Cyclodextrin materials can also be reacted with alkylating agents to produced an alkylated cyclodextrin. Alkylating groups can be used to produce peralkylated cyclodextrin using sufficient reaction conditions exhaustively react available hydroxyl groups with the alkylating agent. Further, depending on the alkylating agent, the cyclodextrin molecule used in the reaction conditions, cyclodextrin substituted at less than all of the available hydroxyls can be produced. Typical examples of alkyl groups useful in forming the alkylated cyclodextrin include methyl, propyl, benzyl, isopropyl, tertiary butyl, allyl, trityl, alkyl-benzyl and other common alkyl groups. Such alkyl groups can be made using conventional preparatory methods, such as reacting the hydroxyl group under appropriate conditions with an alkyl halide, or with an alkylating alkyl sulfate reactant.
Tosyl(4-methylbenzene sulfonyl) mesyl (methane sulfonyl) or other related alkyl or aryl sulfonyl forming reagents can be used in manufacturing compatibilized cyclodextrin molecules for use in thermoplastic resins. The primary --OH groups of the cyclodextrin molecules are more readily reacted than the secondary groups. However, the molecule can be substituted on virtually any position to form useful compositions.
Such sulfonyl containing functional groups can be used to derivatize either of the secondary hydroxyl groups or the primary hydroxyl group of any of the glucose moieties in the cyclodextrin molecule. The reactions can be conducted using a sulfonyl chloride reactant that can effectively react with either primary or secondary hydroxyl. The sulfonyl chloride is used at appropriate mole ratios depending on the number of target hydroxyl groups in the molecule requiring substitution. Both symmetrical (per substituted compounds with a single sulfonyl moiety) or unsymmetrical (the primary and secondary hydroxyls substituted with a mixture of groups including sulfonyl derivatives) can be prepared using known reaction conditions. Sulfonyl groups can be combined with acyl or alkyl groups generically as selected by the experimenter. Lastly, monosubstituted cyclodextrin can be made wherein a single glucose moiety in the ring contains between one and three sulfonyl substituents. The balance of the cyclodextrin molecule remaining unreacted.
Amino and other azido derivatives of cyclodextrin having pendent thermoplastic polymer containing moieties can be used in the sheet, film or container of the invention. The sulfonyl derivatized cyclodextrin molecule can be used to generate the amino derivative from the sulfonyl group substituted cyclodextrin molecule via nucleophilic displacement of the sulfonate group by an azide (N 3 -1 ) ion. The azido derivatives are subsequently converted into substituted amino compounds by reduction. Large-numbers of these azido or amino cyclodextrin derivatives have been manufactured. Such derivatives can be manufactured in symmetrical substituted amine groups (those derivatives with two or more amino or azido groups symmetrically disposed on the cyclodextrin skeleton or as a symmetrically substituted amine or azide derivatized cyclodextrin molecule. Due to the nucleophilic displacement reaction that produces the nitrogen containing groups, the primary hydroxyl group at the 6-carbon atom is the most likely site for introduction of a nitrogen containing group. Examples of nitrogen containing groups that can be useful in the invention include acetylamino groups (-NHAc), alkylamino including methylamino, ethylamino, butylamino, isobutylamino, isopropylamino, hexylamino, and other alkylamino substituents. The amino or alkylamino substituents can further be reactive with other compounds that react with the nitrogen atom to further derivatize the amine group. Other possible nitrogen containing substituents include dialkylamino such as dimethylamino, diethylamino, piperidino, piperizino, quaternary substituted alkyl or aryl ammonium chloride substituents, halogen derivatives of cyclodextrins can be manufactured as a feed stock for the manufacture of a cyclodextrin molecule substituted with a compatibilizing derivative. In such compounds the primary or secondary hydroxyl groups are substituted with a halogen group such as fluoro, chloro, bromo, iodo or other substituents. The most likely position for halogen substitution is the primary hydroxyl at the 6-position.
Hydrocarbyl substituted phosphono or hydrocarbyl substituted phosphato groups can be used to introduce compatible derivatives onto the cyclodextrin. At the primary hydroxyl, the cyclodextrin molecule can be substituted with alkyl phosphato, aryl phosphato groups. The 2, and 3, secondary hydroxyls can be branched using an alkyl phosphato group.
The cyclodextrin molecule can be substituted with heterocyclic nuclei including pendent imidazole groups, histidine, imidazole groups, pyridino and substituted pyridino groups.
Cyclodextrin derivatives can be modified with sulfur containing functional groups to introduce compatibilizing substituents onto the cyclodextrin. Apart from the sulfonyl acylating groups found above, sulfur containing groups manufactured based on sulfhydryl chemistry can be used to derivatize cyclodextrin. Such sulfur containing groups include methylthio (-SMe) , propylthio (-SPr), t-butylthio (--S--C(CH 3 ) 3 ), hydroxyethylthio (--S--CH 2 CH 2 OH), imidazolylmethylthio, phenylthio, substituted phenylthio, aminoalkylthio and others. Based on the ether or thioether chemistry set forth above, cyclodextrin having substituents ending with a hydroxyl aldehyde ketone or carboxylic acid functionality can be prepared. Such groups include hydroxyethyl, 3-hydroxypropyl, methyloxylethyl and corresponding oxeme isomers, formyl methyl and its oxeme isomers, carbylmethoxy (--O--CH 2 --CO 2 H), carbylmethoxymethyl ester (--O--CH 2 CO 2 --CH 3 ). Cyclodextrin with derivatives formed using silicone chemistry can contain compatibilizing functional groups.
Cyclodextrin derivatives with functional groups containing silicone can be prepared. Silicone groups generally refer to groups with a single substituted silicon atom or a repeating silicone-oxygen backbone with substituent groups. Typically, a significantly proportion of silicone atoms in the silicone substituent bear hydrocarbyl (alkyl or aryl) substituents. Silicone substituted materials generally have increased thermal and oxidative stability and chemical inertness. Further, the silicone groups increase resistance to weathering, add dielectric strength and improve surface tension. The molecular structure of the silicone group can be varied because the silicone group can have a single silicon atom or two to twenty silicon atoms in the silicone moiety, can be linear or branched, have a large number of repeating silicone-oxygen groups and can be further substituted with a variety of functional groups. For the purposes of this invention the simple silicone containing substituent moieties are preferred including trimethylsilyl, mixed methyl-phenyl silyl groups, etc. We are aware that certain βCD and acetylated and hydroxy alkyl derivatives are available from American Maize-Products Co., Corn Processing Division, Hammond, Ind.
