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BACKGROUND
[0001] The present disclosure is directed to the improved process of Resin Transfer Molding (RTM), and more particularly use of a silicone elastomer (or functionally equivalent) intensifier inside the closed RTM tool to provide additional pressure during processing, thereby suppressing void formation within the laminate and providing uniform consolidation pressure to ensure wet-out of the fiber preform.
[0002] Fiber-reinforced polymer matrix composites (PMCs) are high-performance structural materials that are commonly used in applications requiring resistance to aggressive environments, high strength/stiffness, and/or low weight. Examples of such applications include aircraft components.
[0003] PMCs comprise layers of fibers that are bonded together with a matrix material, such as a polymer resin. The fibers reinforce the matrix, bearing the majority of the load supported by the composite, while the matrix bears a minority portion of the load supported by the composite and also transfers load across the fibers. In this manner, PMCs may support greater loads than either the matrix or fiber individually while exhibiting a more progressive failure. Furthermore, by tailoring the reinforcing fibers in a particular geometry or orientation, the composite can be efficiently designed to minimize weight and volume.
[0004] In liquid infusion processing, the reinforcing fibers are placed within a mold cavity or other mechanism for net-shape tooling in dry conditions, wetted with the matrix resin, and cured. Liquid infusion processing may be accomplished by a variety of techniques, including high and low pressure Resin Transfer Molding (RTM), Resin Film Infusion (RFI), Vacuum Assisted Resin Transfer Molding (VARTM) and Same Qualified Resin Transfer Molding (SQRTM).
[0005] The liquid infusion process may include any process by which the reinforcing fibers are first placed into a mold cavity, die head, or any other means of net shaped tooling and then wetted with the resinous matrix and cured.
[0006] Ceramic Matrix Composite (CMC) pre-ceramic polymer resins are not chemically stable when heated to temperatures below their pyrolysis temperature and therefore provide a challenge to molding a void/defect free laminate via liquid infusion processes.
[0007] Prior to, during and even after initial cure the pre-ceramic resins have demonstrated a propensity for release of gaseous compounds. These gases interfere with the complete filling of the fiber preform during resin injection, leading to a cured laminate with varying amounts, sizes and shapes of porosity. Unwanted porosity can also be formed for other reasons, such as improper filling of the resins. It is known that during Polymer Infiltration and Pyrolysis (PIP), large pores in the cured laminate will propagate to the pyrolyzed laminate and may remain open within the laminate through final densification.
[0008] It is therefore desirable when using CMC pre-ceramic polymerresin to be able to cure a laminate by liquid infusion such that large pores are not present and the gas/porosity evolution is either suppressed or results in very small, finely dispersed porosity.
SUMMARY
[0009] In accordance with the present disclosure, there is provided a process for manufacturing a ceramic matrix composite component, said process comprising inserting at least one fibrous sheet into a resin transfer molding system. The process includes wetting the at least one fibrous sheet with a pre-ceramic polymer resin. The process includes applying a pressure to the at least one fibrous sheet and pre-ceramic polymer resin with an intensifier responsive to thermal expansion as the resin is heated to its cure temperature, thereby providing resistance to the evolution of gases from the resin before it fully hardens.
[0010] In another embodiment the intensifier is proximate the upper surface.
[0011] In another embodiment the intensifier is configured to expand responsive to thermal energy.
[0012] In another embodiment the intensifier comprises a cured elastomer having a high coefficient of thermal expansion.
[0013] In another embodiment the intensifier comprises a silicone rubber material.
[0014] In another embodiment a pump is fluidly coupled to the inner cavity and is configured to pump a resin into the inner cavity.
[0015] In another embodiment a flexible bag is insertable in the inner cavity between the cover plate and the intensifier and a seal is coupled between the cover plate and the tool and is configured to fluidly seal the inner cavity.
[0016] In another embodiment the intensifier is configured to apply a pressure against at least one fibrous sheet wet up with pre-ceramic polymer resin insertable into the inner cavity adjacent the intensifier.
[0017] In another and alternative embodiment a resin transfer molding system comprises a tool having an upper surface. A cover plate is coupled with the tool proximate the upper surface. An inner cavity is formed between the tool and the cover plate. An intensifier is located in the inner cavity and is thermally coupled to the tool. A thermal energy subsystem thermally coupled to the tool. At least one fibrous sheet wet-up with a pre-ceramic polymer resin is adjacent the intensifier. The intensifier is configured to pressurize the at least one fibrous sheet wet-up with a pre-ceramic polymer resin responsive to thermal expansion of the intensifier.
[0018] In another embodiment the intensifier is configured to suppress void formation resultant from gases formed in the pre-ceramic polymer resin.
[0019] In another embodiment the intensifier is configured to apply a pressure of from about 50 pounds per square inch (psi) to as high as 800 psi.
[0020] In another embodiment the pre-ceramic polymer resin is selected from the group consisting of polycarbosilanes and polysilazanes.
[0021] In another embodiment a thermal energy subsystem is thermally coupled to the tool, the thermal energy subsystem is configured to heat the intensifier.
[0022] In another embodiment at least one of a vacuum pump is fluidly coupled to the inner cavity; and a pump is fluidly coupled to the inner cavity; wherein the pump and the vacuum pump are configured to transport the resin into the inner cavity to wet-up the at least one fibrous sheet.
[0023] In another and alternative embodiment a process for manufacturing a laminate ceramic composite component comprises inserting at least one fibrous sheet into a resin transfer molding system. The process includes wetting the at least one fibrous sheet with a pre-ceramic polymer resin. The process includes applying a pressure to the at least one fibrous sheet and pre-ceramic polymer resin with an intensifier responsive to thermal expansion and curing the pre-ceramic polymer resin.
[0024] In an exemplary embodiment the process further comprises suppressing void formation resultant from gases formed in the pre-ceramic polymer resin.
[0025] In an exemplary embodiment the process further comprises encapsulating the at least one fibrous sheet and pre-ceramic polymer resin between the intensifier and a cover plate. The cover plate is coupled to a tool.
[0026] In an exemplary embodiment the intensifier comprises a cured elastomer having a high coefficient of thermal expansion.
[0027] In an exemplary embodiment the process further comprises heating the intensifier to induce a thermal expansion of the intensifier.
[0028] In an exemplary embodiment the process further comprises uniformly applying pressure to the at least one fibrous sheet and pre-ceramic polymer resin to ensure wet out and consolidation.
[0029] Other details of the resin transfer molding system and process are set forth in the following detailed description and the accompanying drawing wherein like reference numerals depict like elements.
BRIEF DESCRIPTION OF THE DRAWINGS
[0030] The FIG. 1 is a schematic representation of a resin transfer molding system.
DETAILED DESCRIPTION
[0031] Referring now to FIG. 1 , there is illustrated a resin transfer molding system 10 . The resin transfer molding system 10 is typically used to create a composite material that is constructed from a fibrous sheet that is impregnated with a resin. Although a composite material is shown and described, it is to be understood that the present invention can be used to create other parts which are formed by pressure and a tool. It is also noted that the resin transfer molding system 10 is shown as a flat shaped plate, other shapes and forms can be utilized depending on the ultimate final shape of the composite component.
[0032] The resin transfer molding system 10 includes a tool 12 . The tool 12 can be constructed from composite materials, thin film metals, ceramics or conventional metallic materials. The tool 12 includes a cover plate 14 configured to enclose an upper surface 16 of the tool 12 , encapsulate and seal the contents of the tool 12 .
[0033] Adjacent to the tool 12 is at least one fibrous sheet 18 , and shown as multiple sheets 18 , which are used to create the composite material. The fibrous sheet can include any prepreg dry fabrics, tackified fabrics, three dimensional weave pieces, and other previously formed fiber filled sections.
[0034] The sheets 18 are enclosed by the cover plate 14 . The cover plate 14 may be constructed from the same rigged material as the tool 12 . The cover 28 may also include a flexible bag 20 made of a material, such as nylon, which can be sealed to the tool 12 with a seal 22 .
[0035] The cover plate 14 and tool 12 define an inner cavity 24 . The inner cavity 24 is in fluid communication with a pump 26 configured to pump a resin 28 . The pump 26 may be capable of pressurizing the inner cavity 24 . The pump 26 can be fluidly coupled to a source of resin 29 .
[0036] The resin 28 is a material which binds and forms a composite with the fibrous material 18 when subjected to elevated temperatures and pressures. In exemplary embodiments, there are thermoset-type or thermoplastic-type pre-ceramic polymer resins. In an exemplary embodiment, the resin 28 is ceramic matrix composite pre-ceramic polymer resin. Examples of these pre-ceramic polymer resins include polycarbosilanes and polysilazanes. Common commercial resin systems include SMP-10, SMP-730 by Starfire Systems.
[0037] An intensifier 30 is included in the resin transfer molding system 10 . The intensifier 30 comprises a cured elastomer such as silicone rubber material (or functional equivalent) having a high coefficient of thermal expansion that expands when heated. In an exemplary embodiment the coefficient of thermal expansion can be greater than 75 micro in/in Fahrenheit. The intensifier 30 is placed adjacent the upper surface 16 of the tool 12 proximate the fibrous sheets 18 . The intensifier 30 is configured to apply pressure to the fibrous sheets 18 and resin 28 upon being heated.
[0038] To form a composite sheet, the fibrous sheets 18 are first placed onto the tool 12 on top of the intensifier 30 or vice versa. The cover plate 14 is then coupled to the tool 12 to encapsulate the sheets 18 . The pump 26 is coupled to the tool 12 . The tool 12 may be heated by a thermal energy subsystem 32 to remove any residual water that may exist in the sheet or tooling.
[0039] A vacuum is pulled within the inner cavity 24 of the tool 12 by a vacuum pump 34 .
[0040] The resin 28 is introduced to the inner cavity 24 from the resin source. The resin can be induced to flow into the inner cavity 24 by the vacuum created within the tool inner cavity 24 , by positively pumping the resin 28 into the inner cavity 24 , or both. As shown in FIG. 1 , the resin 28 fills the gaps 36 between the fibrous sheets 18 .
[0041] As shown in FIG. 1 , the resin 28 flows through the sheets 18 from the gaps 36 . The diffusion of resin 28 from the gaps 36 , more evenly distributes the resin 28 throughout the sheet 26 and provides a composite part that has a relatively uniform concentration of resin 28 .
[0042] The tool 12 is heated from the thermal energy subsystem 32 . The heat Q from the thermal energy subsystem 32 transfers through the tool 12 into the intensifier 30 . As the intensifier 30 is heated, the intensifier 30 expands and presses the sheets 18 and resin 28 within the mold cavity. In an exemplary embodiment, the intensifier 30 can apply a pressure of from about 50 pounds per square inch (psi) to as high as 800 psi.
[0043] As explained above, prior to, during and even after initial cure the pre-ceramic resins 28 have demonstrated a propensity for release of gaseous compounds. These gases interfere with the complete filling of the fiber preform during resin injection, leading to a cured laminate with varying amounts, sizes and shapes of porosity.
[0044] The intensifier 30 suppresses the formation and release of the gaseous compounds in the laminate formed from the resin 28 and fibrous sheets 18 . By suppressing the outgassing of the resin 28 with the use of the intensifier, unwanted voids and the resultant porosity is avoided in the composite material component. The intensifier 30 also improves the consolidation of the resin 28 and fibrous sheets 18 . In an exemplary embodiment, the intensifier 30 improves the porosity to less than 2% by volume void content.
[0045] By use of the intensifier 30 inside the RTM system 10 , additional internal pressure is provided to the composite material during the cure process, thereby minimizing void formation and providing uniform consolidation pressure to ensure wet-out of the fiber preform.
[0046] Using the ceramic matrix composite pre-ceramic polymer resin with the RTM process can result in large voids and defects in the cured laminate that propagate to the pyrolyzed laminate during PIP and are not filled during final densification. The disclosed resin transfer molding system enables one to cure a laminate by RTM using pre-ceramic polymer resin such that large pores are not present and the gas/porosity evolution is either suppressed or results in very small, finely dispersed porosity.
[0047] For final densification various processes can be employed such as; PIP, Melt Infiltration (MI) or Chemical Vapor Infiltration (CVI).
[0048] The resin transfer molding system and method (or functionally equivalent method) can be applicable to flat panels as well as complex 3-D geometric shapes including those forming functional components.
[0049] The exemplary resin transfer molding system is a closed tool process in which a dry fiber preform is enclosed in matched metal tooling and resin is injected under pressure to wet out the preform. The tool is then heated to cure the resin, resulting in a composite laminate. The system and process do not require any outside source of consolidation pressure, which lowers cost. The closed tooling creates a dimensionally repeatable part.
[0050] By minimizing the voids developed during cure, the exemplary system and method allow for the successful densification of the laminate through processes such as Polymer Infiltration and Pyrolysis (PIP), Melt Infiltration (MI) or Chemical Vapor Infiltration (CVI). A highly dense material is critical to the durability of the material.
[0051] Without the use of the exemplary resin transfer molding system and method a more porous Ceramic Matrix Composite (CMC) would result, the greater porosity compromising the composite and the capacity of the composite to meet target life requirements and ultimately increasing cost.
[0052] There has been provided a resin transfer molding system and process. While the resin transfer molding system and process have been described in the context of specific embodiments thereof, other unforeseen alternatives, modifications, and variations may become apparent to those skilled in the art having read the foregoing description. Accordingly, it is intended to embrace those alternatives, modifications, and variations which fall within the broad scope of the appended claims.
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A process for manufacturing a ceramic matrix composite component, said process comprising inserting at least one fibrous sheet into a resin transfer molding system. The process includes wetting the at least one fibrous sheet with a pre-ceramic polymer resin. The process includes applying a pressure to the at least one fibrous sheet and pre-ceramic polymer resin with an intensifier responsive to thermal expansion and curing the pre-ceramic polymer resin.
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SUMMARY OF THE INVENTION
[0001] The invention is resistance training apparatus having a frame assembly and a shaft rotatably mounted to it. The apparatus will also have a first disk mounted to the shaft, and a first one way clutch configured to transfer rotating torque from the shaft to the first disk in a first direction. This first clutch only allows rotation when rotating torque is imparted to the shaft in the first direction.
[0002] A first caliper frictionally engages the first disk. In that regard, the invention will include a first adjustment means that allows one to selectively adjust an amount of frictional resistance that the first caliper imparts onto the first disk.
[0003] The invention also includes a second disk mounted to the shaft. In a like manner, the invention will have a second one way clutch that transfers rotating torque to the second disk in a second direction. The second clutch, however, will only transfer rotating torque to the second disk when shaft is rotated in the second direction.
[0004] The invention will also have a second caliper that frictionally engages the second disk. Analogously, the invention will include a second adjustment means that allows one to selectively adjustment an amount of frictional resistance that the second caliper imparts onto the second disk.
[0005] It is preferred that the each of the adjustment means be similar, yet independent. In that regard, each of the first and second adjustment means will preferably include a actuator adjustment wheel having coupled to an actuator housing, preferably at a hollow hub that extends from the actuator adjustment wheel. The adjustment means will also require an actuator shaft positioned within the housing such that its first end extends from the housing to engage a respective caliper piston. The shaft also passes through the hollow hub such that its second end extends outwardly a distance from the actuator adjustment wheel.
[0006] The adjustment means of the invention further includes a spring that biases the shaft into engagement with the respective caliper. By rotating the adjustment wheel, frictional resistance is selectively varied because the rotation of the wheel changes the position of the wheel along a longitudinal axis of the shaft, thereby changing the biasing force of the actuator shaft onto the respective caliper piston.
[0007] In a preferred embodiment of the invention, the resistance training apparatus will include an actuator adjustment bearing positioned within the hollow hub of the actuator wheel. The actuator adjustment bearing has an opening allowing the shaft to pass there through. Additionally, a plurality of detents is formed on the actuator adjustment bearing. In this embodiment, a plurality of apertures (or vessels) are formed on the actuator adjustment wheel, and a respective spring plunger is positioned within at least one of the respective apertures. The wheel, aperture, bearing, and spring plunger are all cooperatively configured so that each spring plunger, which is biased into contact with the bearing, creates a tactile feedback signal as the spring plunger passes over the detents when the actuator adjustment wheel is turned. This tactile feedback signal will only be realized when sufficient friction between the spring and bearing are achieved to overcome the bias of a spring plunger against a bearing detent.
[0008] In a preferred embodiment of the invention, apertures that house the spring plungers pass through the actuator adjustment wheel and handles extend outwardly from each aperture. In this embodiment, the spring plunger is biased inwardly toward the actuator adjustment bearing such that it passes over the plurality of detents as the actuator adjustment wheel is rotated.
[0009] The spring plungers passing over the detents provide a means for giving a tactile signal when the actuator adjustment wheel is rotated. Other means, however, are certainly possible and within the scope and spirit of the invention.
[0010] A threaded coupling connects the actuator housing to the actuator adjustment wheel. Rotation of the actuator adjustment wheel, therefore, selectively moves the actuator adjustment wheel along a longitudinal axis of the actuator adjustment shaft, which passes through the wheel. Thus, the movement varies the space between a terminal end of the actuator adjustment wheel and the actuator adjustment housing and further selectively varies the biasing force imparted by the spring that engages both the wheel and the shaft.
[0011] In a preferred embodiment, indicia (such as colored, annular rings) are etched on the second end of the actuator shaft. As the adjustment wheel is rotated, the distance the second end extends outwardly from the wheel varied. This distance is directly correlated to the bias of the spring against the caliper piston and therefore frictional resistance created by the caliper and disk coupling. The indicia, therefore, enable one to visually observe this spring bias and proportionate frictional resistance with greater ease.
[0012] The invention imparts the principle of allowing one to use a single machine to work antagonistic muscle groups by providing resistance in two different directions. In that regard, the machine provides the capability for independent adjustment of these separate directions. For example, the frame assembly may form a leg exercising machine (as shown) that enables a first resistance in a leg extension direction, but a second resistance in a leg curl direction. Additionally, a frame assembly forming an arm exercise machine that allows one to choose a first resistance in the bicep curl direction, and a second resistance in a tricep extension direction. Analogously, the invention may be incorporated into a frame assembly that allows one to perform a chest press, upward using a first resistance, then a lat-pull, downward movement using a second resistance.
[0013] Other objects, advantages and novel features of the present invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is a perspective view showing the resistance training apparatus, according to the principles of the invention.
[0015] FIG. 2 is a cross-sectional view of the disk rotors, calipers, and actuator mechanisms
[0016] FIG. 3 is a perspective and exploded view isolating the parts of a one-way clutch assembly.
[0017] FIG. 4 is a perspective and exploded view showing the parts of the linear actuator mechanism.
[0018] FIG. 5 is a cross-sectional view of the linear actuator mechanism
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0019] FIG. 1 is a perspective view of the inventive resistance training apparatus 10 , according to the principles of the invention. As shown, the apparatus 10 forms a basic leg extension machine having a frame assembly 12 that supports a seat 14 and a back 16 . As will become apparent as further embodiments are discussed, the inventive concept of a dual-directional resistance training apparatus 10 can incorporate any well-known resistance training apparatus, such as fly machines, a bench-press machine (with antagonistic rowing movement resistance), a military press (with antagonistic movement of lat-pull) machine, or the like.
[0020] Still referring to FIG. 1 , the apparatus 10 also bears a pair of rollers 18 for engaging the user's feet or ankles. When a user moves the rollers 18 , movement is imparted to driving wheel 19 , and the rotation is transferred via belt 20 to a driven wheel 22 , which is coupled to a shaft 24 (shown aft).
[0021] As shown in FIG. 1 , the resistance assembly 26 includes a first disk 28 and a second disk 42 , each coupled to the shaft 24 . A first linear actuator apparatus 32 is configured to selectively vary the frictional resistance that a first caliper (not viewable in FIG. 1 , but viewable aft) imparts onto the first disk 28 . A second linear actuator apparatus 40 is configured to selectively vary the frictional resistance that a second caliper (not viewable in FIG. 1 , but viewable aft) imparts onto the second disk 42 .
[0022] FIG. 2 shows a cross-sectional detail of the resistance apparatus 26 coupled to the shaft 24 . The resistance apparatus will include a first disk 28 coupled to a first clutch bearing assembly 30 , each mounted to the shaft 24 . The first clutch bearing assembly 30 is configured to allow rotation of the shaft 24 only in a first direction (i.e., clockwise).
[0023] The first disk 28 frictionally engages a first caliper apparatus 34 with a frictional force that may be varied by the first linear actuator apparatus 32 . The first linear actuator apparatus 32 includes a linear actuator shaft 33 that engages the caliper piston 35 , which in turn urges the caliper pads 36 into contact with the first disk 28 .
[0024] Still referring to FIG. 2 , the resistance apparatus 26 will also include a second disk 42 coupled to a second clutch bearing assembly 44 , each mounted to the shaft 24 . The second clutch bearing assembly is configured to allow rotation of the shaft 24 only in a second direction (i.e., counterclockwise). The second disk 42 frictionally engages a second caliper apparatus 38 with a frictional force that may be varied by the second linear actuator 40 .
[0025] As shown in FIG. 2 , the second linear actuator 40 includes a second linear actuator shaft 35 that engages the caliper piston 37 of the second caliper apparatus 38 , thereby urging the caliper pads 39 of the second caliper apparatus into contact with the second disk 42 .
[0026] FIG. 3 is a perspective view isolating the clutch bearing assembly 30 . As noted in FIG. 2 , the resistance apparatus 26 has a first clutch bearing assembly 30 and a second clutch bearing assembly 44 . It is to be understood that each of the clutch bearing assemblies bear analogous parts, and separate discussion of each would be repetitive. For the sake of brevity, the detail is discussed with regard to the first clutch bearing assembly 30 . The first clutch bearing assembly 30 will include a bearing housing 130 positioned between a primary clutch bearing 132 and a secondary clutch bearing 134 . A primary retaining ring 136 and a secondary retaining ring 138 are respectively positioned adjacent the primary clutch bearing 132 and secondary clutch bearing 134 .
[0027] As shown in FIG. 3 , each of the primary clutch bearing 132 , secondary clutch bearing 134 and an inner surface of the clutch housing 130 bear a slot that is configured to receive a key 139 . Additionally the clutch bearing assembly 30 will also include a rotor adapter 140 coupled to the clutch housing 130 on a first face, and coupled to the first disk 28 (see FIG. 2 ) on its opposite face. In this way, the clutch bearing assembly 30 will rotate with the shaft ONLY when the shaft is turned in a first direction, and will “freewheel” (i.e., not engage) when the shaft is turned in a second direction.
[0028] FIG. 4 is a perspective view that isolates the first linear actuator mechanism 32 . For the sake of brevity, the first linear actuator mechanism is shown in this detailed view, but it is to be understood that each of the first 32 and second 40 linear actuator mechanisms bear analogous parts. The first linear actuator mechanism 32 will have an actuator adjustment wheel 50 bearing a hub 52 . The actuator adjustment wheel 50 has a plurality of apertures 54 around its periphery. As shown, a spring plunger 55 fits within each respective aperture 54 , and a handle 56 is then inserted into the apertures atop the spring plunger 54 .
[0029] As shown in FIG. 4 , the linear actuator mechanism 32 will include an actuator shaft 64 having a first end 68 and a second end 66 , and a raised portion 70 positioned near the first end 68 . The actuator shaft will pass through a compression spring 62 and an actuator bearing 58 that has detents 60 formed adjacent its terminal end. When the linear actuator mechanism 32 is assembled, the spring plungers 55 will engage the bearing 58 and will pass over the detents 60 formed on the bearing 58 , thereby emitting a tactile signal as the actuator adjustment wheel 50 is rotated.
[0030] As shown in FIG. 4 , the linear actuator mechanism 32 will also include an actuator housing 72 that will couple to the hub 52 of the actuator wheel 50 by a threaded connection. Consequently, the actuator housing 72 will attach to the caliper apparatus (Ref No 34 in FIG. 2 ) at one end, and the actuator wheel 50 at the other. When assembled, the first end 68 of the actuator shaft will pass through the actuator housing 72 to engage the caliper piston (Ref 35 in FIG. 2 ).
[0031] FIG. 5 shows a cross-sectional view of the fully-assembled first linear actuator apparatus 32 . The actuator apparatus 32 includes an actuator wheel 50 having handles inserted into apertures 54 that also house spring plungers 55 , which are biased into engagement with the bearing 58 . When the actuator wheel 50 is rotated, the spring plungers pass along the surface of the bearing and engage within detents on the bearing 58 , thereby creating a tactile signal. Additionally, as the actuator wheel 50 is rotated in a clockwise direction A about the longitudinal axis of the actuator shaft 64 , the threaded coupling that joins the hub 52 of the wheel 50 to the actuator housing 72 will urge the wheel in direction d, thereby compressing the spring 62 toward the raised portion 70 of the actuator shaft 64 , which also biases the actuator shaft 64 in direction d.
[0032] Still referring to FIG. 5 , a portion of the First end 68 of the actuator shaft 64 extends outwardly of the actuator housing to engage the caliper piston ( 35 ; see FIG. 2 ), which will thereby increase the frictional force exerted upon the first disk ( 28 ; see FIG. 2 ). As the wheel is rotated in direction a so that it travels in direction d, the second end 66 of the actuator shaft protrudes outwardly a distance from the actuator wheel 50 . The second end 66 may bear indicia that facilitate visual clues as to how much biasing force the actuator shaft 64 puts on the caliper piston.
[0033] The distance that the second end 66 extends is directly correlated to the bias on the spring and therefore the frictional resistance created by the caliper and disc, which is translated into the resistance force felt by the user of the equipment. Generally, the indicia will be annular rings of varying colors. This feature makes it possible for the user to set the same resistance level when returning to the machine on the next workout. Without this observable feature, the user would need to make multiple adjustments until the resistance “felt” correct.
[0034] Additionally, the tactile signal emitted by the spring plungers adds even greater sensitivity and accuracy in the adjustment of the frictional resistance. For example, a user could desire to turn the wheel until the red indicator was exposed on the second end, then continue turning until two (or more) tactile cues were emitted. The combination of the indicia and the detents gives much more repeatability to the user. Additionally, the combination of detents and indicia will provide a predictability and uniformity of resistance that is independent of pad wear.
[0035] Having described and illustrated the invention in detail, it is to be understood that the above and foregoing is for illustration and demonstration only. The descriptions herein are not intended to limit the breadth of this invention. The breadth and scope of the invention shall be limited only by claims.
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The disclosure shows and describes a resistance training apparatus that enables one to use a single machine to exercise antagonistic muscle groups by enabling one to select a first level of resistance in a first direction and select a second level of resistance in a second direction. The apparatus will include a frame assembly, and shaft rotatably mounted to the frame assembly. The apparatus has first and second disks, first and second calipers respectively engaging the disks, and first and second adjustment means that respectively provide varying resistance when one imparts rotating torque is imparted to a first direction or second direction, respectively.
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FIELD OF THE INVENTION
[0001] The present invention relates to an improved process for preparation of S-(−)-betaxolol and salts thereof. More particularly the present invention relates to the preparation of hydrochloride salt of S-(−)-betaxolol of formula (1).
BACKGROUND OF THE INVENTION
[0002] Racemic betaxolol of formula (2) is a β-adrenoreceptor antagonist
with a pharmacological and pharmacokinetic profile for the treatment of chronic cardiovascular diseases like glaucoma. The disease glaucoma is characterized by the progressive damage to the optic nerve caused by the increased pressure within the eye. Glaucoma is a serious disease of the eye, which may lead to the loss of peripheral vision and if untreated total blindness.
[0003] β-adrenoreceptor antagonist (β-blockers) are popularly used to lower intraoccular tension, other conditions of increased intraoccular pressure and management of essential hypertension. The principle effect of β-adrenoreceptor blocker is to reduce cardiac activity by diminishing or preventing β-adrenoreceptor stimulation i.e. by reducing the rate and force of contraction of the heart.
[0004] Betaxolol belongs to aryloxypropanolamine class of drugs having a specific action on the cardiovascular receptor sites. Most of the drugs in this series contain one chiral carbon centre but generally administered as racemates. Pharmacological studies have shown that an organism often reacts in a different way when it interacts with each enantiomer of the same molecule. This has promoted the growth of both the switch from the use of racemic drug to single enantiomer drug and innovation the manufacturing processes to make enantiomerically pure molecules with low cost. Although most of the β-blockers are sold as racemates, only S-isomer is associated with β-blocking activity, while the R-isomer is usually responsible for side effects. (Hussian S. S. et al, Toxiocol, 1989, 12)
[0005] The pharmacological characteristics of S-(−)-Betaxolol (Levobetaxolol ) of formula (3), a single active isomer of betaxolol exhibited a higher affinity at cloned human β-1 than at β-2 receptors while R-(+)-Betaxolol (Dextrobetaxolol) of formula (4) was much weaker at both receptors. Levobetaxolol was 89-times β-1 selective vs. β-2. Levobetaxolol is more potent than Dextrobetaxolol at inhibiting isoproterenol induced CAMP production in human non-pigmented ciliary epithelial cells and exhibited a micro molar affinity for L-type Ca 2+ channels. In conclusion, levobetaxolol is a potent, high affinity and β-1 selective 10P lowering β1 adrenoreceptor antagonist.
PRIOR ART
[0006] Synthesis of S-(−)-betaxolol of formula (3) has been reported by alkylation of phenol derivative with S-(−)-2-phenyl-3-isopropyl-5-hydroxymethyl oxazolidinyl tosylate of formula (12) followed by the acid catalysed hydrolysis (Philippe M. Manoury; Jean L. Binet; Jean Rousseau; J. Med. Chem. 1987, 30, 1003-1011.).
[0007] The enantiomers of betaxolol have been prepared via lipase catalysed kinetic resolution of racemic drug (Giuseppe Di Bono; Antonio Scilimuti; Synthesis, 699, June 1995). The racemic drug on treatment with acetic anhydride afforded N, O-bisacetylated derivative which was hydrolysed enantio-selectively using PPL or lipase K-10. Alternatively trans esterification reaction was performed using vinyl acetate as the acyl doner on the key intermediate 1-chloro-3-[4(2-cyclopropylemethoxy)ethyl]phenoxy propan-2-ol.
DRAWBACKS
[0008] The asymmetric synthesis starting from oxazolidinone derivative of formula (12) involves number of steps. R-glyceraldehyde is converted to the required oxazolidinone derivative in four steps. R-glyceraldehyde is not very stable compound and not commercially available, although it can be prepared from the cleavage of D-mannitol-1,2,5,6-bisacetonide on treatment with lead tetraacetate or sodium periodate among other methods.
[0009] The chemoenzymatic route involves either lipase catalyzed hydrolysis or transesterification but the optical purity upto 80% was noted which needs recrystallisation of hydrochloride to improve ee to ˜90%. The overall yield is moderate upto 50%.
[0010] In both the above processes cyclopropylmethyl halide has been employed for introducing cyclopropyl group as a reactive intermediate. The cyclopropylmethyl halide is not expensive but highly lachrymetric and unstable. These limitations make the reported processes economically inviable and difficult to scale up.
[0011] There is therefore a need to develop an economically viable alternative process for S-(−)-betaxolol and its hydrochloride salt wherein the use of cyclopropylmethyl halide is avoided and also product with improved enantiomeric purity.
OBJECTS OF THE INVENTION
[0012] The object of present invention therefore is to prepare salts of S-(−)-betaxolol with high enantiomeric purity and to avoid use of highly lacrymatric and unstable cyclopropylmethyl halide.
SUMMARY OF THE INVENTION
[0013] Accordingly the present invention provides an improved process for the preparation of S-(−)-betaxolol of the formula, (3) as fully illustrated in hereinafter which comprises following steps
1. Condensing 2-[4-hydroxyphenyl-ethanol] of formula, (5) with benzyl halide in the presence of a base, phase transfer catalyst and organic solvent to obtain 2-[4-benzyloxyphenyl-ethanol] of formula, (6). 2. Condensing 2-[4-benzyloxyphenyl-ethanol] of formula, (6) with an allyl halide in the presence of a base and an organic solvent to obtain 1-(2-allyloxyethyl)-4-benzyloxybenzene of formula, (7). 3. Cyclopropanating 1-(2-allyloxyethyl)-4-benzyloxybenzene of formula (7) by conventional methods such as Simmon smith reaction and Furukawa modification of Simmon smith reaction to obtain the 1-benzyloxy-4-(2-cyclopropyl methoxy-ethyl)-benzene of formula, (8). 4. Deprotecting 1-benzyloxy-4-(2-cyclopropylmethoxy-ethyl)-benzene of formula (8) by hydrogenation to obtain 4-(2-cyclopropylmethoxyethyl)-phenol of formula (9). 5. O-Alkylation of 4-(2-cyclopropylmethoxyethyl)-phenol of formula, (9) by treating with R-(−)-epichlorohydrin in the presence of alkali to obtain the mixture of compounds of the formulae (10+11); treating the mixture of compounds of the formulae, (10+11) with isopropylamine to give S-(−)-betaxolol of the formula, (3). Treating S-(−)-betaxolol of the formula,(3) with alcoholic hydrochloric acid in organic solvent to give S-(−)-betaxolol HCl, of formula (1) or maleic acid in organic solvent to give S-(−)-betaxolol maleate salt.
[0019] In one of the embodiments of the present invention base used in step (1) may be alkali metal carbonates such as carbonates of sodium, potassium or alkali metal hydroxides such as sodium, potassium.
[0020] In another embodiment organic solvent in step (1) may be aliphatic ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclic ethers.
[0021] In still another embodiment allyl halide used in step (2) may be chloride, bromide; bases used may be sodium hydride or potassium t-butoxide and solvents used for reaction may be ethereal solvent such as tetrahydrofuran or polar solvents such as DMSO, DMF.
[0022] In another embodiment cyclopropanation in step (3) may be obtained by Zn—Cu couple (Simmons Smith) or diethyl zinc in hexane (Furukuwa).
[0023] In yet another embodiment deprotection by hydrogenation in step (4) may be carried out using Raney Nickel or as in conventional method by Pd—C.
[0024] In still another embodiment alkali used in step (5) may be alkali hydroxides such as sodium hydroxide or potassium hydroxide.
[0025] In another embodiment solvent used for formation of hydrochloride salt of S(−) Betaxolol may be hydrocarbons such as toluene, cyclohexane and ethers: diisopropyl ether, diethyl ether.
DETAILED DESCRIPTION OF THE INVENTION
[0026] The present invention provides an improved process for the preparation of S-(−)-betaxolol of the formula, (3) as described below. The process of the invention comprises the steps of
1. Condensing 2-[4-hydroxyphenyl-ethanol] of formula, (5) with benzyl halide in the presence of a base, phase transfer catalyst and organic solvent to obtain 2-[4-benzyloxyphenyl-ethanol] of formula, (6). 2. Condensing 2-[4-benzyloxyphenyl-ethanol] of formula, (6) with an allyl halide in the presence of a base and an organic solvent to obtain 1-(2-allyloxyethyl)-4-benzyloxybenzene of formula, (7). 3. Cyclopropanating 1-(2-allyloxyethyl)-4-benzyloxybenzene of formula (7) by conventional methods such as Simmon smith reaction and Furukawa modification of Simmon smith reaction to obtain the 1-benzyloxy-4-(2-cyclopropyl methoxy-ethyl)-benzene of formula, (8). 4. Deprotecting 1-benzyloxy-4-(2-cyclopropylmethoxy-ethyl)-benzene of formula (8) by hydrogenation to obtain 4-(2-cyclopropylmethoxyethyl)-phenol of formula (9). 5. O-Alkylation of 4-(2-cyclopropylmethoxyethyl)-phenol of formula, (9) by treating with R-(−)-epichlorohydrin in the presence of alkali to obtain the mixture of compounds of the formulae (10+11) treating the mixture of compounds of the formulae, (10+11) with isopropylamine to give S-(−)-betaxolol of the formula, (3). 6. Treating S-(−)-betaxolol of the formula,(3) with alcoholic hydrochloric acid in organic solvent to give S-(−)-betaxolol HCl, of formula (1) or maleic acid in organic solvent to give S-(−)-betaxolol maleate salt.
[0033] The base used in step (1) can be an alkali metal carbonate such as carbonates of sodium or potassium or alkali metal hydroxides such as hydroxides of sodium or potassium. The organic solvent in step (1) is preferably an aliphatic ketone such as acetone, methyl ethyl ketone and methyl isobutyl ketone or a cyclic ether. The allyl halide used in step (2) may be chloride, bromide; bases used may be sodium hydride or potassium t-butoxide and solvents used for reaction may be ethereal solvent such as tetrahydrofuran or polar solvents such as DMSO, DMF.
[0034] Cyclopropanation in step (3) may be obtained by Zn—Cu couple (Simmons Smith) or diethyl zinc in hexane (Furukuwa). Deprotection by hydrogenation in step (4) may be carried out using Raney Nickel or as in conventional method by Pd—C. The alkali used in step (5) may be alkali hydroxides such as sodium hydroxide or potassium hydroxide.
[0035] The solvent used for formation of hydrochloride salt of S(−) Betaxolol may be hydrocarbons such as toluene, cyclohexane and ethers: diisopropyl ether, diethyl ether.
[0036] The process of the present invention is described herein below with reference to the following examples, which are illustrative only and should not be construed to limit the scope of the present invention in any manner.
EXAMPLE I
[0037] This example describes the preparation of 4-benzyloxy-(2-phenethyl ethanol) of formula (6).
[0038] In a 250 ml reaction flask 2-(4-Hydroxyphenyl)-ethanol of formula, (5) (10 g, 0.07246 mol), potassium hydroxide (6.1 g, 0.1087 mol) and catalytic amount of phase transfer catalyst tetrabutyl ammonium bromide (0.150 g) was dissolved in 65 ml of THF. Stirred it for 1.5 hr. Benzyl bromide (8.6 ml, 0.07246 mol), was added to the reaction mixture dropwise. Stirred the reaction mixture at room temperature for 4 hrs. The progress of reaction was checked by TLC. Filtered the reaction mixture and concentrated the filtrate on rota-vapour. The crude product was recrystalised from petroleum ether to afford 4-benzyloxy-(2-phenethyl ethanol) of formula (7,), 14.9 g (90%) mp 85-86° C.
EXAMPLE II
[0039] This example describes the preparation of 1-(2-Allyloxyethyl)-4-benzyloxy benzene of formula (7)
[0040] To a stirred solution of alcohol of formula (6), (3 g, 0.013 mol) in dry THF (10 ml), Sodium hydride (60% dispersion in mineral oil, 0.95 g, 0.039 mol) was added portion wise at 0° C. The reaction mixture was stirred for 1 h at room temperature under nitrogen and then allyl bromide (2.4 g, 0.02 mol) was introduced. The reaction mixture was stirred for 15 h, at room temp, quenched with the addition of methanol. The solvent was removed and the residue partitioned between ethyl acetate and water. The organic layer was dried over anhydrous sodium sulphate, filtered and concentrated. The crude product was purified over silica gel column using ethyl acetate-light petroleum ether (1:33) as an eluent to afford compound of formula (6), as a colorless liquid 3 g (85%).
EXAMPLE III
[0041] This example describes the preparation of 1-(2-Allyloxyethyl)-4-benzyloxy benzene of formula (7)
[0042] A reaction flask was charged with 4-benzyloxy phenethyl alcohol of formula (6), (12 g, 0.052 mol), potassium tert-butoxide (8.842 g, 0.079 ml) and 50 ml) and DMSO. The mixture was stirred under nitrogen at 50° C. for 30 minutes. A solution of allyl bronide (6.8 ml, 0.079 mol) was added drop wise to the reaction mixture with cooling about 20-25° C. The mixture was then stirred at 50° C. for 2 h. and cooled to room temperature. The reaction mixture was subsequently quenched with 150 ml of water. The desired product was extracted from neutralized aqueous mixture with toluene. The toluene extract was then washed with water and concentrated under vacuum to afford the title compound of formula (7), 13.9 g, (98%).
EXAMPLE IV
[0043] This example describes the preparation of 1-benzyloxy-4-(2-cyclopropylmethoxy-ethyl)-benzene of formula (8).
[0044] To a stirred solution of compound of formula (7), (12 g, 0.0447 mol) in dry hexane (50 ml) diethyo zinc (1.1 M solution in hexane, 185 ml) was added at 0° C. under nitrogen atmosphere followed by diiodomethane (18 ml, 0.224 mol). The reaction was stirred for 6 h at 0° C. and poured over cold aqueous solution of ammonium chloride. The organic layer was separated and the aqueous layer extracted repeatedly with diethyl ether. The combined organic layer was washed with aq. solution of sodium thiosulphate, dried over anhydrous sodium sulphate, filtered and concentrated. The crude product was purified over silica gel column using ethyl acetate and light petroleum ether (1:50) as an eluent to afford compound of formula (8), as a colorless liquid 11.365 g (90%).
EXAMPLE V
[0045] This example describes the preparation of 1-Benzyloxy-4-(2-cyclopropylmetoxy-ethol)-benzene of formula (8)
[0046] To a suspension of Zn/Cu couple (3.24 g) and dry ether (20 ml) was added to the compound of formula (7), (2 g, 0.0075 mol) in ether (10 ml) followed by the addition of diiodomethane (4.2 ml, 0.052 mol). The reaction mixture was refluxed under nitrogen atmosphere for 72 h (monitored by TLC) and filtered. The filtrate was washed with water, dried, concentrated and the residue purified by column chromatography on silica gel, eluting with light petroleum ether: ethyl acetate (2:50) to afford pure product of formula (8), as an oil 1.8 g (85%).
EXAMPLE VI
[0047] This example describes the preparation of 4-(2-cyclopropylmethoxyethyl)phenol of formula (9)
[0048] The reported debenzylation procedure U.S. Pat. No. 4,348,783 using palladium charcoal was modified given as below.
[0049] A solution of compound of formula (8), (12 g) in methanol (100 ml) was stirred in presence of Raney-Nickel (10 ml slurry) under H 2 pressure (Parr Shaker 65-psi pressure). After 5 h the reaction mixture was filtered through a pad of cellite and the filtrate was concentrated. The crude product was purified by silica gel chromatography using ethyl acetate and light petroleum ether (1:9) as an eluent to afford compound of formula (9), as an oil 7 g (86%).
EXAMPLE VII
[0050] This example describes the preparation of S-(−)-Betaxolol of formula (3)
[0051] A solution of R-(−)-epichlorohydrin (3.855 g, 0.0417 mol) in water (2 ml) was stirred for 10 min. at 0-5° C. and the compound of formula (9), (5 g, 0.0261 mol), NaOH (1.146 g, 0.0287 mol) and benzyl triethyl ammonium chloride (catalytic amount) in water (16 ml) was added over a period of 1 h at 0° C. The reaction mixture was stirred for 80 h at 0° C., (monitored by TLC) and rendered acidic (pH=5) by addition of aqueous 3.5% HCl. To the reaction mixture isopropyl amine (38.5 ml, 0.651 mol) was added and stirred overnight at room temperature. The reaction mixture was concentrated and the residue extracted with chloroform and water. The organic layer was dried over sodium sulfate, concentrated on rota-vapour to afford 7.195 g (90%) chiral S-(−)Betaxolol of formula (3).ee>99 (determined by Chiral HPLC; Column-Chiracel OD 25 cm; mobile phase-hexane:isopropanol: diethyl amine (6:4:0.1); flow rate:0.5 ml/min; λmax:228 nm).
[0052] 1 H NMR:0.20 (q, 2 H, cyp); 0.53 (q, 2 H, cyp); 1.07 (m, 1 H, cyp); 1.08, 1.09 (2 S, 6 H, (CH 3 ) 2 N); 2.69 (, 1 H, CH—CH 3 ); 2.85 (m, 4 H, CH 2 —C, CH 2 —O);3.27 (d, 2 H, O—CH 2 ); 3.61 (t, 3 H, CH—O); 3.95 (d, 2 H, CH 2 —O); 4 (m, 1 H, CH—OH); 6.85, 7.16 (A 2 B 4 H, aromatic); Mass:M + =307.
EXAMPLE VIII
[0053] This example describes the preparation of Maleate salt of S-(−)-Betaxolol
[0054] S-(−)-betaxolol of formula (3) (7.850 g, 0.02557 mol) was dissolved in ether (50 ml) and maleic acid (2.671 g, 0.023 mol) was added to this, stirred for 1 hr. White solid filtered to get maleate sale of S (−)-betaxolol 7.575 g (70%). mp 95-97° C. (Lit. mp 96-97° C.); Specific rotation [α] 22 D −16.33 (Lit [α] 22 D −14.9) (C=2.4, CH 3 OH)
EXAMPLE IX
[0055] This example describes the preparation of hydrochloride salt of S-(−)-betaxolol of formula (1)
[0056] To a solution of S-(−)-Betaxolol of formula (3) (2.50 g) in 15 ml of toluene, Isopropanol-HCl (1eq) (5 ml) was added dropwise under nitrogen atmosphere with stirring. Stirred for 1 h. Concentrated and again added 5 ml of toluene stirred for 15 min. This process was repeated for two times. Finally removed the solvent completely and diethyl ether added to precipitate S-(−)-betaxolol hydrochloride of formula (1), as a solid. Filtered it under nitrogen atmosphere 2.66 g (95%), mp 92-93° C.;
[0057] Specific rotation [α] 22 D −13.46 (C=2, CHCl 3 )
[0058] 1 H NMR: 0.20 (q, 2 H, cyp); 0.53 (q, 2 H, cyp); 1.05 (m, 1 H, cyp); 1.44 1.66 (2 S, 6 H, (CH 3 ) 2 N); 3.16 (m, 1 H, CH—CH 3 ); 2.84 (t, 2 H, CH 2 —C); 3.28 (d, 2 H, O—CH 2 ); 3.45 (m, 2 H, CH 2 —C); 3.59 (t, 3 H, CH—O); 3.97, 4.05 (dd, 2 H, CH 2 —O); 4.61 (m, 1 H, CH—O); 6.75, 7.06 (A 2 B 2 , 4 H, aromatic); 8.51 (bs, 1 H, NH);9.56 (bs, 1 H, NH).
EXAMPLE X
[0059] This example describes the preparation of hydrochloride salt of S-(−)-betaxolol of formula (1)
[0060] To a solution of S-(−)-Betaxolol of formula (3), (2.50 g) in 15 ml of ether, Isopropanol-HCl (1eq) (5 ml) was added dropwise with stirring. Stirred for 1 h. Filtered the S-(−)-betaxolol hydrochloride salt of formula (1) as a white solid. 2.66 g (95%). mp 92-93° C.
[0061] Specific rotation [α] 22 D −13.46 (C=2, CHCl 3 )
ADVANTAGES
[0062] The process describes for the first time in detail the preparation of S (−) Betaxolol hydrochloride salt in good chemical yields and high enantiomeric purity using chiral epichlorohydrin.
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The present invention relates to an improved process for preparation of S-(−)-betaxolol salts. More particularly the present invention relates to the preparation of hydrochloride salt of S-(−)-betaxolol of formula (1).
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FIELD OF DISCLOSURE
[0001] The field of the disclosure relates to food storage and transportation products to provide protection, including but not limited to upright food wares such as cakes, breads, pastries, casseroles, etc. As a non-limiting example, food storage, protection and transportation products may be used with dessert items such as freestanding layer cakes.