Packages and Packed Items
The thermoplastic containing the compatible derivatized cyclodextrin can be used in a variety of packaging formats to package a variety of items. General packaging ideas can be used. For example, the items can be packaged entirely in a film pouch, bag, etc. Further, the film can be used as a film closure on a rigid plastic container. Such containers can have a rectangular, circular, square or other shaped cross-section, a flat bottom and an open top. The container and a thermoplastic film closure can be made of the thermoplastic materials of the invention. Further, the thermoplastics of the invention can be used in the formation of blister pack packaging, clam shell type enclosures, tub, tray, etc. Generally, two product types require packaging in thermoplastic film of the invention having substantial barrier properties. In one product type, protecting the product from contamination from permeant sources outside the packaging material is important. Protecting food items from contamination by aromatic and aliphatic hydrocarbons, fluorocarbons, ink and packaging residue, exhaust from transportation equivalent and other internal combustion engines, perfumes commonly used in a variety of consumer products such as scented paper products, bar soap, scented bath products, cleaners, fabric softeners, detergents, dry bleaches, disinfectants, etc. All food items are the most common material requiring protection from outside contamination, other items can be sensitive to odors. Further, a variety of materials must be packaged in barrier materials preventing the odor of the material from exiting the package. A large variety of food odors are readily transmitted by a variety of packaging materials. Such food odors can attract insect and rodent pests, can be objectionable to customers or employees or can result in the substantial loss of important fragrance notes from packaged materials reducing product value. Important odors requiring substantial barriers include odors derived from coffee, ready to eat cereal, frozen pizza, cocoa or other chocolate products, dry mix gravies and soups, snack foods (chips, crackers, popcorn, etc.), baked foods, dry pet food (cat food, etc.), butter or butter-flavor notes, meat products, in particular butter or butter-flavor notes used in the manufacture of microwave popcorn in microwaveable paper containers, fruits and nuts, etc.
The above explanation of the nature of the cyclodextrin derivatives, thermoplastic films, manufacturing detail regarding the production of film, and the processes of cyclodextrin to make compatible derivatives provides a basis for understanding technology involving incorporating compatible cyclodextrin in thermoplastic film for barrier purposes. The following examples, film preparation and permeation data provide a further basis for understanding the invention and includes the best mode.
After our work in producing derivatives of cyclodextrins and compounding the cyclodextrins in thermoplastic. films, we have found that the cyclodextrins can be readily derivatized using a variety of known chemical protocols. The cyclodextrin material can be melt blended into thermoplastic materials smoothly resulting in clear extrudable thermoplastic materials with the cyclodextrin materials uniformly distributed throughout the thermoplastic. Further, we have found that the cyclodextrin derivatives can be combined with a broad variety of thermoplastic films. The cyclodextrin materials can be incorporated into the films in a broad range of cyclodextrin concentrations. The cyclodextrin containing thermoplastic materials can be blown into films of varying thickness and can be blown free of melt fracture or other film or sheet variation. We have found in our experimentation that the barrier properties, i.e. reduction in transmission rate of aromatic hydrocarbons, aliphatic hydrocarbons, ethanol and water vapor can be achieved using the cyclodextrin derivative technology. We have also found that the use of cyclodextrin materials improve the surface properties of the film. The surface tension of the film surface and surface electrical properties were also improved. Such a result increases the utility of the films of the invention in coating, printing, laminating, hangdling, etc. In initial work we have also found (1) several modified cyclodextrin candidates were found to be compatible with the LLDPE resin and provide good complexation of residual LLDPE volatile contaminants as well as reduce organic permeants diffusing through the film. (2) Unmodified βCD adversely affects transparency, thermal stability, machinability, and barrier properties of the film. Conversely, selected modified βCD (acetylated and trimethylsilyl ether derivatives) have no affect on transparency and thermal stability. The machinability of the extruded plastic material is effected somewhat causing some surface defects, thereby reducing the barrier properties of the film. (3) Films containing a modified PCD composition (1% by weight) reduce aromatic permeants by 35% at 72° F. and 38% at 105° F.; aliphatic permeants were reduced by only 9% at 72 F. These results would improve significantly if worst case shelf-life testing conditions were not used to test the films. (4) Complexation rates were different for aromatic and aliphatic permeants. Films containing modified βCD had better complexation rates for aromatics (gasoline-type compounds) than aliphatic (printing ink-type compounds). Conversely, film coating had significantly better complexation of aliphatic compound than aromatic compounds. (5) βCD containing acrylic coatings were the star performers reducing aliphatic permeants from 466to 88%, while aromatics were reduced by 29%.
QUALITATIVE PREPARATION
Initially, we produced four experimental test films. Three of the films contained p-cyclodextrin βCD at loading of 1%, 3% and 5% (wt./wt.) while the fourth was a control film made from the same batch of resin and additives but without PCD. The 5% loaded βCD film was tested for complexation of residual organic in the test film. Even though βCD . was found to effectively complex residual organics in the linear low density polyethylene (LLDPE) resin, it was incompatible with the resin and formed PCD particle agglomerations.
We have evaluated nine modified Pcyclodextrins and a milled P-cyclodextrin (particle size 5 to 20 microns). The different cyclodextrin modifications were acetylated, octanyl succinate, ethoxyhexyl glycidyl ether, quaternary amine, tertiary amine, carboxymethyl, succinylated, amphoteric and trimethylsilyl ether. Each experimental cyclodextrin (1% loading wt/wt) was mixed with low density polyethylene (LLDPE) using a Littleford mixer and then extruded using a twin screw Brabender extruder.
The nine modified cyclodextrin and milled cyclodextrin LLDPE profiles were examined under an optical microscope at 50X and 200X magnification. The microscopic examination was used to visually check for compatibility between LLDPE resin and cyclodextrin. Of the ten cyclodextrin candidates tested , three-(acetylated, octanyl succinate and trimethylsilyl ether) were found visually to be compatible with the LLDPE resin.