BACKGROUND
[0002] Traditional food product container systems are primarily intended to provide storage and/or means of transportation for various food wares, to divide food wares into equal portions, and/or to provide protection for exposed edges of food products. Lacking from prior-art food product storage, stabilization and/or transportation devices is the capability to make easily customizable adjustments that continuously conform to the diverse geometry of food wares throughout the various instances of consumption. As a non-limiting example, a whole cake can be easily transported via prior-art container devices but ensuing consumption may lead to the need for transporting smaller portions of the cake that are far less stable, which may cause unwanted tipping, crumbling, collapsing, and/or shifting that damages the food products during transportation or storage. Furthermore, prior-art food container systems are principally designed around a whole food product, which can create wasted storage space as food wares are gradually consumed and the larger containers are utilized to store smaller and smaller fractions of partly consumed food wares. Another disadvantage of prior-art food product container systems is the inability to reposition more delicate food wares from one food storage device to another without causing undesirable damage such as tipping, crumbling and/or collapsing. What is needed is an efficient food product stabilization systems employing proportionately designed shapes and expandable/contractible support features to protect, brace, store, transport and continuously maintain various geometry of upright food wares.
SUMMARY OF THE DETAILED DESCRIPTION
[0003] Embodiments disclosed herein include food product stabilization and transport systems employing proportionately designed shapes and expandable/contractible support features to protect, brace, store and transport upright food wares, and related components and methods. Upright food products such as cakes, breads, pastries, casseroles etc. frequently require both protection from the outside environment, for normal food preservation, and means of storage and/or transportation wherein upright food wares are moved from one location to another. In cases where upright food wares are moved, even in instances of moving a short distance, unwanted tipping, crumbling, collapsing, falling and/or shifting may occur, which may damage various food products. In cases where partly consumed and/or smaller portions of food wares are stored in larger containers intended for larger food products, such as a whole cake, wasted space becomes a frequent problem when storing smaller fractional portions of food wares. The food product stabilization, storage and transport systems features proportionately designed shapes and expandable/contractible support features enabling customizable compartments and/or supports. In this manner, upright food wares can be efficiently protected, braced, stored and/or transported more securely thus preventing unwanted damage to food products.
[0004] In this regard, in one embodiment, a food product stabilization system for protecting different varieties of food wares is disclosed. The food product stabilization system comprises an at least one “L” shaped restraint article upon which upright food products are disposed in an abutting horizontal and vertical relationship wherein a first horizontal base surface of the at least one “L” shaped restraint article extends to a second vertical side portion providing stability for any upright food wares. The food product stabilization system may further comprise at least one integrated back-support element and/or at least one panel stiffening facet for additional rigidity and upright stability. The food product stabilization system may still further comprise alternatively designed edge geometry intended to coincide with diverse perimeter geometry of upright food wares. In this manner, upright food wares can be securely held in abutting juxtaposition with the at least one “L” shaped restraint article and thus be efficiently stabilized and/or transported.
[0005] In another embodiment, a food product stabilization system for protecting different varieties of food wares is disclosed. The food product stabilization system comprises an at least one “L” shaped restraint article featuring a vertical axis cylinder around which an at least one vertical upright separating hinge may pivot and lock into specific positions thereby creating customizable divided sections into which upright food products are disposed in an abutting horizontal relationship with the base portion of the restraint article and further disposed in two abutting vertical relationships, the first being the side portion of the “L” shaped restraint article and the second being the vertical edges of the separating hinge. In this manner, customized shapes are easily created by means of a pivoting and lockable separator hinge that provides additional support and conforms to the various geometries of food products and/or during different stages consumption.
[0006] In another embodiment, a food product stabilization system for protecting different varieties of food wares is disclosed. The food product stabilization system comprises an at least one “L” shaped restraint article featuring a plurality of both vertical and horizontal guides and/or slots into which at least one vertical divider panels may be positioned to create multiple customizable compartments to hold various types and/or sizes of food wares. The food product stabilization system may further comprise at least one integrated back-support element designed to pivot upon a vertical hinge axis so that the back-support element may be collapsed into a space-saving position for storage or pivoted into a generally perpendicular relationship to the vertical side of the “L” shaped restraint article and thereby provide additional vertical support and further prevent any unwanted tipping or spillage during storage or transport of the upright food products.
[0007] In another embodiment, a food product stabilization system for protecting different varieties of food wares is disclosed. The food product stabilization system comprises an at least one “L” shaped restraint article featuring a common vertical axis cylinder around which multiple vertically upright separating hinges may each freely pivot and lock into specific positions thereby creating a plurality of customizable divided sections into which many different fractional sizes of upright food products may be disposed in both an abutting horizontal relationship with the base portion of the restraint article and further disposed upon multiple abutting vertical relationships with either the side portion of the “L” shaped restraint article, or the multiple side edges of the plurality of the vertical separating hinges, or both. In this manner, a plurality of customizable and angled compartments are easily created by means of multiple pivoting and lockable separator hinges that each provide additional support and further conform to the various sizes and geometries of food products and/or during the various stages food consumption.
[0008] In another embodiment, a food product stabilization system for protecting different varieties of food wares is disclosed. The food product stabilization system comprises an at least one “L” shaped restraint article featuring a vertical axis cylinder around which an at least one vertical upright separating hinge may pivot and lock into specific positions thereby creating customizable divided sections into which upright food products are disposed in an abutting horizontal relationship with the base portion of the restraint article and further disposed in two abutting vertical relationships, the first being the side portion of the “L” shaped restraint article and the second being the vertical edges of the separating hinge. The food product stabilization system further comprises at least one adjustable height panel to further customize and adjust the upright vertical support-panel geometry for taller or shorter food products and thereby creating added vertical stability for a diverse assortment of differently sized upright food products.
[0009] In another embodiment, a food product stabilization system for protecting different varieties of food wares is disclosed. The food product stabilization system comprises any variety of the aforementioned “L” shaped restraint articles and/or dividing panels and/or hinges and further comprises a horizontal foundational base platform onto which any of the food product stabilization system embodiments may be secured into place. The food product stabilization system further comprises a top-cover, which can be locked securely onto the horizontal base platform and thereby contain the food product stabilization system(s). In this manner, a more complete food product stabilization and protection and/or storage system is created to further protect and preserve food wares.
[0010] In still another embodiment, a food product stabilization system for protecting different varieties of food wares is disclosed. The food product stabilization system comprises any type of the abovementioned “L” shaped restraint articles, dividing panels and/or hinges and further comprises a carrying apparatus that is designed to fit securely onto food product container elements such as a horizontal foundational base platform and/or a vertical top-cover. In this manner, considerably more complete food product stabilization, protection, storage and transportation systems are duly created to efficiently protect, store, brace, preserve and transport any variety of food wares in a secure manner and thus prevent unwanted damage to any assortment or size of upright food products.
[0011] In another embodiment, the food product stabilization system may be readily contained within traditional storage containers and/or utilized to more easily move and transfer different varieties of food wares from any of the food product stabilization system storage containers to any additional variety of traditional food product containers without causing undesirable damage such as tipping, crumbling and/or collapsing. In this manner, a more efficient method is created to transfer and/or relocate food products from one storage device to another and thus prevent unwanted damage to upright food wares.
[0012] Additional advantages and features will be set forth in the detailed description that follows, and in part will be readily apparent to those skilled in the art from the descriptions and/or recognized by practicing the embodiments as described in the written description and claims hereof, as well as within the appended drawings.
[0013] It is to be understood that both the preceding summary description and the following detailed description are merely exemplary, and are intended to provide a general overview and/or framework to understand the nature and structure of the claims.
[0014] The accompanying drawings are included to provide a further understanding, and are incorporated herein and comprise a part of this specification. The drawings illustrate one or more embodiments, and together with the summary description and detailed description serve to explain principles and functions of the various embodiments.
BRIEF DESCRIPTION OF THE FIGURES
[0015] FIG. 1A is close-up perspective side view of an exemplary first embodiment of an upright “L” shaped food product stabilization restraint article that features a circular shaped horizontal lower base and includes at least one integrated back-support element and at least one included panel stiffening facet incorporated into the upright vertical panel of the food product stabilization restraint article;
[0016] FIG. 1B is a perspective side view of an upright “L” shaped restraint article having a rectangular shaped horizontal base and at least one integrated back-support and at least one panel stiffener included in the vertical panel of the upright restraint article;
[0017] FIG. 1C is a side view of either FIG. 1A or FIG. 1B showing a more detailed view of a back-support element as well as the proportional thickness of a panel stiffener;
[0018] FIGS. 2A-2C are perspective side views of another embodiment of a food product stabilization system that employs at least one rotatable hinge that can pivot about an axis and fit securely into an array of slots and/or guides to alter the positions and vary the shapes into which food wares can be stabilized and held firmly in an upright position;
[0019] FIGS. 3A-3B are perspective side views of another embodiment of a food product stabilization system that features at least one incorporated back-support that is hinged and can be collapsed into a space-saving position or pivoted outward to provide additional upright stability; FIGS. 3A-3B also feature at least one vertical divider panels, which fits securely into an array of slots and/or support guides thereby creating variable sized compartments into which diverse geometries of similar or differing food ware types can be stabilized and held firmly in upright positions for storage and/or transportation;
[0020] FIGS. 4A-4B are perspective side views of another embodiment of a food product stabilization system that employs a plurality of rotatable hinges that can each pivot about a common axis and fit securely into an array of slots and/or guides to alter and create multiple compartment positions into which various sized food wares can be accommodated, stabilized and held firmly into numerous customizable upright positions;
[0021] FIGS. 5A-5B are perspective side views of FIGS. 2A-2B , which also feature an at least one adjustable height panel to further customize and adjust the upright vertical support-panel geometry for taller or shorter food wares thereby creating added stability for a wide variety and diverse assortment of differently sized upright food wares;
[0022] FIG. 6A is an exploded perspective side view of FIG. 2A that further comprises an exemplary first embodiment of a horizontal base platform onto which the food product stabilization system of FIG. 2A can be secured, and then another exemplary first embodiment of an upright top-cover can then lock securely onto the horizontal base platform and thereby contain the food product stabilization system of FIG. 2A et al;
[0023] FIG. 6B is an assembled perspective side view of FIG. 6A wherein FIG. 2B et al is securely contained between the horizontal base platform and the upright top cover;
[0024] FIG. 7A is a perspective side view of an exemplary first embodiment of a carrying apparatus that is designed to fit securely onto food product container elements;
[0025] FIG. 7B is an assembled perspective side view of the carrying apparatus seen in FIG. 7A that is now engaged upon another embodiment of a horizontal base featuring locking side-tabs and fitting securely onto another embodiment of an opaque top-cover, enclosing any variety of the food product stabilization elements and/or system(s) and thereby creating an efficient food product stabilization, protection and transport system;
[0026] FIG. 8 depicts a perspective side view of another embodiment of a food product stabilization system with a solid upright panel and a solid rotatable hinge securing a portion of a cake and all being enclosed within a transparent prior-art storage container, demonstrating the ease with which upright food wares can be moved from the food product storage containers of FIGS. 6B and 7B to other traditional food containers without causing undesirable damage such as tipping, crumbling and/or collapsing.
DETAILED DESCRIPTION
[0027] Reference will now be made in detail to the embodiments, examples of which are illustrated in the accompanying drawings, in which some, but not all embodiments are shown. The concepts may be embodied in many different varieties and should not be construed or interpreted as limiting herein; rather the various embodiments are provided so that the whole of this disclosure will satisfy applicable legal requirements. Whenever possible, similarly referenced numbers will be used to refer to like components or parts.
[0028] Embodiments disclosed herein include food product stabilization systems employing proportionately designed shapes, expandable, contractible and/or pivoting support features to protect, brace, store and transport upright food wares, and related components and methods. Upright food products such as cakes, breads, pastries, casseroles etc. frequently require protection from the outside environment, for normal food preservation, and means of storage and/or transportation wherein upright food wares are moved from one location to another. In cases where upright food wares are moved, even in instances of a short distance, unwanted tipping, crumbling, collapsing, falling and/or shifting may occur, which may damage various food products. In cases where partly consumed and/or smaller portions of food wares are stored in larger containers intended for larger food products, such as a whole cake, wasted space becomes a frequent problem when storing smaller fractional portions of food wares. The food product stabilization, storage and transportation systems features one or more proportionately designed shapes, expandable, contractible or pivoting support features. In this regard, upright food wares can be efficiently protected, braced, stored and/or transported in a markedly more secure manner thus preventing unwanted damage to various food wares.
[0029] It is hereby noted that food product stabilization features comprise a diverse combination of customizable geometric, material and structural features provided as part of a food product stabilization, storage and transport system to provide specific bracing, buttressing and protection for food wares throughout different stages of consumption, storage and/or food product transport. Geometric features may include, for example, “L” shaped stands, hinges, divider panels, slots, guides, arcs, lines, contoured edge designs, foundation bases, covers, lids, carrying devices, back supports and/or structural supports.
[0030] In order to illustrate the fundamental concepts of this disclosure, FIG. 1A is a perspective side view of an exemplary food product stabilization article 10 ( 1 ) comprised of a horizontal lower base 16 featuring a semicircle shaped perimeter edge 14 (A), which extends inward toward a vertical side panel 17 thereby creating an “L” shape and further comprising a contoured vertical perimeter edge 19 of vertical side panel 17 upon which back-support features 11 ( 1 ) are incorporated for added upright stability and a plurality of panel stiffeners 12 are integrated for additional upright rigidity, support and stability.
[0031] The food product stabilization article 10 ( 2 ) of FIG. 1B is also an “L” shape formed by means of horizontal lower base 16 extending inward toward vertical side panel 17 , however the horizontal based 16 in FIG. 1B features a rectangular shaped perimeter edge 14 (B) depicting different edge geometry that can be disposed along the boundary edges 14 (A) of FIG. 1A or 14 (B) of FIG. 1B of horizontal base 16 . Indeed, various edge geometries such as contours, arcs, and/or lines can be incorporated into the horizontal perimeter edges 14 (A) of FIG. 1A or 14 (B) of FIG. 1B of horizontal base 16 and/or upon the vertical perimeter edge 19 of vertical side panel 17 of FIGS. 1A-B in order to create custom shapes, which conform to specific edge geometry of various food product types.
[0032] With continuing reference to FIG. 1A-1B , FIG. 1C is a side view of the food product stabilization article embodiments of either 10 ( 1 ) or 10 ( 2 ) to further illustrate the back-support elements 11 ( 1 ) and to further depict the proportional tapered thickness of a panel stiffeners 12 . As seen in FIG. 1C , the back support elements 11 ( 1 ) may extend further outward from vertical panel 17 in order to provide additional buttressing to help avoid tipping when being used to support various food wares. Additionally, at least one panel stiffener 12 may be incorporated into vertical panel 17 to provide added upright structural support and thus prevent unwanted flexing while supporting heavier types of food products. It is noted that panel stiffeners 12 may be thicker toward the horizontal base 16 and gradually taper inward while extending vertically toward the topmost portion of vertical side 17 . In this manner, the desired angle θ° between horizontal base 16 and vertical side 17 may be held more securely fixed and thus prevent unwanted flexing while supporting heavier types of food products. Although angle θ° may be predetermined at time of manufacturing to accommodate different types of food product geometry, in its preferred embodiment, angle θ° is approximately 90° to form an exemplary “L” shaped restraint of the food product stabilization articles of either embodiments 10 ( 1 ) or 10 ( 2 ).
[0033] Now that the “L” shaped stabilization and/or restraint articles 10 ( 1 ) and 10 ( 2 ) have been described using FIGS. 1A-1C , various examples of food product stabilization systems will discussed relative to FIGS. 2A-7B . Then FIG. 8 will be described in relation to an improved method for transferring or relocating various food products from one storage container to another and/or storing disclosed art within traditional containers.
[0034] In this regard, FIGS. 2A-2C are all perspective side views of another embodiment of a food product stabilization system 60 , which features a rotatable hinge panel 20 ( 1 ) used to create customizable food compartments in combination with another “L” shaped embodiment 10 ( 3 ). Similar to previous FIGS. 1A-1C , the food product stabilization article 10 ( 3 ) of FIG. 2A is comprised of an “L” shaped restraint article 10 ( 3 ) having a horizontal base 16 , vertical side panel 17 , panel stiffeners 12 and back-supports 11 ( 1 ) and now further comprises a vertical cylinder 21 ( 1 ) onto which thru-hole 24 ( 1 ) of rotatable hinge panel 20 ( 1 ) may be positioned. FIG. 2A further comprises an array of horizontal slots 22 formed into the horizontal base 16 of restrain article 10 ( 3 ) into which the lower base portion 26 of rotatable hinge panel 20 ( 1 ) may be securely fitted thereby creating a locked vertically upright hinge panel 20 ( 1 ) separator that is held fixed into position by means of the connectivity between thru-hole 24 ( 1 ) and vertical cylinder 21 ( 1 ) and further union of base portion 26 being locked into any of the horizontal slots 22 of horizontal base 16 . It is noted that locking geometry 29 may be incorporated into the rotatable hinge panel 20 ( 1 ) as means of further securing base portion 26 into horizontal slots 22 . Geometry 29 may limit the depth of the lower base 26 into horizontal slots 22 .
[0035] With continuing reference to FIG. 2A , FIGS. 2B-2C are both perspective side views of FIG. 2A with FIG. 2B showing an assembled component view and FIG. 2C depicting the food product stabilization system 60 being used in combination with upright food wares 15 ( 1 ). FIG. 2B illustrates the upright hinge panel 20 ( 1 ) now being assembled onto the “L” shaped restraint article 10 ( 3 ) by thru-hole 24 ( 1 ) fitting onto the vertical cylinder 21 ( 1 ) and thus creating axis A 1 around which the upright hinge panel 20 ( 1 ) may freely pivot. Upright hinge panel 20 ( 1 ) pivots about axis A 1 allowing the base portion 26 to then lock into any part of the array of horizontal slots 22 of horizontal base 16 thereby creating a multitude of customizable positions for bracing and/or supporting food wares.
[0036] FIG. 2C depicts the assembly of FIG. 2B being used in combination with an exemplary upright food product 15 ( 1 ). In this non limiting example, the upright food product 15 ( 1 ) is a portion of a free-standing layer-cake disposed onto the food product stabilization system 60 . In this manner, any segmented size of upright food wares 15 ( 1 ) are disposed in an abutting horizontal relationship with the base portion 16 of the “L” shaped restraint article 10 ( 3 ) and further disposed in two abutting vertical relationships, the first being the vertical side portion 17 of the “L” shaped restraint article 10 ( 3 ) and the second being upon the vertically upright hinge divider panel 20 ( 1 ) of food product stabilization system 60 . In this regard, the upright hinge divider panel 20 ( 1 ) may be removed, depicted in FIG. 2A , and an approximate 180° semi-circle is created as shown by horizontal perimeter edge 14 (A) of the “L” shaped restraint article 10 ( 3 ). Further, the upright hinge divider panel 20 ( 1 ) may be installed, depicted in FIGS. 2B-2C , allowing for customizable positions of bracing and/or stabilizing the upright food product 15 ( 1 ) as smaller and smaller segments are created throughout various stages of food consumption.
[0037] The upright food products 15 ( 1 ), 15 ( 2 ) may vary is size, shape and type creating a potential need for additional separations and/or multiple compartment dividers. FIGS. 3A-3B are perspective side views of another embodiment of a food product stabilization system 70 comprised of a new embodiment of an “L” shaped restraint article 10 ( 4 ) and further embodiments of divider panels 20 ( 2 A)- 20 ( 2 C). The food product stabilization system 70 further comprises a plurality of both vertical slots or guides 18 (A) and horizontal slots or guides 18 (B) into which at least one of the vertical divider panels 20 ( 2 A)- 20 ( 2 C) may be positioned thereby creating customizable compartments 23 into which different sizes and types of upright food wares 15 ( 2 ) may be compartmentalized, divided and held secure. The food product stabilization system 70 may further comprise at least one integrated back-support element 11 ( 2 ) designed to freely pivot upon a vertical hinge axis A 2 of hinge 25 in order for the back-support element 11 ( 2 ) to be collapsed into a space-saving position for storage as depicted in FIG. 3A or the back-support element 11 ( 2 ) may be pivoted outward about axis A 2 of hinge 25 into a generally perpendicular relationship with the vertical side 17 of the “L” shaped restraint article 10 ( 4 ) as depicted in FIG. 3B and thereby provide additional vertical support and further prevent any unwanted tipping or spillage during storage or transport of upright food products 15 ( 2 ). The “L” shaped restraint article 10 ( 4 ) of food product stabilization system 70 may also comprise optional end-panels 13 . The vertical edge portions 27 (A) of divider panels 20 ( 2 A)- 20 ( 2 C) are able to lock into vertical guides 18 (A) and horizontal base portions 27 (B) of divider panels 20 ( 2 A)- 20 ( 2 C) are able to lock into horizontal guides 18 (B).
[0038] With reference back to FIGS. 2A-2C , it may be desirable for the “L” shaped restraint article 10 ( 3 ) of food product stabilization system 60 to feature an ability to hold more than one upright hinge divider panel 20 ( 1 ) to create differently sized food storage compartments, and so FIGS. 4A-4B are perspective side views of another embodiment of a food product stabilization system 80 , which comprises an exemplary embodiment of an “L” shaped restraint article 10 ( 5 ) featuring an elongated vertical cylindrical 21 ( 2 ) and further comprises multiple embodiments of a plurality of vertically upright hinged divider panels 20 ( 3 A)- 20 ( 3 C). FIG. 4A depicts an exploded perspective side view of an “L” shaped restraint article 10 ( 5 ) having a horizontal base 16 , vertical side panel 17 and an array of horizontal slots 22 formed into the horizontal base 16 of restrain article 10 ( 5 ). The “L” shaped restraint article 10 ( 5 ) further comprises an elongated vertical cylindrical 21 ( 2 ) onto which thru-holes 24 ( 2 A)- 24 ( 2 C) of rotatable hinge panels 20 ( 3 A)- 20 ( 3 C) may be positioned in a vertically stackable relationship creating axis A 3 around which hinge panels 20 ( 3 A)- 20 ( 3 C) may freely pivot and adjust. Similar to FIGS. 2A-2C the “L” shaped restraint article 10 ( 5 ) also comprises an array of horizontal slots 22 formed into the horizontal base 16 of restrain article 10 ( 5 ) into which all of the lower base portion 26 of rotatable hinge panels 20 ( 3 A)- 20 ( 3 C) may be securely fitted thereby creating a plurality of locked vertically upright hinge-panel separators 20 ( 3 A)- 20 ( 3 C), which are each held fixed into position by means of the connectivity between thru-holes 24 ( 2 A)- 24 ( 2 C) and the elongated vertical cylinder 21 ( 2 ) and further horizontal union of the base portions 26 being firmly locked into any of the horizontal slots 22 of horizontal base 16 .
[0039] FIG. 4B depicts an assembled perspective side view of FIG. 4A and further illustrates the multiple segmented compartments a( 1 ), a( 2 ), a( 3 ) and a( 4 ) that may be created and customized by differently angled relationships between vertical side panel 17 and the various pivoted positions of the upright hinge-panel separators 20 ( 3 A)- 20 ( 3 C), or solely between the differently angled positions of the vertical hinge-panel separators 20 ( 3 A)- 20 ( 3 C). It is noted that more or less hinge-panel separators may be used to created a greater or lesser number of segmented compartments a( 1 ), a( 2 ), a( 3 ) and a( 4 ). Further, all of the previously described panel separators of FIGS. 2A-4B may include custom designed thru-ways 28 for either aesthetic appeal or material reduction, or both.
[0040] With continuing reference to FIG. 4B , it is noted that the vertically stackable relationship between the elongated vertical cylindrical 21 ( 2 ) of the “L” shaped restraint article 10 ( 5 ), and the thru-holes 24 ( 2 A)- 24 ( 2 C) of rotatable hinge panels 20 ( 3 A)- 20 ( 3 C), may be achieved through differently sized vertical height configurations of thru-holes 24 ( 2 A)- 24 ( 2 C). Additionally, it is further noted that the vertically stackable relationship between the elongated vertical cylindrical 21 ( 2 ) of the “L” shaped restraint article 10 ( 5 ), and the thru-holes 24 ( 2 A)- 24 ( 2 C) of rotatable hinge panels 20 ( 3 A)- 20 ( 3 C), may require gap gamma (y) within side panel 17 to be sufficiently sized along perimeter edge 19 of side panel 17 and the elongated cylindrical 21 ( 2 ) of the “L” shaped restraint article 10 ( 5 ).
[0041] With additional reference back to FIGS. 2A-2C , it may be desirable for the “L” shaped restraint article 10 ( 3 ) of food product stabilization system 60 to feature an ability to exhibit additional vertical height adjustability to accommodate taller food or shorter food products. Accordingly, FIGS. 5A-5B are perspective side views of another embodiment of a food product stabilization system 90 , which comprises the previously disclosed embodiment of an “L” shaped restraint article 10 ( 3 ) of the food product stabilization system 60 of FIGS. 2A-2C , which now further comprises an at least one adjustable height panel 30 ( 1 ) that may be positioned to further customize and adjust the upright vertical support-panel geometry for taller or shorter food products and thereby creating added vertical stability for a diverse assortment of differently sized upright food products. The adjustable height panel 30 ( 1 ) may feature, for example, a thru-way 38 so that rotatable hinge panel 20 ( 1 ) may pivot freely about axis A 4 without obstruction.
[0042] FIG. 5A is an exploded perspective side views depicting one embodiment of an adjustable height panel 30 ( 1 ) placed behind the “L” shaped restraint article 10 ( 3 ) in a manner to demonstrate how the adjustable height panel may be positioned by means of edge-clips 32 . Edge-clips 32 may, for example, be spaced away from panel-face 37 in order to create gap 35 that is sized sufficiently to slide over both perimeter edge 19 and side panel 17 of the “L” shaped restraint article 10 ( 3 ). In this manner, the height of the food product stabilization system 90 may be vertically adjustable to support taller food items, where perimeter edge 39 is now vertically taller than perimeter edge 19 as seen in FIG. 5B . It is noted that the hinge panel 20 ( 1 ) may still function as previously described.
[0043] With supplementary reference back to FIGS. 2A-2C , it may also be desirable for the “L” shaped restraint article 10 ( 3 ) and rotatable hinge panel 20 ( 1 ) of food product stabilization system 60 , as well as any variety of upright food wares 15 ( 1 ) to be enclosed within uniquely designed containers to further protect and store any combination of the previously disclosed food product stabilization systems and associated food wares 15 ( 1 ). Since the disclosed food product stabilization systems are invented partly to protect, brace, and store upright food wares, it may also be desirable for the uniquely designed containers to feature additional restraints and/or bracing facets to provide further stability. It may also be advantageous for uniquely designed containers to exhibit an overall shaped that is formed and intended to provide space savings of less than whole food products. Accordingly, FIGS. 6A-6B are perspective side views of another embodiment of a food product stabilization system 100 , which comprises the previously disclosed embodiment of an “L” shaped restraint article 10 ( 3 ) and the rotatable hinge panel 20 ( 1 ) of the food product stabilization system 60 of FIGS. 2A-2C , but now further comprises a unique base platform 50 ( 1 ) and a formed top cover 40 ( 1 ) each designed to fit securely together.
[0044] Referencing FIG. 6A , which is an exploded perspective side view, the unique base platform 50 ( 1 ) may, for example, feature bracing facets 54 and 59 , where the back bracing facets 59 may secure edge 19 of vertical side panel 17 while the front bracing facets 54 may further secure perimeter edge 14 (A) of horizontal base 16 . In this manner, the “L” shaped restraint article 10 ( 3 ) may fit securely into bracing facets 54 and 59 of the unique base platform 50 ( 1 ) as seen in FIG. 6B and thereby provide additional protection against unwanted sliding during transport of the food product stabilization system 100 . It is noted that a non-slip treatment may exist upon top surface 56 of base platform 50 ( 1 ) creating friction and an enhanced grip between the horizontal base 16 and top surface 56 .
[0045] With continuing reference to FIG. 6A , it is noted that lower perimeter edge 42 of top cover 40 ( 1 ) is expressly formed to fit into the perimeter groove 52 of the unique base platform 50 ( 1 ). The pre-formed shape of top cover 40 ( 1 ) is comprised of a relationship of the lower perimeter edge design 42 extending upward toward a top surface 44 and thusly, can be of any desired perimeter and vertical shape to accommodate any variety of food products and the previously disclosed food product stabilization systems.
[0046] Referencing the assembled food product stabilization system 100 of FIG. 6B , it is observed that the pre-formed top cover 40 ( 1 ) in this example is transparent and may display the contents therein. FIG. 6B further depicts the connective relationship between the back bracing-facets 59 and perimeter edge 19 of vertical side panel 17 , as well as the front bracing-facets 54 and perimeter edge 14 (A) of horizontal base 16 . In this manner, any variety of food products are markedly more braced, secured in place and significantly better protected within the disclosed food product stabilization and storage system 100 .
[0047] With reference back to FIGS. 6A-6B , it may also be desirable for any of the previously disclosed food product stabilization and storage systems to further comprise a method of carrying for easy transportation from one location to another and therefore FIGS. 7A-7B are perspective side views of another embodiment of a new food product stabilization, storage and transportation system 105 , which further comprises at least one carrying strap 55 ( 1 ) featuring quick-connect tabs 57 of straps 53 that are both designed to operate in conjunction with slots 51 of locking-latch 58 of a new embodiment of a base platform 50 ( 2 ). The locking-latches 58 of base platform 50 ( 2 ) may, for example, be pre molded into the base platform 50 ( 2 ) and thereby provide added carrying strength. As seen in FIG. 7A , a convenient carrying handle 51 may be disposed between the carrying straps 53 and located at a topmost position to accommodate a means of suitable carrying. FIG. 7B is an assembled perspective side view that depicts a unique base platform 50 ( 2 ) with locking latches 58 , an opaque top cover 40 ( 2 ), which may enclose and contain any of the previously disclosed food product stabilization systems, and finally a carrying strap 55 ( 1 ) with quick-connect tabs 57 fitting securely into slots 51 of locking latches 58 . Like FIGS. 6A-6B , the lower perimeter edge 42 of top cover 40 ( 2 ) is expressly formed to fit into the perimeter groove 52 of the base platform 50 ( 2 ) as seen in FIG. 7B . Further, it is noted that quick-connect tabs 57 and locking latches 58 may be comprised of any type or style of locking connectors. In this manner, a considerably more complete food product stabilization, storage and transportation system 105 is created to efficiently protect, store, brace, preserve and transport any variety of food wares in a more secure fashion and thus prevent unwanted damage to any assortment, shape or size of upright food products.
[0048] FIG. 8 is a perspective side view of another embodiment of a food product stabilization system 110 that is contained within a traditional food storage and/or display container. In this example, the traditional container is a cake display container, which is comprised of a lower base 125 and an upper lid 120 . As seen in some prior-art display containers, the lower base 125 features a decorative stem 127 , a lower base surface 128 and a perimeter edge 126 onto which an upper lid 120 may be positioned. The upper lid 120 often features a top surface 124 , a topmost handle 121 and side walls 122 that are designed to fit upon the perimeter edge 126 of lower base 125 . Now that the prior-art display container has been described, additional features and benefits will be discussed to describe an improved method for transferring and/or relocating various food products from any storage device to another and thus reduce or prevent any unwanted damage to upright food wares while they are being relocated from one storage container to another.
[0049] FIG. 8 depicts a new embodiment of an “L” shaped restraint article 10 ( 6 ) as well as a new embodiment of a rotatable hinge panel 20 ( 4 ). In this example, the “L” shaped restraint article 10 ( 6 ) is comprised of a stronger, more durable material and does not require panel stiffeners or ancillary back-support elements. Similarly, the rotatable hinge panel 20 ( 4 ) is solid and omits any type of thru-ways. It is noted that both the food product stabilization system 110 and all previously disclosed food product stabilization, storage and/or transport systems and embodiments may be comprised, for example, of almost any type of material such as metals, woods, synthetics, plastics and/or composites or any derivative thereof. In their preferred embodiments, the food product stabilization, storage and/or transport systems and/or embodiments may be manufactured via injection and/or blow molding processes and be comprised of any known polymeric thermoplastic.
[0050] Non-limiting examples of polymeric thermoplastic materials that may be used include polyethylenes, polypropylenes, copolymers, ethylene vinyl acetates, polystyrenes, thermoplastic olefins, thermoplastic polyester, polyvinyl chlorides, ethylene methyl acrylates, chlorinated polyethylene, polyolefins and the like, and derivatives thereof.
[0051] With continuing reference to FIG. 8 , it is observable that the food item 15 ( 1 ), a free standing layer cake in this example, is positioned in horizontal relationship upon lower base 16 portion of the “L” shaped restraint article 10 ( 6 ) and braced in two vertical relationships, the first abutting upon vertical side panel 17 and the second adjoining the vertical and rotatable hinge panel 20 ( 4 ), which is secured by a mating relationship of a thru-hole 24 ( 1 ) and vertical cylinder 21 ( 1 ) as well as the lower base 26 of rotatable hinge panel 20 ( 4 ) being affixed into one of the array of horizontal slots 22 of lower base 16 . In this regard, the upright food product may be easily moved from one storage container as depicted in FIG. 8 to the previously disclosed storage container system 100 , for example, as illustrated in FIGS. 6A-6B , or into the previously disclosed transportation system 105 , for example, as portrayed in FIG. 7B , or any derivative thereof by means of picking and placing any disclosed “L” shaped restraint article, which will continue to hold any upright food products 15 ( 1 ) securely in position during transport from one container to another.
[0052] Lacking from prior art methods of moving upright food wares from one location to another is an ability to fully support the underside of the food product 15 ( 1 ) as well as an absence of vertical buttressing features during transport. In this regards, it is noted that the lower perimeter edges, 14 (A,B) of FIGS. 1A-C for example, of lower base portion 16 of any “L” shaped restraint article may be formed with a blade-like edge in order for any of the perimeter edges 14 (A,B) in combination with lower base portion 16 to function in a manner similar to a spatula edge to easily slide under any food product 15 ( 1 ) regardless of the surface that the food products 15 ( 1 ) may reside upon. It is further noted that, unlike traditional spatulas, the horizontal base 16 of all of the “L” shaped restraint articles may function as an oversized spatula and thus fully encompass the lower portion of food product 15 ( 1 ) during relocation. Additionally, any of the aforementioned vertical panels and/or hinges, as seen in food product stabilization system 60 of FIG. 2C for example, will provide supplementary vertical support upon at least two vertical surfaces of food product 15 ( 1 ) during transport and/or relocation. In these regards, any of the previously disclosed “L” shaped restraint articles may function a both a spatula to easily slide under any upright food product 15 ( 1 ), and as a carrying or transport device that may, in combination with any disclosed vertical panels and/or hinges, easily lift and securely hold large food wares such as cakes, breads, casseroles, pastries and the like. Accordingly, an improved method is realized for transferring or relocating food products from one storage and/or transport device to another thus preventing unwanted damage.
[0053] Many additional alterations, modifications and/or other variations of the embodiments disclosed herein will come to mind to one skilled in the art to which the embodiments may be relevant having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be expressly understood that the descriptions and claims are not to be limiting in any way to the specific embodiments disclosed and that modifications and other embodiments are hereby intended to be included within the scope of the appended claims. It is further intended that the disclosed description and embodiments cover any modifications and variations of the embodiments provided they come within the scope of the appended claims and their equivalents. Although many different specific terms are employed herein, they are used in a generic sense and in a descriptive sense only and not for purposes of limitation.
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Food product stabilization systems employing features to stabilize upright food wares that are subject to tipping, crumbling and/or being damaged during transport or storage. Freestanding upright food wares may have exposed edges requiring some form of protection to reduce and/or prevent unwanted surface deterioration, crumbling, tilting, sliding, collapsing and/or damage resulting from transportation and/or storage. Varieties of food containers are disposed around upright food wares as a general means of protecting against humidity, oxidation and/or contaminates from an outside environment. In cases where upright food wares are dissimilarly shaped or sized disproportionately to food containers, unwanted surface deterioration, crumbling, sliding, spillage or damage may occur. The food product stabilization system comprises proportionately designed shapes and/or extendable/contractible edge support features to better enable the upright food wares to be protected, braced, and held more securely during transportation and/or storage. In this manner upright food wares may be efficiently contained, transported or stored even while subjected to external conditions that might otherwise cause damage.
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BACKGROUND OF THE INVENTION
The present invention relates to a steering system for a motor vehicle.
The steering system has a reduction gear train for transmitting the rotation of a steering wheel to front wheels of the vehicle. It is preferable to vary the gearing ratio in such a manner that it has a small value on either side of the straight-ahead position of the steering wheel and increases as the steering angle of the steering wheel increases. Such a steering system is called a variable ratio steering system and is disclosed various publications, for example U.S. Pat. No. 3,267,763 and Japanese Utility Model Laid Open No. 59-16269.
In the variable ratio steering system, the ratio can not be changed to other ratios than the set values. However, it is desirable for the ratio to be changed in accordance with driving conditions such as vehicle speed, side force exerted on the vehicle and other conditions.
SUMMARY OF THE INVENTION
The object of the present invention is to provide a steering system in which the gearing ratio can be changed in accordance with driving conditions.
The other objects and features of this invention will become understood from the following description with reference to the accompanying drawings.
BRIEF DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 is a schematic diagram showing a steering system according to the present invention; and
FIGS. 2a to 2e are illustrations showing operations of a part of the system.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1, a steering system comprises a steering wheel 1, steering shaft 2, joint 3, intermediate shaft 4, joint 5 and a first rack-and-pinion device 10. The first rack-and-pinion device has a gear box 6 having a pinion 7. The pinion 7 engages with a first rack 8 in a first rack housing 9. A second rack-and-pinion device 11 is provided in parallel with the first rack-and-pinion device 10. A pinion 12 of the device 11 is engaged with a second rack 13 in a second rack housing 14. The pinion 12 is operatively connected with an electric motor 15.
A pair of tie rods 16 connected to the first rack 8 at both ends thereof to form a first tie rod which is pivotally connected to connecting rods 17 by joints 18, respectively. Each tie rod 20 is connected second rack 13 to form a primary tie rod which is connected to the connecting rod 17 through an intermediate rod 21 and joints 22, 23. The primary tie rod and intermediate rods 21 form a second tie rod. A tie rod 24 is connected to the connecting rod 17 through a joint 25 at a position close to the end adjacent the joint 23. The tie rod 24 is operatively connected to a front wheel 26 of a vehicle through a joint 27 and a knuckle arm 28.
The system is provided with a steering angle sensor 30, vehicle speed sensor 31 and lateral acceleration sensor 32.
The outputs of these sensors are supplied to a control unit 33 for controlling the motor 15. The operation of the motor 15 is controlled by an output signal of the control unit 33 and by a feedback signal from an angular position sensor 34 for detecting an angular output of the motor 15. The control unit 33 is arranged to produce a control signal for operating the motor 15 in accordance with the vehicle speed signal fed from the vehicle speed sensor 31. When the vehicle speed is low, the motor operates to move the second rack 13 at a speed approximately equal to the speed of the first rack 8. As the vehicle speed increases, the speed of the second rack 13 is decreased compared with the speed of the first rack 8. In other words, the ratio of the speed of the second rack to the speed of the first rack is one at a low vehicle speed and approaches zero at a high vehicle speed.
If, in a low vehicle speed range lower than 30 Km/h, the ratio of the speed of the second rack to the first rack is set to one, the second rack 13 is moved by the same distance as the first rack 8 as shown in FIG. 2b. Accordingly, the gearing ratio at that case is the same as the ratio (i) of the first rack and pinion device 11.
At a high vehicle speed, for example 100 Km/h, the speed ratio is set to zero, the second rack 13 is not moved as shown in FIG. 2d.
Assuming the length between the connecting portion P on the connecting rod 17 for the tie rod 24 is 1 and the length of the connecting rod 17 is n (FIG. 2a), the ratio of the displacement of the tie rod 24 to the displacement of the first rack 8 is 1/n. Thus, the resultant gearing ratio of the steering system becomes 1/n .i.
At an intermediate speed, for example 60 Km/h, the speed ratio of the second rack is set to a middle value, for example 0.5 as shown in FIG. 2c. The resultant gearing ratio in that case is 0.5 (1+i/n) which is an intermediate value between the ratio i and 1/n .i.
In an extreme low speed range, for example below 3 Km/h, the speed ratio of the second rack is set to a value larger than 1 as shown in FIG. 2a. Accordingly, the resultant gearing ratio becomes larger than the ratio i.
In an extreme high speed range, for example above 120 Km/h, the speed ratio of the second rack is set to a negative value close to zero as shown in FIG. 2e. The resultant gearing ratio becomes smaller than the ratio 1/n .i.
It is preferable that when a vehicle having an understeer characteristic is accelerated during cornering, the steering angle is increased. To meet such a requirement, when the output signal of the vehicle speed sensor 31 increases while the lateral acceleration sensor 32 produces an output which means cornering of the vehicle, the motor 15 is operated to move the second rack 13 to increase the steerig angle.
When the vehicle is subjected to a side force by a side wind during driving, the vehicle may become staggered. In such a case, the lateral acceleration sensor produces an output signal because of the staggering. In response to the output signal, the motor 15 is operated to shift the second rack 13 to correct the steering direction.
It will be understood that the gearing ratio can be controlled in accordance with the output signal of the steering angle sensor 30 in the same manner as the variable ratio steering system.
Although the motor 15 is provided for shifting the second rack 13, other actuators such as a hydraulic cylinder can be used.
While the presently preferred embodiments of the present invention have been shown and described, it is to be understood that this disclosure is for the purpose of illustration and that various changes and modifications may be made without departing from the scope of the invention as set forth in the appended claims.
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A first rack-and-pinion device is operatively connected to a steering wheel of a motor vehicle, and a second rack-and-pinion device is provided to be operated by a motor. Both racks are operatively connected by a pair of link mechanisms. Each link mechanism is arranged to combine gear ratios of the first and second rack-and-pinion devices to steer front wheels of the vehicle at a resultant gearing ratio.
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This is a divisional application of U.S. patent application Ser. No. 10/765,485, filed on Jan. 27, 2004, now U.S. Pat. No. 7,022,783 B2, which is a continuation-in-part application of U.S. patent application Ser. No. 10/331,259, filed on Dec. 30, 2002 now abandoned, which claims the benefit of U.S. Provisional Patent Application Ser. No. 60/345,758, filed on Dec. 31, 2001.
BACKGROUND OF THE INVENTION
In the copolymerization of 1,3-butadiene and isoprene with unmodified neodymium catalysts, the 1,3-butadiene polymerizes about 19 times faster than the isoprene. For this reason, such copolymers do not have a random distribution of monomers. One end of the polymer chains contain mostly repeat units which are derived from butadiene (which polymerized faster) and the other end of the polymer chains contain mostly repeat units which are derived from isoprene (which polymerized slower). As the polymerization proceeds, the availability of butadiene monomer for polymerization diminishes leaving more and more isoprene to polymerize subsequently. This causes such isoprene-butadiene rubbers to be tapered.
U.S. Pat. No. 4,663,405 discloses that conjugated diolefin monomers can be polymerized with a catalyst system which is comprised of (1) an organoaluminum compound, (2) an organometallic compound which contains a metal from Group III-B of the Periodic System, such as lanthanides and actinides, and (3) at least one compound which contains at least one labile halogen atom. U.S. Pat. No. 4,663,405 also discloses that the molecular weight of the polymers made with such catalyst systems can be reduced by conducting the polymerization in the presence of a vinyl halide. However, its teachings do not specifically disclose copolymerizations of isoprene with butadiene and do not provide any technique for making the isoprene monomer polymerize at a rate that is similar to that of the butadiene monomer. Thus, its teachings do not provide a technique for synthesizing random, non-tapered isoprene-butadiene rubbers with catalyst systems which are comprised of (1) an organoaluminum compound, (2) an organometallic compound which contains a metal from Group III-B of the Periodic System, such as lanthanides and actinides, and (3) at least one compound which contains at least one labile halogen atom.
U.S. Pat. No. 5,405,815 discloses a process or preparing a catalyst system which is particularly useful for copolymerizing isoprene and 1,3-butadiene monomers into rubbers which comprises the sequential steps of (1) mixing (a) an organoaluminum hydride, (b) a member selected from the group consisting of aliphatic alcohols, cycloaliphatic alcohols, aliphatic thiols, cycloaliphatic thiols, trialkyl silanols, and triaryl silanols, and (c) optionally, 1,3-butadiene in an organic solvent to produce a modified organoaluminum catalyst component; (2) adding an organometallic compound which contains a metal from Group III-B of the Periodic System to the modified organoaluminum catalyst component to produce a Group III-B metal containing catalyst component; (3) adding a compound which contains at least one labile halogen atom to the Group III-B metal containing catalyst component; and (4) aging the catalyst system after the compound which contains at least one labile halogen atom is added to the modified Group III-B metal containing catalyst component for a period of 10 minutes to 6 hours, wherein the catalyst system is aged at a temperature which is within the range of about 30° C. to about 85° C.
SUMMARY OF THE INVENTION
By utilizing the technique of this invention copolymers of isoprene and butadiene can be synthesized to higher molecular weights and higher cis-microstructure contents at faster polymerization rates. These copolymers also exhibit better processability and exhibit an excellent combination of properties for utilization in tire sidewall rubber compounds for truck tires. By utilizing these isoprene-butadiene rubbers in tire sidewalls, tires having improved cut growth resistance can be built without sacrificing rolling resistance. The isoprene-butadiene rubbers made by the process of this invention can also be employed in tire tread rubber compounds to improve the tread wear characteristics and decrease the rolling resistance of the tire without sacrificing traction characteristics.
The present invention discloses a process for the synthesis of isoprene-butadiene rubber which comprises copolymerizing isoprene monomer and 1,3-butadiene monomer in an organic solvent in the presence of a Group III-B metal containing catalyst system that is made by the sequential steps of (I) reacting an organometalic compound that contains a metal from Group III-B of the Periodic System with an organoaluminum compound at a temperature which is within the range of 50° C. to 100° C. to produce an aluminum modified Group III-B metal containing catalyst component, and (II) mixing the aluminum modified Group III-B metal containing catalyst component with a halogen containing compound, wherein the catalyst system is void of compounds selected from the group consisting of aliphatic alcohols, cycloaliphatic alcohols, aliphatic thiols, cycloaliphatic thiols, trialkyl silanols, and triaryl silanols. In the practice of this invention it is convenient to add the halogen containing compound and the aluminum modified Group III metal containing compound directly to the polymerization reactor as a separate components.
This invention also reveals a process for preparing a catalyst system that comprises the sequential steps of (I) reacting an organometalic compound that contains a metal from Group III-B of the Periodic System with an organoaluminum compound at a temperature which is within the range of 50° C. to 100° C. to produce an aluminum modified Group III-B metal containing catalyst component, and (II) mixing the aluminum modified Group III-B metal containing catalyst component with a halogen containing compound, wherein the catalyst system is prepared in the absence of compounds selected from the group consisting of aliphatic alcohols, cycloaliphatic alcohols, aliphatic thiols, cycloaliphatic thiols, trialkyl silanols, and triaryl silanols.
DETAILED DESCRIPTION OF THE INVENTION
The relative amount of isoprene and butadiene, which can be copolymerized with the catalyst system of this invention, can vary over a wide range. For example, the monomer charge composition can contain from about 1 weight percent to about 99 weight percent butadiene and from about 1 weight percent to 99 weight percent isoprene. In most cases, the monomer charge composition will contain from about 10 weight percent to about 90 weight percent butadiene and from about 10 weight percent to 90 weight percent isoprene. It is normally preferred for the monomer charge composition to contain from about 25 weight percent to about 75 weight percent butadiene and from about 25 weight percent to about 75 weight percent isoprene. It is generally more preferred in the case of automobile tires for the monomer charge composition to contain from about 50 weight percent to about 75 weight percent butadiene and from about 25 weight percent to about 50 weight percent isoprene. It is generally more preferred in the case of truck tires for the monomer charge composition to contain from about 25 to 50 weight percent 1,3-butadiene and 50 to 75 weight percent isoprene.
The polymerizations of the present invention are carried out in a hydrocarbon solvent that can be one or more aromatic, paraffinic, or cycloparaffinic compounds. These solvents will normally contain from 4 to 10 carbon atoms per molecule and will be liquids under the conditions of the polymerization. Some representative examples of suitable organic solvents include pentane, isooctane, cyclohexane, normal hexane, benzene, toluene, xylene, ethylbenzene, and the like, alone or in admixture.
In solution polymerizations which utilize the catalyst systems of this invention, there will normally be from 5 to 35 weight percent monomers in the polymerization medium. Such polymerization mediums are, of course, comprised of an organic solvent, 1,3-butadiene monomer, isoprene monomer, and the catalyst system. In most cases, it will be preferred for the polymerization medium to contain from 10 to 30 weight percent monomers. It is generally more preferred for the polymerization medium to contain 12 to 18 weight percent monomers.
The catalyst system used in the process of this invention is made by a simplified two-step process. In the first step, an organoaluminum compound is reacted with an organometalic compound that contains a metal from Group III-B of the Periodic System. Unlike techniques of the prior art, it is not necessary to react the organoaluminum compound with an alcohol, a thiol, or a conjugated diolefin monomer, such as 1,3-butadiene, to attain good polymerization rates and high conversions. Accordingly, the catalyst systems of this invention are prepared in the absence of alcohols and thiols. Since it is not necessary for the catalyst system of this invention to be prepared in the presence of a conjugated diolefin monomer, such as 1,3-butadiene or isoprene, it is normally also prepared in the absence of such conjugated diolefin monomers.
In this first step, the organoaluminum compound is reacted with the compound that contains a metal from Group III-B of the Periodic System. It is critical for this step to be conducted at a temperature which is within the range of 50° C. to 100° C. The organoaluminum compound will preferably be reacted with the compound that contains a metal from Group III-B of the Periodic System at a temperature which is within the range of 60° C. to 85° C. and will more preferably be reacted at a temperature which is within the range of 65° C. to 75° C. The organoaluminum compound and the organometallic compound that contains a metal from Group III-B of the Periodic System will normally be allowed to react for a period of at least about 5 minutes to produce the aluminum modified Group III-B metal containing catalyst component. A period of about 5 minutes to about 60 minutes will typically be allowed for this reaction to occur. It is preferable to allow 20 minutes to 40 minutes for this reaction to occur.
The organoaluminum compounds that can be utilized are of the structural formula:
in which R 1 , R 2 , and R 3 are selected from the group consisting of alkyl groups (including cycloalkyl), aryl groups, alkaryl groups, arylalkyl groups, and alkoxy groups. It is preferred for R 1 , R 2 and R 3 to represent alkyl groups which contain from 1 to about 12 carbon atoms. It is more preferred for R 1 , R 2 and R 3 to represent alkyl groups which contain from 2 to 8 carbon atoms.
Some representative examples of organoaluminum compounds that can be utilized are trimethyl aluminum, triethyl aluminum, tri-n-propyl aluminum, triisopropyl aluminum, tri-n-butyl aluminum, triisobutyl aluminum, tripentyl aluminum, trihexyl aluminum, tricyclohexyl aluminum, trioctyl aluminum, triphenyl aluminum, tri-p-tolyl aluminum, tribenzyl aluminum, ethyl diphenyl aluminum, ethyl di-p-tolyl aluminum, ethyl dibenzyl aluminum, diethyl phenyl aluminum, diethyl p-tolyl aluminum, diethyl benzyl aluminum and other triorganoaluminum compounds. The preferred organoaluminum compounds include triethyl aluminum (TEAL), tri-n-propyl aluminum, triisobutyl aluminum (TIBAL), trihexyl aluminum, and trioctylaluminum. Organoaluminum hydrides are normally not utilized in making the catalyst systems of this invention.
The Group III-B metal containing organometallic compounds which can be employed may be symbolically represented as ML 3 wherein M represents the Group III-B metal and wherein L represents an organic ligand containing from 1 to about 20 carbon atoms. The Group III-B metal will be selected from the group consisting of scandium, yttrium, lanthanides, and actinides. It is normally preferred for the Group III-B metal to be a lanthanide. The organic ligand will generally be selected from the group consisting of (1) o-hydroxyaldehydes, (2) o-hydroxyphenones, (3) hydroxyesters, (4) β-diketones, (5) monocarboxylic acids, (6) ortho dihydric phenols, (7) alkylene glycols, (8) dicarboxylic acids, and (9) alkylated derivatives of dicarboxylic acids.
The lanthanides which can be used in the organolanthanide compound include lanthanum, cerium, praseodymium, neodymium, promethium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, and lutetium. The preferred lanthanide metals include cerium, praseodymium, neodymium, and gadolinium which have atomic numbers of 58, 59, 60, and 64, respectively. The most preferred lanthanide metal is neodymium.
In the organolanthanide compound utilized, the organic portion includes organic type ligands or groups which contain from 1 to 20 carbon atoms. These ligands can be of the monovalent and bidentate or divalent and bidentate form. Representative of such organic ligands or groups are (1) o-hydroxyaldehydes such as salicylaldehyde, 2-hydroxyl-1-naphthaldehyde, 2-hydroxy-3-naphthaldehyde and the like; (2) o-hydroxyphenones such as 2′-hydroxyacetophenone, 2′-o-hydroxybutyrophenone, 2′-hydroxypropiophenone and the like; (3) hydroxy esters such as ethyl salicylate, propyl salicylate, butyl salicylate and the like; (4) β-diketones such as acetylacetone, benzoylacetone, propionylacetone, isobutyrylacetone, valerylacetone, ethylacetylacetone and the like; (5) monocarboxylic acids such as acetic acid, propionic acid, valeric acid, hexanoic acid, 2-ethylhexanoic acid, neodecanoic acid, lauric acid, stearic acid and the like; (6) ortho dihydric phenols such as pyrocatechol; (7) alkylene glycols such as ethylene glycol, propylene glycol, trimethylene glycol, tetramethylene glycol and the like; (8) dicarboxylic acids such as neodecanoic acid, oxalic acid, malonic acid, maleic acid, succinic acid, o-phthalic acid and the like; and (9) alkylated derivatives of the above-described dicarboxylic acids.
Representative organolanthanide compounds corresponding to the formula ML 3 , which may be useful in this invention include cerium acetylacetonate, cerium naphthenate, cerium neodecanoate, cerium octanoate, tris-salicylaldehyde cerium, cerium tris-8-hydroxyquinolate), gadolinium naphthenate, gadolinium neodecanoate, gadolinium octanoate, lanthanum naphthenate, lanthanum octanoate, neodymium naphthenate, neodymium neodecanoate, neodymium octanoate, praseodymium naphthenate, praseodymium octanoate, yttrium acetylacetonate, yttrium octanoate, dysprosium octanoate, and other lanthanide metals complexed with ligands containing from 1 to about 20 carbon atoms.
The actinides which can be utilized in the Group III-B metal containing organometallic compound include actinium, thorium, protactinium, uranium, neptunium, plutonium, americium, curium, berkelium, californium, einsteinium, fermium, mendelevium, and lawrencium. The preferred actinides are thorium and uranium which have atomic numbers of 90 and 92, respectively. Some representative examples of organoactinides which can be employed include tris(π-allyl) uranium chloride, tris(π-allyl) uranium bromide, tris(π-allyl) uranium iodide, uranium tetramethoxide, uranium tetraethoxide, uranium tetrabutoxide, uranium octanoate, thorium tetraethoxide, tris(π-allyl) thorium chloride, thorium naphthenate, uranium isovalerate, thorium octanoate, tris(π-allyl) thorium bromide, tris(π-allyl) thorium iodide, thorium tetramethoxide, and the like.
The molar ratio of the Group III-B containing organometallic compound added to the amount of aluminum in the organoaluminum compound will typically be within the range of about 1:6 to about 1:40. It is generally preferred for the molar ratio of the Group III-B metal compound, such as the organolanthanide compound, to the organoaluminum compound to be within the range of about 1:8 to about 1:25. It is normally more preferred for the molar ratio of the Group III-B metal compound to the organoaluminum compound to be within the range of about 1:11 to about 1:20.
In the second step of the catalyst preparation procedure, the aluminum modified Group III-B metal containing catalyst component made in the first step is mixed with a halogen containing compound. The halogen containing compound will be void of labile halogen atoms, such as labile bromine atoms, labile chlorine atoms, labile fluorine atoms, and labile iodine atoms. The halogen containing compound can be virtually any halogenated organic compound that does not contain labile halogen atoms, such as a primary alkyl halide or an aryl halide. Some representative examples of halogen containing compounds that can be used include chloroform, carbon tetrachloride, phenyl chloride, phenyl bromide, naphthyl chloride, naphthyl bromide, dibromomethane, dichloromethane, methylenedichloride, methylenedibromide, hexachloroethane, hexabromoethane, and the like.
The molar ratio of the halogen containing compound to the aluminum modified Group III-B metal containing catalyst component will normally be within the range of about 1:1 to about 5:1. It is generally preferred for the molar ratio of the halogen atom containing compound to the Group III-B metal to be within the range of about 1:2 to about 3:1. It is normally more preferred for the ratio of the halogen containing compound to the Group III-B metal to be within the range of 1:1 to about 2:1.
In any case, the catalyst system of this invention will be prepared in the absence of compounds containing labile halogen atoms, such as (1) tertiary alkyl halides; (2) secondary alkyl halides; (3) aralkyl halides; (4) allyl halides; (5) hydrogen halides; (6) alkyl, aryl, alkaryl, aralkyl and cycloalkyl metal halides wherein the metal is selected from the Groups II, III-A and IV-A of the Periodic Table; (7) metallic halides, such as halides of metals of Groups III, IV, V, VI-B and VIII of the Periodic Table; (8) halosilanes; (9) halosulfides; (10) halophosphines; and (11) organometallic halides corresponding to the general formula ML (3-y) Xy wherein M is a metal selected from the group consisting of metals of Group III-B of the Periodic Table having atomic numbers of 21, 39, and 57 through 71 inclusive; L is an organic ligand containing from 1 to 20 carbon atoms and selected from the group consisting of (a) o-hydroxyaldehydes, (b) o-hydroxyphenones, (c) hydroxyquinolines, (d) β-diketones, (e) monocarboxylic acids, (f) ortho dihydric phenols, (g) alkylene glycols, (h) dicarboxylic acids, (i) alkylated derivatives of dicarboxylic acids and (j) phenolic ethers; wherein X is a halogen atom, wherein y is an integer ranging from 1 to 2 and represents the number of halogen atoms attached to the metal M, and wherein the organic ligand L may be of the monovalent and bidentate or divalent and bidentate form.
The catalyst system of this invention will accordingly be prepared in the absence of the following specific compounds that contain labile halogen atoms: (1) inorganic halide acids, such as hydrogen bromide, hydrogen chloride and hydrogen iodide; (2) organometallic halides, such as ethylmagnesium bromide, butylmagnesium bromide, phenylmagnesium bromide, methylmagnesium chloride, butylmagnesium chloride, ethylmagnesium iodide, phenylmagnesium iodide, diethylaluminum bromide, diisobutylaluminum bromide, methylaluminum sesquibromide, diethylaluminum chloride, ethylaluminum dichloride, ethylaluminum sesquichloride, diisobutylaluminum chloride, isobutylaluminum dichloride, dihexylaluminum chloride, cyclohexylaluminum dichloride, phenylaluminum dichloride, didodecylaluminum chloride, diethylaluminum fluoride, dibutylaluminum fluoride, diethylaluminum iodide, dibutylaluminum iodide, phenylaluminum diiodide, trimethyltin bromide, triethyltin chloride, dibutyltin dichloride, butyltin trichloride, diphenyltin dichloride, tributyltin iodide and the like; (3) inorganic halides such as aluminum bromide, aluminum chloride, aluminum iodide, antimony pentachloride, antimony trichloride, boron tribromide, boron trichloride, ferric chloride, gallium trichloride, molybdenum pentachloride, phosphorus tribromide, phosphorus pentachloride, stannic chloride, titanium tetrachloride, titanium tetraiodide, tungsten hexachloride and the like; and (4) organometallic (Group III-B) halides, such as t-butyl-salicylaldehydrocerium (III) chloride, salicylaldehydrocerium (III) chloride, 5-cyclohexylsalicylaldehydrocerium (III) chloride, 2-acetylphenolatocerium (III) chloride, oxalatocerium (III) chloride, oxalatocerium (III) bromide and the like; (5) tertiary alkyl halides, such as t-butyl bromide and t-octyl bromide; (6) secondary alkyl halides, such as isopropyl bromide and isopropyl chloride; (7) aralkyl halides, such as benzyl bromide and bromomethyl naphthalene; and (8) allyl halides, such as allyl bromide, 3-chloro-2-methylpropene, 1-bromobutene-2, and 1-bromopentene-2. The preferred compounds which contain labile halogen atoms are benzyl halides and allyl halides.
The aluminum modified Group III-B metal containing catalyst component and the halogen containing compound can be added to the polymerization medium as separate components. This can be done by simply adding the aluminum modified Group III-B metal containing catalyst component and the halogen containing compound separately to the polymerization medium that contains the isoprene, the 1,3-butadiene, and the organic solvent. In an alternative embodiment of this invention, the aluminum modified Group III-B metal containing catalyst component and the halogen containing compound can be mixed prior to the time that they are introduced into the polymerization reactor.
The catalyst system will typically be added at a level sufficient to provide from 0.05 to 0.5 millimoles of the Group III-B metal per 100 grams of total monomer. More typically, the catalyst system will be added in an amount sufficient to provide from 0.25 to 0.35 millimoles of the Group III-B metal per 100 grams of total monomer. Its use results in the formation of an essentially non-tapered, random isoprene-butadiene rubber that has excellent characteristics for use in making tires. This is due to the fact that the modification procedure causes the catalyst system to polymerize the butadiene monomer at a rate that is only about 1.2 times to 1.5 times faster than the rate of isoprene polymerization.
The polymerization temperature utilized can vary over a broad range of from about 0° C. to about 125° C. In most cases a temperature within the range of about 30° C. to about 85° C. will be utilized. Temperatures within the range of about 50° C. to about 75° C. are generally the most preferred polymerization temperatures. The pressure used will normally be sufficient to maintain a substantially liquid phase under the conditions of the polymerization reaction.
The polymerization is conducted for a length of time sufficient to permit substantially complete polymerization of monomers. In other words, the polymerization is normally carried out until high conversions are attained. The polymerization can then be terminated using a standard technique.
The isoprene-butadiene rubbers, which are made by utilizing the techniques of this invention in solution polymerizations, can be recovered utilizing conventional techniques. It may be desirable to add antioxidants to the polymer solution in order to protect the isoprene-butadiene rubber produced from potentially deleterious effects of contact with oxygen. The isoprene-butadiene rubber made can be precipitated from the polymer solution. The butadiene-isoprene rubber made can also be recovered from the solvent and residue by means such as decantation, filtration, centrification, and the like. Steam stripping can also be utilized in order to remove volatile organic compounds from the rubber.
The isoprene-butadiene rubbers made by the technique of this invention will typically have a glass transition temperature which is within the range of about −65° C. to about −115° C. Such isoprene-butadiene rubbers will also generally have a Mooney viscosity that is within the range of about 50 to about 120. The isoprene-butadiene rubber will more typically have a Mooney viscosity that is within the range of 70 to 100.
The isoprene-butadiene rubbers made by the technique of this invention can be blended with other sulfur-vulcanizable rubbers to make compounds which have excellent characteristics for use in tire treads. For instance, improved rolling resistance and treadwear characteristics can be attained without sacrificing wet or dry traction characteristics. The isoprene-butadiene rubbers of this invention will normally be blended with other polydiene rubbers in making tire tread compounds. More specifically, the isoprene-butadiene rubber can be blended with natural rubber, high cis-1,4-polybutadiene, medium vinyl polybutadiene (having a glass transition temperature which is within the range of −10° C. to −40° C.), synthetic 1,4-polyisoprene, 3,4-polyisoprene (having a glass transition temperature which is within the range of −10° C. to −45° C.), styrene-butadiene rubbers (having a glass transition temperature which is within the range of 0° C. to −80° C.) and styrene-isoprene-butadiene rubbers (having a glass transition temperature which is within the range of −10° C. to −80° C.) to make useful tire tread compounds. A highly preferred blend for utilization in tire treads includes natural rubber, 3,4-polyisoprene rubber and the isoprene-butadiene rubber of this invention.
Various blend ratios can be employed in preparing tire tread compounds which exhibit a highly desirable combination of traction, rolling resistance, and tread wear characteristics. Another specific blend which is highly advantageous for utilization in tire tread compounds is comprised of about 40 weight percent to about 60 weight percent styrene-isoprene-butadiene rubber having a glass transition temperature which is within the range of about −70° C. to about −80° C. and from about 40 weight percent to about 60 weight percent of the isoprene-butadiene rubber prepared in accordance with the process of this invention.
This invention is illustrated by the following examples which are merely for the purpose of illustration and are not to be regarded as limiting the scope of the invention or the manner in which it can be practiced. Unless specifically indicated otherwise, parts and percentages are given by weight.
COMPARATIVE EXAMPLE 1
In this experiment an isoprene-butadiene rubber was synthesized by the technique of this invention. In the procedure employed a one gallon (3.78 liter) reactor was charged with 1000 grams of a dry hexane solution containing 81.9 grams of 1,3-butadiene followed by 663 grams of 1.2 molar diisobutylaluminum hydride (DIBAH) in hexane (25 weight percent DIBAH). Then, a solution containing 21.5 grams of triphenylsilanol dissolved in 260 grams of toluene was charged into the reactor at a temperature of 18° C. and the contents of the reactor. After stirring for 40 minutes, a solution of 105.4 grams of 10.3% neodymium solution (as neodymium neodecanoate), diluted with 165 grams of dry hexane, was charged into the reactor. The solution was allowed to stir for one hour after which 19.1 grams of allylbromide was added. The cooling was stopped and the solution allowed to warm up to ambient temperatures. After stirring for about 90 minutes, the catalyst solution was heat aged at 65° C. for 1–2 hours. The aged catalyst solution was then cooled and stored in a dry container under nitrogen.
Then, 15.6 ml of the 0.025 molar aged neodymium catalyst solution (lanthanide containing catalyst component) was added to a solution containing 130 grams of isoprene and 130 grams of 1,3-butadiene in 1610 grams of dry hexane in a one gallon (3.78 liter) reactor under nitrogen at a temperature of 65° C. The polymerization was carried out with stirring for 3 hours. Periodically during the polymerization, samples of the polymerization solution were coagulated in a 60/40 volume percent mixture of ethanol/decane. The coagulated polymer was allowed to settle at −20° C. followed by gas chromatographic analysis of the supernatant liquid to determine the residual monomer content. Subtraction from the initial monomer concentrations allowed calculation of the individual monomer conversions. These analyses showed that the incorporation of butadiene to isoprene in the polymer was 3 to 2 by weight indicating the formation of a highly random, essentially non-tapered isoprene-butadiene rubber.
COMPARATIVE EXAMPLE 2
In this experiment the copolymerization of Example 1 was repeated using a standard neodymium catalyst system (DIBAH/Nd/Allylbromide/Bd: 15/1/2/20 molar ratios) without the silanol modification of this invention. Gas chromatographic analyses of the residual monomers, as described in Example 1, showed the incorporation of butadiene to isoprene in the polymer was approximately 19 to 1 by weight, indicating the formation of a considerably less random, highly tapered copolymer.
COMPARATIVE EXAMPLE 3
In this experiment, an isoprene-butadiene copolymer rubber was prepared using an alcohol modified neodymium catalyst system. In this procedure, a one gallon (3.78 liter) reactor was charged with 1,214 grams of hexane containing 81.3 grams of butadiene and 558.43 grams of 1.23 molar diisobutylaluminum hydride (DIBAH) in hexane, (i.e., 25% weight percent DIBAH). The reactor was maintained at 20° C. by cooling. N-butanol (11.16 grams) was added with stirring. After stirring for thirty minutes, 107.5 grams of 10.1% neodymium solution (neodymium neodecanoate) diluted with 160 grams of dry hexane, was charged to the reactor. The solution was stirred for another thirty minutes after which time 18.2 grams of allyl bromide was added. The cooling was stopped and the solution was allowed to warm up. A delayed exothermic reaction was noted. After twenty minutes, bring the solution temperatures to about 10° C. above ambient temperature. When the temperature ultimately dropped, the catalyst solution was aged by heating at 65° C. for ninety minutes. The catalyst prepared had a [butanol-DIBAH]Nd-allyl bromide-butadiene molar ratio of [2-13]-1-2-20, respectively, and a concentration of 0.025 molarity with respect to the neodymium.
To a solution of 128.6 grams of isoprene and 129 grams of dry hexane in a one gallon (3.79 liter) reactor under nitrogen at 65° C., was added 20.7 milliliters (0.2 mmoles of neodymium/100 grams of total monomer [Bd+Ip]) of the above prepared catalyst. The polymerization was carried out with stirring for two hours and twenty minutes. Samples were taken during the polymerization as described in Example 1. Analyses of the samples showed that the incorporation of butadiene to isoprene (measured at low conversion) was 1.4/1 by weight indicating formation of a highly random, non-tapered isoprene-butadiene rubber. The yield was 87%. The Mooney of the dried rubber was 87; the Tg was −97° C.
COMPARATIVE EXAMPLE 4
In this experiment, an isoprene-butadiene copolymer was synthesized using an alcohol modified neodymium catalyst system with a different catalyst component molar ratio than that described in Example 3. In this procedure, a one gallon (3.78 liter) reactor was charged with 1,088 grams of hexane containing 93.5 grams of butadiene and 668 grams of 1.23 molar diisobutylaluminum hydride (DIBAH) in hexane (i.e., 25% weight percent DIBAH). To this solution was added 26.22 grams of n-butanol with stirring and with temperatures maintained at 20° C. After stirring for thirty minutes, 107.5 grams of a 10.1% neodymium solution (neodymium neodecanoate), dilute with 158 grams of dry hexane, was charged to the reactor. The solution was stirred for another thirty minutes after which time 21.4 grams of allyl bromide was added. The cooling was stopped and the mixture allowed to warm up to ambient (and above) temperature. After the exotherm subsided, requiring about one hour, the catalyst solution was heat aged at 65° C. for ninety minutes. The aged catalyst was then cooled and stored in a dry container under nitrogen. The catalyst prepared had a [butanol-DIBAH] Nd-allyl bromide-butadiene molar component ratio of [4.7-15.5]-1-2.35-23, respectively, and a concentration of 0.025 molarity with respect to the neodymium.
Using the method described in Examples 1 and 3, a solution of 128 grams of isoprene and 128 grams of butadiene in 1,579 grams of dry hexane was polymerized using 29.6 milliliters of the above prepared catalyst. Samples of the polymerization batch at different time intervals showed a butadiene to isoprene incorporation ratio (measured at low conversion) of 1.35/1. After two hours and ten minutes, an 88% yield of the copolymer was obtained. A Mooney viscosity of the dried copolymer was 97 and its the Tg was −90° C.
COMPARATIVE EXAMPLE 5
In this experiment, an isoprene-butadiene copolymer was synthesized using an alcohol modified neodymium catalyst system modified with 1,4-butanediol. In this procedure, a one gallon (3.78 liter) reactor was charged with 1,093 grams of hexane containing 81.9 grams of butadiene and 663 grams of 1.2 molar diisobutylaluminum hydride (DIBAH) in hexane (i.e., 25% weight percent DIBAH). To this solution was then added 6.78 grams of 1,4-butanediol with stirring and with temperatures maintained at 20° C. The suspension of the butanediol gradually dissolved upon reacting with the DIBAH. After one hour of stirring, 105.4 grams of a 10.3% neodymium solution (neodymium neodecanoate), diluted with 165 grams of hexane, was added to the reactor. The solution was stirred for another thirty minutes after which time 19.1 grams of allyl bromide was added. The cooling was stopped and the mixture allowed to warm up to ambient (and above) temperature. After the exotherm subsided, the catalyst solution was aged by heating at 65° C. for ninety minutes. The catalyst prepared had a [butanediol-DIBAH]-ND-allyl bromide-butadiene molar component ratio of [1-16]-1-2-20, respectively, and a concentration of 0.025 molarity with respect to the neodymium. The aged catalyst was then cooled and stored in a dry container under nitrogen.
Using the polymerization procedure described in the earlier examples, 123 grams of isoprene and 124 grams of butadiene in 1,546 grams of dry hexane was polymerized using 14.2 milliliters of the above prepared catalyst. Analyses of samples taken during the polymerization show the ratio of the incorporation of butadiene to isoprene (measured at low conversion) was 1.44/1. A yield of 87% was obtained after 130 minutes.
COMPARATIVE EXAMPLE 6
In this experiment, an isoprene-butadiene copolymer rubber was prepared using another rare earth metal, praseodymium. In the procedure employed, a one gallon (3.78 liter) reactor was charged with 1,000 grams of a dry hexane solution containing 82 grams of 1,3-butadiene, followed by 663 grams of a 1.2 molar diisobutylaluminum hydride (DIBAH) in hexane. A solution of 21.5 grams triphenylsilanol dissolved in 250 grams of toluene was then charged into the reactor at a temperature of 20° C. After stirring for about forty minutes, 85.9 grams of a 0.826 molar solution of praseodymium octoate, diluted with 195 grams of hexane, was charged to the reactor. The solution was allowed to stir for forty-five minutes after which 19.1 grams of allyl bromide was added. The cooling was stopped and the mixture was allowed to warm up to ambient temperature (and above). After stirring for about one hour, the catalyst system was aged by heating at 65° C. for ninety minutes. The catalyst prepared had a [silanol-DIBAH]-Pr-allyl bromide-butadiene component molar ratio of [1-15]-1-2-20, respectively, and a concentration of 0.025 molarity with respect to the neodymium. The aged catalyst was then cooled and stored in a dry container under nitrogen.
Using the polymerization procedure described in Examples 1 and 3, 124 grams of isoprene and 125 grams of butadiene in 1,439 grams of dry hexane were polymerized using 19.6 milliliters of the above praseodymium-based catalyst. Samples of the polymerization solution during the run showed that the rate of incorporation of the butadiene to isoprene (measured at low conversion) was 1.7/1 by weight. A yield of 37% was obtained after one hour and forty minutes. The Mooney of the dried sample was 64 and its Tg was −96° C.
COMPARATIVE EXAMPLE 7
In this experiment, the copolymerization of Example 6 was repeated with a praseodymium-based catalyst prepared as described in Example 6 except without the triphenylsilanol modifier.
Analyses of the samples of the copolymerization showed that the rate of incorporation of the butadiene to isoprene (measured at low conversion) was 16/1 by weight, indicating formation of a somewhat tapered copolymer, in contrast to the highly random copolymer formed when the triphenylsilanol catalyst modifier was employed.
EXAMPLE 8
An alkylated neodymium catalyst system was made in this experiment. In the procedure used, 30 milliliters of a 0.507 M solution of neodymium neodecanoate (NdV 3 ) in hexanes was charged to a dried 8 oz. (236.6 ml) bottle under a blanket of nitrogen at room temperature. Then, 152.1 ml. of a 1.0 M tri n-octyl aluminum (TOA) in hexanes solution was slowly added to the NdV 3 solution. The resulting light blue mixture was then heated in a rotating polymerization bath at 70° C. for 30 minutes. The molar ratio of TOA to Nd was 10:1. The solution turned darker brown color in less than 10 minutes. The concentration of this Nd catalyst was 0.0835 M. The solution made was soluble in hexanes. These alkylated neodymium catalysts can be prepared in a heated loop or a mixer outside of a polymerization reactor prior to use as the co-catalyst for polymerization in a batch or a continuous system. The catalyst components made by this procedure are vary stable and can be stored for periods of at least one year before being used. Thus, such catalyst components can be stored, shipped, and used as needed.
EXAMPLE 9
In this example, an active preformed neodymium catalyst was prepared. In the procedure used 1.0 ml of carbon tetrachloride was added to a 4 oz (118.3 ml) bottle containing 23.95 ml. of a pre-alkylated neodymium catalyst at room temperature. The molar ratio of neodymium to TOA was 1:10. A lighter color was observed with the final color being a clear dark red.
EXAMPLE 10
In this experiment, a polybutadiene rubber was prepared using the preformed neodymium catalyst described in Example 9. In the procedure used 1293 g of a silica/alumina/molecular sieve dried premix containing 15.47% weight percent 1,3-butadiene in hexanes was charged into a one-gallon (3.8 liters) reactor. Then, 25.95 ml of the preformed neodymium catalyst prepared in Example 9 was added to the reactor. The amount of neodymium utilized was 1.0 mmole per 100 grams of 1,3-butadiene monomer.
The polymerization was carried out at 70° C. The GC analysis of the residual monomer contained in the polymerization mixture indicated that the 90% of butadiene monomer was consumed after approximately 60 minutes. The polymerization was continued for an additional 30 minutes. As the polymer was removed from the reactor it was shortstopped with ethanol and stabilized with 2,6-ditertbutylphenol. The cement was then placed into a drying oven to remove solvent. Final solvent removal was done in a vacuum oven at 50° C. The resulting polybutadiene rubber had a glass transition temperature (Tg) of −109.5° C. with a melting point (Tm) of −11.6° C. The Mooney viscosity (ML-4) at 100° C. for this polymer was determined to be 39. The GPC measurements indicated that the polymer had a number average molecular weight (Mn) of about 160,000 and a weight average molecular weight (Mw) of about 400,000. The polydispersity (Mw/Mn) of the resulting polymer was accordingly 2.5.
EXAMPLE 11
The procedure used in Example 10 was repeated in this experiment except that a 50/50 weight percent mixture of isoprene and 1,3-butadiene was employed as the monomer. Samples taken during the polymerization showed that the ratio of incorporation of 1,3-butadiene to isoprene into the polymer was about 3:2 (at low conversion levels). After a polymerization time of about 2 hours a yield of about 80% was attained. The isoprene-butadiene rubber had a Mooney ML 1+4 viscosity of about 90 and had a glass transition temperature of −90° C.
EXAMPLE 12
The preparation of an alkylated neodymium catalyst is described in this example. In the procedure used, 20 milliliters of a 0.506 M neodymium neodecanoate (NdV 3 ) solution in hexanes was charged to a dried 8 oz (237 ml.) bottle under nitrogen at room temperature. Then, 142 ml. of 1M tri-n-octyl aluminum (TOA) in hexanes (the hexanes solvent used was a mixture of various hexane isomers) was slowly added to above NdV 3 solution. The resulting light blue mixture was then heated in a rotating polymerization bath at 70° C. for 10 to 60 minutes. The molar ratio of TOA to Nd was 14:1. The solution turned darker brown color in less than 10 minutes. The concentration of this Nd catalyst was 0.063 M. Other alkylated Nd catalysts were prepared similarly with tri-ethylaluminum (TEA), tri-isobutyl aluminum (TIBA), di-isobutylaluminum hydride (DIBAH) and tri-n-hexyl aluminum (THA). All alkylated Nd catalysts were soluble in hexanes solvent. These alkylated Nd catalysts can be prepared in a heated loop or a mixer outside of a polymerization reactor prior to use as the co-catalyst for polymerization in a batch or a continuous systems.
EXAMPLE 13
In this example, an active preformed neodymium catalyst was prepared. 0.47 ml of a neat t-amyl chloride (t-AmCl, 7.96 M) was added dropwise, with shaking, to a 4 oz (118 ml.) bottle containing 30 ml. of a pre-alkylated Nd catalyst (0.063 M as described in Example 12) at room temperature. A vigorous reaction took place. The resulting light brown mixture was used for polymerizing isoprene 1,3-butadiene or a mixture of 1,3-butadiene and isoprene. The molar ratio of Nd to TOA and to t-AmCl were 1:14:2.
EXAMPLE 14
In this experiment, a polyisoprene was prepared using a preformed Nd catalyst as described in Example 13. In the procedure used 2000 grams of a silica/alumina/molecular sieve dried premix containing 19.90 weight percent isoprene in hexanes was charged into a one-gallon (3.8 liter) reactor. Then, 14.1 ml of a preformed Nd catalyst made by the procedure described in Example 13 was added to the reactor. The amount of Nd used was 0.22 mmole per 100 grams of isoprene monomer.
The polymerization was carried out at 90° C. The GC analysis of the residual monomer contained in the polymerization mixture indicated that the 90% of isoprene monomer was consumed after 14 minutes. The polymerization was continued for an additional 30 minutes. Then, 1 ml. of neat ethanol was added to shortstop the polymerization. The polymer cement was then removed from the reactor and stabilized with 1 phm of antioxidant. After evaporating hexanes, the resulting polymer was dried in a vacuum oven at 50° C.
The polyisoprene produced was determined to have a glass transition temperature (Tg) at −67° C. It was then determined to have a microstructure, which contained 95.6 percent cis-1,4-polyisoprene units, 1.4 percent trans-1,4-polyisoprene units, and 3.0 percent 3,4-polyisoprene units. The Mooney viscosity (ML-4) at 100° C. for this polymer was determined to be 82. This polymer was also determined to have a stereo regularity count (head to tail) of 99.6%. The GPC measurements indicated that the polymer has a number average molecular weight (Mn) of 429,000 and a weight average molecular weight (Mw) of 1,032,000. The polydispersity (Mw/Mn) of the resulting polymer was determined to be 2.41.
COMPARATIVE EXAMPLE 15
In this example, a polyisoprene was prepared using a pre-alkylated Nd catalyst as described in Example 12 and the co-catalyst t-AmCl was added separately to the reactor containing isoprene monomer. The procedure described in Example 14 was utilized in this example except that a pre-alkylated Nd catalyst (as described in Example 12) was used as the catalyst and, 1.75 ml of a 1M solution of t-AmCl (in hexane) was subsequently added to the reactor containing isoprene premix in the reactor. The GC analysis of the residual monomer contained in the polymerization mixture indicated that 90 percent of isoprene was consumed after 350 minutes at 90° C. The polymerization was continued for an additional 30 minutes. The polymer was then recovered as described in Example 14. The resulting polymer had a glass transition temperature (Tg) at −67° C. It was also determined to have a Mooney viscosity (ML-4) at 100° C. of 72. The GPC measurements indicated that the polymer has a number average molecular weight (Mn) of 476,000 and a weight average molecular weight (Mw) of 1,182,000. The polydispersity (Mw/Mn) of the resulting polymer was 2.48. A rate and polymer characteristics comparison of the polyisoprenes prepared using Nd catalysts described in Examples 12 and 13 are tabulated in Table 1.
TABLE 1
Example
Time to 90%
Tg
Molecular weight by GPC
No
Catalyst
conversion (min.)
(° C.)
ML-4
Mn
Mw
Mw/Mn
14
Preformed Nd with t-AmCl
14
−67
82
429K
1,032K
2.41
15
Pre-alkylated Nd with
350
−67
72
476K
1,182K
2.48
t-AmCl added separately
EXAMPLE 16
In this experiment, a 30/70 isoprene-butadiene rubber (IBR) was prepared using a preformed catalyst described in Example 13. The procedure described in Example 14 was utilized in this example except that a premix containing a 30:70 mixture of isoprene and 1,3-butadiene was used as the monomers. GC analysis of the residual monomer indicated that 90 percent of monomers were consumed after 9 minutes. The polymerization was continued for an additional 21 minutes.
The resulting IBR was then recovered as described in Example 14. It was determined to have a glass transition temperature at −102° C. The Mooney viscosity (ML-4) at 100° C. for this polymer was determined to be 102. It was then determined to have a microstructure which contained 67.7 percent cis-1,4-polybutadiene units, 1.4 percent trans-1,4-polybutadiene units, 0.8 percent 1,2-polybutadiene unit, 28.9 percent cis-1,4-polyisoprene units, 0.3 percent trans-1,4-polyisoprene unit, and 0.9 percent 3,4-polyisoprene unit. The GPC measurements indicated that the IBRs have a number average molecular weight (Mn) of 427,000 and a weight average molecular weight (Mw) of 1,029,000. The polydispersity (Mw/Mn) of the resulting polymer was 2.14.
COMPARATIVE EXAMPLE 17
In this example, a 30/70 IBR was prepared using the procedure described in Example 16 except that a premix containing a 30:70 mixture of isoprene and 1,3-butadiene was used as the monomers. The GC analysis of the residual monomer contained in the polymerization mixture indicated that 90% of isoprene was consumed after 276 minutes at 90° C. The polymerization was continued for an additional 30 minutes. The polymer was then recovered as described in Example 14. The resulting polymer had a Tg at −102° C. It was also determined to have a Mooney viscosity (ML-4) at 100° C. of 103. The GPC measurements indicated that the polymer has a number average molecular weight (Mn) of 417,000 and a weight average molecular weight (Mw) of 1.021,000. The polydispersity (Mw/Mn) of the resulting polymer is 2.44. A rate and polymer characteristics comparison of the IBRs prepared using Nd catalysts described in Examples 12 and 13 are tabulated in Table 2.
TABLE 2
Example
Time to 90%
Tg
Molecular weight by GPC
No
Catalyst
conversion (min.)
(° C.)
ML-4
Mn
Mw
Mw/Mn
16
Preformed Nd with t-AmCl
9
−102
102
427K
1,029K
2.41
17
Pre-alkylated Nd with
276
−102
103
417K
1,021K
2.48
t-AmCl added separately
EXAMPLES 18–19
In these examples, polyisoprenes are prepared using a preformed Nd catalyst as described in Example 13. The molar ratio of Nd to TOA and to t-AmCl was 1:14:2. The procedure described in Example 14 was utilized in these examples except that the polymerization temperature was changed to 60° C. and 40° C., respectively. The time needed for 90% monomer conversion, Tg and ML-4 of the resulting polyisoprenes are listed in Table 3.
TABLE 3
Poly-
merization
Time to 90%
Example
Nd/TOA/t-AmCl
Temperature
Conversion
Tg
No.
Ratio
(° C.)
(min.)
(° C.)
ML-4
14
1/14/2
90
14
−67
82
18
1/14/2
60
21
−67
86
19
1/14/2
40
80
−67
95
EXAMPLES 20–22
In these examples, polyisoprenes were prepared using a preformed Nd catalyst as described in Example 13. However, the molar ratio of Nd to TOA and to t-AmCl was changed to 1:10:2. The procedure described in Example 14 was utilized in these examples and the polymerizations were conducted at 90° C., 75° C., and 60° C. The time needed to attain 90 percent monomer conversion, Tg, and ML-4 of the resulting polyisoprenes are listed in Table 4.
TABLE 4
Poly-
merization
Time to 90%
Example
Nd/TOA/t-AmCl
Temperature
Conversion
Tg
No.
Ratio
(° C.)
(min.)
(° C.)
ML-4
20
1/10/2
90
12
−67
82
21
1/10/2
75
23
−67
87
22
1/10/2
60
60
−67
91
EXAMPLES 23–25
In these examples, polyisoprenes are prepared using a preformed Nd catalyst as described in Example 13. However, the molar ratio of Nd to TOA and to t-AmCl was changed to 1:20:2. The procedure described in Example 14 was utilized in these examples and the polymerization was conducted at 90° C., 75° C., and 60° C. The time needed for 90% monomer conversion, Tg, and ML-4 of the resulting polyisoprenes are listed in Table 5.
TABLE 5
Poly-
merization
Time to 90%
Example
Nd/TOA/t-AmCl
Temperature
Conversion
Tg
No.
Ratio
(° C.)
(min.)
(° C.)
ML-4
26
1/20/2
90
17
−67
53
27
1/20/2
75
23
−67
77
28
1/20/2
60
60
−67
90
EXAMPLES 26–28
In these examples, polyisoprenes are prepared using a preformed Nd catalyst as described in Example 13. However, the molar ratio of Nd to TOA and to t-AmCl was changed to 1:30:2. The procedure described in Example 14 was utilized in these examples and the polymerization was conducted at 90° C., 75° C., and 60° C. The time needed for 90% monomer conversion, Tg and ML-4 of the resulting polyisoprenes are listed in Table 6.
TABLE 6
Poly-
merization
Time to 90%
Example
Nd/TOA/t-AmCl
Temperature
Conversion
Tg
No.
Ratio
(° C.)
(min.)
(° C.)
ML-4
26
1/30/2
90
20
−67
40
27
1/30/2
75
26
−67
51
28
1/30/2
60
80
−67
77
While certain representative embodiments and details have been shown for the purpose of illustrating the subject invention, it will be apparent to those skilled in this art that various changes and modifications can be made therein without departing from the scope of the subject invention.
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The subject invention relates to a process for preparing a catalyst system that comprises the sequential steps of (I) reacting an organometalic compound that contains a metal from Group III-B of the Periodic System with an organoaluminum compound at a temperature which is within the range of 50° C. to 100° C. to produce an aluminum modified Group III-B metal containing catalyst component, and (II) mixing the aluminum modified Group III-B metal containing catalyst component with a halogen containing compound to produce the Group III-B metal containing catalyst system, wherein the catalyst system is void of compounds selected from the group consisting of aliphatic alcohols, cycloaliphatic alcohols, aliphatic thiols, cycloaliphatic thiols, trialkyl silanols, and triaryl silanols, wherein the organometalic compound that contains a metal from Group III-B of the Periodic System is reacted with the organoaluminum compound in the absence of conjugated diene monomers, and wherein the catalyst system is prepared in the absence of compounds that contain labile halogen atoms.
| 2 |
BACKGROUND OF THE INVENTION
This invention relates to a vibration absorbing structure for an outboard motor and more particularly to an improved damping arrangement for damping certain types of vibrations in marine outboard drives.
In conventional marine outboard drives such as outboard motors, the drive shaft housing is resiliently connected to a steering shaft by means of annular elastic bushings that have their axes disposed parallel to the propeller shaft axis. These elastic bushings are very effective in dampening the driving thrust transmitted from the outboard drive to the hull of the associated watercraft. However, there are other types of vibrational forces that are not effectively dampened by these members. For example, torsional vibrations can cause rotational couples about the drive shaft axis and irregular combustion can give rise to couples in the same general direction. If the elastic bushings that connect the drive shaft housing to the steering shaft are made resilient enough to dampen these forces, then there is too much elasticity in the system. This will result in such undesirable effects as unstable straight running, low steering response and propulsion unit oscillations.
It is, therefore, a principal object of this invention to provide an improved vibration damping arrangement for a marine outboard drive.
It is a further object of this invention to provide a damping arrangement for a marine outboard drive which permits not only the damping of propulsion unit thrust, but also couples which may be exerted on the outboard drive without adding excessive elasticity into the system.
SUMMARY OF THE INVENTION
This invention is adapted to be embodied in a thrust absorbing arrangement for a marine outboard drive mounted for pivotal movement about a horizontally extending tilt axis relative to a clamping member that is adapted to be affixed to the transom of an associated watercraft. A propulsion unit is provided at the lower end of the outboard drive for propelling the associated watercraft. In accordance with the invention, elastic abutment means are disposed between the lower end of the outboard drive and the clamping member for absorbing and damping rotational couples.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a side elevational view of an outboard motor constructed in accordance with an embodiment of the invention.
FIG. 2 is an enlarged side elevational view showing the relationship between the drive shaft housing, clamping member and swivel bracket, with portions broken away.
FIG. 3 is a cross sectional view taken along the line 3--3 of FIG. 2.
FIG. 4 is a partial side elevational view, with portions broken away, showing another embodiment of the invention.
FIG. 5 is a cross sectional view taken along the line 5--5 of FIG. 4.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring first to FIG. 1, a marine outboard drive constructed in accordance with an embodiment of the invention is identified generally by the reference numeral 11. The outboard drive 11 is, in the illustrated embodiment, an outboard motor. It is to be understood, however, that certain facets of the invention can be employed with other types of marine outboard drives such as the outboard drive portion of an inboard/outboard drive.
The outboard motor 11 includes a power head 12 that contains an internal combustion engine (not shown) that is contained within a protective cowling. The internal combustion engine may be of any known type and reciprocating engines are normally used in such applications and have their output shafts rotatable about vertically extending axes. Such a construction may be assumed to be utilized in the preferred embodiment.
The output shaft of the engine of the power head 12 drives a drive shaft (not shown) that is rotatably journaled within a drive shaft housing 13 that is positioned at the lower end of the power head 12. A lower unit 14 depends from the drive shaft housing 13 and contains a suitable forward, neutral, reverse transmission for driving a propeller 15 in selected forward and reverse directions.
Referring now in detail additionally to FIG. 2, it will be noted that the drive shaft housing 13 is affixed to a steering shaft, indicated by the reference numeral 16 by means of an assembly that includes a pair of upper and lower fixing bolts 17 which pass through the sleeves of elastic bushings 18. The elastic bushings 18 are affixed against a steering arm 19 at their upper end and a clamping bracket 21 at their lower ends by means of nuts 22 that are affixed to the forward threaded ends of the bolts 17. The elastic sleeves 18 are bonded within outer sleeves 23 which are affixed in a suitable manner to the drive shaft housing 13. The upper and lower elastic connections between the drive shaft housing 13 and the steering shaft 16 are indicated by the reference numerals 24 and 25, respectively.
The steering shaft 16 is, in turn, journaled for steering movement within a swivel bracket 26. The swivel bracket 26 is, in turn, pivotally connected to a clamping bracket 27 by means of a tilt pin 28 so as to permit tilt and trim movement of the outboard motor 11 about a horizontally disposed axis defined by the tilt pin 28.
The clamping bracket 27 is designed to be affixed to a transom 29 of an associated watercraft which is shown partially and in phantom in FIG. 1.
In order to effect trim movement of the outboard motor 11, there may be provided a trim hydraulic motor 31 which has a piston rod 32 that cooperates with a socket 33 fixed to the swivel bracket 26 for effecting trim adjustment. In addition, a tilt fluid motor 34 is affixed between the clamping bracket 27 and the swivel bracket 26 for effecting tilt up movement of the outboard motor.
The construction as thus far described may be considered to be conventional and, for that reason, further details of the construction have not been illustrated nor will they be described. However, in conjunction with the prior art type of constructions, the elastic bushings 24 and 25 have some degree of resilience to dampen the driving thrust between the propeller 15 and the transom 29 of the associated watercraft. However, these elastic bushings cannot effectively absorb rotational couples occurring about the drive shaft axis and caused either by torsional vibrations or by vibrations due to rotational fluctuations caused by irregular combustion. If these bushings had sufficient resilience to dampen those forces, then there would be too much resilience in the system and lack of steering sensitivity, unstable straight running and propulsion unit oscillations would occur.
In accordance with the invention, an arrangement is provided for dampening these forces and which may have a lower spring rate while, at the same time, avoiding any loss of steering accuracy or the other disadvantages discussed above. In this embodiment, this damping arrangement is depicted generally by the reference numeral 35 and is shown in most detail in FIGS. 2 and 3. It will be noted that the lower end of the swivel bracket 26 is provided with a forwardly extending projection 36 which has a pair of spaced apart arms that have arcuate forward edges. These arms are juxtaposed to a rod 37 which spans the clamping bracket 27 and which is affixed thereto by elastic joints 38. The joints 38 have a relatively low spring rate. When the rotational couples aforedescribed are exerted, they will be dampened by these elastic sleeves 38. However, these sleeves 38 add no resilience to the steering connection and hence no loss in steering crispness will be encountered.