Complexed residual film volatiles were measured using cryotrapping procedure to test 5% βCD film sample and three extruded profiles containing 1% (wt/wt) acetylated PCD octanyl succinate βCD and trimethylsilyl ether. The method consists of three separate steps; the first two are carried out simultaneously while the third, an instrumental technique for separating and detecting volatile organic compounds, is conducted after one and two. In the first step, an inert pure, dry gas is used to strip volatiles from the sample. During the gas stripping step, the sample is heated at 120° C. The sample is spiked with a surrogate (benzene-d6) immediately prior to the analysis. Benzene-d 6 serves as an internal QC surrogate to correct each set of test data for recovery. The second step concentrates the volatiles removed from the sample by freezing the compounds from the stripping gas in a headspace vial immersed in a liquid nitrogen trap. At the end of the gas-stripping step, an internal standard (toluene-d8) is injected directly into the headspace vial and the vial is capped immediately. Method and system blanks are interspersed with samples and treated in the same manner as samples to monitor contamination. The concentrated organic components are then separated, identified and quantitated by heated headspace high resolution gas chromatography/mass spectrometry (HRGC/MS). The results of the residual volatile analyses are presented in the table below:
TABLE 1______________________________________ % Volatile ComplexationSample Identification as Compared to Control______________________________________5% βCD Blown Film 801% Acylated βCD Profile 471% Octanyl Succinate βCD Profile 01% Trimethylsilyl ether Profile 481% βCD Milled Profile 29______________________________________
In these preliminary screening tests, βCD derivatives were shown to effectively complex trace volatile organics inherent in low density polyethylene resin used to make experimental film. In 5% βCD loaded LLDPE film, approximately 80% of the organic volatiles were complexed. However, all βCD films (1% and 5%) had an off-color (light brown) and off-odor. The color and odor problem is believed to be the result of direct decomposition of the CD or impurity in the CD. Two odor-active compounds (2-furaldehyde and 2-furanmethanol) were identified in the blown film samples.
Of the three modified compatible CD candidates (acetylated, octanyl succinate and trimethylsilyl ether), the acetylated and trimethylsilyl ether CD were shown to effectively complex trace volatile organics inherent in the LLDPE resin. One percent loadings of acetylated and gtrimethylsilyl ether (TMSE) βCD showed approximately 50% of the residual LPDE organic volatiles were complexed, while the octanyl succinate CD did not complex residual LLDPE resin volatiles. Milled βCD was found to be less effective (28%) than the acetylated and TMSE modified PCD's.
Plastic packaging materials all interact to some degree with the food product they protect. The main mode of interaction of plastic packaging of food is through the migration of organic molecules from the environment through the polymer film into the head space of the package where they are absorbed by the food product. Migration or transfer of organic molecules of the package to the food, during storage, is effected by environmental conditions such as temperature, storage time, and other environmental factors (e.g., humidity, type of organic molecules and concentration thereof). Migration can have both quality (consumer resistance) and toxicological influence. The objective of packaging film testing is to measure how specific barriers may influence the quality of packaged individual foods. To simulated accelerated shelf-life testing for low-water-activity food products, the testing was conducted at a temperature of 72° F. and 105° F., and a relative humidity of 60%. These temperature and humidity conditions are probably similar to those found in uncontrolled warehouses, in transit, and in storage.
If a polymer is moisture sensitive, the relative humidity can affect the film's performance especially in low-water-activity food products. Because a packaging film during actual end-use conditions will be separating two moisture extremes, relative humidity in the permeation device was controlled on both sides of the film. The environment side, representing the outside of the package, was maintained at 60% relative humidity, and the sample side, representing the inside of a package containing a low-water-activity product, at 0.25.
A combination of permeants was used to measure the function and performance of the CD. A combination was used to be realistic, since gasoline (principally an aromatic hydrocarbon mixture) and printing ink solvents (principally an aliphatic hydrocarbon mixture) are not formed from a single compound but are a mixture of compounds.
The aromatic permeant contained ethanol (20 ppm), gtoluene (3 ppm), p-xylene (2 ppm), o-xylene (1 ppm), trimethyl-benzene (0.5 ppm) and naphthalene (0.5 ppm). The aliphatic permeant, a commercial paint solvent blend containing approximately twenty (20) individual compounds, was 20 ppm.
The permeation test device FIG. 3 consists of two glass permeation cells or flasks with cavities of 1200 ml (environment cell or feed side) and 300 ml (sample cell or permeating side).
Experimental film performance was measured in the closed-volume permeation device. High-resolution gas chromatograph (HRGC) operated with a flame ionization detector (FID) was used to measure the change in the cumulative penetrant concentration as a function of time. Sample-side (food product side) compound concentrations are calculated from each compound's response factor. Concentrations are reported in parts per million (ppm) on a volume/volume basis. The cumulative penetrant concentration on the sample-side of the film is plotted as a function of time.
We produced four experimental test films. Three of the films contained ACD at loading of 1%, 3% and 5% (wt/wt) while the fourth was a control film made from the same batch of resin and additives but without PCD.
A second experimental technique was also undertaken to determine whether βCD sandwiched between two control films will complex organic vapors permeating the film. The experiment was carried out by lightly dusting βCD between two control film sheets.
The testing showed the control film performed better than βCD loaded films. The permeation test results also demonstrated the higher the ACD loading the poorer the film performed as a barrier. The test results for sandwiching PCD between two control films showed βCD being twice as effective in reducing permeating vapors than the control samples without ACD. This experiment supported that CD does complex permeating organic vapors in the film if the film's barrier qualities are not changed during the manufacturing process making the film a less effective barrier.
The 1% TMSE βCD film was slightly better than the 1% acetylated ACD film (24% -vs- 26%) for removing aromatic permeants at 72° F. adding more modified CD appeared to have no improvement.
For aromatic permeants at 105° F., both 1% TMSE βCD and 1% acetylated ACD are approximately 13% more effective removing aromatic permeants than 72° F. The 1% TMSE film was again slightly better than the 1% film (36% -vs- 31%) for removing aromatic permeants.
The 1% TMSE film was more effective initially removing aliphatic permeants than the 1% acetylated βCD film at 72° F. But for the duration of the test, 1% TMSE βCD was worse than the control while 1% acetylated βCD removed only 6% of the aliphatic permeants.
We produced two experimental aqueous coating solutions. One solution contained hydroxyethyl βCD (35% by weight) and the other solution contained hydroxypropyl βCD (35 by weight). Both solutions contained 10% of an acrylic emulsion comprising a dispersion of polyacrylic acid having a molecular weight of about 150,000 (Polysciences, Inc.) (15% solids by weight) as a film forming adhesive. These solutions were used to hand-coat test film samples by laminating two LLDPE films together. Two different coating techniques were used. The first technique very slightly stretched two film samples flat, the coating was then applied using a hand roller, and then the films were laminated together while stretched flat. The Rev. 1 samples were not stretched during the lamination process. All coated samples were finally placed in a vacuum laminating press to remove air bubbles between the film sheets. Film coating thicknesses were approximately 0.0005 inches. These CD coated films and hydroxylmethyl cellulose coated control films were subsequently tested.