FIGS. 4 and 5 show another embodiment of the invention. In this embodiment, components which are the same as those of the previously described embodiment have been identified by the same reference numerals and will not be described again, except insofar as is necessary to understand the construction and operation of this embodiment. In this embodiment, the damping mechanism is indicated generally by the reference numeral 51. In this embodiment, a rod 52 spans the clamping bracket 27 and is rigidly affixed to it. However, the projection 36 of the swivel bracket 26 does not engage this rod. Rather, there is provided an elastic block 53 which is affixed thereto by threaded fasteners 54 and which is interposed between the rod 52 and the bracket extension 36. Hence, the elastic block 53 will provide the same damping action as the elastic sleeves 38 of the previously described embodiment. Hence, the same advantages will be achieved.
It should be readily apparent from the foregoing description that the described construction is very effective in providing good damping of both driving thrusts and of rotational couples caused by engine vibrations or fluctuations caused by irregular combustion without loss of steering crispness and straight ahead running ability. Of course, the described embodiments are those of preferred constructions which the invention may take. Various changes and modifications may be made without departing from the spirit and scope of the invention, as defined by the appended claims.
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A vibration absorbing structure for a marine outboard drive that is comprised of an elastic abutment between the drive shaft housing and clamping bracket and which has a greater resilience than the connection between the drive shaft housing and the steering shaft of the outboard drive so as to permit the absorption of rotational couples caused by vibrations without introducing undue resilience in the steering system of the outboard drive.
| 1 |
BACKGROUND OF THE INVENTION
The present invention relates to an actuating unit for a hydraulic brake system which includes a pneumatic brake power booster and a master brake cylinder connected down-stream of the pneumatic brake power booster. The piston of the master brake cylinder confines a hydraulic pressure chamber and is coupled to an annular piston of larger diameter. The annular piston confines a filling chamber which can be connected to the pressure chamber.
A similar actuating unit is disclosed in German patent number 33 17 996. The annular piston of this actuating unit is hollow and is composed of a cylindrical inner wall and a cylindrical outer wall which are connected at one end and which confine an open annular chamber. The cylindrical outer wall of the annular piston is adapted to move through sealing elements arranged in the master cylinder housing into a filling chamber of annular cross-section at the end of the master brake cylinder close to the brake power booster. The filling chamber is arranged radially outward and coaxially relative to the first pressure chamber of the master brake cylinder. The first pressure chamber is bounded by a bottom that forms the primary piston and closes the cylindrical inner wall.
Less favorable aspects of the prior art actuating unit are its considerable axial length and its complicated structure. Another shortcoming of the prior art is that the pressure fluid volume, which on actuation is displaced by the annular piston through a complicated valve into a supply reservoir, is displaced over the entire stroke of the master brake cylinder. Thus, in the event of a slow actuation, the pressure fluid volume flows through the throttle bores provided in the valve into the supply reservoir so that no filling effect is achieved and the actuating travel is not shortened. On the other hand, in the event of a quick actuation, dynamic pressure develops in the filling chamber so that a sealing cup sealing the primary piston is flooded and the pressure in the primary pressure chamber increases until the valve is opened by the dynamic pressure. In this case, however, filling is undefined and depends on the pressure in the filling chamber. In addition, the slowly progressing release action of the actuating unit of the prior art is a disadvantage. The release action progresses slowly because both the primary chamber and the filling chamber are replenished solely through the previously mentioned throttle bores.
SUMMARY OF THE INVENTION
Therefore, it is an object of the present invention to provide an actuating unit for hydraulic brake systems which operates with a precisely defined change-over pressure and lost travel independent of the speed of actuation. Further, the present invention ensures that the displacement of the filling volume by the annular piston does not require an entire stroke of the master cylinder.
This object is achieved by the present invention in that the annular piston uncouples from the primary piston when the hydraulic pressure acting on it reaches a predetermined amount. The pressure acting upon the annular piston is the pressure prevailing in the pressure chamber of the master brake cylinder. Thus, the filling stage is activated only until a defined pressure is reached, and thereafter is terminated. Therefore, the entire actuating unit can become smaller and hence less expensive.
Another favorable improvement of the present invention over the prior art is that the annular piston, after being uncoupled, slides on the piston and cooperates with a stop. This feature limits the maximum possible stroke of the annular piston, which becomes important in the event of failure of the hydraulic circuit connected to the pressure chamber.
Another favorable embodiment of this invention is that the filling chamber serves as a supply chamber for the hydraulic pressure chamber bounded by the piston. This measure eliminates the lost travel, which has to be covered in the pressure chamber of the master brake cylinder on actuation, so that tolerances can be diminished.
Another design variant of this invention, which makes it particularly suitable for anti-lock (ABS) brake systems, is that the central valve of the piston is located between the filling chamber and the pressure chamber.
Another favorable embodiment of the present invention activates the central valve through a pin which is perpendicular to the longitudinal axis of the piston and which is arranged in an axial extension of the annular piston. Thus, guidance of the annular piston on the master cylinder piston is greatly improved.
Another feature of this invention is that the central valve is actuated through a pin disposed perpendicularly to the longitudinal axis of the piston. This pin is arranged in a ring slipped on the piston and abuts the annular piston until the predetermined pressure is reached in the pressure chamber. This design allows reduction of the overall axial length of the actuating unit.
According to another preferred embodiment of this invention, a releasable locking device, provided between the piston and the annular piston, permits the annular piston to be entrained by the piston until the predetermined pressure is reached. Therefore, the annular piston does not have to cover the entire actuating stroke of the master cylinder piston, and the effect of the sealing elements on the annular piston is eliminated. In addition, this measure allows the overall length of the actuating unit to be shortened.
The locking device in the present invention is composed of one or a plurality of resiliently loaded balls which are guided in the piston or the annular piston, respectively, and cooperate with a slope formed in the annular piston or the piston, respectively. This design variant of the present invention lends itself to manufacture at low cost.
A particularly exact adjustment of the change-over pressure acting upon the annular piston is achieved in another embodiment of this invention. In this embodiment, the locking device is formed by one or a plurality of locking elements arranged in radial bores in the piston. The locking elements cooperate with a first slope provided in the annular piston and with a second slope located on a resiliently biassed actuating piston. The actuating piston slides within the piston and is acted upon by the pressure prevailing in the pressure chamber.
Another aspect of the present invention which affords inexpensive manufacture is that the locking device is composed of a radially expandable sleeve which is slipped on the piston. The radial collar of the sleeve cooperates with an annular groove in the piston. Preferably, the annular groove is bounded by two transversely extending flanks of different ascent. The radial collar is confined by a first conical annular surface, adjacent to which is a second conical annular surface that cooperates with the flank of steeper ascent. These measures allow the annular piston and the piston to uncouple with minimal friction.
In another preferred embodiment of this invention, a spring is positioned between the annular piston and the sleeve, permitting transmission of force from the sleeve to the annular piston. Thus, the unlocking force acting between the two pistons may be defined exactly and adjusted, if so required.
Another favorable improvement of the present invention is that the annular piston has a radial annular groove which permits radial expansion of the sleeve on actuation and when the force of the spring is overcome. The friction referred to above can be influenced not only by the design of the transition between the area guiding the collar of the sleeve and the radial annular groove in the annular piston, but also by rating the spring force.
An improvement in the transmission of force between the sleeve and the annular piston is achieved by another aspect of the present invention. This aspect of the invention provides that the spring is supported on a guide portion abutting on the collar and that the cylindrical surface of this portion is guided at the bottom of the radial annular groove shaped in the annular piston.
In still another preferred embodiment of this invention, the collar of the sleeve transitions into a truncated-cone shaped area, adjacent to a cylindrical portion with an internal diameter corresponding to the diameter of the piston. The sleeve contains a plurality of axial slots, evenly spread over its periphery, which subdivide the collar into single segments and which end at the transition between the truncated-cone shaped area and the cylindrical portion. These measures allow the sleeve to properly adapt to the piston, while simultaneously facilitating expansion of the sleeve when the two pistons are uncoupled.
The sleeve is made of plastic, allowing low-noise and low-wear operation of the actuating unit.
Another feature of the present invention is that the volume of pressure fluid flows unhindered into the brake circuit connected to the pressure chamber. This is possible because the filling chamber is in communication with the pressure chamber until the predetermined pressure in the pressure chamber is attained. Thus, the change-over pressure may be precisely defined.
In a preferred embodiment of this invention, the pressure acting on the annular piston is the hydraulic pressure prevailing in the filling chamber. This ensures that undesirable variations in volume will not occur in the filling chamber after the filling stage has been deactivated. It is particularly expedient in this respect that the central valve is actuated through a pin which is perpendicular to the longitudinal axis of the piston and is arranged in a ring. This ring is slipped on the piston and abuts a stop formed fast with the master cylinder housing in the release position. This solution offers great freedom of design with respect to the opening mechanism of the central valve.
Another advantageous design of this invention is that the central valve is operated by the transmission of force between its closure member and the actuating piston guided in the piston. This design favorably conforms the closure travel of the central valve to the point in time when the locking device is deactivated.
The diameter of the piston in the area adjacent to the pressure chamber is either equal to or larger than its diameter in the guide area of the annular piston.
In order to return the annular piston to its initial position after the filling stage is deactivated, a compression spring is provided between the stop of the annular piston in the master cylinder housing and the annular piston.
Finally, the safety of an automotive vehicle equipped with an actuating unit of the present invention can be enhanced by placement of a contact device in the abutment area of the annular piston. This contact device activates a warning apparatus such as a lamp in the driver's field of vision which, by flashing, indicates to the driver an incipient malfunction in the brake system.
BRIEF DESCRIPTION OF THE DRAWINGS
Further details, features and advantages of the present invention can be taken from the following description of six embodiments with reference to the accompanying drawings.
FIG. 1 is a first embodiment of the actuating unit according to the present invention,
FIG. 2 is a second embodiment of the master cylinder of the actuating unit according to the present invention,
FIGS. 3 to 6 illustrate a third, a fourth, a fifth and a sixth embodiment of the master brake cylinder of the actuating unit according to the present invention,
FIG. 7 is the sixth embodiment of the master brake cylinder according to FIG. 6 in the actuated condition,
FIG. 8 is an axial view of a sleeve which serves as a locking device in the embodiment according to FIGS. 6 and 7, and
FIG. 9 is a cross-section of the sleeve shown in FIG. 8 taken along the line of intersection 9--9 according to FIG. 8.
DETAILED DESCRIPTION OF THE INVENTION
The actuating unit shown in the drawing includes a vacuum brake power booster 1 and a master brake cylinder, preferably a tandem master cylinder 2. Tandem master cylinder 2 is connected downstream of the vacuum brake power booster 1 and communicates with a pressure fluid supply reservoir (not shown). The vacuum brake power booster 1 is operated through an actuating member 3 by a brake pedal (not shown). The vacuum brake power booster 1 is comprised of two shell-shaped housing halves 56 and 57, which are fitted with their open sides and which form a booster housing 10. The housing half 56, which is on the left in FIG. 1, is provided with a pneumatic port and is rigidly connected with the tandem master brake cylinder 2. The control housing 12, which accommodates a control valve 4, slides within and is sealed and guided by the right-hand housing half 57.
The booster housing 10 is subdivided into an evacuatable vacuum chamber 5 and a working chamber 6 by a first movable wall 7 which is arranged in the housing. The first movable wall is composed of a diaphragm plate 8 and a rolling diaphragm 9 which abuts on the diaphragm plate 8. The working chamber 6 can be connected either with the vacuum chamber 5 or, when the control valve 4 is actuated, with the atmosphere.
The control valve 4 is operated by a valve piston 17 which is coupled to the actuating member 3. The first sealing seat 11 of the control valve 4 is carried by the actuating member 3, while second sealing seat 18 of control valve 4 is provided in the control housing 12.
A resetting spring 16, which is supported on a flange on the vacuum-side end wall of the booster housing 10, keeps the movable wall 7 in the initial position shown. Via a rubber-elastic reaction disc 13 accommodated in a frontal recess of the control housing 12 as well as via a push rod 14 having a head flange 15, the brake force is transmitted onto a first piston (primary piston) 19 of the tandem master cylinder 2. The primary piston 19 cooperates with a second (secondary) piston 20, and together pistons 19, 20 confine pressure chambers 21 and 22 in the master cylinder housing 30. Brake circuits (not shown) are connected to the master cylinder housing 30.
An annular piston 23 of large diameter arranged coaxially relative to the primary piston 19 confines in the master cylinder housing 30 a filling chamber 24 of annular cross-section. The filling chamber 24 is connected via a pressure fluid channel 25 to a compensating or pressure fluid supply reservoir (not shown). The filling chamber 24 is also connected to the primary pressure chamber 21 through a central valve 26, which is preferably arranged in the primary piston 19, so that the filling chamber 24 simultaneously serves as a supply chamber for the primary pressure chamber 21.
The annular piston 23, which is sealed in relation to the master cylinder housing 30 by a sealing cup 27, is in force-transmitting connection with the primary piston 19 via a detachable locking device 28. The annular piston 23 cooperates with a stop 31 formed by a step designed in the master cylinder housing 30. The stop 31 supports a compression spring 29 which biasses the annular piston 23 in opposition to the actuating direction. In the release position or, respectively, in the actuated position after the locking device 28 is released, the annular piston 23 is pressed against a second stop 58 by the compression spring 29.
The annular piston 23 is provided with an axial extension 32 which supports a pin 33 that actuates the central valve 26. The locking device 28 can be formed by one or a plurality of resiliently preloaded balls 34, which are guided in the primary piston 19 and which cooperate with a slope 35 formed in the annular piston 23. For the employment of the described actuating unit in anti-lock brake systems, it is particularly expedient that the secondary piston 20 is designed as a plunger piston which cooperates with an immovable sealing cup 36 arranged in the master cylinder housing 30.
When the input member 3 is displaced by the brake pedal in the actuating direction, to the left in FIG. 1, the first sealing seat 11 provided on the valve piston 17 opens so that the working chamber 6 is ventilated. Since the vacuum chamber 5 is in permanent connection with a suitable vacuum source during operation, the pneumatic difference in pressure acting upon the movable wall 7 causes movement of the control housing 12 connected with the movable wall 7 in the actuating direction. This movement is transmitted to the primary piston 19 via the reaction disc 13 and the push rod 14. Because of the operative connection between the primary piston 19 and the annular piston 23, the latter is entrained by the primary piston 19, and the central valve 26 is kept open by its closure member 37 abutting on the pin 33. As a result, hydraulic pressure develops through the sealing cup 27 located on the annular piston 23 in both the filling chamber 24 and in the primary pressure chamber 21. This pressure causes displacement of the secondary piston 20 in the actuating direction.
Once the pressure developing in pressure chambers 21 and 24 reaches the level at which the force component acting on the balls 34 of the locking device 28 via the slope 35 formed in the annular piston 23 overcomes the force of the compression spring 38 biassing the balls 34, the locking device 28 will be released. This causes the annular piston 23 to uncouple from the primary piston 19 in terms of force transmission, and allows it to be reset to its initial position on the stop 58 by the effect of the compression spring 29. Simultaneously, the closure member 37 of the central valve 26 lifts from the pin 33, so that the primary pressure chamber 21 is isolated from the filling chamber 24. Further pressure increase in the primary pressure chamber 21 takes place via the sealing element of the primary piston 19.
It is also possible to provide a contact device 80 in the area of the stop 31 of the annular piston 23 by which an optical warning apparatus can be activated. Preferably, the optical warning device is a lamp, located in the field of vision of the vehicle driver.
As shown in FIGS. 2 and 3, the pin 33 forming the opening mechanism of the central valve 26 is arranged perpendicularly to the longitudinal axis of the master cylinder 2. The pin 33 is supported in a ring 39 slipped on the primary piston 19. In the release position of the actuating unit, the ring abuts axially on a radial annular surface 40 on the primary piston 19 and on the annular piston 23. While the design of the locking device 28 shown in FIG. 2 corresponds to the embodiment shown in FIG. 1, the locking device 28 shown in FIG. 3 is formed by one ball or a plurality of balls 41 guided in the annular piston 23 and cooperating with a slope 42. Slope 42 is provided in the primary piston 19 and is formed by a radial groove 43.
In the embodiment of the present invention shown in FIG. 4, ring 39 abuts on a stop formed fast with the master cylinder housing. This stop is formed by an annular disc 44 situated in the stop area of the annular piston 23. The result is that the primary pressure chamber 21 and the filling chamber 24 are already isolated from each other at the commencement of the actuation. Thus, fluid overflows the sealing cup 45 located on the primary piston 19 during the filling action. For this purpose, the primary piston 19 is furnished with axial bores 46 and the annular disc 44 contains passages 47.
In the design variant of the present invention shown in FIG. 5, the closure member 37 of the central valve 26 abuts the end surface of an actuating piston 48 which slides within and is guided by the primary piston 19. The actuating piston 48 bounds a cylindrical chamber 49 which, as is shown, may be in communication with the vacuum chamber 5 of the brake power booster 1 via a bore 50 provided in the primary piston 19. The chamber 49 accommodates a compression spring 51, which biasses the actuating piston 48 in opposition to the closing direction of the central valve 26. In this embodiment, the locking device 28 is formed by locking balls 52, which are arranged in radial bores 53 of the primary piston 19. These locking elements cooperate with a first slope 54 provided in the annular piston 23 as well as with a second slope 55 provided on the actuating piston 48.
As described above, hydraulic pressure develops in pressure chambers 21 and 24 on actuation. The effect of this pressure on the actuating piston 48 generates a force which counteracts the force of the compression spring 51. When this spring force is overcome, the actuating piston 48 displaces to the right in the drawing, thereby closing central valve 26.
Simultaneously, the locking balls 52 move radially inward over the second slope 55 until they disengage the first slope 54 formed in the annular piston 23. As a result, the annular piston 23 uncouples from the primary piston 19 and can be positioned in the initial position by the compression spring 29.
Finally, as shown in FIGS. 6-9, locking device 28 is formed of a sleeve 60 which, preferably, is made of plastic and which, when slipped on the piston 19, is expandable in the radial direction. Sleeve 60 has a radial collar 61 with a radial inwardly disposed area of smaller diameter that defines a first conical annular surface 64 (FIG. 7). In the release position, the annular surface 64 is received in an annular groove 59 provided in the piston 19.
Annular groove 59 preferably has two transversely extending flanks 62 and 63, each of a different ascent. The first conical annular surface 64 of the collar 61 transitions into a second conical annular surface 65 which, on actuation of the piston 19, cooperates with the flank 63 of steeper ascent, as illustrated on the right-hand side of FIG. 6. The radial outwardly disposed larger-diameter area of the collar 61 is formed by a cylindrical surface 73, the diameter of which corresponds to the internal diameter of the annular piston 23. This cylindrical surface 73 serves as radial support for the sleeve 60 on the annular piston 23.
Force is transmitted between the sleeve 60 and the annular piston 23 via a spring 66 located between the sleeve 60 and the annular piston 23. The sleeve-side end of spring 66 is supported on a guide portion 67 which abuts axially on the collar 61. The annular piston is furnished with a radial annular groove 68 of rectangular cross-section. The radial annular groove 68 permits radial expanding of the sleeve 60, and thus unlocking of the locking device 28 after the force of the spring 66 has been overcome and the pistons 23 and 19 have separated. Simultaneously, the bottom of the annular groove 68 serves as a guide surface for the guide portion 67.
As shown in FIGS. 8 and 9, a truncated-cone shaped area 69 is located adjacent to the radial collar 61 of the sleeve 60. The truncated-cone shaped area 69 transitions into a cylindrical portion 70, of internal diameter corresponding to the external diameter of the piston 19. The radial expansion of sleeve 60 during the unlocking of the locking device 28 is facilitated by a plurality of axial slots 71 which are evenly spread over the periphery of the sleeve 60. These axial slots 71 end at the transition between the cylindrical portion 70 and the truncated-cone shaped area 69 of the sleeve 60. The axial slots 71 subdivide the collar 61 and the area 69 into radially resilient segments 72.
The function of locking device 28 described above is almost identical to the function of those locking devices depicted in FIGS. 1 and 5. When the piston 19 is displaced in the actuating direction, the actuating force acting axially on the piston 19 is transmitted via the inclined flank 63 of the annular groove 59 to the second conical annular surface 65 of the collar 61, so that the annular piston 23 is entrained through the guide portion 67 and the spring 66. Simultaneously, a radial outwardly acting force component results. When the force of the spring 66 is overcome and the locking device 28 is unlocked, this radial outwardly acting force causes radial expansion of the collar 61 with concomitant expansion of the segments 72. The segments 72 are received in the annular groove 68, in the area of the annular groove 68 shaped in the annular piston 23.
List of Reference Numerals
1 vacuum brake power booster
2 tandem master cylinder
3 actuating member
4 control valve
5 vacuum chamber
6 working chamber
7 movable wall
8 diaphragm plate
9 rolling diaphragm
10 booster housing
11 sealing seat
12 control housing
13 reaction disc
14 push rod
15 head flange
16 resetting spring
17 valve piston
18 sealing seat
19 primary piston
20 secondary piston
21 pressure chamber
22 pressure chamber
23 annular piston
24 filling chamber
25 pressure fluid channel
26 central valve
27 sealing cup
28 locking device
29 compression spring
30 master cylinder housing
31 stop
32 extension
33 pin
34 ball
35 slope
36 sealing cup
37 closure member
38 compression spring
39 ring
40 annular surface
41 ball
42 slope
43 radial groove
44 annular disc
45 sealing cup
46 bore
47 passage
48 actuating piston
49 chamber
50 bore
51 compression spring
52 locking element
53 bore
54 slope
55 slope
56 booster housing half
57 booster housing half
58 stop
59 annular groove
60 sleeve
61 collar
62 flank
63 flank
64 annular surface
65 annular surface
66 spring
67 guide portion
68 annular groove
69 area
70 portion
71 slot
72 segment
73 surface
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An actuating unit for a hydraulic brake system for automotive vehicles which operates by a precisely defined change-over pressure and with lost travel independent of the speed of actuation. The actuating unit includes a pneumatic brake power booster and a master brake cylinder connected downstream of the pneumatic brake power booster. The master brake cylinder contains a primary piston coupled with an annular piston of larger diameter. The annular piston confines a filling chamber which may be connected to the hydraulic pressure chamber. The annular piston is adapted to uncouple from the primary piston when the pressure acting on the annular piston reaches a predetermined amount. Thus, the displacement of the filling volume by the annular piston does not require an entire stroke of the master brake cylinder.
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BACKGROUND OF THE INVENTION
I. Field of the Invention
The present invention relates to the application of crop protection chemicals such as fertilizers, herbicides, insecticides, fungicides and the like. More specifically, the present invention relates to nozzle arrangements for fluid spray applicators that ensure fluid is evenly dispersed over a broad area.
II. Description of the Related Art
Most agricultural sprayers are mounted to a motor vehicle. These sprayers typically include one or more tanks in which material to be applied to a farm field is stored, a boom, a plurality of spray nozzles mounted along the boom, plumbing for carrying materials from the tank to the nozzles, and at least one pump for forcing material from the tank, through the plumbing and out the nozzles.
Most boom and nozzle arrangements are designed so that the chemicals are sprayed straight down on the plants. However, recent studies suggest that advantages can be achieved if the boom and nozzles are turned to angle the nozzles back about 10 to 20 degrees. One advantage is that angling the nozzles back ensures some overlap of the spray pattern delivered by adjacent nozzles and, thus, more complete chemical coverage. Another advantage is that angling the nozzles helps the chemical reach weeds that may be hidden underneath the foliage of the crop. For example, if one sprays straight down, the chemical may be blocked by the leaves of soybean plants and never reach the weeds hiding beneath these leaves.
Many boom and nozzle arrangements are designed so that it is either not possible to angle the nozzles back or requires substantial labor or retrofitting to do so. Thus, there is a real need for a nozzle that can be used on a conventional boom and with a traditional nozzle holder for providing all the advantages of angling the boom and nozzles without the labor and expense associated with angling the boom and nozzles.
SUMMARY OF THE INVENTION
The present invention provides a nozzle tip that provides all of the advantages of angling the boom of an agricultural spray system without the cost and labor involved modifying the spray system to angle the boom. The nozzle tip of the present invention can be used with any nozzle cap designed to hold ISO size nozzle tips. The nozzle tip includes an inner member and an outer member which work in combination to generate the desired pattern. The nozzle tip of the present invention uses a unique eduction mixing system and an angled discharge opening to provide all of the benefits without the expense of angling the spray boom.
Other objects and advantages of the present invention will become apparent from the following detailed description of the preferred embodiment in view of the drawings which are described below.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the nozzle of the present invention.
FIG. 2 is a front view of the nozzle of the present invention.
FIG. 3 is a side view of the nozzle of the present invention.
FIG. 4 is a top view of the nozzle of the present invention.
FIG. 5 is a bottom view of the nozzle of the present invention.
FIG. 6 is a cross-sectional view of the outer member of the nozzle of the present invention.
FIG. 7 is a side view of the inner member of the nozzle of the present invention.
FIG. 8 is a cross-sectional view of the inner member of the nozzle of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The nozzle 1 has an outer member 2 and an inner member 3 . The nozzle 1 is designed to fit within a holder or cap (not shown) designed to receive and hold standard ISO nozzles. As such, the nozzle 1 has certain features common with other ISO nozzles.
For example, the outer member 2 has a flange 4 and a central section 5 each sized and shaped to cooperate with a standard cap design. Specifically, the central section 5 is designed to fit within an opening the cap and the flange 4 engages the surfaces of the cap to ensure the nozzle 1 remains affixed to the cap.
The nozzle 1 of the present invention, however, is very different from a standard ISO nozzle in a variety of respects. As shown in FIGS. 1-6, the outer member 2 also includes a generally cylindrical extension 6 that terminates in a semi-spherical tip 8 . The tip 8 has a generally V-shaped discharge slot 10 formed by a pair of walls 12 and 14 . The wall 12 is generally parallel to the longitudinally axis of the nozzle 1 . The wall 14 is not parallel to this axis and, instead, extends at an angle in the range of 10° to 20° (and preferably 15°) from the longitudinal axis. To provide a clear indication of which wall is parallel and which wall is angled, an exterior projection 16 is provided. As shown, projection 16 is on the side of the parallel wall 12 and opposite that of the angled wall 14 .
Another important feature of the outer member 2 is the series of openings 17 between the central section 5 and the cylindrical extension 6 . The openings 17 provide a path for air to be educted into the flow stream. Also, because a plurality of smaller openings 17 are provided, as opposed to a single larger opening, the air is filtered of debris, the chance of clogging the entire area of the openings is reduced, and the air flow into the stream is more uniform.
The outer member 2 has an inner lumen 18 (see FIG. 6) which is wider in the area of the flange 4 , has a smaller diameter in the area of the central section 5 , and is smaller yet in the area of the extension 6 . Surrounding the lumen 18 in the are of the flange 4 is a channel 19 that is used to lock the inner member 3 to the outer member 2 .
FIGS. 7 and 8 show the construction of the inner member 3 . The inner member 3 has a flange 20 having a projection 21 that fits within the channel 19 of the outer member 2 . The inner member 3 also has a central ring 22 and an extension 24 . The space 27 between the extension 24 and the ring 22 is generally open. A pair of posts 25 and 26 hold the ring 22 and extension 24 in spaced apart relation.
FIG. 8 shows the shape of the lumen 28 that runs through the inner member 3 . As shown, the lumen 28 has a frusto-conical portion 30 in the area of the flange 20 . As it continues, it narrows to a cylindrical section 32 in the area of the ring 22 . It also has a frusto-conical section 34 in the area of the extension 24 .
When the inner and outer members are assembled, the end of the extension 24 of the inner member 3 resides within the extension 6 of the outer member 2 . Also, a chamber is created between the outer wall of the extension 24 of the inner member 3 and the inner wall of the central section 5 of the outer member 2 . This chamber, in combination with the openings 17 of the outer member 2 and the space between the ring 22 and the extension 24 of the inner member 3 , creates a flow path through which air can be educted into the stream of liquid passing through the nozzle 1 . That stream of liquid passes through the lumen 28 of the inner member 3 , mixes with the air, passes through the extension 6 of the outer member 2 and then through the slot 10 . The nature of the flow path and the shape of the slot 10 give the fluid exiting the nozzle 1 the same motion as if the boom were tipped approximately 15°.
Nozzles constructed in accordance with the preferred embodiment offer a variety of advantages. First, such nozzles eliminate the need to change the angle of the boom to ensure a comprehensive spray pattern irrespective of the height of the boom. Second, such nozzles are preset to provide the correct delivery angle for the chemicals providing improved penetration into the crop canopy so the chemicals reach weeds hiding under crop foliage. Third, the nozzles of the present invention fit standard booms and standard nozzle body holders or caps. Fourth, no tools are needed to change the nozzles. Fifth, the nozzles can be used to provide either an angled back or an angled forward delivery of chemicals and are clearly marked to assist in assembly and installation to achieve whichever type of angled delivery is required. Sixth, the design of the eduction system and the slot design permit the nozzle 1 to be used effectively at lower operating pressure to deliver a more open spray pattern. Finally, the preferred embodiment can be constructed in a variety of sizes either to fit different ISO or other sized caps or holders.
While the preferred embodiment described above shows the wall 14 angled of 15° from the longitudinal axis of the nozzle 1 , the wall 14 can be set at different angles (preferably in the range of 10° to 20°) to modify the discharge pattern and impart a different spray angle. These and other changes can be made to the preferred embodiment of the invention without departing from the scope of the invention as defined by the following claims.
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Nozzle attached to the boom of agricultural sprayers each include an improved air eduction system and discharge slot eliminating the need to change the angle of the boom and nozzle to ensure a comprehensive spray pattern irrespective of boom height and improved penetration of the material sprayed into and under the crop canopy.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of application Ser. No. 09/303,980, filed May 3, 1999, which is hereby incorporated by reference in its entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to a vacuum deaeration device in which a transmission film for allowing only gas to pass therethrough and preventing liquid from being transmitted is mounted within a vacuum container, a pressure within the vacuum container is reduced by a vacuum pump or the like to deaerated resolved gas from liquid (deaerated liquid) contacted with the aforesaid transmission film. More particularly the invention is a vacuum deaeration device suitable for removing resolved gas from liquid (deaerated liquid) in various kinds of production process facilities, such as a liquid chromatograph as well as various kinds of physical and chemical and analytical devices, pharmaceutical engineering, semi-conductors and liquid crystals.
DESCRIPTION OF RELATED ART
[0003] Analytical processing is performed using analytical equipment, such as a liquid chromatograph device. Resolved gas is removed (deaerated) from sample liquid or solvent, or liquid to improve reliability in measurement data. A fluorine transmission film for allowing only gas to pass therethrough and preventing liquid from being transmitted is used at a location of the deaeration device in contact with the foresaid sample liquid or solvent, or liquid.
[0004] The transmission film used in this type of deaeration device is usually manufactured by7 a method wherein residual gasoline substances (e.g., naphtha or white oil) are added to and mixed a powder fluorine plastic substrate to form paste. The past material is extruded and backed under a relatively high temperature (approximately 100° C. to approximately 400° C.).
[0005] At this time, liquid of a relatively low boiling point such as the aforesaid gasoline residuals is evaporated during baking operation and removed. However, actually, liquid of relatively low boiling point, in particular, aromatic substances and olefin substances are not completely evaporated and a relatively small amount of the substances remain in the transmission film. These remaining substances in the transmission film are freely separated when liquid (deaerated liquid) is contacted with the transmission film, resolved into deaerated liquid, and bad influence (a measurement error) is applied to the measurement result performed by the liquid chromatograph device or quality keeping controls in various kinds of production processes.
[0006] SUMMARY OF THE INVENTION
[0007] The present invention overcomes the aforesaid disadvantages as above in the prior art. Specifically, the present invention is directed to a vacuum deaeration device having no possibility that aromatic substances or olefin substances applying bad influence against the measurement result performed by analytical equipment and quality keeping controls at various kinds of production processes are resolved into liquid (deaerated liquid) contacted with the transmission film.
[0008] The vacuum deaeration device of the present invention accomplishing the aforesaid object is a vacuum deaeration device in which a transmission film for allowing only gas to pass therethrough and preventing liquid from being transmitted is mounted within a vacuum container. A pressure within the vacuum container is reduced to cause resolved gas to be deaerated from the deaerated liquid through the transmission film. Applied to the transmission film is a product of relatively high volatility in which dispersion liquid composed of a single, not containing both aromatic, and olefin substances is added to a particle plastic substrate to form a paste material that is extruded and baked.
[0009] In one preferred embodiment of the present invention, the dispersion liquid is a single solution of linear chain-like paraffin, not containing unsaturated hydrocarbon or having a volatile characteristic and not containing aromatic substances and olefin substances, while the plastic substrate is polytetrafluoroethylene (PTFE).
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] [0010]FIG. 1 is an exemplary diagram of a vacuum deaeration device in accordance with the present invention; and
[0011] [0011]FIG. 2 is a chromatogram detected by a gradient resolved chromatography.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0012] An exemplary embodiment of the present invention is described in detail.
[0013] In FIG. 1, the vacuum deaeration device includes a vacuum container 1 , a tube-shaped transmission film 2 mounted within the vacuum container 1 so as to pass only gas and prevent transmission of liquid, a vacuum pump 3 for reducing pressure inside the vacuum container 1 .
[0014] In the case of the exemplary preferred shown in FIG. 1, the vacuum deaeration device is construed so that the transmission film 2 is formed into a tube with a predetermined length. One or a plurality of films are mounted within the vacuum container and at the same time a liquid inlet 21 and a liquid outlet 22 of the tube-shaped transmission film 2 is placed outside the vacuum container 1 . The deaerated liquid flows from the liquid inlet 21 of the tube-shaped transmission film 2 while a pressure of the inside part of the vacuum container 1 is reduced using a vacuum pump 3 . Resolved liquid is deaerated from the deaerated liquid while the liquid is discharged out of the outlet 22 .
[0015] In addition, a pressure sensor 4 and a check valve 5 are operated with a specified pressure, respectively. These devices need not be arranged in a predetermined orientation. If the pressure sensor 4 or check valve 5 is mounted, then the pressure within the vacuum container 1 may be controlled in a more precise and positive manner.
[0016] The transmission film 2 of the present invention is manufactured by a method wherein dispersion liquid is added to and mixed with particle-like plastic substrate to form a paste. The plastic substrate in paste form is extruded by an extruder into a tube, a film, or a membrane, and baked at a relatively high temperature (approximately 100° C. to approximately 400° C.). The transmission film is mounted within the vacuum container 1 in such a way that may be contacted with the deaerated liquid.
[0017] In the present specification, it is assumed that the term “particle” includes a relatively fine particle.
[0018] The plastic substrate used in the manufacturing of the transmission film 2 may include fluorine to allow only gas to pass and while preventing the transmission of liquid. Preferably, a polymer comprising fluorine such as polytetrafluoroethylene (PTFE) or fluoric ethylene propylene (FEP), or ethylene tetrafluoroethylene (ETFE) is used.
[0019] The dispersion liquid added to and mixed with partible plastic substrate is a single solution of relatively high volatility that does not comprise aromatic substances and olefin substances, such as linear chain-like paraffin substances that do not comprise non-saturated hydrocarbon. In one embodiment of the present invention, the dispersion liquid is composed of at least two substrates selected from the group of n-hexane, n-heptane, and n-octane, not containing any aromatic and olefin substances.
[0020] A polytetrafluoroethylene (PTFE) plastic substrate was used with linear chain-like paraffin substances not comprising non-saturated hydrocarbon. The liquid was added to and mixed with the particle PTFE to produce a paste PTFE. This paste PTFE was then extruded into a tube-form by an extruder and baked to attain a tube-shaped transmission film.
[0021] The tube-shaped transmission film made of PTFE is assembled into a vacuum deaeration device for use in removing (deaerating) gas in advance from sample liquid or solvent, dampening liquid at a liquid chromatograph device and then detected by gradient solution liquid chromatography. In this case of gradient solution liquid chromatography, a concentration of moving phase (solvent) is changed continuously during chromatograph operation. Contaminated substances separated in the moving phase are condensed in the gradient solution in the separating column and solved with a rate of corresponding solution agent in gradient. Accordingly, when aromatic substances having ultra-violet ray absorbing characteristics enters into a sensor, for example, ultraviolet ray absorption sensor, it may interfere with the measurement.
[0022] [0022]FIG. 2 shows a chromatogram detected by a gradient solution liquid chromatography, wherein waveform i is attained by a liquid chromatograph having a prior art PTFE tube-shaped transmission film, and waveform ii is attained by a liquid chromatograph having a PTFE tube-shaped transmission film manufactured in accordance with the present invention. As the sensing operation, a mixture of acetonitrile-water was used as the sensing operation together with, an ultra-violet ray absorbing sensor having a wave-length of 210 nm.
[0023] As is evident in FIG. 2, in waveform i contamination generating a bad influence (error) on a measurement result in the liquid chromatograph is produced when using a conventional PTFE tube-shaped transmission, whereas a substantially flat baseline ii is produced and interference is scarcely detected in a quantitative measurement of sample when using a PTFE tube-shaped transmission in accordance with the present invention.
[0024] In accordance with the vacuum deaeration device of the present invention, a dispersion liquid of relatively high volatility comprising a single solution not containing both aromatic substances and olefin substances is added to a particle plastic substrate to form a paste material. The paste material is extruded, baked and used as a transmission film for allowing only gas to pass while preventing liquid from being transmitted. Therefore, the aromatic substances and olefin substances are not originally present at the transmission film contacted with the deaerated liquid, thereby eliminating the possibility that both aromatic substances and olefin substances are freely separated and resolved into the deaerated liquid when the deaerated liquid is contacted with this transmission film. As a result, there no possibility exists that a bad influence (a measurement error or the like) will be applied to a measurement result performed by the liquid chromatograph device or quality keeping control at various kinds of production processes.
[0025] An example of manufacturing of a vacuum deaeration device in accordance with the present invention is provided below.
EXAMPLE
[0026] PTFE powder, such as that manufactured by ASAHI ICI FLUOROPOLYMERS KK, was used as a plastic substrate. The plastic powder was sieved with the screen of 4-8 mesh into a container. N-Hexane as a dispersing liquid was added to the powder and the container was sealed to prevent vaporization of the dispersing paste PTFE substrate. The paste substrate was pressed in a preforming mold to remove the entrained air and to be preformed in the form of the mold.
[0027] This preform was then moved into an extrusion cylinder and extruded into a tube-like shape. The extruded substrate was subsequently moved into the drying zone in an oven. The temperature of the drying zone was controlled at approximately 60° C., which is below the boiling point of n-hexane, in the area of the inlet and continuously increased to approximately 250° C. as the substrate moved into the oven in order to diffuse and vaporize the dispersing liquid in the tube-like substrate. The tube-like substrate which removed the dispersing liquid through the drying zone was finally baked through a sintering zone at 360-390° C. to obtain a PTFE tube. Therefore, the PTFE tube did not include any aromatic or olefinic substances.
[0028] Having described specific preferred embodiments of the invention with reference to the accompanying drawings, it will be appreciated that the present invention is not limited to those precise embodiments, and that various changes and modifications can be effected therein by one of ordinary skill in the art without departing from the scope of the invention as defined by the appended claims.
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This invention's object is to eliminate a possibility that both aromatic substances and olefin substances are resolved into deaerated liquid contacted with a transmission film. As a transmission film for allowing only gas to pass and preventing liquid from being passed therethrough, there is applied a product of high volatile characteristic in which dispersion liquid composed of single solution is added to particle plastic substrate to form paste material is extruded and baked.
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BACKGROUND OF THE INVENTION
This invention relates generally to a vehicle electrical junction box that is mounted to a battery.
Modern vehicles are provided with many electrical systems and components. All of these draw power from the battery. Typically, a battery cable has supplied electrical power from the battery to a remote junction box. The junction box typically includes appropriate controls and connections to distribute the electrical power as appropriate. Wire harnesses are attached to the junction box to communicate to the electrical systems and components.
In most vehicles the junction box is mounted to a wall in an engine compartment or to an interior sidewall of a passenger compartment. Generally, a terminal is mounted to a post of a battery and the battery cable connects the terminal to the junction box. Oftentimes, the junction boxes are located in places which are not conveniently accessible. In addition, the typical placement of the junction box requires long cable runs between the battery and the junction box and from the junction box to electrical components within the vehicle.
Therefore, it is desirable to provide a junction box that is located closely adjacent to the battery to reduce the length of cable required to distribute power from the battery to the electrical systems and to provide easier access to the junction box. This invention permits a junction box to be mounted directly to a battery, thereby eliminating the need to include a battery cable extending between the terminal and the junction box . The invention also provides a more convenient location for the junction box.
SUMMARY OF THE INVENTION
In general terms, this invention provides a means for mounting a junction box adjacent to a battery. In essence, the junction box includes a plurality of electrical outlets for receiving the electrical output from a terminal connected to a battery. The junction box is attached to the battery through a terminal. Preferably, the terminal and the outputs are formed as a single rigid piece. Moreover, the junction box is preferably mounted and supported directly on the battery.
Preferably, the terminal is mounted to a battery post of the battery to secure the junction box. The plurality of electrical outputs are coupled to a printed circuit board for distribution of the electrical power. A second plurality of outputs directs the electrical power from the printed circuit board to wiring harnesses for further distribution of the electrical power. The printed circuit board and at least a portion of the terminal are preferably enclosed within a sealed housing. The housing is secured closely adjacent to the battery by the terminal, and is preferably supported on the battery.
These and other features and advantages of this invention will become more apparent to those skilled in the art from the following detailed description of the presently preferred embodiment. The drawings that accompany the detailed description can be described as follows.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an exploded side view of a battery mounted junction box designed according to this invention;
FIG. 2 is an end view of a battery mounted junction box designed according to this invention; and
FIG. 3 is a side view of a battery mounted junction box designed according to this invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
The present invention is directed to a unique mounting system for a junction box for distributing power from a vehicle battery. One particular junction box will be disclosed, however, it should be understood that other junction boxes would come within the scope of this invention.
A battery mounted junction box is generally indicated at 10 in FIG. 1. A terminal 12 having a hole 14 is mounted to a post 16 on battery 18. Terminal 12 is illustrated positioned below a sealing boot 44. In practice terminal 12 is actually mounted in sealing boot 44. The post 16 has a set of external threads 20 adapted to receive a nut 22 and a washer 23. The nut 22 secures the terminal 12 to the post 16 of the battery 18. The terminal 12 extends to a series of electrical outputs 24 and an optional connector 26. The outputs 24 and connector 26 serve to distribute the power from battery 18 to the electrical systems and components. The terminal 12 is shown as being generally rigid and L-shaped. However, as will be appreciated by those skilled in the art, the terminal 12 could be of a variety of other shapes. In addition, the terminal 12 need not be a single rigid piece, as shown. The terminal 12 extends from the post 16 into a first housing 32. A screw 33 secures the terminal 12 to the first housing 32.
The first housing 32 includes a first half 34 which is matable with a second half 36. A pair of clips 38 are mounted on two opposite sides of the second half 36, and snap fit over a pair of posts 40 on corresponding sides of the first half 34 to secure the first half 34 to the second half 36. As will be appreciated by one of ordinary skill in the art, other ways could be used to secure the first half 34 to the second half 36. A sealing lip 42 surrounds the first half 34 and seals the first housing 32 when the first half 34 and the second half 36 are secured to each other. A sealing boot 44 seals terminal 12 from post 16 to first half 34 of first housing 32. Another sealing boot 45 seals terminal 12 at connector 26 when connector 26 is included. Boots 44 and 45 are preferably made of silicone and in combination with the sealing lip 42, seal the first housing 32 when the first half 34 is mated with the second half 36. Sealing boot 44 also includes a cap 46 positioned to cover the nut 22 and washer 23, as shown by arrow 47, when the terminal 12 is secured to the post 16.
Some of the electrical outputs 24 of the terminal 12 plug into a set of terminals 48 in a printed circuit board 50. An insulation spacer 52, partially illustrated, is sandwiched between the terminal 12 and the printed circuit board 50. A set of printed circuit board blades 54 extend from the printed circuit board 50 into a set of terminals 56 mounted to a dielectric carrier board 58. A series of clips 60 snap fit the dielectric carrier board 58 to the printed circuit board 50. A set of relays 61 and a set of fuses 62 are received in the terminals 56 opposite the printed circuit board blades 54.
A plurality of electrical outputs 64 extend from the printed circuit board 58 through the first housing 32. The electric outputs 64 provide electrical continuity between the printed circuit board 50 and end plugs 66 of wiring harnesses 68.
A second housing 70 includes a pair of snap fit clips 72 that mount the second housing 70 to the first housing 32. Second housing 70 is optional and can be included when terminal 12 does not include connector 26. Either output post 76 or connector 26 is used to distribute electrical power to the engine starter (not shown) and alternator (not shown) through power feed 78 or a power feed 80, respectively.
If housing 70 is used, one electric output 24 of the terminal 12 is secured to an input post 74 mounted to the second housing 70. An electrical power regulation element 75, known as a mega fuse, electrically couples the input post 74 to an output post 76 that is mounted to the second housing 70. A power feed 78 is connected to the output post 76. A sealing boot 81 seals the output 24 from the terminal 12 at the point where it exits the first housing 32 and enters the second housing 70. The sealing boot 81 is preferably made of silicone. A second housing cover 82 has two pairs of clips 84 mounted on opposite sides of the housing cover 82 that snap fit over two pairs of corresponding posts 86 on the second housing 70 to join the cover 82 to the second housing 70. The advantage of including second housing 70 with the power regulation element 75 rather than connector 26 is that it provides a fusible link between the battery 18 and the starter and alternator. When connector 26 is not included then sealing boot 45 is also not included because the terminal 12 ends within the first housing 32. When the second housing 70 and the power regulation element 75 are not included then sealing boot 81 is not necessary because no output 24 extends between the first hosing 32 and the second housing 70.
In FIG. 2 an end view of the battery mounted junction box 10 is shown mounted to the battery 18. As can be appreciated from FIG. 2, the junction box 10 is mounted and supported directly on the battery 18. The terminal 12 connects the junction box 10 to the battery 18 and secures the junction box 10 on the battery 18. However, the junction box 10 is itself supported on the top surface 90 and side surface 94 of the battery.
In FIG. 3, a side view of the battery mounted junction box 10 is shown mounted on the battery 18. In this embodiment, the first housing 32 is substantially L-shaped and a shorter portion 88 of the first housing 32 is supported on a top surface 90 of the battery 18. A longer portion 92 of the first housing 32 contacts a side surface 94 of the battery 18.
As will be appreciated by one of ordinary skill in the art, the shape of the first housing 32 could be rectangular rather than L-shaped as shown in the embodiment in FIG. 3. In addition, the post 16 of the battery 18 could be mounted on the side surface 94 of the battery 18 rather than the top surface 90 of the battery 18.
The foregoing description is exemplary rather than limiting in nature. Variations and modifications to the disclosed embodiment may become apparent to those skilled in the art and do come within the scope of this invention. Accordingly, the scope of legal protection afforded this invention can only be determined by studying the following claims.
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A junction box has a housing mounted directly to a battery. The junction box includes a terminal that mounts to the post of the battery and secures the housing to the battery. Enclosed within the housing is a printed circuit board for receiving outputs from the terminal and distributing electrical power to a second set of outputs, which can communicate with a wiring harness for further distribution of the electrical power.
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This is a continuation of application Ser. No. 07/940,202 filed on Sep. 1, 1992/now abandoned, which is a continuation of U.S. Ser. No. 07/664,370, filed Mar. 4, 1991 which is now abandoned.
BACKGROUND OF THE INVENTION
It is recognized in the art that in aqueous iodine compositions wherein the iodine is formulated with organic substances with which it reacts, such as water soluble organic solvents, iodine complexing polymers or surface active agents, the elemental iodine concentration decreases on storage leading to decreased germicidal effectiveness and lack of reproducibility of results.
One method of overcoming the problem of elemental iodine stability which has been suggested involves adding iodate or iodide ions to the aqueous solution. For example, U.K. Specification No. 2060385, describes aqueous germicidal iodine compositions comprising an aqueous solution of elemental iodine and at least one organic substance which slowly reacts with iodine wherein iodine loss on storage due to reaction with the organic substance is controlled by providing balanced sources of iodide ion in the range of about 0.025% to 0.5% and iodate ion in the range of about 0.005% to 0.2% and controlling the pH within the range of pH 5 to 7. In this way, iodine loss in the iodine composition is balanced by iodine formed from reacting iodate, iodide and hydrogen ions, the rate of formation of iodine being governed by the pH selected.
The need for stable pharmaceutical iodine compositions with less irritancy than known compositions still exists.
SUMMARY OF THE INVENTION
It is accordingly a primary object of the present invention to provide stable pharmaceutical iodine compositions with reduced irritancy.
It is another object of the present invention to provide for the method of producing such compositions and further to provide for germicidal treatment with such compositions.
Other objects and advantages of the present invention will be apparent from a further reading of the specification and of the appended claims.
Thus, the present invention relates to pharmaceutical iodine compositions, to processes for their preparation and to their medical use, and in particular, to stable germicidal iodine compositions in which the elemental iodine concentration level is maintained by the addition of iodate ions.
With the above and other objects in view, it has been found according to the present invention that stable compositions with unexpectedly reduced irritancy are obtained by adding iodate ions in the range of 0.01% to 0.04% by weight to aqueous iodine compositions.
Thus, the present invention provides a pharmaceutical composition comprising an aqueous solution of elemental iodine and at least one organic substance which reacts with iodine, whereby iodine loss is controlled by providing a source of iodate ions sufficient to provide from 0.01% to 0.04% by weight iodate ions, preferably from 0.02% to 0.03% by weight iodate ions.
Suitable organic substances for use in the present invention include those conventionally used in the art. Those include for example, water soluble solvents (such as ethanol, propanol, polyethylene glycol); iodine solubilizers; iodine complexing polymers such as polyvinylpyrrolidone or non-ionic, cationic or anionic detergent carriers or surface active agents (such as nonoxynol or sodium lauryl sulphate).
According to the invention, elemental iodine is preferably present in the range of 0.1 to 1.4% by weight, most preferably 0.75 to 1.25% by weight. Conveniently, the composition according to the invention comprises an aqueous solution of a complex of iodine with an organic iodine-complexing agent, preferably a polyvinylpyrrolidine-iodine complex. Where polyvinylpyrrolidone-iodine is used, the same is preferably present in the range of from 1% to 12% by weight to give from 0.1% to 1.4% of the available iodine in solution.
The iodate ions for use in the present invention may be obtained from any convenient source for example sodium or potassium iodate.
The pH range of compositions according to the present invention is desirably maintained within the range from pH 3 to 7, preferably pH 4 to 6. The pH is conveniently maintained in the desired range by addition of a conventional buffer such as a citrate or phosphate buffer.
Compositions according to the present invention may be formulated for administration by any convenient route conventional in the art. Such compositions are preferably in a form adapted for use in medicine, in particular human medicine, and can conveniently be formulated in conventional manner using one or more pharmaceutically acceptable carriers or excipients. Compositions according to the present invention are conveniently formulated for topical or mucosal administration in the form of solutions, soaps, ointments, gels or paints.
In a further aspect there is provided a process for preparing a pharmaceutical iodine composition according to the invention, comprising forming a solution of iodine and at least one organic substance with which iodine reacts and adding iodate ions in the range of from 0.01% to 0.04% by weight.
In an alternative aspect, there is provided a method for the germicidal treatment of a mammal, including man, comprising administering a composition as defined above. It will be appreciated that reference to treatment is intended to include phophylaxis.
BRIEF DESCRIPTION OF THE DRAWINGS
The present invention is further illustrated in connection with the accompanying drawings in which:
FIG. 1 is a graphical representation of mean visual erythema assessment;
FIG. 2 is a graphical representation of mean erythema meter readings, and
FIG. 3 is a graphical representation of blood flow measurements,
all in connection with tests with respect to the compositions of the present invention.
DESCRIPTION OF PREFERRED EMBODIMENTS
The following example is given to further illustrate the present invention. The scope of the invention is not, however, meant to be limited to the specific details thereof.
EXAMPLE
The following iodine compositions were prepared.
______________________________________ I II (Comparative) III (ComparativeConstituents % w/w % w/w % w/w______________________________________Povidone-iodine 10.00 10.00 10.00(Overage %) (0) (20) (0)Glycerol 1.0 1.0 1.0Nonoxynol 9 0.25 0.25 0.25Potassium iodate 0.03 -- 0.225Citrate/phosphate 1.11 0.20 1.1Buffer (Approx.Sodium hydroxide q.s. q.s. q.s.Purified water to 100.00 to 100.00 to 100.00______________________________________
A portion of the purified water (60%) was placed in a suitable vessel. Glycerol was added and mixed until the solution was uniform. Povidone-iodine was mixed until dissolved. Potassium iodate was dissolved in a separate small quantity of purified water and added to the povidone-iodine solution. The citrate phosphate were dissolved in water and added to the solution with mixing following by the addition of Nonoxynol 9. The solution was made up with the remaining purified water and the pH adjusted to within the desired range.
The cutaneous irritancy of the three compositions was assessed in a panel of 12 normal volunteer subjects.
Each subject received 7 applications of each material under occlusive patches to separate sites on the back. The treatments were applied to 21 sites on the lower and upper parts of the back using 12 mm aluminum Finn chambers on Scanpor tape with filter paper inserts. 50 mol of the solution was pipetted onto the filter paper. The chamber and filter paper was then applied to one of the sites on the back and the procedure repeated for all 21 sites.
One chamber per treatment was removed after 1, 2, 3, 4, 5, 6 and 8 hours following application and the skin assessed. Assessments were performed 30 minutes after removal of the chambers to allow for any erythema due to chamber removal to subside.
Following removal of the chambers, irritancy was assessed using three procedures.
Sites were assessed for erythema/oedema using the following categorical scale:
0 - No reaction
0.5 - Slight patch erythema
1 - Slight uniform erythema
2 - Moderate erythema
3 - Strong erythema
4 - Strong erythema, spreading outside patch
5 - Strong erythema, spreading outside patch with either swelling or vesiculation
6 - Severe reaction with erosion
When at any time point a site was scored at Grade 3 (strong erythema) or more, then the applications were removed from all remaining sites of that solution on that subject. In this situation, the sites were assessed at the same time points as originally scheduled as if no severe reactions had occurred.
Erythema was also assessed using an Erythema Meter.
Cutaneous blood flow was measured using a Laser Doppler blood flow device (periflux blood flow meter, Perimed, Sweden).
METHOD OF ANALYSIS
In the clinical study the data was either non-parametric in nature or not normally distributed or not of equal variances. Therefore, it was decided that a non-parametric method of analysis was the most suitable.
As the data is based on within subject comparison (each subject receiving all three treatments) the Friedman non-parametric analysis of variance was considered appropriate. Comparisons were made between treatments at t=1, t=2, t=3 and t=4 hours for the three parameters measured.
If a significant value for the test statistic was found, then a multiple comparison procedure was carried out in order to determine individual treatment difference. The threshold value for significance was set at 5%.
Analysis was not carried out at the later time points as in some subjects the treatments had been removed.
RESULTS
The results (means and standard deviations) for visual erythema assessment, erythema meter readings and blood flow measurements are shown in FIGS. 1-3.
The results for all three methods of assessment show a clear difference in the irritancy potential of the three solutions. From the results it can be seen that composition III is the most irritant, producing the greatest rate of increase of parameters assessed as well as the highest mean value. Composition II produced the second highest values while composition I produced the least irritancy. Statistical analysis confirmed these differences at the 2, 3 and 4 hour time points. It will be appreciated that these time periods are important in the clinical situation of an operation.
An in-vitro study to compare the bactericidal activity of solutions I, II and III using standard microbiological dilution techniques against a test bacterial organism, Staphylococcus aureus NCTC 29213 showed no difference in the bactericidal activity of the three solutions.
While the invention has been illustrated with respect to particular compositions, it is apparent that variations and modifications of the invention can be made within departing from the spirit or scope of the invention.
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A stable pharmaceutical composition with reduced irritancy is provided, the composition comprising an aqueous solution of elemental iodine and at least one organic substance which reacts with iodine, whereby iodine loss is controlled by providing a source of iodate ions in an amount sufficient to provide from 0.01% to 0.04% by weight iodate ions, preferably from 0.02% to 0.03% by weight iodate ions.
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FIELD
[0001] This disclosure relates to the field of train management systems and increasing safety in such systems.
BACKGROUND
[0002] One example of a train management system is the Lockheed Martin Advanced Train Management System (ATMS) that uses on-train processing and advanced digital communications to keep track of and manage the location and speeds of trains on a railway. This permits railroads to increase capacity by reducing distance between trains and increase reliability through better on-time performance. In addition, safety is increased through authority and speed limit enforcement.
[0003] The ATMS uses a track database containing a variety of data including geographical coordinates of a number of trackside features that are disposed along the railway tracks as well as a unique identifier for each of the trackside features. The track database is used to create a virtual model of the track in the control system of the train.
[0004] Track databases have many components that are constructed by a team of surveyors, software operators, database administrators, and other staff, and are distributed by radio links to trains from central data servers. However, the track database can have errors. The track line's 3-D trajectory can have errors (location/curvature/heading/grade), which can degrade the ability to accurately compute offset into track segment. In addition, errors in feature-coordinate assignments can result in erroneous visual presentation of upcoming trackside features and track line characteristics to train crew and can have several unintended consequences. For example, errors in content can result in erroneously determining train's track occupancy (parallel track), computing actual location along a track, affecting braking enforcement distance calculations, and miss-identifying physical features used in authority limits.
[0005] Physical trackside features such as kilometer posts, turnouts, speed limits, passenger platforms, division boundaries, yard limits, etc. are used for two-way traffic management and speed management. However, these trackside features can have errors in their partition offsets which results in track database content errors. In addition, trackside features such as kilometer posts and control points can be unintentionally swapped along the track line (for example kilometer post 130 is actually 129 and vice versa). For this example, an authority issued between kilometer posts 135 and 130 on single track could cause an unintentional physical conflict with an opposing train travelling in the opposite direction, as their movement authorities are generated and deconflicted by km post value by a train dispatcher/controller, not by geographic coordinates.
SUMMARY
[0006] Methods and systems are described that can be used to verify a track database of a train management system, for example that the track database has not been corrupted, built with critical errors, or is not being used properly by the software application.
[0007] In some circumstances, software and hardware data of a train management system have to meet safety integrity level (SIL) 3 and above compliance. One recognized way to meet SIL requirements for the underlying ATMS track database is to create and use an independent database, which has the characteristics of a different design, different creation method, generated by a different process with different assets, and maintained by different team members.
[0008] The described methods and systems provide real time, continual, train centric techniques to ensure that each train is using its part of the track database without safety reducing navigation errors, is processing the track database correctly, and has correct information on the actual placement of trackside features so that the actual placements match the track database contents which is used to construct the virtual model of the track.
[0009] In one embodiment, radio frequency identification (RFID) tags are mounted on the trackside features contained in the track database. The tags contain data such as the geographical coordinates of the trackside features and a unique feature identifier that uniquely identifies the respective feature. As the train passes the trackside feature, a tag reader on the train reads the tag to gather the geographical coordinates and the feature identifier. The train management system then compares the geographical coordinates and/or the feature identifier from the tag with the expected geographical coordinates and/or the expected feature identifier in the track database.
[0010] An advantage of the described methods and systems is that the team or individuals that load the data into the RFID tags can be independent from the team that created the track database. This diversity and independence between the two teams are important attributes for a SIL environment.
[0011] In one embodiment, the RFID tag is mounted on the trackside feature in a vertical orientation, and the RFID reader on the train has a wide vertical field of view, and a narrow horizontal field of view, in order to detect the trackside feature's passing when it is close to broadside to the train. In one example, the RFID reader is located in the engine or locomotive of the train, such as adjacent to the front end of the locomotive. However, the RFID reader can be located at other locations on the train as long as its location is accounted for when comparing the read RFID data to the expected data from the track database. In addition, in some embodiment, more than one RFID reader may be provided on the train, with each RFID reader reading the RFID tag as it passes the trackside feature.
[0012] In one specific embodiment, a method of verifying a railway track database of a train management system is provided. The track database contains information on a plurality of trackside features located adjacent to a railway track including an identifier that uniquely identifies each trackside feature and a geographical coordinate location of each trackside feature. In this example, the method includes, as the train is traveling on the railway track, reading a radio frequency identification tag that is affixed to a first one of the trackside features using a reader disposed on the train. The reader obtains from the tag a feature identifier that uniquely identifies the first trackside feature and geographical coordinates of the first trackside feature, where the feature identifier and the geographical coordinates are stored in memory of the tag. The feature identifier and the geographical coordinates read by the reader are then compared with an expected identifier and expected geographical coordinates obtained from the track database.
[0013] In another specific embodiment, a method includes, as a train is traveling on a railway track and passes a trackside feature disposed adjacent to the railway track, reading data from a radio frequency identification tag disposed on the trackside feature using a reader located on the train.
[0014] In still another specific embodiment, a method includes mounting radio frequency identification tags to a plurality of trackside features adjacent to a railway track, each tag having memory in which is stored geographical coordinates of the trackside feature to which the tag is fixed and a feature identifier that uniquely identifies the trackside feature to which the tag is fixed.
[0015] In still another specific embodiment, a radio frequency identification tag includes a tag body, an antenna on the tag body, and memory on the tag body. The memory includes stored therein geographical coordinates of a railway trackside feature to which the RFID tag is intended to be or has been fixed and a feature identifier that uniquely identifies the railway trackside feature to which the RFID tag is intended to be or has been fixed.
[0016] In addition, a system includes a plurality of radio frequency identification tags mounted to a plurality of trackside features disposed adjacent to a railway track, each tag having memory in which is stored geographical coordinates of the trackside feature to which the tag is fixed and a feature identifier that uniquely identifies the trackside feature to which the tag is fixed. The system also includes a tag reader mounted on a train, the tag reader is capable of reading the radio frequency identification tags as the train passes the trackside features, and a processor on the train that is connected to the tag reader, the processor receiving the geographical coordinates and the feature identifier of each tag from the tag reader.
DRAWINGS
[0017] FIG. 1 illustrates a virtual model of a railway track line with trackside features.
[0018] FIG. 2 is a diagram illustrating one embodiment of deriving geographic coordinates from a partition offset using data from a track database.
[0019] FIG. 3 illustrates an RFID system that can be used to verify the track database.
[0020] FIG. 4 illustrates one example of verifying a railway track database.
DETAILED DESCRIPTION
[0021] With reference initially to FIG. 1 , a virtual model of a railway track line 10 as one may see displayed as part of a train management system is illustrated along with a plurality of trackside features 12 disposed on either side of the track line. The track line 10 represents the centerline of the railway on which a train 14 is travelling in the direction T. FIG. 1 shows the train at different times as it travels along the track.
[0022] The trackside features 12 can be any structures typically located along a railway track that are used for such tasks as traffic and/or speed management including, but not limited to, kilometer posts, turnouts, speed limits, division boundaries, yard limits, etc.
[0023] The track line 10 can be any railway track on which a train travels including, but not limited to cargo, freight, passenger, and/or commuter train tracks. The train 14 generally includes a locomotive or engine and one or more additional cars connected to the locomotive.
[0024] The train 14 is controlled by a train management system on the train, typically on the locomotive, that includes a track database that is used to keep track of the location and speed of the train on the track. The function and construction of track databases and train management systems is well known to those having ordinary skill in the art. An example of a track database is described in U.S. Pat. No. 8,392,103.
[0025] When it is created, the track database contains the geographical coordinates of some or all of the trackside features 12 as well as a unique identifier for each of the trackside features in the track database. The train management system includes a location determination unit (LDU), such as a head end rail guide, that determines instantaneous offset into track partition and uses the track database to determine current geographic coordinates from the offset. For example, with reference to FIG. 2 , the position of the locomotive 16 of the train is shown as being offset a distance, for example 5000 cm, between two consecutive trackside features 12 a, 12 b. The track database knows the geographical coordinates of the trackside features 12 a, 12 b which have been stored in the database. Therefore, the geographical coordinates of the locomotive at the offset position can be determined. FIG. 2 illustrates an exemplary calculation that takes place to determine the geographical coordinates of the locomotive 16 at the offset location. Further information on calculating partition offset can be found in U.S. Patent Application Publication 2012/0116616 filed on Nov. 9, 2011, which is incorporated herein by reference in its entirety.
[0026] This calculation of the geographical coordinates and the use of the geographical coordinates of the trackside features 12 a, 12 b is used by the train management system to help control operation of the train. However, as indicated above, there could be errors in the track database that can result in errors in the coordinate calculations as well as errors in advising the train operators which trackside features they are coming up on or have passed. Therefore, a continual, train-based means to validate the data in the track database would be useful.
[0027] With reference to FIG. 3 , the track database can be validated in real-time using an RFID system. In particular, each of the trackside features 12 (corresponding to the trackside features stored in the track database) is provided with an RFID tag 20 . The RFID tag 20 is of standard mechanical and electrical construction including a tag body 22 , an antenna 24 embedded in or otherwise disposed on the tag body, memory 26 for storing data, and other conventional elements.
[0028] In one embodiment, the tags 20 are mounted on the trackside features 12 and programmed by a crew that is independent from the team involved with creating the track database. This independence greatly reduces the chances that a common error is made both in the track database and in the tag 20 .
[0029] For each tag 20 , the crew loads into the memory 26 a feature identifier that uniquely identifies the trackside feature 12 to which that tag will be or has been mounted, as well as the geographical coordinates of that trackside feature. The loading of the data into each tag 20 can occur prior to or when the tag is mounted on the trackside feature. The geographical coordinates for each trackside feature 12 can be obtained using a conventional GPS receiver, which are then loaded into the tag memory 26 . The loading of the data into tag memory can occur via wired or wireless means well known in the art.
[0030] The feature identifier in tag memory can be any identifier that uniquely identifies the feature, and in one embodiment matches the feature identifier stored in the track database for the corresponding feature. The feature identifier can be any number and combination of alphanumeric characters and symbols.
[0031] The geographical coordinates loaded into the tag memory 26 can be any coordinates that directly or indirectly indicate the geographical location of the feature. In one embodiment, the geographical coordinates are 3-D Cartesian coordinates (Earth Centered Earth Fixed) that indicate the location on Earth, which can also be represented as Geodetic coordinates by latitude, longitude and altitude of the trackside feature.
[0032] The RFID system also includes an RFID tag reader 30 that is used to read the data from the memory 26 of the RFID tags 20 on the trackside features. The tag reader 30 is mounted on the train at any location that is suitable for reading the tags 20 . In one embodiment, the tag reader 30 is mounted at or adjacent to the front or head end of the locomotive or other forwardmost unit of the train. The tag reader 30 is of conventional construction including an antenna 32 and suitable communication electronics.
[0033] The tag reader 30 is in communication with a control unit 34 that receives the tag data signals 36 from the tag reader 30 . The control unit 34 includes a microprocessor 38 that is programmed to take the data from the tag memory 26 and use that data to validate the data in the track database.
[0034] In one embodiment the RFID tags 20 are mounted on the trackside features 12 so that the tags 20 extend vertically. In addition, the reader 30 on the train is designed to have a wide vertical field of view and a narrow horizontal field of view in order to detect the trackside feature's passing when it is close to broadside to the locomotive.
[0035] With reference to FIG. 4 , in one process 40 the RFID tags 20 are installed on the trackside features 12 . Either prior to or after mounting the tags, the geographical coordinates and the unique feature identifier for that feature are loaded into the tag memory 26 .
[0036] In another part of the process, as the train moves down the track and passes one of the trackside features, the reader 30 reads the tag 20 on that trackside feature as indicated in box 42 . As the head end of the train sequentially encounters trackside features with tags, the reader 30 responds with an event time, and reads the geographical data (e.g. the 3-D Cartesian coordinates or the Geodetic coordinates latitude/longitude/altitude) and the unique feature identifier.
[0037] The train management system also determines the expected location of the train using data from the track database as indicated at box 44 . In this step, the head end LDU captures the instantaneous offset into track partition at that trackside feature, and computes equivalent geographic coordinates in the manner illustrated in FIG. 2 .
[0038] The data read from the RFID tag is then compared to the expected location data as indicated at box 46 . The train management system differences the LDU determined location at the event with the data read from the tag 20 . This can be simplistically stated as LAT/LON/ALT of the locomotive minus LAT/LON/ALT of the trackside feature. However, in actuality the Cartesian coordinate components would be individually differenced.
[0039] If the locomotive is navigating properly (e.g. not built up an offset error), and if the trackside features and track geometry model in the complex track database are correct for that partition, then the coordinates read from the RFID tag will be very close (for example under 3 meters, or even within 1-2 meters) to those computed by the train borne computer. This event would be given a pass. Small differences confirm performance of the train management system and data correctness in the track database. Therefore, the geographical coordinates need not be identical in order to determine that there is a match.
[0040] The unique identifier read from the RFID tag matching the track database feature identifier confirms the correct trackside feature known to be at this location.
[0041] Any errors in either the geographical coordinates or the unique identifier can be logged and sent to a central location, such as a train management system office, and the train can be dropped out of automatic control.
[0042] If there is a match of feature identifier and coordinate locations, that means, at that time and for that train, the LDU's computed offset into partition is correct, the underlying track database is correct (at that time), and the train's crew operational display is correctly showing the track line and trackside features (but not features ahead of it). This type of checking is temporal, not continuous, only occurring every 1 km or less, depending on trackside feature density.
[0043] In an alternate embodiment, one could verify the coordinates without verifying the identifier, and vice versa.
[0044] This described method of cross checking, being physically performed on the track, also has beneficial use as a way to verify proper database content for both the underlying track database, the data in the tag memory, and LDU navigation performance, after track physical maintenance and database updates are put in place. In other words, it is a good test and verification tool to be employed after track and data changes are implemented on the network.
[0045] In addition to or separately from the track database validation described above, the systems and methods described herein can be used for other train management purposes. For example, since the geographical coordinates of the trackside features are known and the time between two readings is known, reading the tags of two consecutive trackside features can be used to determine the rate of travel between the trackside features and thus as a check of the speed of the train.
[0046] In addition, although the systems and methods have been described above as employing a single tag reader on the train, a train can have multiple tag readers spread along the length of the train. Each tag reader can read the tag on the trackside feature as the train passes. Failure of a reader to read the tag can indicate a potential problem with the train, such as decoupling of cars of the train from the locomotive.
[0047] The examples disclosed in this application are to be considered in all respects as illustrative and not limitative. The scope of the invention is indicated by the appended claims rather than by the foregoing description; and all changes which come within the meaning and range of equivalency of the claims are intended to be embraced therein.
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Methods and systems are described that can be used to verify a track database of a train management system, for example that the track database has not been corrupted, built with critical errors, or is not being used properly by the software application. In one embodiment, radio frequency identification (RFID) tags are mounted on the trackside features contained in the track database. The tags contain data such as the geographical coordinates of the trackside features and a unique feature identifier that uniquely identifies the respective feature. As the train passes the trackside feature, a tag reader on the train reads the tag to gather the geographical coordinates and the feature identifier. The train management system then compares the geographical coordinates and/or the feature identifier from the tag with the expected geographical coordinates and/or the expected feature identifier in the track database.
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CROSS-REFERENCES TO RELATED APPLICATIONS
This application is a continuation of U.S. patent application Ser. No. 12/105,584, filed Apr. 18, 2008, now U.S. Pat. No. 8,235,920, which claims the benefit of U.S. Provisional Patent Application Ser. No. 60/913,050, filed Apr. 20, 2007, the entire contents of each of which are hereby incorporated by reference in this application.
STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
(NOT APPLICABLE)
BACKGROUND OF THE INVENTION
There is a need for support surfaces to provide a therapeutic vibrational action or force to a patient suffering from respiratory ailments. Percussors and vibrators are known to stimulate the expectoration of mucous from the lungs. Vibratory or undulating action applied to the body adjacent the thoracic cavity aids in postural draining or coughing up of sputum and thereby reduces the amount of mucous that lines the inner walls of the alveoli.
It is commonly regarded that vibrational therapy can provide both percussion and vibration. Vibration, for example, provides approximately 1 to 7 beats per second, while percussion typically provides 7 to 25 beats per second.
There are support surfaces on the market today that operate a mechanical or pneumatic external device that imparts the vibratory action. Others use many solenoid valves in combination to control and regulate flow, pressurizing and venting of the vibration air cells. Others use a cam action, large diaphragms or alternating action of relatively large size dual valves to move the air in and out of the vibration air cells.
All the current methods have extensive mechanical and electro-mechanical components such as valves, motors, lever arms, cams, large diaphragms, fluidic connections and the like. They also use finger shaped air cells for the vibratory air cells.
BRIEF SUMMARY OF THE INVENTION
In an exemplary embodiment, a vibration and modulation system is provided for an array of air cells. The vibration and modulation system includes an air source, a high-pressure reservoir in fluid communication with the air source, and at least one valve coupled between the high-pressure air source and the array of air cells. A control assembly is coupled with the at least one valve and selectively controls a position of the valve to effect a vibratory action in the array of air cells. The air source is preferably a pump, although other sources may be suitable. A size of the high-pressure reservoir is preferably determined based on a total volume of air required to inflate the air cell array to a minimum pressure.
The control assembly may include a pressure sensor in the high-pressure reservoir that triggers a position of the at least one valve according to a pressure in the high-pressure reservoir. Alternatively, the control assembly may include a check valve with a predetermined cracking pressure disposed between the high-pressure reservoir and the at least one valve. The predetermined cracking pressure is determined according to a desired frequency of vibratory action. In still another variation, the control assembly includes a timing circuit coupled with the at least one valve that controls a position of the at least one valve on a predetermined time interval. In still another alternative arrangement, the control assembly includes a pilot valve coupled with the at least one valve that enables high pressure fluid from the high-pressure reservoir to control a position of the at least one valve.
In one arrangement, the air source and the high-pressure reservoir are coupled with the at least one valve in parallel.
The system may additionally include evacuation structure coupled with the air cell array that enables quick deflation of the air cell array. In this context, the evacuation structure may comprise a vent on the at least one valve. The evacuation structure may additionally include a vacuum source coupled with the vent.
In another exemplary embodiment, a support surface includes an array of air cells, and the described vibration and modulation system coupled with the air cell array, where the vibration and modulation system effects vibratory action on the air cell array. Preferably, when deflated, the air cells are substantially flat. Each of the air cells may additionally include an air cell node including a foam insert disposed in an air sealable container.
In yet another exemplary embodiment, a vibration and modulation system for an array of air cells for use with a support surface includes an air source, a high-pressure reservoir in fluid communication with the air source, and a multi-position valve coupled between the high-pressure air source and the array of air cells. In a first position, the valve permits air to flow from the high-pressure reservoir to the air cells, and in a second position, the valve evacuates air from the air cells to atmosphere. A control assembly is coupled with the valve and selectively controls a position of the valve to effect a vibratory action in the array of air cells.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic diagram of a vibration and modulation system according to a first embodiment;
FIG. 2 is a schematic diagram of a second embodiment;
FIG. 3 is a schematic diagram of a system including a vacuum source for rapid evacuation of the air cells;
FIG. 4 shows an exemplary two-dimensional air cell array; and
FIG. 5 shows an exemplary three-dimensional air cell array.
DETAILED DESCRIPTION OF THE INVENTION
With reference to FIG. 1 , an exemplary embodiment includes an air source 12 , such as a pump, connected to a high-pressure reservoir 14 , connected to a valve 16 such as a 3-way solenoid valce. A connecting valve 18 connects to the air cells 20 used for vibration and percussion, and a vent port 22 is a vented to atmosphere, which vents the air cells 20 . The air cell array 20 includes small air cells, either generally flat when deflated (two-dimensional) or nodal cylinders or other shape (three-dimensional) connected together in a pattern.
The vibratory system of the described embodiments can be used and integrated into any support mattress system and hospital bed frame. Alternatively, the system can be a stand-alone system used on any patient on any hospital mattress and bed frame.
Reservoir
The reservoir 14 can be any soft sided or hard-sided container of any suitable shape. It is preferably large enough to contain enough pressurized fluid (air, water, etc.) to allow the air cells 20 to quickly inflate. The total volume of air required for the air cells 20 to inflate quickly to a minimum high pressure and the pressure levels in the reservoir 14 determines the reservoir size.
Air Source
The air source 12 can be any type of pump (compressor, diaphragm, rotary, etc.) that supplies a sufficient volume of air to keep the reservoir 14 full of pressurized fluid.
Frequency Control
The vibration or modulation frequency (beats/sec) is controlled either by pressure or by time.
Pressure Method
(a) In one arrangement, a pressure sensor transducer 24 senses the pressure in the reservoir 14 . At certain pressures, the transducer 24 sends a signal to the solenoid valve 16 for it to either open or close, thereby allowing filling of the air cells 20 or venting of the air cells 20 . By changing and setting the desired pressures, the frequency of the vibratory action can be controlled by the caregiver. (b) In another arrangement, a check valve 26 is connected between the high-pressure reservoir 14 and the solenoid valve 16 . Check valves have a set cracking pressure (i.e., the valves are held open when a certain pressure is maintained). When the pressure drops below that level, the valve 26 closes again. By choosing the desired check valve 26 with its predetermined cracking pressure, the frequency of pressure variations and therefore the frequency of vibratory action can be controlled.
Valves
There are two exemplary methods, both using valves, to control the high-pressure air filling the air cells 20 .
(a) Solenoid valves, such as a 3 -way solenoid valve 16 shown in FIG. 1 , allow the inlet port to pass air (from reservoir 14 ) to the exit port (to the air cells 20 ), and the vent port 22 allows air from the air cells 20 to vent to atmosphere. If the vent port 22 is open, the inlet port to the air cells is closed. The valve 16 opens and closes upon signals, for instance, from a timing circuit 28 . The valve 16 opens and closes its ports using electro-magnetic force or the like. The larger the required ports in the valve, the higher the wattage requirement of the valve. (b) Pilot valves (not shown) may also be suitable. Since the pressure is high from the reservoir 14 , a pilot valve may be used instead of the typical solenoid valve 16 . With this structure, the high-pressure fluid itself will move the valve instead of the electro-magnetic force or the like.
Timing Method
A timing circuit or a timing chip 28 can be connected to the solenoid valve 16 . The circuit 28 opens and closes the solenoid valves 16 , which in turn allows the air cells 20 to fill and then to vent within a set period. The timing circuit 28 can have either a fixed on/off period or could be programmed by the user through the use of microprocessors.
Pressure Reservoir
The utilization of a pressure reservoir 14 allows for a continuous supply of high pressure to be quickly released, via the valve 16 , to the air cells 20 , allowing very rapid inflation of the air cells 20 . The reservoir 14 avoids complete reliance on the pump 12 to rapidly fill the air cells. If a reservoir was not used, a significantly larger capacity pump would be required to guarantee a sufficient supply of air. An example of a suitable pump is a centrifugal pump known as “Windjammer” made by Ametek. This type of high volume but low pressure blower is widely used in the industry. The supplied air would be most likely be at a lower pressure than the reservoir 14 , but the larger capacity pump 12 would be needed to quickly inflate the air cells. Also, with lower pressure air directly from the pump 12 , the air cells 20 may not reach a high pressure within the short time frame, and this affects the quick venting required to provide the vibratory action. At lower pressures, the venting action would be slower. As can be seen, this high pressure reservoir vibration system is particularly useful in support surfaces that utilize a smaller piston or diaphragm pump with relatively low CFMs.
In a variation of the first embodiment, with reference to FIG. 2 , the reservoir 14 can have a parallel (Tee) connection 30 between the pump 12 and the valve 16 . This allows air to flow not only from the reservoir 14 , but also from the pump 12 at the same time. This variation might be used, for example, if the size of the reservoir 14 had to be limited.
Deflation of Air Cells
As previously mentioned, with a high-pressure reservoir 14 it is possible, in the described embodiments, to quickly deflate the air cells 20 simply by venting through the solenoid valve 16 . If large air cells are desired, or other conditions exist which inhibit the natural venting, however, a vacuum source 32 can be utilized to deflate the air cells. The vacuum source 32 is shown in FIG. 3 .
Air Cells
The air cells 20 used for inflation, otherwise known as bladders, have either a 2D or 3D configuration. For the two-dimensional variation, with reference to FIG. 4 , the cells are relatively small circles, oblongs, rectangles or squares. They are generally flat (2D) in the deflated condition. For example, a circular shape might have an OD of 3″ in the deflated condition. A multitude of these small shapes make up an array, with individual circles connected with tubing or passageways between the circles.
For the three-dimensional shape, with reference to FIG. 5 , each cell is a small node, something like a cylindrical canister. Again these nodes can be connected to form a nodal array as shown. An example of suitable construction is described in U.S. patent application Ser. No. 11/866,602, the contents of which are incorporated by reference. The nodes could have a foam insert 21 inside each one. A vacuum source is used to deflate each node. When the vacuum is turned off, the foam 21 expands and helps to re-inflate each node, causing the vibratory action.
Whether 2D or 3D, these cell shapes have less volume than the finger cells currently on the market. The smaller volume allows for a more effective and quick control of the air or fluid entering and leaving the air cell. The smaller the volume of the vibrating air cells, the better the percussion or vibration will be, i.e., more beats per second and at higher pressure.
The air cells can be constructed out of any suitable material such as urethane, supported urethanes, vinyl, and supported vinyl. The air cells are preferably sealed to form an airtight volume. The sealing process could be RF welding, heat or ultrasonic sealing, adhesive or other methods.
The vibratory air cells are placed under the patient's back around the chest area. They may be used alone or in conjunction with other support surfaces.
Comparison of Other Inventions
The exemplary embodiments described herein differ from others in that the reservoir 14 , or accumulator, is used that is at a pressure higher than atmosphere and higher than that developed by a relatively small pump. Typical pressures might be 1 to 8 psi. By utilizing a high-pressure reservoir 14 , smaller solenoid valves 16 can be used, which have smaller opening ports. The high pressure passed through the solenoid valve 16 allows the air cells 20 to inflate very rapidly and to a high pressure. Other systems use air directly from the air source, which passes through valves and then into the air cells. A high-pressure reservoir is not utilized.
While the invention has been described in connection with what is presently considered to be the most practical and preferred embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalent arrangements included within the spirit and scope of the appended claims.
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A vibration and modulation system is provided for an array of air cells. The vibration and modulation system includes an air source, a high-pressure reservoir in fluid communication with the air source, and at least one valve coupled between the high-pressure air source and the array of air cells. A control assembly is coupled with the at least one valve and selectively controls a position of the valve to effect a vibratory action in the array of air cells.
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CONTRACTUAL RIGHTS IN THE INVENTION
The United States has contractual rights in this invention pursuant to contract No. W-31-109-ENG-38 between the U.S. Department of Energy and the University of Chicago representing Argonne National Laboratory, and under Grant Number DE-FG02-86ER45229 between the U.S. Department of Energy and Northwestern University. The Aluminum Company of America, through award number PO TC924977TC, also sponsored research which led to this patent application.
This is a continuation of application Ser. No. 08/402,999 filed Mar. 10, 1995, now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to nanocrystalline materials and a method for producing nanocrystalline materials and more specifically this invention relates to nanocrystalline materials having components with predetermined sizes and in predetermined weight ratios that confer superior mechanical characteristics, and a method for producing these mechanically superior nanocrystalline materials.
2. Background of the Invention
The term nanocrystalline, or nanophase, materials refers to solids containing crystallites of approximately 1-100 nm in diameter. Much of the research to date on this relatively new class of materials has been aimed at elucidating the microstructure and properties of pure metals and oxides. The interest in these materials has stemmed from the fact that they are relatively easy to produce and useful as model systems. However, the development of a method to produce more complex multicomponent and multiphase nanocrystalline systems is of industrial significance. For example, there is industrial interest in the development of alloys of transition metals having high specific strengths that can be exploited in elevated temperature applications. The strengthening of these alloys can be attributed to a dispersion of second phase particles that inhibit dislocation motion. In order to produce alloys that are strong enough for current and future applications, the development of new synthesis techniques leading to materials with increased particle volume fractions is desired. It is also desired that these new materials exhibit grain size and phase stability at elevated temperatures.
Rapid solidification has been one method of developing alloys with refined microstructures and relatively large second phase volume fractions. Traditional internal oxidation methods create materials with hard ceramic (oxide) reinforcements embedded at the grain boundaries of larger softer crystals.
The conventional procedures outlined supra limit the concentration of minority phase in a multiphase alloy to that determined by the equilibrium phase diagram of the system in question. For example, the equilibrium solubility of Si in Cu is less than 15 atomic percent; therefore, synthesis of a Cu--SiO x two phase alloy by oxidation of the Si in a Cu--Si solid solution is limited to a maximum SiO x :Cu mole fraction corresponding approximately to this solubility limit. For analogous reasons, the volume fraction of desirable second phase particles in the case of rapidly solidified Al--Zr--V alloys is limited to approximately 0.10.
Procedures of first producing ultra-pure powders in separate batch processes further requires mixing these powders in an additional step prior to sintering. In as much as many of the elements comprising the powders are oxidizable at ambient oxygen concentrations, this mixing and sintering has to be performed under vacuum conditions.
Resistive heating, the conventional evaporation technique for synthesis of nanocrystalline metals, has limited potential for the production of multicomponent nanphase materials. For example, resistive heating does not provide the ability to evaporate a wide variety of materials having high melting points or low vapor pressures. Often, reactive gases can not be used in the process. Lastly, cleanliness of the process is sacrificed, in as much as resistive heating techniques thermally treat both the material to be evaporated and the surrounding structures, potentially leading to oxidation of the evaporation source and contamination of the nanophase powder.
As such, processes to more efficiently produce these materials continue to elude researchers. Prior to the instant teaching, production of nanophase materials has been developed (U.S. Pat. No. 5, 128,081) to produce single component systems. However, such processes require a second step to facilitate the subsequent oxidation of said single metal components.
A need exists in the art for a process for producing ultra-pure multi-component nanoscale materials in an efficient manner whereby multiple production processes are avoided and grain sizes are minimized. Any subsequent sintering processes also should be operable at room temperatures for selected alloys.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a process to produce multi-component and multiphase nanophase materials that overcomes many of the disadvantages of the prior art.
It is another object of the present invention to provide a process for producing multi-component and multiphase nanoscale materials. A feature of the invention is the use of electron beam evaporation to separately vaporize components. An advantage of the invention is that the ratio of elemental species within the composite can be varied by independently controlling the crucible dwell times during evaporation processes.
Yet another object of the present invention is to provide a gas condensation process for producing nanophase composites of specified elemental and phase compositions. A feature of the invention is the use of electron beam evaporation in a controlled atmosphere to independently vaporize elements and subsequently form oxides or nitrides of the elements in a single step if desired. An advantage of the invention is the production of composites having controllable mechanical properties that are characteristic of specific component ratios.
Briefly, the invention provides for a process for producing multicomponent and multiphase nanophase materials comprising supplying a controlled atmosphere, enclosing a plurality of elements in said controlled atmosphere, simultaneously evaporating the elements in said controlled atmosphere so as to vaporize the elements, allowing the now vaporized elements to mix with each other in the controlled atmosphere, condensing the now mixed elements, removing the condensed elements from the controlled atmosphere, and consolidating the condensed elements. The invention also provides for a multicomponent and multiphase nanocrystalline material of predetermined elemental and phase composition having component grain sizes of between approximately 1 nm and 100 nm. In this embodiment this material comprises a single element in combination with a binary compound. In more specific embodiments, the single element in this material can be a transition metal element, a non-transition metal element, a semiconductor, or a semi-metal, and the binary compound in this material can be an intermetallic, an oxide, a nitride, a hydride, a chloride, or other compound. In particular, the single element can be selected from titanium, iron, cobalt, nickel, iron, nickel, zinc, zirconium, palladium, silver, platinum, tungsten, molybdenum, chromium, magnesium, manganese, iridium, niobium, gold, copper, aluminum, silicon, and germanium. The binary compound can be selected from an intermetallic such as TiAl, Ti 3 Al, NiAl, Ni 3 Al, Al 3 Zr, TiSi 2 ,Ti 5 Si 3 , NiTi, MoSi 2 and Al 3 Ti or from an oxide or a nitride of an element such as titanium, iron, cobalt, nickel, copper, zirconium, palladium, silver or platinum.
BRIEF DESCRIPTION OF THE DRAWING
These and other objects and advantages of the present invention will become readily apparent upon consideration of the following detailed description and attached drawing, wherein:
FIG. 1 is a schematic diagram of a method for producing nanocrystalline materials, in accordance with the features of the present invention;
FIG. 2 is a graph depicting average grain sizes for components of nanocrystalline materials, in accordance with the features of the present invention; and
FIG. 3 is a graph depicting the relationship of grain size to hardness characteristics of nanocrystalline materials, in accordance with the features of the present invention.
FIGS. 4A, 4B and 4C are diagrammatic illustrations of methods for making multi-component materials.
DETAILED DESCRIPTION OF THE INVENTION
A new nanophase material preparation system has been developed, whereby electron beam heating is used to vaporize materials in inert or reactive gaseous environments. A wide variety of materials in nanophase form are produced with this system, and with minimum contamination. An exemplary list of materials includes, but is not limited to, transition group metals such as titanium, iron, cobalt, nickel, copper, zirconium, palladium, silver, platinum, and gold. Oxides that can be produced include, but are not limited to, ZrO 2 , Al 2 O 3 , TiO 2 , NiO, Y 2 O 3 and Y 2 O 3 --ZrO 2 . Intermetallic materials which can e produced from the method include, but are not limited to, TiAl, NiAl, Ni 3 Al, Al 3 Zr and alloys of aluminum and alloys of other metals, and composites of Cu and SiO x .
Besides enabling the production of pure metals, including refractory materials, the system is designed to produce alloys and multi-component materials by simultaneous evaporation of two or more elements. The electron beam position and dwell time are set by computer, thereby allowing for greater control of evaporation conditions. A key feature of the invention is that at least one additional component is added in a one-step process while under condensation conditions to form multi-component nanophase materials.
The invention also provides for the production of nanocrystalline multicomponent materials containing intermetallic and/or oxide particles to provide materials of enhanced hardness and thermal stability. The strength of these materials is superior to those composites that are currently commercially prepared using the processes outlined supra. The strength of the new materials also are superior to single phase nanophase materials.
The invented process combines a feature of simultaneous evaporation of selected materials in a closed, controlled environment, having a predetermined partial pressure of reactive gas such as oxygen, nitrogen, hydrogen, methane, chlorine, or ammonia, depending on the final product desired, said partial pressure selected based on the reactivities of the components to be reacted.
The materials to be mixed are first evaporated. Evaporation can be effected by a variety of heating means, including an electron beam, RF heating, plasma heating or laser beam irradiation. Sputtering also may be used to obtain vaporization.
Upon collision with gas molecules in the closed environment, the materials condense back into solids. If oxide production is desired, however, and if one of the evaporated materials (e.g. silicon) has a higher affinity for the reactive gas (e.g. oxygen) than another evaporated component (e.g. copper), then oxide (e.g. SiO x ) formation occurs without formation of oxides of the other component. The two types of particles (e.g. SiO x and Cu-metal) arethen collected and later sintered.
Simultaneous evaporation of desired nanophase metals provides complete homogenous mixture of the materials that leads to phase mixtures that are unattainable with prior methods. The concentration of minority phase in a multiphase alloy produced by this evaporation method is not limited by the equilibrium phase diagram of the system in question.
Uses of the invented materials are numerous. Nanocrystalline metal-metal oxide and/or metal-intermetallic composites such as Al--Al 3 Zr may be incorporated into aircraft or automobile structural components. These composite materials might also be used in elevated temperature applications such as turbine engines. Yet another application is coatings for cutting tools such as drill bits.
An exemplary device embodying the process is depicted in FIG. 1 as numeral 10. Generally, an inert gas condensation process with electron beam evaporation is used to produce nanocrystalline materials. A voltage and current-controlled electron beam 22, generated in a 2×10 -6 Pa vacuum from a tungsten filament 12, is rastered on a millisecond time scale among several materials contained in separate crucibles 17, said crucibles integrally molded with a water-cooled copper hearth 16. The electron beam 22 is focused and translated by three pairs of focusing and deflection coils 24 longitudinally disposed along the differentially pumped column 26 leading from the tungsten filament 12 to the main chamber 14. The chamber is back-filled with a predetermined pressure of ultra-high purity inert gas, or predetermined partial pressures of reactive gas. Pressures can range from between approximately 0.1 torr and 2.0 torr and typically about 0.3 torr.
Upon evaporation, the materials travel as an evaporant plume by convection and adhere to a liquid nitrogen cooled plate or finger 18 to be collected as ultra-pure powders. These powders are then scraped into a funnel and transported under vacuum to a suitable consolidation unit 20 where the powders are compressed at about 1.4 GPa into dense (70-95+% of theoretical density) disks. Compaction is performed at a variety of temperatures, and more conveniently at room temperature for some materials, using the compaction unit 20. Sinter temperatures can range from room temperature (26° C.) to 400° C., depending on the material. For example, while aluminum and copper sinter at very low temperatures, zirconium-containing materials often require temperatures of approximately 300° C. A more detailed discussion of the inert gas condensation (IGC) process with electron beam heating is found in M. N. Rittner et al., Scripta Metall. 31,7, 841 (1994), incorporated herein by reference.
The above-described inert gas condensation method with electron beam heating has been used by the inventors to synthesize a myriad of different types of nanocrystalline multi-phase samples.
EXAMPLE 1
Nanocrystalline aluminum-zirconium alloys of various zirconium concentrations have been produced. These materials have been characterized using x-ray diffraction, Rutherford backscattering (RBS), and various microscopy techniques, including transmission electron microscopy (TEM), scanning electron microscopy (SEM) and x-ray energy dispersive spectroscopy (EDS). The hardness and thermal stability of the nanocrystalline Al--Zr alloys also have been investigated by Vickers microhardness measurements and TEM experiments at room and elevated temperatures.
The alloys contain nanocrystalline intermetallic Al 3 Zr uniformly embedded within samples composed primarily of nanocrystalline aluminum. The identification of the Al 3 Zr (cubic) structure as a second phase in these materials is significant because the particles retain small diameters (of approximately 10 nm)in conventional aluminum alloys even after exposure to 425° C. (0.75 Tm of aluminum for 1200 hours. The presence of this well-dispersed phase demonstrates that the aluminum and zirconium are mixing and reacting during the synthesis process, despite non-simultaneous evaporation and cooling, or condensation, of the two species. The elements are separated by approximately 1 cm in different crucibles of the hearth and the evaporated atoms have mean free paths far shorter than this distance; thus it is clear that pure aluminum and pure zirconium clusters form initially and subsequently react in the solid state to form Al 3 Zr. The quantity of this phase produced is a function of the amount of zirconium evaporated during the synthesis process, and thus can be controlled.