A reduction in aromatic and aliphatic vapors by the hydroxyethyl βCD coating is greater in the first several hours of exposure to the vapor and then diminishes over the next 20 hours of testing. Higher removal of aliphatic vapors than aromatic vapors was achieved by the hydroxyethyl βCD coating; this is believed to be a function of the difference in their molecular size (i.e., aliphatic compounds are smaller than aromatic compounds). Aliphatic permeants were reduced by 466 as compared to the control over the 20 hour test period. Reduction of aromatic vapors was 29% as compared to the control over the 17 hour test period.
The Rev. 1 coated hydroxyethyl βCD reduced the aliphatic permeants by 87% as compared to the control over the 20 hour test period. It is not known if the method of coating the film was responsible for the additional 41% reduction over the other hydroxyethyl βCD coated film.
The hydroxyethyl βCD coating was slightly better for removing aromatic permeants than the hydroxypropyl PCD coating (29% -vs- 20%) at 72° F.
LARGE SCALE FILM EXPERIMENTAL
Preparation of Cyclodextrin Derivatives
Example I
An acetylated β-cyclodextrin was obtained that contained 3.4 acetyl groups per cyclodextrin on the primary --OH group.
Example II
Trimethyl Silyl Ether of P-cyclodextrin
Into a rotary evaporator equipped with a 4000 milliliter round bottom flask and a nitrogen atmosphere, introduced at a rate of 100 milliliters N 2 per minute, was placed three liters of dimethylformamide. Into the dimethylformamide was placed 750 grams of β-cyclodextrin. The β-cyclodextrin was rotated and dissolved in dimethylformamide at 60° C. After dissolution, the flask was removed from the rotary evaporator and the contents were cooled to approximately 18° C. Into the flask, placed on a magnetic stirrer and equipped with a stir bar, was added 295 milliliters of hexamethyldisilylazine (HMDS-Pierce Chemical No. 84769), followed by the careful addition of 97 milliliters of trimethylchlorosilane (TMCS-Pierce Chemical No. 88531). The careful addition was achieved by a careful dropwise addition of an initial charge of 20 milliliters and after reaction. subsides the careful dropwise addition of a subsequent 20 milliliter portions, etc. until addition is complete. After the addition of the T XCS was complete, and after reaction subsides, the flask and its contents were placed on the rotary evaporator, heated to 60° C. while maintaining an inert nitrogen atmosphere flow of 100 milliliters of N 2 per minute through the rotary evaporator. The reaction was continued for four hours followed by removal of solvent, leaving 308 grams of dry material. The material was removed from the flask by filtering, washing the filtrate with deionized water to remove the silylation products, vacuum oven drying (75° C. at 0.3 inches of Hg) and stored as a powdered material and maintained for subsequent compounding with a thermoplastic material. Subsequent spectrographic inspection of the material showed the β-cyclodextrin to contain approximately 1.7 trimethylsilylether substituent per β-cyclodextrin molecule. The substitution appeared to be commonly on a primary 6-carbon atom.
Example III
An hydroxypropyl β-cyclodextrin was obtained with 1.5 hydroxypropyl groups per molecule on the primary 6--OH group of the PCD.
Example IV
An hydroxyethyl β-cyclodextrin was obtained with 1.5 hydroxyethyl groups per molecule on the primary 6--OH group of the PCD.
Preparation of Films
We prepared a series of films using a linear low density polyethylene resin, βCD and derivatized βCD such as the acetylated or the trimethylsilyl derivative of a Pcyclodextrin. The polymer particles were dry blended with the powdered β-cyclodextrin and β-cyclodextrin derivative material, a fluoropolymer lubricant (3M) and the antioxidant until uniform in the dry blend. The dry blend material was mixed and extruded in a pellet form in a Haake System 90, 3/4" conical extruder. The resulting pellets were collected for film preparation.
Table IA displays typical pelletizing extruder conditions. The films were blown in the apparatus of FIG. 2. FIG. 2 shows extruded thermoplastic tube 21 exiting the die 22. The tube is collapsed by die 23 and layered by rollers 24 into the film 25. The extruded tube 21 is inflated using air under pressure blown through air inlet tube 26. The thermoplastic is melted in the extruder. The extruder temperature is taken at the mixing zone 27. The melt temperature is taken in the melt zone 28 while the die temperature is taken in the die 29. The extrudate is cooled using an air blown cooling stream from the cooling ring 20. The general schematic background of FIG. 2 is representative of the Kiefel blown film extruder, 40 mm die diameter, used in the actual preparation of the blown film. The film is manufactured according to the above protocol and reported in Table IB. The film was tested for transmission rates at a variety of environmental conditions. Environmental test conditions are shown below in Table II.
TABLE IA______________________________________0.5% TMSE Pelletizing 1-19-94______________________________________Run Time 0 min Torque 4866 meter-gram Rotor 198 rpm 13 sec Tot. Torque 0.0 mkg-min Aux. 0%______________________________________Channels 1 2 3 4 5 6______________________________________Melt Temp 37 41 41 41 41 °C.Set Temp 150 160 160 170 0 0 °C.Deviation 0 0 0 0 0 0 °C.Cooling Yes Yes Yes YesPressure 0 0 2739 0 0 psi______________________________________
TABLE IB__________________________________________________________________________Extruded Films (Exxon LL3201)Made With Low Density PolyethyleneRoll Fluoropolymer Extruder Temp. Melt Die Temp. DieNo. Sample ID Additive.sup.1 Zone 3 (F.) Temp (F.) Zone 3 (F.) Lbs./Hr RPM Gap Comments__________________________________________________________________________1 Control 500 ppm 428 406 406 30.1 50 242 1% Ex. I 1000 ppm 441 415 420 29.7 50 353 1% Ex. I 1000 ppm 441 416 420 28.5 50 354 1% Ex. I 500 ppm 441 415 420 29.9 50 355 1% Ex. I 500 ppm 418 405 414 29.9 50 356 1% Ex. I 500 ppm 421 397 414 29.0 50 357 0.5% Ex. I 500 ppm 421 403 415 29.0 50 358 2% Ex. I 500 ppm 421 404 415 27.7 50 35 Very slight melt fracture9 1% Ex. II 500 ppm 421 406 415 28.3 50 35 Particlee in film.10 1% Ex. II 500 ppm 426 410 415 26.7 50 35 Particles in film.11 1% Ex. II 500 ppm 432 415 414 29.0 50 35 Particles in film. Very slight yellowing to film.12 1% Ex. II 500 ppm 431 414 415 21.5 39 35 Particles in film.13 0.5% Ex. II 500 ppm 431 415 415 27.7 50 35 Particles in film.14 0.5% Ex. II 500 ppm 425 410 415 28.9 50 35 Particles in film.15 2% Ex. II 500 ppm 410 414 415 20.2 38 35 Particles in film. Very slight yellowing to film.16 2% Ex. II 500 ppm 422 415 415 20.5 38 35 Particles in film. Very slight yellowing to film.17 2% Ex. II 500 ppm 422 416 415 20.5 38 35 Particles in film.__________________________________________________________________________ Very .sup.1 Also contains 500 ppm Irganox 1010 antioxidant and 1000 ppm IrgaFo 168.