FIG. 2 depicts the average grain sizes and grain size ranges for the aluminum matrix in nanocrystalline Al--Zr for a number of samples. The average grain size of all the specimens shown in FIG. 2 is <˜20 nm, and is found to correlate with the evaporation rates of the component materials, as observed through changes in the chamber pressure during the evaporation process. The higher the evaporation rate, the larger the average grain size of the resulting samples. Thus, the average grain size and grain size distribution of the nanocrystalline samples can be controlled via adjustments in the machine variables (e.g., electron beam current, voltage, focus, and heating time) that affect the evaporation rates.
Vickers microhardness data is illustrated in FIG. 3. A 100 gram load was applied for 20 seconds for a total of 10-20 measurements per sample. Up to six-fold increases in hardness have been found in the nanocrystalline Al--Zr alloys compared to coarse-grained aluminum, and up to approximately two-fold increases in hardness are observed when comparing multiphase Al--Zr nanocrystalline samples with nanocrystalline aluminum samples that do not contain zirconium. FIG. 3 illustrates that zirconium additions to nanocrystalline aluminum contribute to an increase in material hardness, as does the grain size reduction inherent in these materials.
It has also been found that significant grain coarsening (to 100+) nm at room temperature occurred in samples containing less than approximately 2 weight percent of zirconium. After being held at room temperature for approximately one year, samples having on average 13 and 35 weight percent of zirconium showed no signs of grain growth. Conversely, a nanocrystalline aluminum specimen containing no zirconium and about 1 weight percent of oxygen coarsened considerably with some grains growing to as large as 10--20 times their initial average size of 16 nm.
The nanocrystalline Al--Zr samples have exhibited stability at elevated temperatures as well, as demonstrated by preliminary TEM annealing experiments. Two samples containing on average 13 and 18 weight percent of zirconium retained their nanostructures during in-situ heating experiments to 0.72 and 0.79 Tm of aluminum. The observed stability is attributed to the presence of the Al 3 Zr cubic phase, although pores and any impurities (such as oxides) may also contribute to coarsening resistance.
EXAMPLE 2
Nanocrystalline materials composed of copper, silicon, and oxygen were produced. In this instance, copper and silicon are evaporated simultaneously in a controlled mixture of helium and oxygen, such that the partial pressure of oxygen is sufficient to oxidize the silicon but not the copper.
Gas condensation in a mixture of inert and reactive gases is a novel process, as is the idea of selective oxidation of one component when evaporating multiple components. In general, at least one of the phases will have grain sizes of between 1 nm and 100 nm. More commonly, all metal and oxide phases are to exhibit such nanoscale (1-100 nm) grain sizes. In this instance, the resulting samples contain nanocrystalline copper and nanocrystalline oxidized silicon.
While increased Si solubility in Cu is an advantage to the invention, the materials made by the invented process are not dependent on silicon solubility in Cu. Thus, the inventors can fabricate Cu--SiO x nano-composites such that the SiO x phase accounts for any (0-100) weight percentage. Traditional internal oxidation treatments will only allow for an oxide concentration of not more than about 15 weight percent for this system. For other systems, the upper limit on minority phase concentration can be even lower when prepared via internal oxidation.
These materials have great technological potential due to composite reinforcement strengthening. Hard particles (the oxide) in a softer matrix (the metal) resist dislocation motion in materials. Since dislocation motion is associated with deformation in metals, hard particles can make metals harder and stronger. Also, demands for new materials often call for maintenance of good mechanical properties at high- or elevated temperatures. Many enhanced properties are due to a specific grain size and grain structure. Since higher temperatures and/or high deformation encourage grain growth, recrystallization, and modification of grain size, resistance to these internal changes is desirable. Hard-phase reinforcements retard grain growth.
For example, fine-grained, multiphase materials can exhibit superplastic deformation at certain temperatures and strain rates. Such materials are able to be deformed to strains as high as 6000 percent, far larger than for typical deformation processes. Such properties are crucial for advanced formation of many airplane parts that must be light and strong. Many materials that hold potential for superplastic deformation are not useful because grain growth occurs during deformation. This change in structure retards superplasticity. The process described in this example holds promise as a method for creating the multiphase, nanoscale structure necessary for stable superplastic deformation.
This new processing technique is an improved alternative to the traditional internal oxidation processes for making metal-oxide composites, particularly where higher oxide concentrations are desired.
Oxidation of one of the components (e.g. Si) is achieved by the introduction of a controlled partial pressure of oxygen into the system during the evaporation. Since Si is expected to oxidize at oxygen partial pressures of 10 -6 torr or less, 10 -6 torr was the lower limit on the oxygen partial pressure. Pressures higher than 10 -3 torr will oxidize the copper, which is not desired. A precision leak valve is used to introduce between 5×10 -5 and 5×10 -4 torr of oxygen. This method, illustrated in FIG. 4A, can be used to selectively oxidize any component as long as the component has a greater affinity for oxygen than any components that are not to be oxidized. Another method, illustrated in FIG. 4B, for oxidizing the second phase comprises first collecting the nanoparticles on the cold finger, and then allowing the optimum partial pressure of oxygen into the system. Yet another oxidizing method is incorporating a traditional internal oxidation treatment whereby nanocrystalline powders such as Cu and Si, first collected on a cold plate are compacted into a disc, with said disc then embedded into a Cu--Cu 2 O substrate to be heated in an inert atmosphere. This internal oxidation method is illustrated in FIG. 4C.
Higher oxide concentrations are technologically useful for purposes of increasing strength and hardness. Also, as the oxide concentration approaches 50 volume percent, cermet strengthening begins to take effect. Grain sizes for consolidated Cu--SiO x samples were 16-20 nm as calculated by analyzing peak broadening from high angle x-ray diffraction experiments. Grain sizes for unconsolidated powders were found to lie in the 5-20 nm range as measured by transmission electron microscopy in both bright- and dark-field modes.
The silicon content was measured to be 5-8 weight percent by EDS. Since the EDS detector has a thin window, oxygen is detectable. The oxygen concentration was found to be 11-13 weight percent. Since the peak positions of x-ray diffraction line scans showed only peaks of pure copper and the samples appear metallic with a copper hue, it is evident that the copper was not oxidized. The silicon oxide may be present in the amorphous state.
Hardness values averaged 2.4-2.8 GPa, larger than the 2.1-2.5 GPa of pure nanophase copper. Compositional data imply a hardness correlation with Si and O content. Sample densities were 6.8-7.6 grams/cubic centimeter. This range corresponds to 86-97 percent of the calculated theoretical values for Cu--SiO x .
As with SiO x , similar limited second phase concentrations have heretofore existed for many other commercially important alloy systems. The invented process provides a method to overcome these limitations, with the inventors applying their partially inert-partially reactive gas condensation technique to produce still other nanophase powders. Titanium and zirconium are other choices. The resulting oxides of Ti could be TiO, TiO 2 , TiO x , or any other stoichiometry or combination. Likewise, the resulting oxides of zirconium could be ZrO, ZrO 2 , ZrO x --Al 2 O 3 , or any other stoichiometry. In fact, any material may be used as the oxide phase in this method, as long as its affinity for oxygen is greater than that of the other metal phase. For example, TiO 2 or Al 2 O 3 powders are formed by evaporating Ti or Al in 0.2 torr of oxygen. In both cases, low temperature phases (the anatase phase of TiO 2 and the gamma phase of Al 2 O 3 ) form with a particle size of less than 5 nm. Nitrides such as Fe 4 N, and NbN also have been prepared in this system by evaporating metals in nitrogen gas.
Likewise, any material may be used as the non-oxidize (metal) phase as long as its affinity for oxygen is less than that of the material to be oxidized. Iron, silver, and gold are all examples of metal phase possibilities.
While the invention has been described with reference to details of the illustrated embodiment, these details are not intended to limit the scope of the invention as defined in the appended claims.
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A process for producing multi-component and multiphase nanophase materials is provided wherein a plurality of elements are vaporized in a controlled atmosphere, so as to facilitate thorough mixing, and then condensing and consolidating the elements. The invention also provides for a multicomponent and multiphase nanocrystalline material of specified elemental and phase composition having component grain sizes of between approximately 1 nm and 100 nm. This material is a single element in combination with a binary compound. In more specific embodiments, the single element in this material can be a transition metal element, a non-transition metal element, a semiconductor, or a semi-metal, and the binary compound in this material can be an intermetallic, an oxide, a nitride, a hydride, a chloride, or other compound.
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FIELD OF THE INVENTION
[0001] The present invention relates to a work tray apparatus, and more specifically, but not by a work of limitation, to a work tray adaptable to be configured to a plurality of sloped surfaces such as but not limited to roofs. The work tray includes a mechanism which allows the work tray to be oriented in a substantially level manner so as to facilitate retention of the items placed therein while the work tray is engaged with the sloped surface.
BACKGROUND
[0002] Individuals and/or professionals routinely find it necessary to engage in a repair or other similar task that requires working on a sloped surface, such as on the rooftop of a house. Facilitating the repairs of water leaks or painting are just a few of the many tasks that require an individual to work from the rooftop of a house.
[0003] One problem with performing repairs or painting from a sloped surface such as a rooftop is that the required tools such as but not limited to wrenches, brushes and paint cans slide down and fall to the ground when placed on the sloped surface. This requires that the individual either have a belt that can accommodate all the tools necessary to perform the desired task or that the individual be assisted by another person that is responsible for the tools or paint.
[0004] Another problem specifically relates to painting surfaces while positioned from or working on a rooftop. Paint containers that are full of paint can not be placed on the roof as the container will either slide down the roof and fall to the ground or the container will lose some of the paint contained therein as placing the container on a sloped surface causes the paint to spill from the container.
[0005] Accordingly there is a need for a work tray that can accommodate a plurality of different type of tools and containers such as but not limited to paint cans, and that can be adjusted to create a level surface so that tools and paint can contained therein remain secure when the work tray is engaged with a sloped surface. Furthermore, at least a portion of the work tray should be coated with a material or be designed so as to inhibit sliding of the tray.
SUMMARY OF THE INVENTION
[0006] It is the object of the present invention to provide a container that is adjustable in order to provide a level surface for retaining items therein such as but not limited to paint cans and tools while the container is engaged with a sloped surface such as but limited to a rooftop.
[0007] It is another object of the present invention to provide a container that can adjust to a plurality of sloped surfaces and maintain the container in a level position.
[0008] Yet another object of the present invention to provide a container that is adjustable in order to provide a level surface that also includes a method of securing the work tray upon engagement with a sloped surface.
[0009] It is a further object of the present invention to provide a container that can be adjusted to provide a level working surface while engaged with a sloped surface that is lightweight and inexpensive.
[0010] To the accomplishment of the above and related objects the present invention may be embodied in the form illustrated in the accompanying drawing. Attention is called to the fact that the drawing is illustrative only. Variations are contemplated as being a part of the present invention, limited only by the scope of the claims.
BRIEF DESCRIPTION OF THE DRAWING FIGURE
[0011] A more complete understanding of the present invention may be had by reference to the following Detailed Description and appended claims when taken in conjunction with the accompanying Drawing wherein:
[0012] FIG. 1 is a perspective view of an embodiment of the present invention.
DETAILED DESCRIPTION
[0013] Referring now to the embodiments in FIG. 1 and wherein the various elements depicted therein are not necessarily drawn to scale, there is illustrated a work tray 100 constructed according to the principles of the present invention.
[0014] The work tray 100 comprises a storage compartment 10 generally hollow and rectangular in shape. The storage compartment 10 has four walls 20 and a bottom 15 configured to define an interior volume of the storage compartment 10 and an opening 17 at the top of the storage compartment 10 . The four walls 20 and bottom are constructed of plastic or other suitable rigid material such as but not limited to aluminum. The storage compartment 10 is configured to receive objects therein such as but not limited to paint cans or tools. Although it is shown as one generally rectangular compartment, it is further contemplated within the scope of the present invention that the storage compartment 10 could consist of a plurality of different sized compartments adapted for holding specific objects. More specifically but not by way of limitation, the storage compartment 10 could have disposed therein an additional wall generally annular in shape and being of an appropriate diameter to receive a standard one gallon paint can therein.
[0015] Although no specific measurement is required for the storage compartment 10 , good results have been achieved with a storage compartment that is approximately twenty inches in length and eighteen inches in width. Although no specific measurement is required for the height of the walls 20 , good results have been achieved with walls 20 that are approximately two inches in height. Those skilled in the art will recognize that numerous configurations using a plurality of wall configurations could be used in place of and/or in conjunction with the configuration of the walls 20 described herein to achieve the functionality of the storage compartment 10 as described herein. Those skilled in the art will recognize that although the storage compartment 10 illustrated is generally rectangular in shape, it is further contemplated within the scope of the present invention that numerous different shapes of the storage compartment 10 could be used in place of and/or in conjunction with the shape illustrated to achieve the functionality suggested herein of the storage compartment 10 .
[0016] Pivotally mounted on opposing side walls 55 and adjacent thereto is the first component of the level assembly 60 , a pair of pivot arms 25 . The pivot arms 25 are generally flat and rectangular in shape and constructed of a suitable rigid material such as but not limited to plastic or aluminum. The pivot arms 25 have a first end 26 that are mounted approximately in the middle of each of the side walls 55 with an attachment mechanism 50 . The attachment mechanism 50 rotatably secures the pivot arms 25 in a multiplicity of positions with an approximate range of one hundred and eighty degrees of motion with respect to the bottom 15 of the storage compartment 10 . This allows a user to secure the pivot arms 25 within a range including a first position generally extending downward from the bottom 15 of the storage compartment 10 to a second position wherein the pivot arms 25 are generally parallel with the side walls 55 . In the second position, the second end 27 of the pivot arms 25 are adjacent to and parallel with the front wall 40 . The pivot arms 25 must be of sufficient length whereby in the second position the second end 27 of the pivot arms 25 extends beyond the front wall 40 . The pivot arms 25 can be secured at any point within this range by the attachment mechanism 50 in order to position the work tray 100 in a level manner when placed on a sloped surface. The attachment mechanism 50 is constructed of a conventional wingnut and bolt with a lock washer to prevent the pivot arms 25 from slipping once secured in a desired position. Those skilled in the art will recognize that numerous conventional mechanical fasteners could be utilized in place of and/or in conjunction with the attachment mechanism in order to achieve the desired functionality suggested herein.
[0017] Contiguous with the second end 27 of each pivot arm 25 and integrally formed therewith is the support arm 30 . The support arm 30 is intermediate of each second end 27 of opposing pivot arms 25 . The support arm 30 is generally perpendicular with the second end 27 of each pivot arm 25 being flat and rectangular in shape and manufactured from the same suitable rigid material as the pivot arms 25 . The support arm 30 provides support for the storage compartment 10 upon placement of the work tray 100 on a sloped surface. The support arm 30 swings beneath the plane of the bottom 15 to engage with the sloped surface underneath the work tray 100 . Upon engagement with a sloped surface the leveling assembly 60 can be secured in a plurality of positions that will allow the user to position the bottom 15 of the storage compartment 10 in a generally level manner. This will allow objects placed therein to remain in position regardless of the slope of the surface upon which the work tray 100 has been placed, such as but not limited to a rooftop.
[0018] The support arm 30 has a coating 35 substantially disposed thereon. The coating 35 is manufactured from conventional rubber or plastic and is designed to prevent the support arm 30 from slipping on the sloped surface once the leveling assembly 60 has been secured in the desired position to place the bottom 15 of the storage compartment 10 in a generally level manner. Although a coating 35 to prevent slippage of the leveling assembly 60 is shown in the illustration submitted herewith, it is further contemplated within the scope of the present invention that the support arm 30 could be configured in numerous configurations to prevent slippage. More specifically but not by way of limitation, the support arm 30 could further be comprised of a plurality of teeth integrally formed along the bottom to engage with the sloped surface and prevent slippage of the work tray 100 upon placement in a level position.
[0019] Those skilled in the art will recognize that numerous different shapes of the leveling assembly 60 could be used in place of and/or in conjunction with the shape suggested herein. More specifically but not by way of limitation the leveling assembly could be constructed of an aluminum flat bar. Although the leveling assembly 60 is shown with two pivot arms 25 and a support arm 30 mounted therebetween, it is further contemplated within the scope of the present invention that the leveling assembly 60 could consist of a single pivot arm 25 attached to the work tray 100 with a support arm 30 perpendicularly secured to the pivot arm 25 .
[0020] Mounted opposite the front wall 40 is the rear wall 45 . The rear wall 45 is integrally formed with the bottom 15 and adjacent side walls 55 . The rear wall 45 is configured in a manner upon where the angle of configuration is generally 90 degrees with respect to the bottom 15 and side walls 55 .
[0021] It is further contemplated to be within the scope of this invention that a small level could be either integrated with one of the walls 20 , or could be removably attached with a clip or the like. The small level would ensure that work tray 100 is positioned level during use.
[0022] Referring to the drawing submitted herewith, a description of the operation of the work tray 100 is as follows. In use, the user will transport the work tray 100 to the desired work location such as a rooftop. The user will then place the rear wall 45 generally adjacent to the rooftop. The user then releases the attachment mechanism 50 and engages the support arms 30 of the leveling assembly 60 in a position such that the bottom 15 of the work tray is configured in a generally level manner. Once the desired level position has been achieved, the user then secures the pivot arms 25 of the leveling assembly 60 to prevent the leveling assembly 60 from moving with the attachment mechanisms. The design and/or coating 35 of the support arm 30 facilitates the prevention of slippage of the work tray 100 on the rooftop. The user then places the desired objects such as paint cans or tools into the storage compartment 10 . After performing the desired task, the user will repeat this process in a second desired location on the rooftop.
[0023] In the preceding detailed description, reference has been made to the accompanying drawings that form a part hereof, and in which are shown by way of illustration specific embodiments in which the invention may be practiced. These embodiments, and certain variants thereof, have been described in sufficient detail to enable those skilled in the art to utilize the invention. It is to be understood that other suitable embodiments may be utilized and that logical changes may be made without departing from the spirit or scope of the invention. The description may omit certain information known to those skilled in the art. The preceding detailed description is, therefore, not intended to be limited to the specific forms set forth herein, but on the contrary, it is intended to such alternatives, modifications, and equivalents, as can be reasonably included within the spirit and scope of the appended claims.
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A portable work tray designed to receive objects therein whereby the tray has a leveling assembly operatively connected thereto to allow the tray to be placed in a generally level manner upon engagement with a sloped surface. The tray includes four walls and a bottom with a pair of pivot arms oppositely mounted along two of the walls. Intermediately mounted to the pivot arms distal to walls is a support arm. The support arm has substantially disposed thereon a coating and/or a serrated edge to prevent the tray from traversing down the sloped surface.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention concerns a powdered tea concentrate, a method for foaming the concentrate when dispersed in water and a delivery system for providing the resultant foamed tea product.
2. The Related Art
Teas are considered to be elegant beverages. They can be served hot or cold. Additional ingredients are sometimes incorporated into the beverage. Sweetener is most prominent. Sometimes a creaming agent and even spices are blended into the beverage. One example is chai tea which is a combination of tea extract, dairy or non-dairy creamer and spices such as cardamon, cinnamon, ginger, black pepper and even vanilla.
Some of the aforementioned beverages froth slightly when initially prepared. Foam is found in a number of beverages. These include beer, malteds and cappuccino. Consumers consider the frothed portions of these products to at least some extent enhance their digestive pleasure. A need exists for more exciting tea-based drinks and desserts; foamed products may answer such need.
Accordingly, it is an object of the present invention to provide a tea-based product sporting a head of foam.
Another object of the present invention is to provide a quick delivery system for preparing whipped or foamed tea-based beverages.
Still another object of the present invention is to provide a method and apparatus for delivering foamed tea-based beverages of improved physical stability and taste characteristics.
SUMMARY OF THE INVENTION
A foamed tea beverage delivery system is provided which includes:
i) a powdered tea composition including:
a) a powdered tea;
b) a creaming agent for whitening the beverage; and
c) a sweetening agent to increase sweetness of the beverage;
ii) a dispenser which includes:
a) a housing;
b) a hopper for the powdered tea composition, the hopper being positioned within the housing;
c) a water inlet into the housing;
d) a mixing chamber;
e) a rotating impeller functioning to aerate the beverage, the impeller spinning within the mixing chamber; and
f) conduits for delivering the powdered tea and water from respective hopper and water inlet into the mixing chamber.
Furthermore, a method for foaming tea beverages is provided which includes the steps of:
i) charging a hopper of a beverage dispensing machine with a powdered tea composition, the composition including powdered tea, a creaming agent for whitening the beverage and a sweetening agent;
ii) delivering a measured charge of powdered tea composition and water to a mixing chamber of the dispenser;
iii) aerating contents of the mixing chamber by activating an impeller to whip the powdered tea composition and water together to obtain a foamed tea beverage;
iv) discharging from the mixing chamber the foamed tea beverage; and
v) receiving the discharged foamed tea beverage in a receptacle outside the machine.
Also provided is a foamed tea beverage exhibiting a foam head maintaining a height above a liquid level of the beverage greater than 1 cm, preferably greater than 2 cm, optimally greater than 3 cm for at least two minutes after being dispensed, the beverage being generated from a combination of water and powdered tea composition comprising:
a) a powdered tea;
b) a creaming agent for whitening the beverage; and
c) a sweetening agent to increase sweetness of the beverage.
DETAILED DESCRIPTION OF THE DRAWINGS
Further objects, features and advantages of the present invention will become more evident through consideration of the following drawings in which:
FIG. 1 is a front perspective view of a dispenser for delivering foamed tea products according to the present invention;
FIG. 2 is a cross-sectional view of the dispenser taken along 2--2 of FIG. 1; and
FIG. 3 is an expanded view of the materials flow system from powder to foamed tea shown in frontal view by FIG. 2.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 illustrates a countertop dispenser for preparing the foamed tea products of the present invention. The dispenser includes a housing 2, a set of four hoppers 4 storing dry powdered tea concentrate, a water inlet 6 delivering water into the housing, and a materials flow system 8 to combine powdered concentrate with water. Access to the hoppers 4 for purposes of refilling dry powdered concentrate into the hopper is facilitated by a door 10 pivotable along hinges 12. Along the front of the door is a panel 14 with push-buttons 16 which activate transfer of a pre-set powdered tea concentrate charge and water into a mixing system. Power control 18 and power light 20 operate to heat the water, activate drive motors and indicate readiness of the system.
FIGS. 2 and 3 best illustrate the tea beverage preparation materials flow system. Pressure on a tea beverage type selection button 16 initiates a drive motor to turn for a pre-set number of revolutions a slip coupling 5 which then rotates auger 7. Coupling and auger are positioned at a lower end of hopper 4. Rotation of the auger causes delivery of a pre-set amount of powdered tea concentrate from hopper 4 sequentially through an L-shaped diverter tube 9, a cover conduit 11 having a vapor exhaust outlet 22, and then a pre-mix bowl 24. Water from the inlet 6, which has been preheated within housing 2 is dispensed through conduit 26 in measured amount into bowl 24. Upon combination the charge of powdered concentrate/hot water is directed into mixing chamber 28. Sensors note the charge in the mixing chamber and activate a motor 29 rotating a motor shaft 30 which connects via a backing plate and coupling 31 to an impeller shaft 32 terminating in an impeller 34. Thereby the spinning blades of the impeller 34 rapidly mix the charged ingredients. Subsequent to a predetermined mixing time, the resultant hot foamed tea product is dispensed through nozzle tube 36 whose end protrudes through the housing. A cup or other receptacle 38 is placed beneath tube 36 receiving product in a ready to serve state.
Normally the dispenser will provide a hot foamed tea beverage. If a foamed iced version is desired, essentially identical equipment can be employed, except that cold water will replace the hot and ice can be supplied subsequent to dispensing into receptacle 38.
Dispensers of the present invention have been employed for purposes other than delivering foamed tea. These dispensers can be purchased from Cecilware Corporation, Long Island City, N.Y.
Powdered tea concentrates of the present invention include three essential elements. These are powdered tea, a sweetening agent and a creaming agent. Tea solids will be present in amounts from 0.01 to 2%, preferably from 0.04 to 1%, optimally from 0.10 to 0.6% by weight of the powdered concentrate. The term "tea solids" as used herein is defined as solids extracted from tea materials. Extraction is generally achieved through steeping of tea leaves which may be black, green or oolong type. Advantageously at least a portion of the tea solids are green tea having not undergone any fermentation of the leaves as occurs with the black variety.
Sweetening agents may be selected from mono- and di- saccharides. These include sucrose, fructose, dextrose, maltose, lactose and invert sugar. Synthetic substitutes may also be utilized either alone or in combination with the saccharides. These substitutes include aspartame, saccharin, cyclomate and acetosulfam-K. Amounts of the sweetening agent may range from 0.01 to 30%, preferably from 1 to 20%, optimally from 5 to 15% by weight of the powdered concentrate.
Creaming agents for whitening the foamed tea product are also included within the powdered concentrate. Typical creaming agents include yogurt, whey, non-fat dry milk (NFDM) and non-dairy creamers such as partially hydrogenated coconut or soybean oils. Most preferred is non-fat dry milk because it also functions to improve foam in the final tea product. Amounts of the creaming agent may range from 0.1 to 30%, preferably from 1 to 20%, optimally from 5 to 15% by weight of the powdered concentrate.
A variety of flavors will also be included in the powdered concentrate. Illustrative but not limiting examples include such flavors as chai, Irish creme, hazelnut, chocolate, amaretto, vanilla, butter and mixtures thereof. Amounts of the flavor may range from 0.01 to 5%, preferably from 0.1 to 2%, optimally from 0.15 to 0.8% by weight of the total concentrate.
Spices may also be included within the powdered concentrate. Examples include cardamom, cinnamon, allspice, ginger, black pepper, cloves, nutmeg and mixtures thereof. Amounts of the spices may range from 0.05 to 5%, optimally from 0.1 to 2% by weight of the powdered concentrate.
Polysaccharide thickeners may optionally be present. Examples include sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, xanthan gum, alginate, carageenan, pectin, gum arabic, guar gum and mixtures thereof. Amounts of the thickener when present may range from 0.01 to 2%, optimally from 0.2 to 0.6% by weight of the powdered concentrate.
The following examples will more fully illustrate the embodiments of this invention. All parts, percentages and proportions referred to herein and in the appended claims are by weight unless otherwise indicated.
EXAMPLE
Illustrative powdered tea concentrates for use in the present invention are described in the Table.
TABLE__________________________________________________________________________ IRISH FRENCHINGREDIENT CREME VANILLA AMARETTO HAZELNUT CHAI__________________________________________________________________________Sugar 13.38 13.40 13.49 13.42 13.70NFDM 10.40 9.79 10.60 10.40 10.53Tea Flavor 0.12 0.12 0.12 0.12 0.12Kenyan Tea 0.46 0.46 0.46 0.46 0.46Dark Green Tea 0.04 0.04 0.08 0.10 0.04Irish Creme Flavor 0.66 0.00 0.00 0.00 0.00Cream Flavor 0.14 0.00 0.08 0.04 0.12Hazelnut Flavor 0.00 0.00 0.00 0.46 0.00Chocolate Flavor 0.00 0.00 0.00 0.20 0.00Amaretto Flavor 0.00 0.00 0.37 0.00 0.00Vanilla Flavor 0.00 0.80 0.00 0.00 0.00Ethyl Vanillin 0.00 0.55 0.00 0.00 0.00Butter Flavor 0.00 0.04 0.00 0.00 0.03Chai Flavor 0.00 0.00 0.00 0.00 0.20Total (g) 25.20 25.20 25.20 25.20 25.20__________________________________________________________________________
Numbers in the Table reflect the gram weight per serving of finished foamed tea product. In the above Examples, 25.20 grams of powdered tea concentrate was mixed with 74.80 grams of hot water in an apparatus as described above and shown in FIGS. 1-3. Each of the frothed hot tea products exhibited an excellent head of foam.
The foregoing description and examples illustrate selected embodiments of the present invention. In light thereof variations and modifications will be suggested to one skilled in the art, all of which are within the spirit and purview of this invention.
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A powdered tea concentrate, method for foaming the concentrate dispersed in water and a delivery system are provided to obtain a resultant foamed tea product. The powdered tea concentrate includes tea solids, sweetening agent and creaming agent. Delivery of foamed tea beverage is through a dispenser that includes a housing, a hopper for the powdered tea concentrate, a water inlet into the housing, a mixing chamber with an aerator mechanism and conduits for delivering the concentrate and water from respective hopper and inlet into the mixing chamber.
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BACKGROUND OF THE INVENTION
The invention concerns new acyl ureas, insecticides containing these compounds as well methods for their production.
1-acyl-3-phenylurea with insecticidal activity is already known from German Patent DE-OS No. 2 123 236. Their activity is, however, not always satisfactory.
SUMMARY OF THE INVENTION
It is therefore the object of the present invention to provide an insecticide which controls insects more successfully than the known compounds.
This object is attained according to the present invention by an insecticide characterized by a content of one or more compounds of the general formula ##STR2## in which R 1 is halogen or C 1 -C 6 -alkyl, R 2 is hydrogen or halogen, R 3 is hydrogen, halogen or methyl, R 4 is hydrogen, halogen or methyl, and R 5 , R 6 and R 7 are the same or different and are hydrogen, C 1 -C 6 -alkyl or aryl.
The designation C 1 -C 6 -alkyl encompasses, for example, the radicals methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl and hexyl.
Aryl includes, for example, phenyl or substituted phenyl, such as chlorphenyl, and halogen represents fluorine, chlorine, bromine or iodine.
The compounds according to the present invention display in surprising manner an insecticidal activity superior in comparison to the known structurally analogous active agents, or other advantages with regard to the control of various determined insects.
An outstanding selective insecticidal activity is displayed by the compounds according to the present invention against significant harmful insects, in particular those belonging to the classes Diptera, Coleoptera, as well as Lepidoptera.
The use of the compounds according to the present invention can follow in concentrations of about 0.0005 to 5.0%, preferably from 0.001 to 0.1%.
The compounds according to the present invention can be used either alone, in mixture with one another, or with other insecticidal agents. If necessary, other plant protection or parasite control agents, such as for example acarizides or fungicides, can be added according to the desired purpose.
A promotion of the intensity and speed of activity can be obtained, for example, with activity increasing additives, such as organic solvents, wetting agents and oils. Such additives accordingly allow, if necessary, a decrease in the dosaging of the active agent.
The characterized active agents, or mixtures thereof, are expediently used in the form of preparations such as powders, dusting agents, granulates, solutions, emulsions or suspensions, with the addition of liquid and/or solid carriers, or diluting agents and, if necessary, wetting, adhesion, emulsifying and/or dispersing adjuvants.
Suitable liquid carriers include, for example, water, aliphatic and aromatic hydrocarbons, futhermore cyclohexanone, isophorone, dimethylsulfoxide, dimethylformamide and mineral oil fractions.
Mineral earths, for example tonsil, silica gel, talc, kaolin, attaclay, limestone, silicic acid, and plant products, for example flour, are suitable as solid carriers.
As surface active substances, the following are mentioned by way of example: calcium, lignin sulfonate, polyoxyethylene-alkylphenylether, naphthalene sulfonic acids and their salts, phenol sulfonic acids and their salts, formaldehyde condensates, fatty alcohol sulfates, as well as substituted benzene sulfonic acids and their salts.
The portion of active agent(s) in the different preparations can vary within wide limits. For example, the agent may contain about 5-80% by weight active substance, about 95-20% liquid or solid carrier, as well as if necessary up to 20% by weight surface active substances, with corresponding decrease in the amount of active agents and/or carrier when surface active agents are used.
Circulation of the agent can follow in customary manner, for example with water as carrier in spray amounts of about 100 to 3,000 liter/ha. Use of the agent in so-called low-volume and ultra-low-volume methods is likewise possible, as is their application in the form of so-called microgranulates.
Production of these preparations can be performed in known manner, for example through milling or mixing methods. If desired, the individual components can also be mixed first briefly before their use, for example, as carried out in practice by the so-called tank mix method.
For production of the preparations, the following components, for example, are added:
(a)
80% by weight active agent
15% by weight kaolin
5% by weight surface active material based upon the sodium salt of N-methyl-N-oleyl-taurine and the calcium salt of lignin sulfonic acid
(b)
50% by weight active agent
40% by weight clay minerals
5% by weight cell pitch
5% by weight surface active material based upon a mixture of the calcium salt of lignin sulfonic acid with alkylphenolpolyglycolether
(c)
20% by weight active agent
70% by weight clay minerals
5% by weight cell pitch
5% by weight surface active material based upon a mixture of calcium salt of lignin sulfonic acid with alkylphenylpolyglycolether
(d)
5% by weight active agent
80% by weight tonsil
10% by weight cell pitch
5% by weight surface active material based upon a fatty acid condensation product
Of the compounds according to the present invention, those displaying a particularly good insecticidal activity are those for which in the above given general formula R 1 is chlorine or fluorine, R 2 is hydrogen, chlorine or fluorine, R 3 is hydrogen, chlorine or methyl, R 4 is hydrogen, chlorine or methyl, and R 5 , R 6 and R 7 are the same or different and are hydrogen or methyl.
The compounds according to the present invention may be produced by bringing together for reaction
(a) alkoxyaniline of the general formula ##STR3## with benzoylisocyanate of the general formula ##STR4## if necessary with use of a solvent, or
(b) reacting alkoxyphenolisocyanate of the general formula ##STR5## with benzamide of the general formula ##STR6## if necessary in the presence of a solvent, with R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 having the above given meanings.
As solvent, materials inert in relation to the reactants are suitable, such as aromatic and aliphatic hydrocarbons, if necessary chlorinated, such as toluene, chlorbenzene, chloroform and hexane, ethers, such as diethyl ether and tetrahydrofuran, esters, such as acetic acid ethyl ester, as well as nitriles, such as acetonitrile and benzonitrile.
The reaction temperatures can vary within wide limits. Preferred for method variation (a) is the range from about 20° to 100° C., and with the method variant (b) the range of about 80° to 200° C. The reactions follow in general at normal pressure.
The acylureas according to the present invention are colorless and odorless crystalline compounds. They dissolve only very poorly in water or toluene, better in acetic ester, and well in dimethylformamide.
The novel features which are considered as characteristic for the invention are set forth in particular in the appended claims. The invention itself, however, both as to preparation and method of use, together with additional objects and advantages thereof, will be best understood from the following description of specific embodiments.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The following example illustrates the production of the compounds according to the present invention.
EXAMPLE 1
1-[4-(2,2-dichlorcyclopropyloxy)-phenyl]-3-(2-methylbenzoyl)-urea
6.54 g (0.03 Mol) of 4-(2,2-dichlorcyclopropyloxy)-aniline, dissolved in 50 ml dry tetrahydrofuran, are added dropwise with 4.84 g (0.03 Mol) of 2-methylbenzoyl-isocyanate, with stirring. The temperature increases mildly therewith. After cooling, the product is precipitated with pentane, withdrawn by suction, after-washed with pentane and dried.
Yield: 8.3 g (74% of theoretical amount)
MP: 175°-176° C.
In analogous manner, the following compounds according to the present invention are produced:
______________________________________ PhysicalCompound Name Constant______________________________________1-[3-chlor-4-(2,2-dichlor-3,3-dimethyl- MP: 153° C.cyclopropyloxy)-phenyl]-3-(2-chlorobenzoyl)- (decomposition)urea1-[4-(2,2-dichlor-3,3-dimethylcyclopropyl- MP: 186-187° C.oxy)-3-methylphenyl]-(2,6-dichlorobenzoyl)-urea1-(2-chlorbenzoyl)-3-[4-(2,2-dichlor-3,3- MP: 184-185° C.dimethylcyclopropyloxy)-3-methylphenyl]-urea1-[4-(2,2-dichlor-3,3-dimethylcyclopropyl- MP: 204-205° C.oxy)-3-methylphenyl]-3-(2,6-difluorbenzoyl)-urea1-[3-chlor-4-(2,2-dichlor-3,3-dimethyl- MP: 200-202° C.cyclopropyloxy)-phenyl]-3-(2,6-difluor-benzoyl)-urea1-[4-(2,2-dichlor-3-methylcyclopropyl- MP:187-189° C.oxy)-3-methylphenyl]-3-(2-methyl-benzoyl)-urea1-(2-chlorbenzoyl)-3-[4-(2,2-dichlor-3- MP: 170-172° C.methylcyclopropyloxy)-3-methylphenyl]-urea1-[4-(2,2-dichlor-3-methylcyclopropyl- MP: 165-167° C.oxy)-3-methylphenyl]-3-(2,6-dichlor-benzoyl)-urea1-(2,6-dichlorbenzoyl)-3-[4-(2,2- MP: 199-200° C.dichlorcyclopropyloxy)-phenyl]-urea1-[4-(2,2 dichlorcyclopropyloxy)-phenyl]- MP: 189-190° C.3-(2,6-difluorbenzoyl)-urea1-(2-chlorbenzoyl)-3-[4-(2,2-dichlor- MP: 160-162° C.cyclopropyloxy)-phenyl]-urea1-(2,-chlorbenzoyl)-3-[4-(2,2-dichlor- MP: 144-146° C.cyclopropyloxy)-3,5 dimethylphenyl]-urea1-(2-chlorbenzoyl)-3-[3-chlor-4-(2,2- MP: 195-197° C.dichlorcyclopropyloxy)-phenyl]-urea1-[4-(2,2-dichlorcyclopropyloxy)- MP: 159-161° C.phenyl]-3-(2-fluorbenzoyl)-urea1-(2-brombenzoyl)-3-[4-(2,2-dichlor- MP: 162-165° C.cyclopropyloxy)-phenyl]-urea1-[3-chlor-(2,2-dichlorcyclopropyloxy)- MP: 205-207° C.phenyl]-3-(2,6-dichlorbenzoyl)-urea______________________________________
The benzamide and benzoylisocyanate to be used as starting materials are known, or can be produced according to known methods.
The required aniline is obtained, for example, through reduction of the corresponding nitro-compound(s) according to known methods. These nitro-compounds can be produced, for example, from corresponding phenols through etherification with allylhalogenides, whereby the resulting phenyl allylethers are then isomerized with strong bases into phenylenolethers. These then give, with dichlorcarbene and subsequent nitrogenation, the desired nitro-compounds.
According to another method, nitrophenols are converted, with acetic acid vinyl ester in the presence of catalytic amounts of mercury acetate and acid, into vinyl ethers, which are then brought into reaction with dichlorcarbene, preferably using the so-called phase transfer method.
The mentioned vinylethers can also be produced in a two-stage reaction, in which the phenols are initially reacted with 1,2-dibromoethane, in the presence of a weak base, into bromoethylether, and these are then dehydrobrominated with a strong base into vinylethers.
The following describes production of one of the starting materials:
4-(2,2-dichlorocyclopropyloxy)-aniline
104 g (0.75 Mol) of 4-nitrophenol are dissolved in 420 ml (4.5 Mol) acetic acid vinyl ester. After washing with nitrogen, successively 3.0 g mercury acetate and 0.2 ml BF 3 -etherate are added. The reaction mixture is stirred for 4 hours at 50° C. After cooling, 2 g sodium acetate are added, evaporated, and the residue then dissolved in ether. There follows washing three times with 2 n-caustic soda, three times with water, drying and evaporation. The residue is recrystallized from ether. 65 g (52% of theoretical amount) of 4-nitrophenylvinylether are obtained, with a melting point of 59°-61° C.
41.3 g (0.25 Mol) of the vinyl ether and 0.6 g benzyltriethylammonium chloride are dissolved in 150 ml chloroform, and with strong stirring, reacted with 150 ml 50% caustic soda. The reaction mixture is stirred for 5 hours, with the temperature being held, initially through cooling, then through heating, between 55° and 60° C. It is subsequently mixed with 200 ml each of chloroform and water, and filtered across celite. The organic phase is separated, washed with water, dried and evaporated. There remains behind 40 g (64% of theoretical amount) of 4-(2,2-dichlorcyclopropyloxy)-nitrobenzene, as a dark oil, which is used without further purification. n D 20 =1.5856.
70 ml ethanol are reacted with 9.7 ml (0.2 Mol) hydrazine hydrate and 5 g Raney-nickel. With stirring, 12.4 g (0.05 Mol) of the cyclopropyloxy-nitrobenzene, dissolved in 20 ml ethanol, are then dripped in; in so doing the interior temperature should not exceed 40° C. The reaction mixture is then after-stirred for an hour, filtered, the filtrate evaporated, and then dissolved in ether. This solution is washed three times with water, dried and evaporated once again. There remains as residue 9 g (82% of theoretical amount) of 4-(2,2-dichlorcyclopropyloxy)-aniline, a brown oil, which is used without further purification. n D 20 is 1.5773.
The following example illustrates possibilities of use for the compounds according to the present invention, which follow in the form of their preparations.
EXAMPLE 2
The substances according to the present invention are employed as aqueous suspensions with an active agent concentration of 0.05%.
Bush bean plants (Phaseolus vulgaris) in the primary leaf stage are soaked in these active agent preparations. Four plant stalks with a total of eight primary leaves are put in a glass vase filled with water and then caged in a glass cylinder, for each test.
Five larvae of the Mexican bean beetle (Epilachna varivestis) in the third larval stage are then placed in each glass cylinder, and held therein for 5 days. The criterion for an estimation of effectiveness is the mortality of the larvae, in percent, after a test duration of 5 days.
______________________________________ Active AgentCompound According to Concentra- Mortalitythe Invention tion in % in %______________________________________1-[3-chlor-4-(2,2-dichlor-3,3- 0.05 100dimethylcyclopropyloxy)-phenyl]-3-(2-chlorbenzoyl)-urea1-[4-(2,2-dichlor-3,3-dimethyl- 0.05 100cyclopropyloxy)-3-methylphenyl]-3-(2,6-dichlorbenzoyl)-urea1-(2-chlorbenzoyl)-3-[4-(2,2-di- 0.05 100chlor-3,3-dimethylcyclopropyloxy-3-methylphenyl]-urea1-[3-chlor-4-(2,2-dichlor-3,3-di- 0.05 100methylcyclopropyloxy)-phenyl]-3-(2,6-difluorbenzoyl)-urea1-[4-(2,2-dichlor-3-methylcyclo- 0.05 100propyloxy)-3-methylphenyl]-3-(2-methylbenzoyl)-urea1-(2-chlorbenzoyl)-3-[4-(2,2-di- 0.05 100chlor-3-methylcyclopropyloxy)-3-methylphenyl]-urea1-[4-(2,2-dichlor-3-methylcyclo- 0.05 100propyloxy)-3-methylphenyl]-3-(2,6-dichlorbenzoyl)-urea1-(2,6-dichlorbenzoyl)-3-[4-(2,2- 0.05 100dichlorcyclopropyloxy)-phenyl]-urea1-[4-(2,2-dichlorcyclopropyloxy)- 0.05 100phenyl]-3-(2,6-difluorbenzoyl)-urea1-(2-chlorbenzoyl)-3-[4-(2,2-di- 0.05 100chlorcyclopropyloxy)-phenyl]-urea1-(2-chlorbenzoyl)-3-[4-(2,2-di- 0.05 100chlorcyclopropyloxy)-3,5-dimethyl-phenyl]-urea1-(2-chlorbenzoyl)-3-[3-chlor-4- 0.05 100(2,2-dichlorcyclopropyloxy)-phenyl]-urea1-(2-brombenzoyl)-3-[4-(2,2-di- 0.05 100chlorcyclopropyloxy)-phenyl]-urea______________________________________
EXAMPLE 3
The compounds according to the present invention are applied as aqueous suspensions with an active agent concentration of 0.01%. The comparison agents are used in the same manner. Two cauliflower leaves per test are sprayed with 4 mg active agent preparation per cm 2 , dosed into polystyrene Petrie dishes. After drying of the spray coating, ten young caterpillars, of the so-called cabbage moth species (Plutella maculitennis) are put into each Petrie dish, and exposed to the treated food in the laboratory for 8 days. Criteria for the determination of effectiveness are the mortality of the caterpillars after 2 days, the suppression of consumption of the caterpillars in percent, as well as the prevention of emergence of moth in percent after 8 days. The results are presented in the following table:
__________________________________________________________________________ Active Agent Suppression Prevention of Concentra- Mortality of Consumption Moth Emergence tion in % in % in % in %__________________________________________________________________________Compounds According to the Invention1-[4-2,2-dichlorcyclopropyloxy)- 0.01 75 80 100phenyl]-3-(2,6-difluorbenzoyl)-urea1-(2-chlorbenzoyl)-3-[4-(2,2- 0.01 85 70 100dichlorcyclopropyloxy)-phenyl]-ureaCOMPARISON AGENT ACCORDING TODE-OS 2,123,236N--(2,6-difluorbenzoyl)-N'--(p- 0.01 30 50 100chlorphenyl)-ureaN--(2,6-dichlorbenzoyl)-N'--(p- 0.0 10 30 0chlorphenyl)-ureaUNTREATED CONTROL 0.0 10 30 0__________________________________________________________________________
EXAMPLE 4
The compounds according to the present invention are applied as aqueous suspensions with a concentration of active agent of 0.001%. The comparison agents are applied in the same manner. Plant dishes (20×20 cm), containing 25-30 bush bean plants (Phaseolus vulgaris) in the primary leaf stage, are sprayed dripping wet with the active agent preparations. The so-treated dishes are placed in a greenhouse for 24 hours. Thereafter, 4 plant stalks with 8 primary leaves are withdrawn per test, placed in glass vases filled with water, and caged in glass cylinders. 5 larvae of the Mexican bean beetle (Epilachna varivestis) in the third larval stage are then placed in each glass cylinder, and held there for 6 days.
Criteria for the determination of activity are the mortality and the suppression of consumption of the larvae in percent after a test duration of 6 days.
______________________________________ Suppres- Active sion of Agent Mor- Con- Concentra- tality sumption tion in % in % in %______________________________________Compounds According tothe Invention1-(2-chlorbenzoyl)-3-[4-(2,2-dichlor- 0.001 100 803-methylcyclopropyloxy)-3-methyl-phenyl]-urea1-[4-(2,2-dichlorcyclopropyloxy)- 0.001 100 80phenyl]-3-(2,6-difluorbenzoyl)-urea1-(2-chlorbenzoyl)-3-[4-(2,2-dichlor- 0.001 100 80cyclopropyloxy)-phenyl]-ureaCOMPARISON AGENT accord-ing to DE-OS 2,123,236N--(2,6-difluorbenzoyl)-N'--(p- 0.001 60 30chlorphenyl)-ureaUNTREATED CONTROL 0.0 0 0______________________________________
It will be understood that each of the elements described above, or two or more together, may also find a useful application in other types of pest control differing from the types described above.
While the invention has been illustrated and described as embodied in acyl ureas, insecticides containing these compounds, as well as methods for their production, it is not intended to be limited to the details shown, since various modifications and structural changes may be made without departing in any way from the spirit of the present invention.
Without further analysis, the foregoing will so fully reveal the gist of the present invention that others can, by applying current knowledge, readily adapt it for various applications without omitting features that, from the standpoint of prior art, fairly constitute essential characteristics of the generic or specific aspects of this invention.
|
New acyl urea of the general formula ##STR1## in which R 1 is halogen or C 1 -C 6 -alkyl,
R 2 is hydrogen or halogen,
R 3 is hydrogen, halogen or methyl,
R 4 is hydrogen, halogen or methyl, and
R 5 , R 6 and R 7 are the same or different and are hydrogen, C 1 -C 6 -alkyl or aryl,
insecticidal agents containing these compounds as well as methods for their production. The compounds are effective in particular for the control of insect pests belonging to the classes Diptera, Coleoptera, as well as Lepidoptera.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority to U.S. Provisional Patent Application Ser. No. 60/612,068, filed on Sep. 21, 2004, the disclosure of which is incorporated herein by reference in its entirety. This application also incorporates herein by reference a U.S. patent application filed of even date herewith and identified by Attorney Docket No. ZCO-109A.
FIELD OF THE INVENTION
[0002] The present invention relates to apparatus and methods for servicing 3D printers, for example, for cleaning and aligning the printheads used in the 3D printers.
BACKGROUND
[0003] Generally, 3D printing involves the use of an inkjet type printhead to deliver a liquid or colloidal binder material to layers of a powdered build material. The printing technique involves applying a layer of a powdered build material to a surface typically using a roller. After the build material is applied to the surface, the printhead delivers the liquid binder to predetermined areas of the layer of material. The binder infiltrates the material and reacts with the powder, causing the layer to solidify in the printed areas by, for example, activating an adhesive in the powder. The binder also penetrates into the underlying layers, producing interlayer bonding. After the first cross-sectional portion is formed, the previous steps are repeated, building successive cross-sectional portions until the final object is formed. See, for example, U.S. Pat. Nos. 6,375,874 and 6,416,850, the disclosures of which are incorporated herein by reference in their entireties.
[0004] 3D printers produce colored parts by using colored binder materials to solidify the powder. Clear binder is used to produce white part surfaces, and three primary colors are used in varying proportions to produce a gamut of colors. The printer must apply the variously colored binder droplets at precise locations to render the part surfaces in accurate color. 3D printers use a separate printhead to apply each binder color. In general, non-uniformity in printheads and mechanical variations in printhead mounting features produce inaccuracies in the positioning of binder droplets that must be characterized and corrected.
[0005] Additionally, apparatus for carrying out 3D printing typically generates dust, which can detrimentally effect the operation of the printheads. For example, the dust can clog the jet nozzles that dispense the binder material, which can result in no binder material being dispensed or the binder material being dispensed inaccurately.
[0006] It is, therefore, an object of the present invention to provide apparatus and methods for continuously and efficiently servicing 3D printers.
SUMMARY
[0007] Generally, the invention relates to apparatus and methods for producing three-dimensional objects, such as casting cores, toys, bottles, cans, architectural models, automotive parts, molecular models, models of body parts, cell phone housings, and footwear, more rapidly and efficiently than heretofore achievable. Additionally, the invention relates to systems and methods for maintaining and operating the aforementioned apparatus.
[0008] More specifically, the invention relates to apparatus and methods for aligning multiple printheads and apparatus and methods for cleaning the printheads. In one example, the alignment method is an automatic method of determining droplet-positioning errors that is particularly suited to 3D printing. In one example, a test pattern is printed with the printheads to be aligned, assuming that they are perfectly positioned. The resulting image is then scanned to determine the deviation of the images printed from perfect position. The information thus gained is then available to correct the identified errors. The present approach differs from the prior art in at least its use of the harmonic content of the signal obtained from scanning an alignment pattern to characterize misalignment. A scan traverses a multiplicity of nominally identical bar pairs, averaging out the irregularities inherent in an image printed in powder. Imaging optics are unnecessary since no edge detection is involved.
[0009] In one aspect, the invention relates to a method of creating a test pattern with a plurality of printheads of a three-dimensional printer. The method includes the steps of defining an area on a build surface for receiving the test pattern, selecting a reference printhead capable of printing with a high contrast, printing a reference line with the reference printhead, and printing a test line proximate to the reference line with at least one of the remaining printheads.
[0010] In various embodiments, the step of defining an area includes producing a contrast-enhancing sublayer on the build surface. The contrast-enhancing sublayer can be produced by printing the area in a solid, high contrast color using at least one of the printhead and overlaying the printed area with at least one unprinted layer of build material. In one embodiment, the area is printed with all of the available printheads at a maximum discharge level to saturate the area.
[0011] The step of selecting a printhead includes the steps of printing a target above the contrast-enhancing sublayer with each of the printheads, comparing the targets to identify which target has a highest contrast relative to an unprinted area, and selecting a printhead associated with the highest contrast target. Further, the method can include the step of depositing a layer of a build material on the build surface prior to each printing step. The printing steps can include depositing a liquid binder in a predetermined pattern on the build material. The printheads, in one embodiment, print with a liquid binder having a color selected from the group consisting of magenta, yellow, cyan, clear and black. Other colors and combinations of colors are contemplated and within the scope of the invention.
[0012] Additionally, the step of printing a test line can include printing alternating bars of color with at least two of the remaining printheads. The steps of printing a reference line and printing a test line can include printing a plurality of reference lines and printing a corresponding plurality of test lines. In one embodiment, the reference lines and the test lines can be printed in multiple passes. The step of printing a plurality of lines can include printing a plurality of horizontal lines and a plurality of vertical lines. Also, the step of printing a reference line can include printing ten horizontal reference lines and printing ten vertical reference lines proximate thereto, and the step of printing a test line can include printing ten corresponding horizontal test lines and printing ten corresponding vertical test lines. In some embodiments, two reference lines may be printed. In other embodiments, 20 reference lines may be printed.
[0013] In a particular embodiment of the method, the steps of printing a reference line and printing a test line include printing a plurality of nominally identical line pairs parallel to a fast-axis travel of the printheads, each line pair comprising one reference line and one test line, and printing a plurality of nominally identical line pairs perpendicular to the fast-axis travel of the printheads, each line pair comprising one reference line and one test line. In one embodiment, each plurality of line pairs is arranged as an equally spaced linear array. Each test line can include a series of test bars, where each of the remaining printheads prints a central test bar that is nominally located at a distance from a corresponding reference line equal to ½ of a nominal array spacing of the reference lines. In one embodiment, each remaining printhead prints a plurality of additional test bars that are incrementally displaced about the central test bar.
[0014] In another aspect, the invention relates to a test pattern for aligning a plurality of printheads in a three-dimensional printer. The test pattern includes a plurality of substantially evenly spaced solid reference lines and a plurality of test lines disposed in an alternating pattern with the plurality of reference lines, wherein each of the test lines comprises at least one bar of a non-reference color. In one embodiment, the colors are printed in an alternating pattern. In various embodiments, the plurality of lines is oriented substantially vertically, or in a particular embodiment, parallel to a fast-axis printhead travel. Further, the test pattern can include a second test pattern disposed proximate the first test pattern. The second test pattern includes a second plurality of substantially evenly spaced solid reference lines and a second plurality of test lines disposed in an alternating pattern with the second plurality of reference lines. Each of the test lines comprises at least one bar of a non-reference color, and the second plurality of lines can be oriented substantially perpendicular to the fast-axis printhead travel.
[0015] In another aspect, the invention relates to a method of determining a correction factor(s) for aligning a plurality of printheads. The printheads need to operate in concert to produce colored images. Due to printhead and mounting variations, the relative positions of the printheads need to be measured, and corrections need to be applied to the printhead drive signals to cause the various colors to be printed in the proper registration. Generally, a test pattern is printed with the printheads to be aligned, assuming that they are perfectly positioned. The resulting image is then scanned to determine the deviation of the images printed from their perfect position. The information thus gained is then available to correct the identified errors. The present approach differs from the prior art in at least its use of the harmonic content of the signal obtained from scanning the test pattern to characterize misalignment. A scan traverses a plurality of nominally identical line pairs, averaging out the irregularities inherent in an image printed in powder. Imaging optics are unnecessary, since no edge detection is involved.
[0016] Specifically, the method includes the steps of printing a test pattern on a build surface, generating a set of electrical signals representative of the test pattern, analyzing the electrical signals to determine their harmonic content at at least one frequency, and determining a correction factor(s) based on the harmonic content of the electrical signals. The test pattern can include a line pair array. In one embodiment, the method includes generating a plurality of electrical signals for analysis and determining a plurality of correction factors based on the harmonic content of the plurality of electrical signals.
[0017] In various embodiments, the method includes generating the electrical signal by illuminating the test pattern and measuring reflectance of the test pattern at predetermined locations. In one embodiment, the step of analyzing the electrical signal includes applying an analog filter (e.g., using op-amps) to the signal. In another embodiment, the step of analyzing the electrical signal includes digitizing the signal and applying a digital filter (e.g., a Fast Fourier Transform) to the signal. In one embodiment, the correction factor can be determined from a set of third harmonic values. In another embodiment, the correction factor can be determined from a set of first harmonic values. The correction factor can be near a nominal test bar displacement for which a lowest value of the selected harmonic is determined. The correction factors can be determined by locating a minimum value of an analytical curve that has been fitted to, or representative of the set of third harmonic values. One embodiment of the method includes the steps of extracting third harmonic values from the signals acquired by scanning the sensor across the array, comparing the set of third harmonic values obtained for each color, and determining the correction factors based on the minimum third harmonic values.
[0018] In another aspect, the invention relates to the servicing of a plurality of printheads in a three-dimensional printer. In general, quality of the parts produced in the 3-D printing process depends upon the reliable and accurate delivery of droplets of binder liquid from the nozzle arrays located on the faces of the printheads. To maintain high performance standards, the printheads must be serviced frequently during the 3-D printing process. The impact of droplets of binder liquid on the surface of the powder bed causes powder particles to be ejected from the surface of the bed. Some of the ejected material collects on the faces of the printheads, interfering with the delivery of binder liquid droplets. A principal purpose of the printhead servicing is to remove this accumulated debris from the printhead faces.
[0019] One aspect of printhead servicing is a service station, which includes a cleaning station, a discharge station, and a capping station. In one embodiment, the printheads are disposable within a carriage capable of moving in at least two directions relative to the service station. Another aspect of printhead servicing is a software algorithm that specifies when each printhead needs to be serviced. In one embodiment, the printheads are disposable within a carriage capable moving in at least two directions relative to the service station.
[0020] Various embodiments of the cleaning station include at least one receptacle for receiving a printhead, at least one nozzle for spraying a cleaning fluid towards a printhead face (or printing surface) of the printhead, and a wiper disposable in close proximity to the printhead face for removing excess cleaning fluid, in some cases without contacting the printhead face. The cleaning station can further include a splash guard for isolating the printhead face and preventing the cleaning fluid from migrating beyond the printhead face. The splash guard includes an open position and a sealed position, where the splash guard is biased open and is actuated from the open position to the sealed position by contact with a printhead. The splash guard can include a sealing lip that circumscribes the printhead face when in the sealed position. In one embodiment, the sealing lip is generally rectangular in shape. The wiper can be formed by one side of the sealing lip and can include a notched portion configured and located to correspond to a location of a jet nozzle array on the printhead face to prevent the wiper from contacting the jet nozzle array. The wiper is capable of movement relative to a printhead.
[0021] Further, the cleaning station can include a fluid source for providing the cleaning fluid to the at least one nozzle under pressure. The cleaning fluid can be provided to the at least one nozzle via a manifold. In one embodiment, the at least one nozzle includes an array of nozzles. The at least one nozzle can be positioned to spray the cleaning fluid across the printhead face. In one embodiment, the printheads are disposed within a carriage capable of movement in two directions with respect to the service station.
[0022] Various embodiments of the discharge station include a receptacle defining an opening that generally corresponds to a printhead face of a printhead. The receptacle defines a plurality of corresponding openings in one embodiment. The receptacle can include a tray for capturing and/or directing discharged fluids. In one embodiment, the discharge from the printheads is directed into a standing pool of waste liquid.
[0023] Various embodiments of the capping station include a printhead cap carrier and at least one printhead cap disposed on the carrier for sealing a printhead face of a printhead. The cap is moved between an off position and a capped position by the printhead contacting the carrier. The capping station can include a plurality of caps disposed on the carrier. In one embodiment, the carrier is biased to maintain the at least one cap in an off position. The discharge station and the capping station can be a combined station. In such an embodiment, the discharge from the printheads can be constrained in a cavity defined by a printhead face, a printhead cap, and the standing pool of waste liquid.
[0024] In another aspect, the invention relates to an apparatus for cleaning a printhead. The apparatus includes at least one nozzle for spraying a cleaning fluid towards a printhead face of the printhead and a wiper disposable in close proximity to the printhead face for removing excess cleaning fluid from the printhead face.
[0025] In one embodiment, the apparatus includes a splash guard for isolating a printhead face and preventing cleaning fluid from migrating beyond the printhead face. The splash guard can include an open position and a sealed position, where the splash guard is actuated from the open position to the sealed position by contact with a printhead. In addition, the splash guard can include a sealing lip that circumscribes the printhead face when in the sealed position. The sealing lip is generally rectangular in shape. In one embodiment, the wiper is formed by one side of the sealing lip. The wiper can include a notched portion configured and located to correspond to a location of a jet nozzle array on the printhead face to prevent the wiper from contacting the jet nozzle array. The wiper is capable of movement relative to a printhead. Additionally, the apparatus can include a fluid source for providing cleaning fluid to the at least one nozzle under pressure. The at least one nozzle can an array of nozzles and can be positioned to spray the cleaning fluid across a printhead face.
[0026] In another aspect, the invention relates to a method of cleaning a printhead. The method includes the steps of positioning a printhead face of the printhead relative to at least one nozzle, operating the at least one nozzle to spray cleaning fluid towards the printhead face, and causing relative movement between a wiper and the printhead to pass the wiper in close proximity to the printhead face to remove excess cleaning fluid. The wiper can include a notch configured and located on the wiper to correspond to a jet nozzle array on the printhead face to prevent the wiper from contacting the jet nozzle array.
[0027] In various embodiments, the step of positioning the printhead face includes sealing the printhead face to prevent the cleaning fluid from migrating beyond the printhead face. The operating step can include spraying the cleaning fluid across the printhead face. In addition, the printhead can be operated to discharge any cleaning fluid ingested by the printhead during cleaning. In one embodiment, the at least one nozzle comprises an array of nozzles.
[0028] In another aspect, the invention relates to an apparatus for cleaning a printhead used in a three-dimensional printer. The apparatus includes a sealing cap defining a cavity and capable of engagement with a printhead face of the printhead, a cleaning fluid source in communication with the cap for cleaning the printhead face, and a vacuum source in communication with the cap for removing used cleaning fluid and debris. In operation, the vacuum source creates a negative pressure within the cavity, the negative pressure preventing the cleaning fluid from entering a jet nozzle, drawing the cleaning fluid into the cavity from the cleaning fluid source, and/or drawing at least one of a binder fluid and debris from the jet nozzle. The apparatus may further include a wiper disposed proximate the cap, the wiper positioned to engage the printhead face as the printhead disengages from the cap.
[0029] In another aspect, the invention relates to a method of cleaning a printhead used in a three-dimensional printer. The method includes the steps of engaging a printhead face of the printhead with a sealing cap defining a cavity, drawing a vacuum in the cavity, and introducing a cleaning fluid into the cavity and into contact with the printhead face. The method may further include the step of removing the cleaning fluid from the cavity. In one embodiment, the method includes the steps of disengaging the cap from the printhead face and wiping the printhead face with a wiper. The step of drawing a vacuum creates a negative pressure within the cavity, the negative pressure drawing the cleaning fluid into the cavity, preventing the cleaning fluid from entering a jet nozzle and/or drawing at least one of a binder fluid and debris from the jet nozzle.
[0030] In still other embodiments, the invention can include alternative methods and apparatus for cleaning the printheads apparatus. Methods of cleaning the printhead can include wiping the printhead with a roller including a cleaning fluid, drawing a vibrating member across the printhead, drawing a cleaning fluid across the printhead by capillary action through a wick, and/or combinations thereof. In addition, the methods can include optionally the step of applying a vacuum to the printhead to remove debris. The apparatus for cleaning a printhead used in a 3D printer can include a wick disposed adjacent the printhead for drawing a cleaning fluid across the printhead.
[0031] In another aspect, the invention relates to an apparatus for cleaning a printhead used in a 3D printer. The pressure in the interior of a printhead is typically lower than atmospheric pressure. This negative pressure is balanced by the surface tension of the meniscuses that form over the outlets of the printhead nozzles. It is desirable to flush the accumulated powder off the face of the printhead with a clean wash solution without allowing the solution to be drawn into the printhead when the meniscuses are destroyed. This goal is achieved in this apparatus by maintaining an environment outside the printhead in which the pressure is lower than the pressure inside the head. In addition, this induced pressure differential causes binder to flow out of the heads through the nozzles, flushing out any powder that may have lodged in the nozzle passageways. The apparatus includes a base, a cam track disposed within the base, a cap carrier slidably engaged with the cam track, and a sealing cap defining a cavity and disposed on the carrier. The cap being transportable into engagement with the face of the printhead by the carrier. In various embodiments, the apparatus includes a cleaning fluid source in communication with the cap for cleaning the printhead face and a vacuum source in communication with the cap for removing used wash fluid and debris.
[0032] In further embodiments, the apparatus can also include a spring coupled to the carrier and the base to bias the carrier into a receiving position for receiving the printhead. In one embodiment, the carrier includes a stop disposed on a distal end of the carrier for engaging the printhead as the printhead enters the apparatus. The printhead slides the carrier rearward along the cam track after engaging the stop and until the printhead face and cap sealably engage. In a further embodiment, the apparatus includes a latch pawl coupled to the base for engaging with the carrier to prevent forward movement of the carrier and a wiper disposed on a proximal end of the carrier. The wiper is positioned to engage the printhead face as the printhead exits the apparatus.
[0033] In still another aspect, the invention relates to a method of cleaning a printhead used in a 3D printer. The method includes the step of receiving the printhead within an apparatus that includes a base, a cam track disposed within the base, a cap carrier slidably engaged with the cam track, and a sealing cap defining a cavity and disposed on the carrier. Additional steps include engaging the face of the printhead with the cap, drawing a vacuum on the cavity, and introducing a cleaning fluid into the cavity and into contact with the printhead face. In one embodiment, the method includes the step of removing the cleaning fluid from the cavity. The method can further include disengaging the cap from the printing surface and wiping the printing surface with a wiper as the printhead is withdrawn from the apparatus.
[0034] In another aspect, the invention relates to an apparatus for cleaning or reconditioning a printhead. The apparatus includes a nozzle array for spraying a washing solution towards a face of a printhead and a wicking member disposed in proximity to the printhead face for removing excess washing solution from the printhead face.
[0035] In various embodiments, the nozzle array includes one or more individual nozzles. The wicking member and the printhead are capable of relative movement. A fluid source can also be included in the apparatus for providing washing solution to the nozzle array under pressure. In another embodiment, the wicking member includes at least one of a permeable material and an impermeable material.
[0036] The nozzle array can be positioned to spray the washing solution at an angle with respect to the printhead face. In another embodiment, the wicking member is disposed in close proximity to the printhead face, without contacting print nozzles located on the printhead face. The spacing between the wicking member and the print nozzles can be automatically maintained. In one embodiment, the spacing is maintained by causing a portion of the wicking member to bear on the printhead face in a location removed from the print nozzles. The apparatus can also include a basin for collecting washing solution and debris.
[0037] In another aspect, the invention relates to a method of cleaning or reconditioning a printhead. The method includes the steps of positioning a face of the printhead relative to at least one nozzle and operating the at least one nozzle to spray washing solution towards the printhead face. Excess washing solution is then removed from the printhead face by passing a wicking member in close proximity to the printhead face, without contacting the printhead face.
[0038] In one embodiment, the step of operating the at least one nozzle includes spraying the washing solution at an angle to the printhead face. In another embodiment, the method can include the step of operating the printhead to expel washing solution ingested by the printhead during cleaning. The method can include automatically maintaining a space between the wicking member and print nozzles located on the printhead face by, for example, causing a portion of the wicking member to bear on the printhead face in a location removed from the print nozzles.
[0039] In another aspect, the invention relates to a method of determining when a printhead needs to be serviced. Servicing is needed to maintain adequate printhead performance. Servicing is a time-consuming activity, however, and some aspects of the servicing process are damaging to the printhead. It is therefore desirable to service a printhead on a schedule that balances the positive and negative impacts of the process.
[0040] One approach to identifying a printhead in need of service is to infer the state of the printhead indirectly from the information available about the ongoing printing process. It is common, for example, to perform printhead servicing at intervals based on the time elapsed since last service, the number of droplets dispensed since last service, and the number of layers printed since last service. Printhead service is performed when one or another of these indicative factors reaches a predetermined trigger value. Alternatively, service-triggering variables may be defined that are weighted functions of two or more indicative factors. In one implementation, the trigger values for one or more of the indicative factors are adjusted to match the characteristics of the powder and binder liquid materials in use. The specific factors and corresponding trigger values may be selected to suit a particular application, environment, and/or printhead.
[0041] It is particularly desirable to identify characteristics of the images being printed that can be related quantitatively to the need for printhead service. One such factor is based on the observation that the impact of droplets printed on the powder bed ejects less debris when the underlying previous layer was printed. The binder printed on the previous layer tends to bind the powder in the fresh layer, resulting in less debris being ejected, and correspondingly less debris accumulating on the printhead face. Accordingly, in one implementation, printhead servicing is performed when the number of droplets printed over previously unprinted powder reaches a predetermined trigger value. Alternatively, a service interval based on the number of droplets dispensed since the last service may be modified to take into account the proportion of the droplets that were printed over previously unprinted powder. In another implementation, the underlying layer is considered to be unprinted if the pixel immediately underneath or any of its near neighbors are unprinted.
[0042] In another aspect, the invention relates to a method of determining a condition of a printhead in use in a three-dimensional printer. The method includes the steps of acquiring a data value for at least one operational parameter of the printhead and comparing the data value to a threshold value, the relationship of the data value to the threshold value indicative of the condition of the printhead. In one embodiment, the method includes the step of initiating a service routine on the printhead if the data value exceeds the threshold value. The operational parameter can be selected from the group consisting of time elapsed, number of droplets dispensed by the printhead, number of layers printed, droplets dispensed over previously printed powder, droplets dispensed over previously unprinted powder, and combinations thereof. Additionally, the data value can be compensated during acquisition to account for an operational environmental factor of the three-dimensional printer, such as, for example, temperature, humidity, binder material, and/or build material.
[0043] In another aspect, the invention relates to a method of determining a condition of a printhead in use in a three-dimensional printer. The method includes the steps of counting droplets dispensed by the printhead and determining a percentage of the droplets that were dispensed over previously unprinted pixels. The method can include the step of initiating a service routine on the printhead if the percentage exceeds a threshold value.
[0044] These and other objects, along with advantages and features of the present invention herein disclosed, will become apparent through reference to the following description, the accompanying drawings, and the claims. Furthermore, it is to be understood that the features of the various embodiments described herein are not mutually exclusive and can exist in various combinations and permutations.
BRIEF DESCRIPTION OF THE DRAWINGS
[0045] In the drawings, like reference characters generally refer to the same parts throughout the different views. In addition, the drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention. In the following description, various embodiments of the present invention are described with reference to the following drawings, in which:
[0046] FIG. 1 is a schematic perspective view of a three dimensional printer in accordance with one embodiment of the invention;
[0047] FIG. 2 is a schematic perspective view of a printhead carriage in accordance with one embodiment of the invention;
[0048] FIGS. 3A and 3B are a schematic perspective view and a schematic plan view, respectively, of a service station in accordance with one embodiment of the invention;
[0049] FIG. 4 is a schematic representation of the interaction between the carriage and the service station during performance of a discharge function in accordance with one embodiment of the invention;
[0050] FIGS. 5A-5D are schematic representations of one embodiment of a printhead capping operation in accordance with one embodiment of the invention;
[0051] FIGS. 6A-6D are schematic representations of a printhead discharge and capping operation in accordance with an alternative embodiment of the invention;
[0052] FIGS. 7A-7D are schematic representations of a printhead cleaning station in accordance with one embodiment of the invention;
[0053] FIGS. 8A-8H are schematic representations of an alternative embodiment of a printhead cleaning station in accordance with the invention;
[0054] FIGS. 9A and 9B are schematic representations of another alternative embodiment of a printhead cleaning station in accordance with the invention;
[0055] FIGS. 10A-10D are schematic representations of yet another alternative embodiment of a printhead cleaning station in accordance with the invention;
[0056] FIGS. 11A-11J are schematic representations of one embodiment of an apparatus and method for cleaning a printhead in accordance with the invention;
[0057] FIG. 12 is a schematic representation of a step of the method of cleaning a printhead in accordance with the embodiment of the invention depicted in FIGS. 11A-11J ;
[0058] FIG. 13 is a schematic perspective view of a printing operation in accordance with one embodiment of the invention;
[0059] FIGS. 14A and 14B are schematic representations of the impact of a liquid binder droplet on a build surface;
[0060] FIG. 15 is a schematic perspective view of a printhead alignment process in accordance with one embodiment of the invention;
[0061] FIGS. 16A and 16B are schematic representations of a contrast test target and test pattern alignment method in accordance with one embodiment of the invention;
[0062] FIGS. 17A-17D are schematic representations of an alignment sensor system and associated electronics in accordance with one embodiment of the invention;
[0063] FIG. 18 is a schematic representation of one step in a method of aligning color printheads in accordance with one embodiment of the invention;
[0064] FIGS. 19A and 19B are detailed schematic representations of a test pattern in accordance with one embodiment of the invention;
[0065] FIGS. 20A-20D are detailed schematic representations of the horizontal alignment process in accordance with one embodiment of the invention; and
[0066] FIGS. 21A and 21B are detailed schematic representations of the vertical alignment process in accordance with one embodiment of the invention.
DETAILED DESCRIPTION
[0067] Embodiments of the present invention are described below. It is, however, expressly noted that the present invention is not limited to these embodiments, but rather the intention is that variations, modifications, and equivalents that are apparent to the person skilled in the art are also included.
[0068] In brief overview, FIG. 1 is a schematic representation of a 3D printer 10 for creating an object in accordance with one embodiment of the invention. The printer 10 produces three-dimensional objects by depositing alternating layers of build material and binder liquid on a build surface 165 or in a container to print multiple layers that ultimately form the three-dimensional object. In some embodiments, the build material may include a powder and the binder liquid may be incorporated into the build material. In some embodiments, the printer 10 may be used to create physical prototypes for viewing and design review. In other embodiments, the printer 10 may be used to create molds for casting operations, or prototypes that may be used to collect market feedback on a potential product.
[0069] The printer 10 shown includes a gantry 12 , a carriage 14 , a service station assembly 16 , and a test pattern 18 . Typically, the gantry 12 is actuatable along the X-axis to manufacture the object layer by layer. In some embodiments a motor may be coupled to the gantry 12 . In other embodiments, the gantry 12 may be coupled to a screw, such that rotation of the screw moves the gantry 12 along the X-axis. In some embodiments, the gantry 12 may be actuatable along the vertical Z-axis. Other positioning systems may be employed, as desired.
[0070] The carriage 14 typically includes printheads 20 capable of dispensing binder materials necessary for creating an object (see FIG. 2 ). In some embodiments, as the gantry 12 moves along the X-axis, the carriage 14 moves back and forth along the Y-axis. The carriage 14 is coupled to the gantry 12 . Thus, as the carriage 14 moves along with the gantry 12 across the printer 10 , binder material may be deposited in a two dimensional pattern during travel across the surface of the printer 10 along the X-axis and the Y-axis. Then, typically, the next pass across the printer 10 will be at a different plane in the Z-axis, and material deposited in that z-plane on the Z-axis will bind with previously deposited material as part of the formation of the desired object. In one embodiment, a stepping-motor-driven piston underneath the build table provides Z-axis motion.
[0071] To further improve performance, the printer 10 also includes the service station 16 . In some embodiments, the service station 16 is located at a fixed point on the printer 10 . Generally, the service station 16 services the printheads 20 carried by the carriage 14 . The service station 16 is generally the physical location where debris or excess materials that are on or about the printheads 20 are removed. In some embodiments, excess binder material is removed or discharged from the carriage 14 . Generally, the carriage 14 is actuated into the service station 16 for maintenance, storage, or preservation from damage. Typically, the service station 16 may be located at any point on the printer 10 where it is possible for the carriage 14 to be actuated to engage the service station 16 . Also included in the printer 10 is a test pattern 18 . In some embodiments, the test pattern 18 is a test area passed over by the printhead 20 to refine alignment of the carriage 14 in creation of an object.
[0072] In some embodiments, the carriage 14 can be moved for diagnostic or service purposes. Moving the carriage 14 provides the user with access to the printheads 20 for maintenance purposes, such as cleaning or replacement. Printhead cleaning is described in detail with respect to FIGS. 6A-6D , 7 A- 7 D, 8 A- 8 J, 9 A- 9 B, 10 A- 10 D, 11 A- 11 J, and 12 . In some embodiments, the printheads 20 may be actuated to run a diagnostic routine of the printheads 20 . In an alternative embodiment, the carriage 14 can be raised from the printer 10 for service purposes.
[0073] In one embodiment, the printer 10 includes an enclosure cover to contain any dust or other debris generated during a printing operation. The enclosed area can be heated to facilitate better reactions between the build material and the binder materials. Better reactions include, for example, faster reaction times and improved bonding. In one embodiment, the heating is accomplished by introducing warm air at a low velocity to the enclosed area. The flow of air is typically not directed at the build surface to prevent disturbing the build material after spreading. In one example, the enclosure temperature is maintained from about 90 degrees F. to about 150 degrees F., preferably from about 110 degrees F. to about 135 degrees F., and more preferably about 125 degrees F.
[0074] FIG. 2 depicts one embodiment of the carriage 14 in more detail. The carriage 14 generally includes one or more printheads 20 . Typically, a printhead 20 is the apparatus through which binder liquid is ejected during the creation of an object. FIG. 2 shows four printheads 20 ; however, in other embodiments there may be more or fewer printheads 20 . In some embodiments, the printheads 20 may be inserted into the carriage 14 such that they are offset from one another along the X-axis. In some embodiments, this offset is by substantially the same distance along the X-axis. In other embodiments, the printheads 20 may be staggered within the carriage 14 such that the distances between the printheads 20 vary.
[0075] FIGS. 3A and 3B depict one embodiment of the service station 16 in greater detail. The service station 16 typically includes a discharge station 22 , a printhead capping station 24 , and a printhead cleaning station 29 . In various embodiments, the carriage 14 may engage the discharge station 22 , the printhead capping station 24 , and the printhead cleaning station 29 in any order, and any number of times. In some embodiments, the carriage 14 may engage the same station, for example the discharge station 22 , multiple times consecutively. In other embodiments, the carriage 14 can alternate repeatedly between any of the discharge station 22 , the printhead capping station 24 , and the printhead cleaning station 29 in any order, any number of times. In some embodiments, the printheads 20 of the carriage 14 engage the service station 16 in order to perform maintenance upon the printheads 20 during creation of an object.
[0076] Generally, the discharge station 22 includes discharge openings 28 through which the printheads 20 may discharge debris, such as, for example, contaminated binder. The number of the discharge openings 28 may vary. The discharge station 22 is typically an area where the printheads 20 may expel such material, thus preventing excess buildup of contaminants in the printheads 20 that could effect printing quality. Typically, debris entering the discharge station is contained so that it does not contaminate the printheads 20 , the carriage 14 , the service station 16 , or any other component of the printer 10 .
[0077] In some embodiments, the printheads 20 may be actuated to a point immediately above the discharge openings 28 , where the printheads 20 discharge excess binding material or other waste through the discharge openings 28 . Generally, this waste is collected in a receptacle 47 (see FIG. 4 .) In some embodiments, the carriage 14 is actuated into a position immediately above the service station 16 and the printheads 20 are positioned above the discharge openings 28 at the surface of the service station 16 . In some embodiments, the bottom surfaces of the printheads 20 may extend below the plane of the surface of the discharge openings 28 , where the printheads 20 may discharge material in order to rid the printheads 20 of contamination or excess building materials. This material then enters the receptacle 47 . In one embodiment, the discharge openings 28 are located above the receptacle 47 . Generally, the receptacle 47 is a location below the discharge openings 28 where the printheads 20 discharge their material. In some embodiments, the receptacle 47 may include a reservoir for containing the discharged material.
[0078] Generally, the printhead capping station 24 is the area where the printheads 20 are capped by the printhead caps 26 . In one embodiment, there is one printhead cap 26 for each printhead 20 . Generally, as a result of the carrier 14 engaging the printhead capping station 24 , the printhead caps 26 are actuated into a position circumscribing the printheads 20 , such that the printhead caps 26 form a seal around the printhead face 54 (see FIG. 5D ). The printhead caps 26 protect the printheads 20 against contamination, debris, and physical damage resulting from contact with the printheads 20 , deterioration, and the elements in general. Generally, the printhead capping station 24 may cap printheads 20 at any point in time relative to the printheads 20 engaging the discharge station 22 or the printhead cleaning station 29 . Generally, the printhead caps 26 enclose the printheads 20 in order to form a seal to prevent damage, such as drying out, from occurring to the printheads 20 . In some embodiments, maintenance may include cleaning on or about the printheads 20 . Only a single service station 16 is shown for descriptive purposes; however, multiple stations 16 may exist. Alternatively, a single service station 16 may service multiple printheads 20 by, for example, successively positioning the printheads 20 relative to the service station 16 .
[0079] The printhead cleaning station 29 generally includes the area where the printheads 20 may be cleaned. In one embodiment, the printheads 20 may be cleaned with a pressurized washing solution 92 (see FIG. 8E ). In some embodiments, the printheads 20 enter the printhead cleaning station 29 after the printheads 20 discharge material into the receptacle 47 . In other embodiments, the printheads 20 may enter the printhead cleaning station 29 without first discharging material into the receptacle 47 . In further embodiments, the printheads 20 may enter both the printhead cleaning station 29 and the discharge station 22 repeatedly and in any order. Typically, the cleaning station 29 cleans the printheads 20 by washing them in such a manner that any debris is removed from the printheads 20 and the pressurized washing solution 92 itself is contained so it does not contaminate the printheads 20 , or any other part of the printer 10 . For example, in one embodiment, the printheads 20 are cleaned in a sealed environment to contain any debris and cleaning materials. In another embodiment, the printheads 20 are protected during cleaning so that there is no excess debris or cleaning materials left on the printheads 20 that may later drip onto any component of the printer 10 , for example, the build surface 165 . In one embodiment, the printheads 20 are cleaned one at a time. In another embodiment, the printheads 20 may be cleaned simultaneously. In other embodiments, the printhead(s) 20 may be cleaned repeatedly, in any order, and at any time relative to engagement of the carrier 14 with any other components of the service station 16 . In one embodiment, the printer 10 includes logic for determining when to clean the printheads 20 , as discussed in greater detail hereinbelow.
[0080] FIG. 3B is a plan view of the service station 16 of FIG. 3A . From this perspective, the carriage 14 is actuated along the X-axis such that the printheads 20 are aligned with the discharge openings 28 . In one embodiment, upon completion of this alignment, the printheads 20 discharge residual or waste material through the discharge openings 28 . In some embodiments, the discharge may include binder material or other building material. In some embodiments, after discharge, the printheads 20 are further actuated along the X-axis to the printhead capping station 24 , where the printhead caps 26 form a seal around the printheads 20 . The seal formed by the printhead caps 26 around the printheads 20 generally protects the printheads 20 from the elements, contamination from debris or left over binding material, and prevents the printheads 20 from drying out.
[0081] FIG. 4 is a graphical representation of the discharge function of an embodiment of the invention, whereby binder material and debris 41 is discharged from the printhead 20 . In some embodiments, the binder debris 41 may include excess building material. In some embodiments, this discharge function is performed after every pass of the carriage 14 across the build surface 165 . In other embodiments, the discharge function may be performed periodically after any given number of passes of the carriage 14 . In still other embodiments, this function may be performed at fixed time intervals. In this illustrative embodiment, the carriage 14 is positioned above the service station 16 such that the printhead 20 is lined up over a spatial gap in between the aperture plates 40 . In some embodiments, the aperture plates 40 include the solid surface surrounding the discharge openings 28 (see FIG. 3B ). After proper positioning of the carriage 14 , the printhead 20 discharges the debris 41 or other waste. Generally, this debris 41 includes contaminants, such as, for example, excess binder material left in the printhead 20 . In one embodiment, the debris 41 joins the waste liquid 42 in the waste liquid catch tray 43 . In some embodiments, the waste liquid 42 may include discharge from past discharges of the printheads 20 . Upon discharge, the droplets of binder liquid 41 impinge upon the surface of the standing pool of waste liquid 42 , minimizing splash and the consequent generation of undesirable waste liquid aerosols. A spillway 44 is located at a distance above the bottom of receptacle 47 sufficient to maintain the standing pool of waste liquid 42 . Generally, the waste liquid 42 then proceeds down the spillway 44 where it eventually exits the service station 16 via a drain 45 . In some embodiments, any overflowing waste liquid 46 also exits the waste liquid catch tray 43 via the drain 45 , thus preventing contamination to the service station 16 .
[0082] FIG. 5A illustrates one embodiment of the capping function of the invention, whereby each printhead 20 is sealed by a cap. In some embodiments, this capping function may be performed after any given number of passes across the printer 10 . In still other embodiments, this function may be performed at a fixed time interval or after completion of printing. In FIG. 5B , the carriage 14 is actuated along the X-axis and positioned over the service station 16 . In this illustrative embodiment, there is a spatial gap between the printhead 20 and the printhead cap 26 . At this point, the printhead cap 26 has not yet capped the printhead 20 . Generally, the printhead cap 26 remains stationary until the printhead cap actuator 50 engages the printhead cap carrier 52 . In some embodiments, the carriage 14 has already moved beyond the aperture plate 40 and the discharge openings 28 and, thus, in some embodiments, the printhead 20 may have already expelled debris 41 into the waste liquid catch tray 43 . In some embodiments, the carriage 14 may have already actuated over the printhead cleaning station 29 . In some embodiments, as the carriage 14 continues actuation along the X-axis, the printhead cap actuator 50 engages the printhead cap carrier 52 . Generally, the printhead cap actuator 50 may include metal, plastic, or rubber appendages of sufficient rigidity to move the printhead cap carrier 52 along the X-axis along with the carriage 14 .
[0083] FIGS. 5C-5D illustrate the completion of the capping function. Typically, the printhead cap carrier 52 is a metal or other solid material fixed to the service station 16 and including a spring coefficient, such that movement of the carriage 14 and the printhead cap actuator 50 along the X-axis causes the printhead cap carrier 52 to move along the X-axis in this same direction. In some embodiments, this X-axis movement of the printhead cap carrier 52 then causes the printhead caps 26 to move along the Z-axis where they eventually cap the printheads 20 . In other embodiments, the carriage 14 , including the printhead cap actuators 50 , and the printhead cap carrier 52 cease movement in the direction of carriage motion 53 , and the printheads 20 are capped.
[0084] Generally, the printhead cap actuator 50 engages the printhead cap carrier 52 , causing the printhead cap carrier 52 to move in the direction of the printhead cap actuator 50 motion. In some embodiments, the printhead cap carrier 52 includes a spring element 601 , whereby the printhead cap carrier will pivot relative to the outer wall of the service station 16 when the spring 601 element is compressed. This pivot results in an uneven actuation of the printhead cap 26 towards the printhead 20 . As a result, the edge of the printhead cap 26 farthest from the printhead cap actuator 50 will initiate contact with the printhead 20 . In other embodiments, it is the edge of the printhead cap 26 located closest to the printhead cap actuator 50 that initially contacts the printhead 20 first. In either of the above illustrative embodiments, the printhead cap 26 continues actuation towards the printhead 20 until the printhead cap 26 levels off and circumscribes the printheads 20 . In some embodiments, the printhead cap 26 forms a seal around the printheads 20 . In one embodiment, one printhead 20 is capped by one printhead cap 26 . In one embodiment multiple printhead caps 26 cap multiple printheads 20 . Generally, there is one printhead cap 26 used each printhead 20 . Generally, the printheads 20 may be capped by the printhead caps 26 any number of times and in any order relative to engagement of the carriage 14 with any other component of the printer 10 .
[0085] As shown in FIGS. 5C and 5D , the printhead cap carrier 52 includes an arm 600 , a spring element 601 , and a plate 602 . Generally, the arm 600 is engaged by the printhead cap actuator 50 and is moved in the direction of the printhead cap actuator 53 motion. This movement causes the spring element 601 to compress, resulting in a pivoting motion. This pivoting motion causes the plate 602 to move towards the printhead 20 . The printhead cap 26 is typically disposed on a top surface of the plate 602 . In one embodiment, the plate 602 is rigid and, thus, the printhead cap 26 approaches the printhead 20 on a skew, such that one edge of the printhead cap 26 engages the printhead 20 before any of the other edges of the printhead cap 26 engage the printhead 20 . In various embodiments, any edge of the printhead cap 26 may first engage the printhead 20 . Typically, after the first engagement between any edge of the printhead cap 26 and the printhead 20 the plate 602 continues its motion until the printhead cap 26 circumscribes the printhead 20 . Specifically, the plate 602 may bend or flex in response to the actuation force of the carriage 14 until the plate 602 adopts a substantially horizontal orientation.
[0086] FIG. 5C includes a cutaway cross-sectional view of the service station 16 and the carriage 14 . In this illustrative embodiment, the carriage 14 is actuated along the X-axis in the indicated direction of carriage motion (arrow 53 ). The printhead cap actuator 50 will come into contact with the printhead cap carrier 52 and both the printhead cap actuator 50 and the printhead cap carrier 52 will move in the direction of carriage motion 53 . In this illustrative embodiment, the printhead cap 26 is located upon the printhead cap carrier 52 . Thus, movement of the printhead cap carrier 52 in the direction of carriage motion 53 causes the printhead cap 26 to move along the Z-axis. FIG. 5C includes a cut-away graphical representation of the carriage 14 and the service station 16 . FIG. 5C illustrates the point of contact between the printhead cap actuator 50 and the printhead cap carrier 52 as the carriage 14 moves in the direction of carriage motion 53 . In this embodiment, at this point, there is a spatial gap between the printhead 20 and the printhead cap 26 and therefore the printhead cap 26 has not sealed the printhead 20 .
[0087] FIG. 5D is a graphical representation of the carriage 14 and the service station 16 at a point forward in time from that of FIG. 5C , such that the printhead cap 26 has capped the printhead face 54 of the printhead 20 . Typically, the printhead face 54 includes the bottom face of the printhead 20 including and surrounding the point where the binder material is expelled from the printhead 20 . In this illustrative embodiment, the carriage motion 53 has caused the printhead cap actuator 50 to engage and move the printhead cap carrier 52 in the direction of carriage motion 53 . In this embodiment, the printhead face 54 has a protective seal formed around it by the printhead cap 26 . Generally, the cap or seal is sufficient to protect the printhead face 54 from damage or contamination. In some embodiments, the seal formed by the printhead cap may be airtight.
[0088] FIG. 6A is a partial cross sectional side view of an alternative embodiment of a service station 16 including a combined discharge and capping station. In this illustrative embodiment, the carriage 14 is actuated in the direction of carriage motion 53 , (along the X-axis) and positions itself over the service station 16 . In some embodiments, this actuation of the carriage 14 may be in preparation for discharge from the printhead 20 . In this illustrative embodiment, the waste liquid catch tray 43 includes waste liquid 42 . Generally, this waste liquid 42 was produced by previous discharges from past passes of the printhead 20 over the service station 16 . In some embodiments, the lower edge of the printhead cap 60 may extend into the area defined by the waste liquid catch tray 43 , but generally the lower edge of printhead cap 60 does not contact the bottom surface of the waste liquid catch tray 43 and, thus, waste liquid 42 flows freely and collects in waste liquid catch tray 43 until the waste liquid surface 61 rises to the top of spillway 44 . At this point, the waste liquid 42 then enters the waste liquid overflow tube 63 via overflow slot 62 . Generally, waste liquid overflow tube 63 carries the waste liquid 42 out of the service station 16 .
[0089] FIGS. 6B through 6D depict the capping and the discharge functions in greater detail. The carriage 14 is moving in the direction of carriage motion 53 , and is being positioned over the service station 16 . FIG. 6B illustrates an embodiment where contact has been made between the printhead cap actuator 50 and the printhead cap carrier 52 , but where the printhead cap carrier has not yet moved far enough in the direction of carriage motion 53 to lift the printhead cap 26 to a position where it caps the printhead 20 . FIG. 6C illustrates an embodiment of a point further in time from that of FIG. 6B . As shown in FIG. 6C , the printhead cap carrier 52 has moved the necessary distance in the direction of the carriage motion 53 to lift the printhead cap 26 to a point where it has formed a seal around the printhead 20 . The capping function is substantially similar to that described with respect to FIGS. 5A-5D . In some embodiments, the printhead cap 26 includes a discharge column 67 that defines a cavity 64 . The printhead 20 discharges to the waste liquid catch tray 43 through the discharge column. As shown in FIG. 6C , the printhead 20 expels debris 41 into the waste liquid catch tray 43 , where it mixes with any existing waste liquid 42 . In some embodiments, the collection of the waste liquid 42 will cross the spillway 44 and proceed to travel through the overflow slot 62 and down waste liquid overflow tube 63 as overflowing waste liquid 65 , where it is eventually expelled from service station 16 . Generally, this discharge procedure ensures a clean and clog free printhead 20 and printhead face 54 to maintain the highest possible quality three dimensional printing. In some embodiments, multiple printheads 20 may discharge material at substantially the same time.
[0090] Referring again to FIG. 6C , in some embodiments, a seal may be formed in the area defined by the discharge cavity 64 . Generally, the cavity 64 is bounded on the top by the printhead 20 and the printhead cap 26 , on the bottom by the waste liquid surface 61 , and on the sides by the discharge column 67 . In one embodiment, the level of the surface of the waste liquid 61 in the waste liquid catch tray 43 is sufficiently high to submerge a bottom portion of the discharge column 67 . The bottom portion of the discharge column 67 has a lowest point below the lowest point of the spillway 44 , which prevents the waste liquid 42 from dropping below the lowest portion of the discharge column. In such a case, and where the printhead cap 26 is sealed against the printhead face 54 of the printhead 20 , the cavity 64 is airtight, thereby preventing the printhead face 54 from drying out. In this embodiment, the discharge 41 is prevented from escaping the cavity 64 in any direction other than through the waste liquid overflow tube 63 , where it harmlessly exits the service station 16 . This exemplary embodiment minimizes the risk of contamination by the discharge 41 to any components of the printer 10 .
[0091] FIGS. 7A-7D depict one embodiment of a printhead cleaning station 500 in accordance with the invention. The printhead cleaning station 500 may also be mounted in the service station 16 . The printhead cleaning station 500 includes a reservoir 542 that holds a washing solution 543 and a pump 545 that delivers the washing solution 543 under pressure to at least one nozzle 540 and preferably an array of nozzles 540 . The nozzles 540 are capable of producing a high velocity stream of washing solution 543 . In operation, the nozzles 540 are directed to the printhead face 577 of the printhead 520 . When directed onto the printhead face 577 , the washing solution 543 loosens and removes contaminants, such as build material and binding material, from the printhead face 577 . The orientation of the nozzles 540 may be angled with respect to the printhead face 577 , such that a fluid flow is induced across a plane of the printhead face 577 . For example, the washing solution can contact the printhead 520 at the side nearest the nozzles 540 and drain from the side of the printhead 520 furthest from the nozzles 540 . This approach improves the efficacy of the stream of washing solution 543 by reducing the accumulation of washing solution on the printhead face 577 , as well as the amount of washing solution 543 and debris that would otherwise drain near and interfere with the nozzles 540 . A splash guard may also be included in the printhead cleaning station 500 to contain splashing resulting from the streams of liquid washing solution 543 .