TABLE II______________________________________Test Conditions______________________________________Roll Sample Temp. Sample Environ.ID Number (F.) Side Side Permeant.sup.2______________________________________Roll #2 72 Rm % RH Rm % RH Aromatic/AlcoholRoll #3Roll #5Roll #6Roll #5 72 Rm % RH Rm % RH Aromatic/AlcoholRoll #8Roll #7 72 0.25 Aw 60% RH Aromatic/AlcoholRoll #5Roll #8Roll #7 72 .60 Aw 30% RH Aromatic/AlcoholRoll #5Roll #8Roll #2 105 Rm % RH Rm % RH Aromatic/AlcoholRoll #3Roll #4Roll #5Roll #6Roll #8Roll #12Roll #7 105 0.25 Aw 15% RH Aromatic/AlcoholRoll #5Roll #8Roll #13 72 Rm % RH Rm % RH Aromatic/AlcoholRoll #14Roll #9Roll #9Roll #11Roll #12______________________________________Roll Sample Temp. Sample Environ.ID Number (F.) Side Side Permeant.sup.34______________________________________Roll #15Roll #16Roll #17Roll #14 105 Rm % RH Ra % RH Aromatic/AlcoholRoll #1510% Ex. III 72 0.25 Aw 60% RH Aromatic/Alcoholin PVdC20% Ex. IIIin PVdC5% Ex. III/ 72 Rm % RH Rm % RH Aromatic/AlcoholAcrylic10% Ex. III/AcrylicRoll #7 72 Rm % RH Rm % RH NaphthaRoll #5Roll #8Roll #12 72 Rm % RH Rm % RH NaphthaRoll #15______________________________________ .sup.2 7 ppm aromatic plus 20 ppm ETOH. .sup.3 7 ppm aromatic plus 20 ppm ETOH. .sup.4 40 ppm Naphtha
The results of the testing show that the inclusion of a compatible cyclodextrin material in the thermoplastic films of the invention substantially improves the barrier properties by reducing transmission rate of a variety of permeants. The data showing the improvement in transmission rate is shown below in the following data tables.
__________________________________________________________________________Comparison of Transmission Rates in Modified β-Cyclodextrin - LPDEFilms__________________________________________________________________________Temperature 72° F.Sample Side: Room % RHEnvironment: Room % RH Aromatics % Tot. Volitiles %Sample Aromatic Improvement Total Volitiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________Control Film 3.35E-04 0% 3.79E-04 0%1.0% CS-001 (Roll #2) 3.18E-04 5% 3.61E-04 5%1.0% CS-001 (Roll #3) 2.01E-04 40% 2.55E-04 33%1.0% CS-001 (Roll #5) 2.67E-04 20% 3.31E-04 13%1.0% CS-001 (Roll #6) 3.51E-04 -5% 3.82E-04 -1%__________________________________________________________________________Temperature 72° F.Sample Side: Room % RHEnvironment: Room % RH Naphtha %Sample Aromatic ImprovementIdentification Transmission Rate* Over Control__________________________________________________________________________Control Film (Roll #1) 7.81E-03 0%0.5% CS-001 (Roll #7) 7.67E-03 2%1% CS-001 (Roll #5) 7.37E-03 6%2% CS-001 (Roll #8) 6.53E-D3 16%__________________________________________________________________________Temperature 72° F.Sample Side: Room % RHEnvironment: Room % RH Aromatics % T. Volatiles %Sample Aromatic Improvement Total Volatiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________Control Film (Roll #1) 5.16E-04 0% 5.63E-04 0%1.0% CS-001 (Roll #5) 4.01E-04 22% 5.17E-04 8%2.0% CS-001 (Roll #8) 2.91E-04 44% 3.08E-04 45%__________________________________________________________________________Temperature 72° F.Sample Side: Room % RHEnvironment: Room % RH Naphtha %Sample Aromatic ImprovementIdentification Transmission Rate* Over Control__________________________________________________________________________Control Film (Roll #1) 7.81E-03 0%0.5% CS-001 (Roll #7) 7.67E-03 2%1% CS-001 (Roll #5) 7.37E-03 6%2% CS-001 (Roll #8) 6.535-03 16%__________________________________________________________________________Temperature 72° F.Sample Side: 0.25 AwEnvironment: 60% RH Aromatics % T. Volatiles %Sample Aromatic Improvement Total Volatiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________Control Film (Roll #1) 3.76E-04 0% 3.75E-04 0%0.5% CS-001 (Roll #7) 2.42E-04 36% 2.41E-04 36%1% CS-001 (Roll #5) 3.39E-04 10% 3.38E-04 10%2% CS-001 (Roll #8) 2.48E-04 34% 2.47E-04 34%__________________________________________________________________________Temperature 105° F.Sample Side: Room % RHEnvironment: Room % RH Aromatics % T. Volatiles %Sample Aromatic Improvement Total Volatiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________Control Film (Roll #1) 1.03E-03 0% 1.13E-03 0%1% CS-001 (Roll #2) 5.49E-04 47% 5.79E-04 49%1% CS-001 (Roll #3) 4.74E-04 54% 5.00E-04 56%1% CS-001 (Roll #4) 6.41E-04 38% 6.83E-04 40%1% CS-001 (Roll #5) 5.22E-04 49% 5.54E-04 51%1% CS-001 (Roll #6) 4.13E-04 60% 4.39E-04 61%2% CS-001 (Roll #8) 5.95E-04 42% 6.18E-04 45%1% TMSE (Roll #12) 8.32E-04 19% 8.93E-04 21%__________________________________________________________________________Temperature 105° F.Sample Side: Room % RHEnvironment: Room % RH Aromatics % T. Volatiles %Sample Aromatic Improvement Total Volatiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________Control Film (Roll #1) 4.34E-04 0% 4.67E-04 0%0.5% CS-001 (Roll #7) 4.03E-04 7% 4.41E-04 6%1.0% CS-001 (Roll #5) 5.00E-04 -15% 5.33E-04 -14%2.0% CS-001 (Roll #8) 3.96E-04 9% 3.94E-04 16%__________________________________________________________________________Temperature 72° F.Sample Side: Room % RHEnvironment: Room % RH Aromatics % T. Volatiles %Sample Aromatic Improvement Total Volatiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________Control Film 3.09E-04 0% 3.45E-04 0%0.5% TMSE (Roll #13) 2.50E-04 19% 2.96E-04 14%0.5% TMSE (Roll #14) 2.37E-04 23% 2.67E-04 33%1% TMSE (Roll #9) 2.67E-04 14% 3.05E-04 12%1% TMSE (Roll #10) 4.85E-04 -57% 5.27E-04 -53%1% TMSE (Roll #11) 2.58E-04 17% 2.92E-04 15%1% TMSE (Roll #12) 2.1SE-04 31% 2.55E-04 26%2% TMSE (Roll #15) 2.54E-04 18% 3.04E-04 12%2% TMSE (Roll #16) 2.79E-04 10% 3.21E-04 7%2% TMSE (Roll #17) 2.81E-04 9% 3.24E-04 6%__________________________________________________________________________Temperature 72° F.Sample Side: Room % RHEnvironment: Room % RH Naphtha %Sample Aromatic ImprovementIdentification Transmission Rate* Over Control__________________________________________________________________________Control Film (Roll #1) 9.43E-03 0%1% TMSE (Roll #12) 1.16E-02 -23%2% TMSE (Roll #15) 1.56E-02 -65%__________________________________________________________________________Temperature 72° F.Sample Side: Room % RHEnvironment: Room % RH Aromatics % T. Volatiles %Sample Aromatic Improvement Total Volatiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________Control Film (Roll #1) 8.36E-04 0% 9.05E-04 0%0.5% TMSE (Roll #14) 6.77E-04 19% 7.25E-04 20%2% TMSE (Roll #15) 6.36E-04 24% 6.81E-04 25%__________________________________________________________________________Temperature 72° F.Sample Side: Room 0.25 AwEnvironment: 60% RH Aromatics % T. Volatiles %Sample Aromatic Improvement Total Volatiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________PVdC Control 6.81E-05 0% 1.05E-04 0%PVdC w/ 10% HP B-CyD 1.45E-05 79% 2.39E-05 77%PVdC w/ 20% HP B-CyD 9.71E-05 -42% 1.12E-04 -7%__________________________________________________________________________Temperature 72° F.Sample Side: Room % RHEnvironment: Room % RH Aromatics % T. Volatiles %Sample Aromatic Improvement Total Volatiles ImprovementIdentification Transmission Rate* Over Control Tranamission Rate* Over Control__________________________________________________________________________Control Acrylic 2.07E-06 0% 2.10E-05 0%5% HP B-CyD/Acrylic 1.50E-06 27% 2.07E-05 1%10% HP B-CyD/Acrylic 4.13E-06 -100% 4.30E-05 -105%__________________________________________________________________________ ##STR2##
We prepared a series of aqueous coatings containing hydroxypropyl ACD. One of the coatings was prepared from a 10% acrylic emulsion (a polyacrylic acid polymer having a molecular weight of about 150,000 purchased from Polysciences, Inc.). The 10% acrylic emulsion contained hydroxypropyl βCD at a 5% and 10% by weight loading. These solutions were used to hand-coat test film samples by laminating two films. The coatings were applied to linear low density polyethylene film sheet containing 0.5% acetylated βCD (Roll No. 7) and to a second film sheet containing 2% acetylated βCD (Roll No. 8) using a hand roller and then laminating the films. The films were not stretched during lamination. All coated samples were placed in a vacuum laminating press to remove air bubbles between the film sheets. The acrylic coating thickness was about 0.0002 inch. An acrylic coated control was prepared in an identical manner containing no hydroxypropyl PCD. The multilayer structure was tested with the 0.5% acetylated βCD film facing the environmental flask side of the test cell (FIG. 3).
A second coating was prepared from a vinylidene chloride latex (PVDC, 60 wt-% solids) purchased from Dagax Laboratories, Inc. The PVDC latex coating was prepared with two levels of hydroxypropyl βCD - 10% and 20% by weight of the derivatized cyclodextrin. These solutions were used to hand-coat linear low density polyethylene test film samples by laminating the two films together. The coatings were applied to two control film sheets (rolled into one) using a hand roller and laminated together. The films were not stretched during lamination process. All coated samples were placed in a vacuum laminating press to remove air bubbles between the film sheets. The PVDC coating thickness was approximately 0.0004 inch. A PVDC coated control was prepared in an identical manner but without hydroxypropyl PCD.
The data following the preparatory examples showing improvement in transmission rate was obtained using the following general test method.
Method Summary
This method involves experimental techniques designed to measure the permeability of selected organic molecules through food packaging films, using a static concentration gradient. The test methodology simulates accelerated shelf-life testing conditions by implementing various storage humidities, product water activities and temperature conditions and using organic molecule concentrations found in previously tested food products to simulate outside-the-package organic vapors in the permeation test cell. This procedure allows for the determination of the following compounds: ethanol, toluene, p-xylene, o-xylene, 1,2,4-trimethyl benzene, naphthalene, naphtha solvent blend, etc.
______________________________________ Threshold Environmental Odor Conc. Cell Conc.Test Compounds ul/L ppm ul/L ppm______________________________________Ethanol 5-5000 20Toluene 0.19-20 3p-Xylene 0.5 2o-Xylene 0.03-12 11,2,3-Trimethyl Benzene NA 0.5Naphthalene 0.001-0.03 0.5Naphtha Solvent Blend NA 40______________________________________
Table 1. Permeant Test Compounds
In a typical permeation experiment, three steps are involved. They are (a) the instrument sensitivity calibration, (b) film testing to measure transmission and diffusion rates, and (c) the quality control of the permeation experiment.
Film samples are tested in a closed-volume permeation device. High-resolution gas chromatograph (HRGC) operated with a flame ionization detector (FID) is used to measure the change in the cumulative penetrant concentration as a function of time.
Sample-side and environment-side test compound concentrations are calculated from each compound's response factor or calibration curve. Concentrations are then volume-corrected for each specific set of permeation cells if permeant mass is desired.
The cumulative penetrant concentration is plotted as a function of time on both the upstream (environment) and downstream (sample) side of the film. The diffusion rate and transmission rate of the permeant are calculated from the permeation curve data.
1.0 Equipment and Reagents
2.1 Equipment
Gas chromatograph (HP 5880) equipped with flame ionization detector, a six-port heated sampling valve with 1 ml sampling loop and data integrator
J&W capillary column. DB-5, 30M×0.250 mm ID, 1.0 umdf.
Glass permeation test cells or flasks. Two glass flasks with cavities of approximately 1200 ml (environment cell or feed side) and 300 ml (sample flask or permeating side) (FIG. 3).
Permeation cell clamping rings (2).
Permeation cell aluminum seal rings (2).
Natural Rubber Septa. 8 mm OD standard-wall or 9 mm OD (Aldrich Chemical Company, Milwaukee, Wis.).
Assorted laboratory glass ware and syringes.
Assorted laboratory supplies.
2.2 Reagents
Reagent water. Water in which interferences are not observed at the MDL of the chemical analytes of interest. A water purification system is used to generate-reagent water which has been boiled to 80% volume, capped, and allowed to cool to room temperature before use.
Stock Ethanol/Aromatic Standard solution. Ethanol (0.6030 gram), toluene (0.1722 gram), p-xylene (0.1327 gram), o-xylene (0.0666 gram), trimethylbenzene (0.0375 gram) and naphthalene (0.0400 gram) package in 1 ml sealed glass ampules. Naphtha blends standard is a commercial paint solvent blend containing approximately twenty (20) individual aliphatic hydrocarbon compounds obtained from Sunnyside Corporation, Consumer Products Division, Wheeling, Ill.
Triton X-100. Nonylphenol nonionic surface active agent (Rohm and Hass).
2.0 Standards Preparation
2.2 Permeation Working Standard
A stock permeant test standard solution is used. These standards are prepared by weight from neat certified reference compounds, actual weight and weight percent are shown.
The working ethanol/aromatic standard is prepared by injecting 250 ul of the stock standard solution into 100 ml of reagent water containing 0.1 gram of surfactant (Triton X-100). It is important that the Triton X-100 is completely dissolved in the reagent water prior to adding the permeant stock standard. This will insure dispersing the test compounds in the water. In addition, the working standard should be mixed thoroughly each time an aliquot is dispensed. It is advisable to transfer the working standard to crimp-top vials with no headspace to minimize losses due to the large headspace in the volumetric flask used to prepare the standard.
A working naphtha blend standard is prepared by injecting 800 μL of the "neat" naphtha solvent blend into 100 milliliters of reagent water containing 0.2 gram of surfactant (Triton X-100). An
An opened stock standard solution should be transferred from the glass snap-cap vial to a crimp-top vial for short-term storage. The vials may be stored in an explosion-proof refrigerator or freezer.
2.1 Calibration Standards
Calibration standards are prepared at a minimum of three concentration levels by adding volumes of the working standard to a volumetric flask and diluting to volume with reagent water. One of the standards is prepared at a concentration near, but above, the method detection limit. The other concentrations correspond to the expected range of concentrations found in the environment and sample side cells.
3.0 Sample Preparation
3.1 Film Sample Preparation
The environment flask FIG. 3 and sample flask are washed before use in soapy water, thoroughly rinsed with deionized water, and oven-dried. Following cleaning, each flask is fitted with a rubber septum.
The film test specimen is cut to the inside diameter of the aluminum seal ring using a template. The film test specimen diameter is important to prevent diffusion losses along the cut edge circumference. The film sample, aluminum seals, and flasks are assembled as shown in FIG. 3, but the clamping ring nuts are not tightened.
The test cell (FIG. 3) is prepared. First the sample flask 32 and environment flask 31 are flushed with dry compressed air to remove humidity in the sample and environment flasks. This is done by puncturing the sample system 33 and environment septum 34 with a needle and tubing assembly which permits a controlled flow of dry air through both flasks simultaneously. The clamp rings 35 are loosely fitted to the flasks to eliminate pressure buildup on either side of the film 30. After flushing both glass for approximately 10 minutes, the needles are removed and the clamp rings tightened, sealing the film 30 between the two flasks. Rubber faced aluminum spacers 36a, 36b are used to ensure a gas tight fit.
The sample side is injected with 2 μL of water per 300 ml flask volume. Since the sample flasks vary in volume, the water is varied to correspond to the volume variations. The 2 μL of water in the 300 ml flask volume is comparable to a 0.25 water activity product at 72° F. Next, 40 μL, the permeation ethanol/aromatic working standard or 40 μL of the naphtha blend working standard prepared according to section 2.2, is injected into the environmental flask. Either of these working standards will produce a 60% relative humidity at 72° F. with a permeant concentration (parts per million-volume/volume) in the 1200 ml volume flask indicated in Table I. Other humidities or permeant concentrations may be employed in the test method by using psychrometric chart to determine humidity and using the gas loss to calculate permeant concentration. The time is recorded and the permeation cell placed into a thermostatically controlled oven. Samples may be staggered to accommodate GC run time. Three identical permeation devices are prepared. Triplicate analyses are used for QC purposes.
At the end of each time interval, a sample from the group is removed from the oven. The environmental flask is analyzed first, using a heated six-port sampling valve fitted with a 1 ml loop. The loop is flushed with a 1 ml volume of the environment-side or sample-side air. The loop is injected onto the capillary column. The GC/FID system is started manually following the injection. Up to eight lml sample injections may be taken from the sample and environment side of a single permeation experiment.
Sample side and environment side test compound concentrations are calculated from each compound's calibration curve or response factor (equation 1 or 3). Concentrations are then volume-corrected for each specific set of permeation flasks if permeant mass is desired.
4.0 Sample Analysis
4.1 Instrument Parameters
Standards and samples are analyzed by gas chromatography using the following method parameters:
Column: J&W column, DB-5, 30 M, 0.25 mm ID, 1 umdf
Carrier: Hydrogen
Split Vent: 9.4 ml/min
Injection Port Temp: 105° C.
Flame Detector Temp: 200° C.
Oven Temp 1: 75° C.
Program Rate 1: 15° C.
Oven Temp 2: 125° C.
Rate 2: 20° C.
Final Oven Temp: 200° C.
Final Hold Time: 2 Min
The six-port sampling valve temperature is set to 105° C.
4.2 Calibration
A three point calibration is prepared using standards in the range of the following test compounds:
______________________________________ Calibration Curve RangeTest Compounds ppm (μL)______________________________________Ethanol 2-20Toluene 0.3-3p-Xylene 0.2-2o-Xylene 0.1-11,2,4-Trimethyl Benzene 0.05-0.5Naphthalene 0.05-0.5Naphtha Solvent Blend 4.0-40______________________________________
To prepare a calibration standard, add an appropriate volume of the working standard solution to an aliquot of reagent water in a volumetric flask.
4.2.1 Secondary Dilutions of Working Standard for
Calibration Curve
5 to 1 dilution: Place 5 ml of working standard into a 25-ml volumetric flask, stopper, then mix by inverting flask.
2.5 to 1 dilution: Place 10 ml of working standard into a 25-ml volumetric flask, stopper, then mix by inverting flask.
Analyze each calibration standard and tabulate compound peak area response versus the concentration of the test compound in the environment side cell. The results are used to prepare a calibration curve for each compound. The naphtha solvent blend is a commercial paint solvent containing approximately twenty (20) individual aliphatic hydrocarbon compounds. The response versus concentration is determined by totaling the area under each of the twenty individual peaks. Method of least squares is used to fit a straight line to the calibration curve. The slope of each test compound's calibration curve is then calculated for determining the unknown concentration. The average response factor may be used in place of the calibration curve.
The working calibration curve or response factor must be verified on each working day by measurement of one or more calibration standards. If the response of any compound varies more than 20%, the test must be repeated using a fresh calibration standard. If the results still do not agree, generate a new calibration curve.
4.3 Analysis of Calibration Curve and Method Detection
Level Samples
Recommended chromatographic conditions are summarized above.
Calibrate the system daily as described above.
Check and adjust split vent rate and check rate with soap film flow meter.
To generate accurate data, samples, calibration standards and method detection level samples must be analyzed under identical conditions.
Calibration standards and method detection samples are prepared in the environment flask only. This is accomplished by using a 1/2 inch plastic disk and aluminum sheet disk the diameter of the environment flange in place of the sample flask. A single sealing ring is placed onto the environmental glass flange followed by an aluminum sheet, and then the plastic disk.
The environment flask is flushed with dry compressed air to remove humidity in the sample and environment flask. This is done by puncturing the environment septa with a needle and tubing assembly which permits a controlled flow of dry air through the flask. The clamp rings are loosely fitted to the flask to eliminate pressure buildup. After flushing both flasks for approximately 10 minutes, the needle is removed and the clamp rings tightened, sealing the aluminum sheet against the seal ring.
Next, 40 μl of the permeation ethanol/aromatic working standard or secondary dilutions of the working standard is injected into the environment flask. Alternatively, 40 μL of the naphtha solvent blend or secondary dilutions of the working standard is injected into the environmental flask. The time is recorded and the flask is placed into a thermostatically controlled oven.
At the end of 30 minutes, the environment flask is removed from the oven. The environmental flask is analyzed using a heated six-port sampling valve fitted with a 1 ml loop. The loop is flushed with a 1 ml volume of the environment-side or sample-side air. The loop is injected onto the capillary column. The GC/FID system is started manually following the injection.
4.4 Calculation of Results
4.4.1 Test Compound Response Factor
Sample-side and environment-side test compound concentrations are calculated for each compound's calibration curve slope or response factor (RF). Concentrations are then volume-corrected for each specific set of permeation cells if permeant mass is desired. ##EQU1##
The cumulative penetrant mass is plotted as a function of time on both the upstream (environment) and downstream (sample) side of the film. The diffusion rate and transmission rate of the permeant area calculated from the transmission curve data.
4.4.2 Transmission Rate
When a permeant does not interact with the polymer, the permeability coefficient, R, is usually characteristic for the permeant-polymer system. This is the case with the permeation of many gases, such as hydrogen, nitrogen, oxygen, and carbon dioxide, through many polymers. If a permeant interacts with polymer molecules, as is the case with the permeant test compounds used in this method, P is no longer constant and may depend on the pressure, film thickness, and other conditions. In such cases, a single value of P does not represent the characteristic permeability of the polymer membrane and it is necessary to know the dependency of P on all possible variables in order to obtain the complete profile of the permeability of the polymer. In these cases, the transmission rate, Q, is often used for practical purposes, when the saturated vapor pressure of the permeant at a specified temperature is applied across the film. Permeability of films to water and organic compounds is often expressed this way. ##EQU2##
In this application, Q is represented in units of ##EQU3##
One of the major variables in determining the permeation coefficient is the pressure drop across the film. Since the transmission rate Q includes neither pressure nor concentration of the permeant in its dimensions, it is necessary to know either vapor pressure or the concentration of permeant under the conditions of the measurement in order to correlate Q to P.
The pressure-drop across the film from environment side to sample side is principally due to water vapor pressure. The water concentration or humidity does not remain constant and is not measured during the time intervals the organic compounds are analyzed, and therefore the pressure across the membrane is not determined.
The above examples of thermoplastic films containing a variety of compatible cyclodextrin derivatives shows that the invention can be embodied in a variety of different thermoplastic films. Further, a variety of different compatible derivatized cyclodextrin materials can be used in the invention. Lastly, the films can be manufactured using a variety of film manufacturing techniques including extrusion and aqueous dispersion coating to produce useful barriers.
The above specification, examples of substituted cyclodextrin, extruded thermoplastic films and test data provide a basis for understanding the technical aspects of the invention. Since the invention can be made with a variety of embodiments, the invention resides in the claims hereinafter appended.
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A barrier film composition can comprise a thermoplastic web comprising a thermoplastic polymer and a dispersed cyclodextrin composition having substituents that compatibilize the cyclodextrin in the film. The thermoplastic/cyclodextrin film obtains substantial barrier properties from the interaction between the substituted cyclodextrin in the film material with a permeant. The substituents on the cyclodextrin molecule causes the cyclodextrin to be dispersible and stable in the film material resulting in an extrudable thermoplastic. Such materials can be used as a single layer film material, a multilayer film material which can be coated or uncoated and can be used in structural materials wherein the thermoplastic is of substantial thickness resulting in structural stiffness. The cooperation between the cyclodextrin and the thermoplastic polymer provides barrier properties to a web wherein a permeant can be complexed or entrapped by the cyclodextrin compound and held within the film preventing the permeant from passing through the film into the interior of a film, an enclosure or container. The permeant can comprise a variety of well known materials such as moisture, aliphatic or aromatic hydrocarbons, monomer materials, off flavors, toxic compounds etc.
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