[0092] It is desirable to remove a large portion of the washing solution 543 that remains on the printhead face 577 after the operation of the nozzles 540 is complete. This is conventionally accomplished by drawing a wiping element across the printhead face 577 . A disadvantage of this approach is that contact between the wiping element and the printhead face 577 may degrade the performance of the printhead 520 by, for example, damaging the edges of the inkjet nozzle orifices. Accordingly, it is an object of this invention to provide a means of removing accumulated washing solution from the printhead face 577 , without contacting the delicate region around the inkjet nozzles. In one embodiment, a wicking member 544 may be disposed such that the printhead face 577 may pass one or more times over its upper surface 546 in close proximity, without contact, allowing capillary forces to draw accumulated washing solution 543 away from the printhead face 577 . The wicking member 544 may be made from rigid, semi-rigid, or compliant materials, and can be of an absorbent or impermeable nature, or any combination thereof.
[0093] For the wicking member 544 to effectively remove accumulated washing solution 543 from the printhead face 577 , the gap between the upper surface 546 of the wicking member 544 and the printhead face 577 must be small, a desirable range being between about 0 inches to about 0.03 inches. A further object of this invention is to provide a means for maintaining the gap in this range without resort to precise, rigid, and costly components.
[0094] In another embodiment, the wicking member 544 may consist of a compliant rubber sheet oriented approximately orthogonal to the direction of relative motion 547 between the wicking member 544 and the printhead 520 and with a portion of its upper surface 546 disposed so that it lightly contacts or interferes with the printhead face 577 only in non-critical areas away from the printhead nozzle orifices. The upper surface 546 of the wicking member 544 may include one or more notches 548 at locations where the wicking member 544 might otherwise contact delicate components of the printhead face 577 . System dimensions are selected so that the wicking member 544 always contacts the printhead face 577 , and is deflected as the printhead 520 passes over it, independent of expected variations in the relative positions of the printhead 520 and the printhead cleaning station 500 . The upper surface 546 accordingly follows the position of the printhead face 577 , maintaining by extension a substantially constant space between the printhead face 577 and the relieved surface notch 548 . To further prolong the life of the printhead 520 , a bending zone of the wicking member 544 can be of reduced cross-section to provide reliable bending behavior with little deformation of the upper surface 546 of the wicking member 544 .
[0095] FIGS. 7B-7D illustrate a reconditioning cycle in accordance with the invention. FIG. 7B shows the printhead 520 approaching the printhead cleaning station 500 along a path designated by arrow 547 . When the printheads 520 lightly contact the wicking member 544 , as shown in FIG. 7C , motion stops along the path 547 and the washing solution 543 is directed at the printhead face 577 by the nozzle array 540 . When the spraying operation is complete, the printhead 520 continues to travel along the path 547 , as shown in FIG. 7D . The wicking member 544 is further deflected to allow passage of the printhead 520 , and the accumulated washing solution 543 is wicked away from the printhead face 577 . After being sprayed and wiped, in some embodiments the printhead 520 may print a plurality of droplets to eject any washing solution that may have been ingested during the reconditioning process.
[0096] Additional cleaning methods are contemplated, such as wiping the printhead face 577 with a cylindrical “paint roller” that cleans and moistens itself by rolling in a reservoir of wash fluid. In another embodiment, a cleaning system could include a continuous filament that carries wash fluid up to printhead face 577 and carries debris away to a sump. The system may include a small scraper that can be run over the filament to remove built up debris.
[0097] FIG. 8A depicts an alternative embodiment of cleaning a station 529 in accordance with the invention. Generally, the printer 10 is capable of determining when to clean the printheads 20 via the service station 16 , as will be described in greater detail hereinbelow. In some embodiments, only a single printhead 20 is cleaned by the service station 16 . In other embodiments, multiple printheads 20 are cleaned. In some embodiments, the service station 16 includes a nozzle manifold 80 . Generally, the nozzle manifold 80 includes at least one nozzle 540 and preferably and array of nozzles 540 . In some embodiments, the service station 16 includes a splash guard 81 . Generally, the splash guard 81 is included in the printhead cleaning station 529 to contain splashing resulting from the streams of the washing solution 543 . Typically, the splash guard 81 prevents contamination of powder or binding material by containing the washing solution 543 . Generally, the cleaning station 529 operates the same as the cleaning station 500 described with respect to FIGS. 7A-7D , except for the addition of the manifold 80 and the splash guard 81 .
[0098] FIG. 8B is a graphical representation of the splash guard 81 that is located in the printhead cleaning station 529 . The splash guard 81 generally includes a notch 82 , a drain aperture 83 , an actuation face 89 , a flexure point 85 , and a sealing lip 86 . FIGS. 8C-8H depict the operation of the cleaning station 529 . Typically, the printhead 20 is actuated such that the printhead face 54 passes immediately over the notch 82 without contacting the surface of the notch 82 . Typically, avoiding contact between the printhead face 54 and notch 82 prevents damaging or altering the trajectory of jet nozzles on the printhead face 54 . In one embodiment, the sealing lip 86 may act as a wiper, contacting the printhead 20 adjacent to the printhead face 54 without contacting the printhead face 54 itself. Once the printheads 20 have cleared the notch 82 , they enter the space immediately above the drain aperture 83 . Generally, the drain aperture 83 is for passing the washing solution 543 . Once the printhead 20 is positioned roughly over the drain aperture 83 , the printhead 20 engages the actuation face 89 . Typically, the printhead 20 engages the actuation face 89 in such a way as to cause the splash guard 81 to flex along the flexure point 85 . In some embodiments, the flexure point 85 includes a pivot point allowing at least the portion of the splash guard 81 including the notch 82 , the drain aperture 83 , the actuation face 89 , and the sealing lip 86 to pivot in the direction of actuation of the printhead 20 . Generally, this pivot at the flexure point 85 raises the drain aperture 83 to the printhead 20 such that the sealing lip 86 contacts the printhead 20 . Generally, the sealing lip 86 is actuated into a position where it forms a seal around the printhead face 54 . Typically, the seal formed by the sealing lip 86 is watertight, thus preventing the washing solution 543 from contaminating the printer 10 . Generally, the only available outlet for used washing solution 543 is through the drain aperture 83 .
[0099] FIG. 8C includes another perspective of the printhead 20 as it approaches the service station 16 . FIG. 8C generally represents the starting position of the cleaning operation performed by the service station 16 . In this illustrative embodiment, the printhead 20 is actuated in the direction of the printhead motion 87 such that the printhead face 54 is brought above the service station 16 . As the printhead 20 is being actuated, the printhead side 88 will engage the actuation face 89 of the splashguard 81 . After this engagement, the printhead 20 moves the actuation face 89 such that the sealing lip 86 forms a seal around the printhead face 54 (see FIG. 8D ). In some embodiments, the actuation face 89 pivots at the flexure point 85 . In some embodiments, the flexure joint 85 may include a spring element. Generally, this procedure results in the forming of a watertight seal by the splash guard 81 around the underside of the printhead 20 adjacent to the printhead face 54 .
[0100] FIG. 8D depicts the printhead 20 moved into its desired position over the service station 16 . Generally, this is the point at which the service station 16 will clean the printhead 20 . As illustrated in FIG. 8D , the actuation face 89 seals the printhead 20 around part of the printhead face 54 . The seal is completed around the printhead face 54 by the splash guard lip 86 . Generally, the splash guard lip 86 is part of the splash guard 81 . In one embodiment, as the printhead 20 is actuating the splash guard 81 via its contact with the actuation face 89 , the resulting movement of the splash guard 81 also moves the sealing lips 86 into a position against the bottom of the printhead 20 and along the printhead face 54 . In some embodiments, the sealing lips 86 come to rest against the underside of the printhead 20 against the printhead face 54 . Generally, forming a seal around the printhead 54 on the underside of the printhead 20 , as opposed to along the printhead side 88 , is desired as it prevents contamination of the printhead side 88 , or any other side of the printhead 20 . For example, washing solution left on the printhead 20 can drip off during printing, thereby effecting print quality.
[0101] FIG. 8E is a partially sectioned side view of the service station 16 during cleaning of the printhead 20 by the service station 16 in accordance with one embodiment of the invention. Subsequent to the forming of a seal around the printhead face 54 , the nozzle manifold 80 sprays the washing solution streams 91 . Generally, the nozzle manifold 80 includes the pressurized washing solution 92 . In one embodiment, the pressurized washing solution 92 is sprayed onto the printhead face 54 in a single stream 91 . In other embodiments, there are multiple streams 91 of the pressurized washing solution 92 . In operation, the washing solution streams 91 are directed at the printhead face 54 of the printhead 20 . When directed onto the printhead face 54 , the washing solution streams 91 loosen and remove contaminants, such as binder material, from the printhead face 54 . The orientation of the washing solution streams 91 may be angled with respect to the printhead face 54 , such that a fluid flow is induced across a plane of the printhead face 54 . For example, in one embodiment, the washing solution stream 91 may contact the printhead 20 at the side nearest the nozzle manifold 80 and drain from the side of the printhead 20 furthest from the nozzle manifold 80 . This approach improves the effectiveness of the washing solution streams 91 by reducing the accumulation of the washing solution 92 on the printhead face 54 , as well as the amount of the pressurized washing solution 92 and debris that would otherwise drain near and interfere with the nozzle manifold 80 . FIG. 8F is another partially sectioned view of the invention illustrated in FIG. 8E . The printhead face 54 is in proper position for cleaning. The sealing lips 86 have formed a seal around the printhead face 54 thus protecting the remainder of the printhead 20 from contamination.
[0102] FIG. 8G illustrates the movement of the printhead 20 out of the service station 16 after a cleaning operation has been performed. The printhead 20 now moves in the direction of printhead motion 93 away from the service station 16 . This is generally the same as the direction of carriage motion 53 that was used to enter the service station 16 . As the printhead 20 is actuating out of the service station 16 , the printhead face 54 is carried over the sealing lip 86 and the notch 82 . In some embodiments, the sealing lip 86 may act as a wiper and remove debris and washing solution 92 from the area on the bottom of the printhead 20 adjacent to the printhead face 54 ; however, the notch 82 prevents contact between the sealing lip 86 and printhead face 54 in an area corresponding to the location of the jet nozzles. Contact between the sealing lip 86 and the printhead face 54 may degrade the performance of the printhead 20 by, for example, damaging the edges of the inkjet nozzle orifices on the printhead face 54 . However, it is still desirable to remove a large portion of the washing solution 92 that remains on the printhead face 54 after the operation of the nozzle manifold 80 is complete. Accordingly, it is an object of this invention to provide a means of removing accumulated washing solution from the printhead face 54 , without contacting the delicate region around the jet nozzles on the printhead face 54 . Because the notch 82 prevents direct contact between the sealing lip 86 and the printhead face 54 , in one embodiment, a wicking member 544 (as described above) may be disposed such that the printhead face 54 may pass one or more times over the wicking member 544 in close proximity, without contact, allowing capillary forces to draw the accumulated pressurized washing solution 92 away from the printhead face 54 . FIG. 8H illustrates a partially sectioned bottom perspective view of the service station 16 of FIG. 8A . Here it can be seen that the sensitive portion of the printhead face 54 passes over the notch 82 as the printhead 20 is actuated away from the service station 16 after a cleaning. Generally, the sensitive portion of the printhead face 54 includes the printhead jet nozzle array.
[0103] FIGS. 9A and 9B illustrate an alternative embodiment of the splash guard 81 of FIG. 8B . In this embodiment, the splash guard 81 includes tapered sealing surfaces 94 . Generally, the tapered sealing surfaces 94 are shaped so that they will form a seal around the corners formed by the printhead edges 95 . Thus, the seal in this embodiment is formed by the tapered sealing surfaces 94 contacting both the printhead face 54 , and the printhead side 88 of the printhead 20 . Thus, the seal formed by this embodiment wraps around the edges of the printhead 20 to contain the washing solution 92 during the cleaning operation. The operation of the alternative splash guard 81 of FIGS. 9A and 9B and the associated cleaning components is substantially similar that described hereinabove.
[0104] FIGS. 10A-10D illustrate another alternative embodiment of the splash guard 81 of FIG. 8B . In this embodiment, the splash guard 81 again forms a seal with the splash guard sealing lips 86 ; however, in this embodiment, the splash guard 81 is actuated into its sealed position around the printhead face 54 by a splashguard support spring 102 . This procedure is analogous to the procedure used to cap the printhead 20 in the capping operation. Generally, the printhead 20 is carried over the service station 16 in the direction of a first printhead motion (arrow 100 ). Once roughly positioned over the drain aperture 83 , the direction of the printhead motion changes direction to a substantially perpendicular printhead motion (arrow 101 ). In some embodiments, the direction of the printhead motion 101 is orthogonal to the previous direction of printhead motion 100 . The printhead 20 now proceeds in the second direction of the printhead motion 101 until the printhead side 88 engages the splash guard support spring 102 . (See FIG. 10 B) As FIG. 10C illustrates, the splash guard support spring 102 moves in the direction of the second printhead motion 101 . This movement engages the splash guard 81 with the printhead face 54 .
[0105] Once the cleaning operation is performed as described above, the printhead 20 moves in a third direction of printhead motion (arrow 103 ) away from the service station 16 . Generally, the third direction of printhead motion 103 is opposite the first direction of printhead motion 100 , as the printhead 20 disengages from the service station 16 . This disengagement breaks the seal formed by the splash guard sealing lip 86 , and the printhead face 54 is carried over the sealing lip 86 where a wiper operation may be performed to remove debris or the washing solution 92 from the printhead face 54 . As described above, a wicking operation may also be performed.
[0106] FIGS. 11A-11J illustrate an alternative system 146 for cleaning the printhead 20 . The system 146 is located in the service station 16 ( FIG. 1 ). In one embodiment, the system 146 includes a cleaning station 148 made up generally of a latch pawl 152 , a spring 154 , a wiper 156 , a printhead cap 158 , a cap carrier 192 , a second spring 162 , and a cam track 164 . Only a single cleaning station 148 is shown for descriptive purposes; however, multiple stations 148 may be disposed in the service station 16 . Alternatively, a single cleaning station 148 may service multiple printheads 20 by, for example, successively positioning the printheads 20 relative to the cleaning station 148 .
[0107] FIG. 11A represents a starting position of the cleaning system 146 . As shown in FIG. 11B , the printhead 20 approaches the cleaning station 148 and engages the latch pawl 152 . The latch pawl 152 is actuated as the printhead 20 passes over the latch pawl 152 . The printhead 20 continues to move past the latch pawl 152 and engages the wiper 156 ( FIG. 11C ). The printhead 20 passes over a wiper 156 . As shown in FIG. 11D , the printhead 20 contacts the cap carrier 192 , which is driven along the cam track 164 and compresses the spring 162 . The printhead cap 26 is positioned against a printhead face 54 ( FIGS. 11E and 11F ). As shown in FIG. 11F , the printhead cap 26 seals against the printhead face 54 while the face 54 is rinsed with washing solution 92 (see FIG. 11F ).
[0108] After the printhead face 54 is cleaned, the printhead 20 begins to move out of the service station 16 ( FIG. 11G ). The latch pawl 152 engages the cap carrier 192 , halting its movement. As shown in FIG. 11H , the printhead 20 engages the wiper 156 , which wipes the printhead face 54 . In an alternative embodiment, the wiper 156 vibrates to further clean the printhead face 54 . In an alternative embodiment, the wiper 156 may be notched in an area corresponding to the location of the jet nozzles, thereby preventing contact between the wiper 156 and the printhead face 54 . The printhead 20 continues its forward movement, actuating the latch pawl 152 ( FIG. 11I ), which, in turn, releases the cap carrier 192 ( FIG. 11J ). The cap carrier 192 snaps back to the start position. After the printhead face 54 is cleaned, the printhead 20 begins to move out of service station 16 ( FIG. 11G ). The system 146 is now ready to clean another printhead 20 .
[0109] FIG. 12 depicts the system 146 for cleaning a printhead 20 . ( FIG. 12 also depicts FIG. 11F in greater detail) The printhead 20 is positioned with the printhead face 54 against the printhead cap 26 , which in this embodiment is made of rubber. The cap includes a seal lip 172 for sealing about the printhead face 54 . The service station 16 is coupled to a wash fluid supply container 182 via a supply duct 184 and a wash fluid return container 186 via a return duct 188 . The wash fluid return container 186 is in communication with a vacuum source 180 , in this case a vacuum pump, via a vacuum duct 190 . Additionally, a valve 178 is located in the return duct 188 . The valve 178 may be manually or automatically actuated.
[0110] In operation, the vacuum source 180 creates a vacuum within a cavity 174 in the printhead cap 54 . The vacuum pulls wash fluid from the supply container 182 through the supply duct 184 . The wash fluid enters the cavity 174 as a spray 176 against the printhead face 54 . The spray 176 washes debris, such as excess build material and dried binder, off the printhead face 54 . The used wash fluid and debris are drawn out of the cavity 174 by the vacuum source 180 and into the return container 186 via the return duct 188 . Additionally, the negative pressure created in the cavity 174 by the vacuum source 180 prevents the wash fluid from entering the jet nozzles and, in fact, may cause a small amount of binder to flow out of the nozzles to flush any powdered build material out of the nozzles. Blockages or obstructions in the jet nozzles can cause the jets to fire in the wrong direction. Once the operation is complete, the system 146 moves onto the step depicted in FIG. 11G . In an alternative embodiment, printhead(s) 20 are disposed above the service station 16 . The sealing lip 86 is actuated into alignment with the printheads 20 , and the printheads 20 are wiped and lubricated from beneath to remove any accumulated grit and to improve the flow of binding material out of the printheads 20 . Specifically, a lubricator applies a lubricant to the printhead face 20 to moisten any debris on the printhead face 54 . Then, the printhead 20 is moved to pass the printhead face 54 over sealing lips 86 , which act as a wiper and wipes the printhead face 54 clean.
[0111] FIG. 13 depicts a typical printing operation with a 3D printer in accordance with the invention. Only one printhead 220 is shown for clarity. The printhead 220 moves over a powder bed 200 that has been spread over a build surface of the 3D printer (se, for example, FIG. 1 ). As previously described, the printhead 220 can move along an X-axis and a Y-axis. In the operation depicted, the printhead 220 is moving in a single direction (arrow 202 ). As the printhead 220 travels above the powder bed 200 , the printhead 220 performs a printing operation by depositing droplets 212 of liquid binder on to the powder bed 200 in a predetermined manner, thereby resulting in printed sections 204 and unprinted sections 206 in the powder bed 200 .
[0112] After printing on the powder bed 200 , a new layer of powder is spread over the powder bed 200 in preparation for receiving the new printing 218 . As the printhead 220 deposits the droplets 212 onto the powder bed 200 , particles 210 of the powder are ejected by the impact of the droplets 212 on the powder bed 200 (see FIGS. 14A and 14B ). These particles 210 may eventually contact and adhere to the printhead 220 . The resulting debris 216 degrades the quality of printing by, for example, interfering with a printhead nozzle 208 . The amount of particles 210 ejected will depend, in part, on whether the powder is “wet” or “dry.” The powder is wet if the underlying layer was previously printed (see FIG. 14B ). The powder is dry if the underlying layer was previously unprinted (see FIG. 14A ).
[0113] As shown in FIG. 14A , the printhead 220 is depositing droplets 212 on to a dry powder bed 200 . As the droplets 212 impact the powder bed 200 , a relatively large volume of particles 210 are displaced and a crater 214 is created in the powder bed 200 . The particles 210 are ejected upwardly towards the printhead 220 , where they may collect as debris 216 on a face of the printhead 220 .
[0114] As shown in FIG. 14B , the printhead 220 is depositing droplets 212 on to a wet powder bed 200 . As the droplets 212 impact the powder bed 200 , a relatively small volume of particles 210 are displaced and a relatively small crater 214 is created in the powder bed 200 . The binder printed on the previous layer tends to bind the powder in the fresh layer, thereby resulting in fewer particles being ejected, and correspondingly less debris accumulating on the printhead face.
[0115] The 3D printer includes logic for monitoring the condition of the printhead 220 based on, at least in part, the number of droplets printed over previously printed and/or unprinted powder, since the last cleaning. Other factors include; for example, time in use, number of droplets dispensed, and number of layers printed. The 3D printer can determine the frequency and duration of any necessary cleaning routine, based on any one of the aforementioned factors or combination of factors reaching a set threshold value. For example, the printhead 220 may be cleaned after every five minutes of continuous use. The threshold values of any particular factor can be varied depending on the types of liquid binder and powder materials used and other operational environmental factors, such as temperature and humidity, that can affect printhead condition.
[0116] Additionally or alternatively, the 3D printer can utilize other systems and methods for monitoring and maintaining the cleanliness of the printhead 220 . For example, in one embodiment, the 3D printer could include an imaging system for viewing the printhead face. A user could either manually determine that the printhead 220 requires cleaning or the 3D printer could include the imaging system for automatically determining the need for cleaning. In a manual system, an image of the printhead face is displayed to the user, for example on a video monitor, and the user can initiate a cleaning routine if deemed necessary. In one example of an automatic system, the actual image of the face of the printhead in service is sent to a processor for comparison to an image of a clean printhead face, (i.e., a test image). In one embodiment, the printhead face is dark and the powder is relatively light in color. If a significant portion of the printhead face is covered with debris, there will be a difference in contrast between the actual image and the test image. If the difference in contrast reaches a predetermined threshold, the system initiates the cleaning routine.
[0117] In some embodiments, the cleanliness of the printhead face can be maintained by the use of an air curtain or an electro-static charge. The system can supply a low pressure curtain of air across the printhead face that would reduce or prevent debris from collecting on the printhead face. Alternatively, the printhead face could have an electro-static charged placed thereon that is the same charge that is applied to the powder, thereby resulting in the powder particles being repelled from the printhead face.
[0118] FIG. 15 is a schematic representation of a printhead alignment process in accordance with one embodiment of the invention. Specifically, the printhead carriage 14 described hereinabove is depicted in relation to an alignment test pattern 129 . The test pattern 129 is printed on the build surface 165 of the three-dimensional printing system 10 (see FIG. 1 ). The test pattern 129 includes a contrast-enhancing sublayer 130 that defines an area upon which an X-axis alignment pattern 133 and a Y-axis alignment pattern 134 are printed. The X and Y-axis alignment patterns 133 , 134 are line pair arrays made up of alternating reference lines 135 and test lines 136 . Also included on the sublayer 130 is a contrast optimization pattern 131 , which is described in greater detail with respect to FIGS. 16A and 16B . The carriage 14 includes an alignment sensor system 132 that is used to scan the test pattern 129 . The system 132 is described in greater detail with respect to FIGS. 17A-17D .
[0119] The pattern 129 is created by first spreading a layer of build material on the build surface 165 . The printheads 20 are then used to print the contrast-enhancing sublayer 130 on the layer of build material powder. Generally, the contrast-enhancing sublayer 130 provides a background reference to create a contrast between a printed layer and its surroundings. Generally, it is desirable to perform the alignment process (e.g., creating the test pattern 129 ) using the same binder solutions that will later be used to print the three-dimensional parts. Clear binder can present a particular problem, in that an image printed on powder with clear binder is difficult to distinguish from its unprinted surroundings. This problem can be solved by printing the contrast-enhancing sublayer 130 , though it is not required.
[0120] The contrast-enhancing sublayer 130 is printed on the build surface 165 of dimensions sufficient to underlie the whole array of alignment pattern objects (e.g., the X-axis alignment pattern 133 , the Y-axis alignment pattern 134 , and the contrast optimization pattern 131 ). In some embodiments, a dark color such as magenta or cyan may be used. The area may be printed more than once to increase the darkness of the color. A layer of fresh powder is then spread over this sublayer 130 , obscuring the dark color. When an image is then printed on the fresh layer with clear binder, the powder is wetted in the printed areas and becomes somewhat transparent, revealing the dark color of the sublayer 130 . In some embodiments, the contrast-enhancing sublayer 130 and the powder spread over it may collectively be referred to as the contrast-enhancing sublayer 130 . The printed area then contrasts more clearly with its surroundings to be detected more readily by the alignment sensor system.
[0121] Next, the contrast optimization pattern 131 is printed on the contrast-enhancing sublayer 130 . In some embodiments, the contrast optimization pattern 131 includes a printed area or target 143 - 146 (see FIG. 16A ) from each of the printheads 20 . The alignment sensor system 132 then determines the area of highest contrast between the printed targets 143 - 146 that collectively form the contrast optimization pattern 131 with contrast-enhancing sublayer 130 to determine which target 143 - 146 of the contrast optimization pattern 131 (and its corresponding printhead 20 ) has the greatest contrast relative to an unprinted area 141 (see FIG. 16A ) of the contrast-enhancing sublayer 130 .
[0122] The general procedure is to adopt one of four colors as a reference standard and to characterize the positional errors of the other colors with respect to the reference color. In one embodiment, the four colors include clear (printed area 143 ), yellow (printed area 144 ), magenta (printed area 145 ), and cyan (printed area 146 ). It may be desirable to adopt as a reference the color that contrasts most with the unprinted background. To this end, a target is printed in each color and then examined with the alignment sensor system 132 . The color that produces the least photo sensor output may be selected.
[0123] FIGS. 16A and 16B further detail the contrast optimization pattern 131 . FIG. 16A is a graphical representation of the contrast optimization pattern 131 including the aforementioned targets 142 - 146 . FIG. 16B shows the relationship between light source current and photo sensor output (e.g., alignment sensor current). As the light impinging on a photo sensor increases, it will eventually reach a level where the sensor output approaches a maximum and becomes insensitive to further increases in light input. This state of insensitivity is commonly called saturation, and is indicated by the saturated region 147 in FIG. 16B . The proportional region of the sensor output is indicated by the proportional region 148 in FIG. 16B . To maximize the information content of the sensor output signal, it is desirable to avoid saturating the sensor under normal operating conditions. The powders used in 3D printing may vary widely in reflectivity, resulting in large variations in maximum sensor illumination. To compensate for this effect, the alignment sensor assembly is positioned over an unprinted area 142 above the build surface and senses unprinted area 142 (see FIG. 16A ). The input current through the light source is gradually increased until diminishing sensor output indicates saturation. The light source current is then reduced to provide a safe operating margin within the proportional region 148 . Alternatively, the light source current can be gradually increased until a predetermined safe photo sensor output is reached.
[0124] Referring back to FIG. 15 , two substantially identical arrays of line pairs disposed substantially at right angles to each other make up the X-axis alignment test pattern 133 and the Y-axis alignment test pattern 134 . In one embodiment, one of the test patterns represents a slow axis printing and the other test pattern represents a fast axis printing of the three-dimensional printer 10 . Generally, the X-axis alignment test pattern 133 and Y-axis alignment test pattern 134 are processed in sequence, and the processes are identical. Generally, both the X-axis alignment pattern 133 and the Y-axis alignment pattern 134 include the reference line 135 and the test line 136 . In one embodiment, the reference line 135 is created by the printhead 20 that was determined to have the greatest contrast relative to the contrast-enhancing sublayer 130 . The line pairs are discussed in greater detail hereinbelow with respect to FIGS. 18, 19A , 19 B, and 21 A.
[0125] In some embodiments, to determine the highest contrast between the contrast optimization pattern 131 and the contrast-enhancing sublayer 130 , the carriage 14 may include a light source 137 , for example a light emitting diode (LED), which produces a cone of light 138 . Alternatively, the light sources could be a laser or a lamp, and multiple light sources could be utilized. The LED light source 137 illuminates the general area under examination. In some embodiments, the LED light source 137 is a blue-green color to produce a high level of contrast between printed and unprinted areas. An optical filter passes light only in a narrow wavelength window that includes the LED output. Ambient room light contains relatively little light of the wavelength passed by the filter, so that the great majority of the light that reaches the photo sensor originates from the light source. As a result, the system is relatively insensitive to ambient room light variations.
[0126] In another embodiment, ambient light insensitivity is achieved by modulating the light source 137 output at a frequency much higher than the signal of interest. The photo sensor output is filtered electronically to pass only the frequency of the modulated light. This increases the sensitivity of the system to low light levels. An optional lens can increase the sensitivity of the system to low light levels.
[0127] FIGS. 17A-17D depict the alignment sensor system 132 in greater detail. The system 132 is typically part of the printhead carriage 14 . In a particular embodiment, the system 132 is mounted on a printed circuit board 160 that includes, for example, the logic for directing the carriage 14 , firing the printheads 20 , and operating the alignment sensor system 132 . The system 132 generally includes the light source 137 , an optical filter 161 , a light entrance 162 , a photo sensor 163 , and an optional lens 164 . The light source 137 is used to illuminate a spot on the test pattern 129 that is about the same diameter as the width of the colored lines being scanned. The light source 137 and the photo sensor 163 could each be focused or unfocused. FIGS. 17C-17D depict different operational states of the alignment sensor system 132 . FIG. 17C illustrates the illumination of an illuminated area 166 on the build surface by the light cone 138 . In one embodiment, the light source floods the area of interest with light. In FIG. 17D , a sensed area 142 on the illuminated build surface 165 reflects light back to the photo sensor 163 . Typically, the sensed area 142 corresponds to a print target 142 - 146 or a portion of the reference line 135 or test line 136 and is smaller in area than the illuminated area 166 . The tubular light entrance channel 162 restricts the field of view of the photo sensor to a spot small relative to the illuminated area. In some embodiments, the photo sensor 163 may include the capability of detecting a surface photovoltage from the illuminated area 166 of the printing surface. In other embodiments, the system 132 may include an optional lens 164 to focus the reflected light on the sensor 163 .
[0128] FIG. 18 depicts the X-axis alignment pattern 133 of FIG. 15 . The X-axis alignment pattern 133 and the Y-axis alignment pattern 134 are substantially identical, with the exception that the line pairs are oriented substantially perpendicularly, although alternative configurations are contemplated and considered within the scope of the invention. As previously described, the X-axis alignment pattern 133 includes a series of reference lines 135 and test lines 136 . Generally, each reference line 135 is printed by the printhead 20 with the highest contrast relative to the contrast-enhancing sublayer 130 , and each test line 136 is printed in an alternating pattern by at least one of the three remaining printheads 20 with lesser relative contrasts. As the number of printheads may vary in different embodiments, the number of corresponding color bars in each test line 136 also may vary. In one exemplary embodiment, the reference line 135 may be made of clear deposited material, and test line 136 may be sequentially repeating yellow, magenta, and cyan color deposits. Typically, the test pattern 129 is printed by the printheads 20 in order to determine if the printheads 20 are properly aligned. The test pattern 129 is printed assuming the printheads 20 are perfectly positioned. Once the test pattern 129 has been printed, the carriage 14 is actuated over the surface of the test pattern 129 and the alignment sensor system 132 scans at least a portion of test pattern 129 to determine the deviation of the test line 136 from the perfect position. The scanned results are then used to correct any identified errors.
[0129] FIGS. 19A-19B illustrate the scan spot travel paths 171 across a test pattern. FIG. 19A illustrates a nominal X-axis alignment pattern 170 . As the sensed area 142 passes over the printed lines in the direction of line pair replication direction 173 , the photo sensor 163 receives reflected light that originated from the light source 137 . The reflectances of the color bars differ from the unprinted background (in one example, the unprinted background is white), and the reflectances of the colors vary amongst themselves. As illustrated by FIG. 19B , the basic unit of the target is a line pair, such as line pair 174 , which comprises a solid reference line 135 and a test line 136 including an array 181 of systematically varying short bars 191 including a first color bar 176 , a second color bar 177 , and a third color bar 178 . Alternative embodiments may have more or fewer color bars. Collectively, the color bars 176 , 177 , 178 , are components of the test line 136 . This line pair 174 is periodically repeated in the direction shown with a constant pitch (“P”) 197 between successive reference lines, for example, reference lines 135 . In the illustrative embodiment of FIG. 19B , the line pair 174 is repeated 11 times; however, the number of line pairs will vary to suit a particular application and/or desired level of accuracy.
[0130] In one embodiment, the scan spot traverses the array of line pairs 174 along travel paths perpendicular to the reference line 135 . In the embodiment illustrated by FIG. 19B , complete examination of the target requires 33 scan spot passes. Three typical scan path travel paths 171 are indicated (see FIG. 19A ). In one embodiment, the width of the color bars 176 , 177 , 178 , the minimum anticipated space between the bars, and the size of the scan spot should be substantially equal. The color bars 176 , 177 , 178 shown in FIG. 19B vary systematically around a spacing equal to about one half of the reference line pitch P 197 . An exemplary short bar is identified as short bar 191 . In one embodiment, the increment of variation, (“δ”), may typically be 2 pixels at 300 dpi or 0.007 inches. The position of the uppermost group of three short bars of the color bars 176 , 177 , 178 is nominally printed equidistant between two of the reference lines 135 . Progressing down the array, the groups of three color bars 176 , 177 , 178 diverge from the central position by increasing amounts, for example +/−nδ, where “n” is an integer (e.g., 1δ, 2δ, 3δ, etc.). The width and pitch of the reference lines 135 and test lines 136 are selected to optimize the signal contrast. The dimensions given herein are for illustrative purposes only and are in no way to be considered limiting.
[0131] FIGS. 20A-20D illustrate one embodiment of the alignment process with respect to a single scan spot travel path 171 . FIGS. 20A and 20B illustrate the single scan spot pass travel path 171 in the direction of carriage motion 193 across reference lines 135 and test lines 136 . As the scan spot passes over the printed color bars, the photo sensor receives reflected light that originated from the light source 137 . The reflectances of the color bars differ from the unprinted background, and the reflectances of the colors vary amongst themselves. FIG. 20C illustrates the sensor output signal, which represents strong periodicity related to the color bar spacing and peak amplitude variations due to different color reflectances.
[0132] As shown in FIG. 20D , any signal can be represented as the sum of an arbitrarily large number of sinusoids, each having a constant discrete frequency, a constant amplitude, and a constant phase relationship to a fixed standard. The process of extracting the sinusoidal constituents of a signal is called Fourier analysis. A common practical approach is to digitize the signal and to then employ a computational algorithm, such as a Fast Fourier Transform (“FFT”). FIG. 20D shows the principle harmonic constituents of the signal shown in FIG. 20C . The frequency of these constituents is fixed by the geometric constraints placed on the test pattern 129 . The magnitude of the each constituent is affected by differences in color reflectivity and by the displacement (“E”) 183 (see FIG. 20B ) of the adjustable color bar relative to its central position. The magnitude of the harmonic component whose frequency is three times the reference bar frequency increases with color test bar displacement from perfect alignment, and can be used to determine the magnitude of the displacement. FIG. 20D is a graphical representation of the sensor output indicating spatial frequency and a first harmonic peak 185 , a second harmonic peak 186 , a third harmonic peak 187 , and a fifth harmonic peak 188 . The first harmonic peak 185 may also be used as an indicator of misalignment.
[0133] FIGS. 21A and 21B illustrate an alignment pattern showing misalignment in one embodiment of a test pattern in accordance with the invention. As discussed above, the alignment pattern in FIG. 19A was shown as it would be printed by printheads 20 in perfect alignment. FIG. 21A shows an alignment pattern printed by misaligned printheads 20 . Each adjustable color bar, including second color bar 192 , is actually printed in a position displaced from its nominal true position. To determine the positional error 183 of each color using this alignment pattern, a total of eleven scans across this pattern are needed, as shown. Each scan will produce a signal of the sort shown in FIG. 20C . For each of these signals, the magnitude of the third harmonic can be extracted by digital FFT or analog filtering. Although the magnitude of the third harmonic increases reliably with misalignment, the misalignment is only one component of the magnitude of the harmonic. A portion of the peak is constant and depends on the line width/space ratio. A portion of the peak is variable and depends on how well the color bars are centered between the reference lines 135 .
[0134] Determining at which nominal color bar displacement the magnitude of the third harmonic is minimized can factor these other components out. The maximum value of the harmonic of interest, for example the third harmonic, for each scan is collected. By fitting a curve of these data points and determining the minimum point of this fitted curve (see FIG. 21B ), it is possible to determine the misalignment to within a fraction of the alignment pattern step resolution. If, for example, the printhead under examination were perfectly aligned, the minimum point of the fitted curve would coincide with a nominal color bar displacement 175 of zero.
[0135] The location of the minimum yields an accurate correction factor. In one embodiment, the correction factor is used to alter the timing of a firing signal to a printhead, thereby altering the location of the printhead output. Specifically, this actual measured misalignment can be used as a corrective, geometric offset, causing the printhead 20 to “fire” either early or late, so that the mechanical misalignment can be automatically compensated for during printing. As a result, a very high level of printing accuracy can be achieved, resulting in the production of dimensionally accurate three-dimensional articles, even when employing multiple printheads. In one embodiment, the alignment process is carried out prior to printing any three-dimensional parts and/or after a printhead is replaced.
[0136] Having described certain embodiments of the invention, it will be apparent to those of ordinary skill in the art that other embodiments incorporating the concepts disclosed herein may be used without departing from the spirit and scope of the invention. The described embodiments are to be considered in all respects as only illustrative and not restrictive.
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The invention relates to apparatus and methods for producing three-dimensional objects and auxiliary systems used in conjunction with the aforementioned apparatus and methods. The apparatus and methods involve 3D printing and servicing of the equipment used in the associated 3D printer.
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FIELD OF THE INVENTION
[0001] The present invention relates to the development of a Positron Emission Turnover (PET)-tracer that could be used to diagnose a whiplash-associated disorder (WAD). The present invention further relates to methods for the diagnostic use of a PET tracer that can be used for WAD. The present invention further relates to the studies of underlying biological mechanisms that could contribute to identifying new diagnosis and treatment targets for WADs.
BACKGROUND OF THE INVENTION
[0002] The commonly used term Whiplash is defined as an acceleration-deceleration mechanism of energy transfer to the neck which may result from rear-end or side impact, predominately in motor vehicle accidents and from other mishaps. The energy transfer may result in bony or soft tissue injuries (whiplash injury) which may in turn lead to a wide variety of clinical manifestations such as whiplash associated disorders. (Spitzer W O, Skovron M L, Salmi L R et al., Scientific monograph of the Quebec Task Force on WAD: redefining whiplash and its management”, Spine, 1995).
[0003] Whiplash injuries are common; the incidence has been estimated to be approximately 4 per 1000 people (Barnsley L, Lord S., Bogduk N., “Whiplash injury”, Pain, 1994). Although many people involved in motor vehicle accidents recover quickly, between 4% and 42% of patients with accident-related neck injuries report symptoms several years later. (Lord S M, Barnsley L., Wallis B J, Bogduk N., “Chronic cervical zygapophysial joint pain after whiplash: a placebo-controlled prevalence study”, Spine, 1996).
[0004] Chronic pain syndromes which include whiplash-associated disorders (WAD) are prevalent, cause significant individual suffering, and are high societal costs. In contrast to other injuries due to traffic accidents, neck injuries have increased. For example, neck injuries associated with at least 10% disability have increased from roughly 30 to roughly 60% during the two latest decades.
[0005] Like chronic pain syndromes, WAD causes significant individual suffering as well as high societal costs. For example, over 29 billion dollars per year is spent on whiplash injuries and litigation in the United States. Roughly ⅓rd of all WAD patients develop chronic problems. (Lord S M, Barnsley L., Wallis B J, Bogduk N., “Chronic cervical zygapophysial joint pain after whiplash: aplacebo-controlled prevalence study”, Spine, 1996).
[0006] A continuous search is under way for new treatment modalities of WAD, but at present, much work is focused on the early identification of patients with WAD. Although generally accepted diagnostic criteria for WAD as well as outcome measures exist, prognostic markers are lacking. Present methods do not allow important subgroups of patients to be clearly distinguished. The need for more precise methods to determine severity and prognosis as well as a treatment response is urgent. Conventional radiology only gives information about already established injuries. Magnetic Resonance Imaging tomography (MRI), computer tomography (CT) and radioisotope methods have shown potentials of visualizing signs of biological processes, but more work is needed before they can be used as an objective and quantitative assessment of WAD and different therapeutic strategies.
[0007] Positron emission tomography (PET) imaging is not currently used in the diagnosis of WAD, although PET has been used to demonstrate high glucose metabolism in joints of rheumatoid arthritis patients. PET has also been used in conjunction with the tracer D-[methyl- 11 C]-deprenyl (also known as DDE or 11 C-D-deprenyl) in diagnosing and treating patients with arthritis. (Danfors T., Bergstrom, M. et al., “Positron Emission Tomography with” 11 C-D-deprenyl in Patients with Rheumatoid Arthritis”, Scan J Rheumatol, 1997).
[0008] Furthermore, DDE has been used as a negative control for the demonstration of selective MAO-B-binding by 11 C-L-deprenyl. 11 C-L-deprenyl is an enantiomer of DDE. An enantiomer exists when a chemical structure and its mirror image are not superposable. In a range of pituitary adenomas, 11 C-L-deprenyl showed significant retention in both a tumourous and normal brain, whereas in most of the tumours, DDE showed a rapid washout from both tumour and normal brain. However, in some tumours, DDE was retained in the tumour but not in the normal brain. The washout suggested that DDE had negligible binding to MAO-B, but the retention in some tumours suggested an additional mechanism of retention of DDE. (Danfors T., Bergstrom, M. et al., “Positron Emission Tomography with 11 C-D-deprenyl in Patients with Rheumatoid Arthritis”, Scan J Rheumatol, 1997). MAO-B is monoamine oxidase B which is identified as a member of the family of the imidazoline binding proteins.
[0009] Moreover, there has yet to be found a PET-tracer that could be used for WAD. Accordingly, there has been a long felt need for the development of a PET-tracer that could be used to diagnose WAD as well as study underlying biological mechanisms that retain a PET-tracer which could contribute to identifying new diagnosis and treatment targets for WAD.
[0010] Discussion or citation of a reference herein shall not be construed as an admission that such reference is prior art to the present invention.
SUMMARY OF THE INVENTION
[0011] In view of the long felt need for diagnosing whiplash-associated disorder (WAD), the present invention relates to both the development of a PET-tracer that could be used to diagnose WAD and the study of underlying biological mechanisms that could contribute to identifying new diagnosis and treatment targets for WADs.
[0012] In one embodiment, a Positron Emission Tomograhpy (PET) tracer for diagnosing whiplash-associated disorder is disclosed wherein the PET tracer is D-[methyl- 11 C]-Deprenyl (DDE). The PET tracer could also be [ 11 C]-GR205171 (GLD).
[0013] In a further embodiment, a biological mechanism that is a specific molecular structure or enzyme which is expressed in the inflammed joint tissue, wherein the biological mechanism could contribute to identifying treatment targets according to WADs is also disclosed.
[0014] In another embodiment, a method for the preparation of an enzyme or molecular structure according to the steps of using capillary electrophoresis to aid in separating out proteins such as MAO-B proteins; and then detecting the radioacitivity by 11 C-labelled precursors to guide a skilled artisan as to which MAO-B protein would bind to either DDE and GLD is also presented.
[0015] The present invention further provides for a kit in the preparation of a molecular structure or enzyme according to the steps of using capillary electrophoresis to aid in separating out proteins such as MAO-B proteins; and then detecting the radioacitivity by 11 C-labelled precursors to guide which MAO-B protein would bind to either DDE and GLD.
BRIEF DESCRIPTION OF THE FIGURES
[0016] FIG. 1 shows a PET-imaging picture that depicts an increased DDE uptake in one of the WAD patients.
DETAILED DESCRIPTION OF THE INVENTION
[0017] The present invention relates to examining patients with Whiplash associated-syndrome (WAD) by investigating the presence of local changes, caused by local micro-lesions and producing an increased 11 C-D-deprenyl (DDE) uptake revealed through Positron Emission Tomography (PET) that is impossible to be revealed by computer tomography (CT) or Magnetic Resonance Imaging tomography (MRI).
[0018] PET imaging is a tomographic nuclear imaging technique that uses radioactive tracer molecules that emit positrons. When a positron meets an electron, they both are annihilated and the result is a release of energy in the form of gamma rays, which are detected by the PET scanner. By employing natural substances that are used by the body as tracer molecules, PET does not only provide information about structures in the body but also information about the physiological function of the body or certain areas therein. Furthermore, the choice of a tracer molecule depends on what is being scanned. Generally, a tracer is chosen that will accumulate in the area of interest, or be selectively taken up by a certain type of tissue, e.g. cancer cells. Scanning consists of either a dynamic series or a static image obtained after an interval during which the radioactive tracer molecule enters the biochemical process of interest. The scanner detects the spatial and temporal distribution of the tracer molecule. PET also is a quantitative imaging method allowing the measurement of regional concentrations of the radioactive tracer molecule. Commonly used radionuclides in PET tracers are 11 C, 18 F, 15 F 13 N or 76 Br.
[0019] Furthermore, tracers labeled with short-lived positron emitting radionuclides (e.g. 11 C, t 1/2 =20.3 min) are frequently used in various non-invasive in vivo studies in combination with PET. Because of the radioactivity, the short half-lives and the submicromolar amounts of the labeled substances, extraordinary synthetic procedures are required for the production of these tracers. An important part of the elaboration of these procedures is the development and handling of new 11 C-labelled precursors. This is important not only for labeling new types of compounds, but also for increasing the possibility of labeling a given compound in different positions.
[0020] When compounds are labeled with 11 C, it is usually important to maximize specific radioactivity. In order to achieve this, the isotopic dilution and the synthesis time must be minimized. Isotopic dilution from atmospheric carbon dioxide may be substantial when [ 11 C]carbon dioxide is used in a labeling reaction. Due to the low reactivity and atmospheric concentration of carbon monoxide (0.1 ppm vs. 3.4×10 4 ppm for CO 2 ), this problem is reduced with reactions using [ 11 C]carbon monoxide.
[0021] There are several advantages in using the PET technique in the diagnosis of WAD. One advantage is that the PET technique offers a potential for recording various functional and biochemical characteristics in the affected joints. Another advantage is that the PET technique has a potential to supply objective and quantitative estimates of disease intensity rather than secondary structural information.
[0022] One embodiment of the invention is to provide a Positron Emission Tomography (PET) tracer for diagnosing whiplash-associated disorder wherein a PET tracer is D-[methyl-11-C]-Deprenyl (DDE). The PET tracer can also be [11C]-GR205171 (GLD).
[0023] Another embodiment of the present invention includes either DDE or GLD or in combination thereof can be used for joint diseases comprising arthritis, rheumatoid arthritis, gout, osteoarthritis, ankylosis, bursitis, temporomandibular joint disorders, synovial chrondromatosis, hemarthrosis, acquired joint deformalities, metatarsalgia, arthralgia, arthrogryposis, joint instability, synovitis, neurogenic arthropathy, hallux rigidus, hydrathrosis, joint loose bodies, and similar diseases thereof.
[0024] In a further embodiment, a biological mechanism that is a specific molecular structure or enzyme which is expressed in the inflammed joint tissue of a patient, wherein the biological mechanism identifies treatment targets according to WADs is also disclosed. A patient used herein is a human being or any kind of animal thereof.
[0025] In yet another embodiment, a method for the preparation of a molecular structure or an enzyme according to the steps:
i) using capillary electrophoresis to aid in separating out MAO-B proteins; and then ii) detecting the radioactivity by 11 C-labelled precursors to guide a skilled artisan as to which MAO-B protein would bind to either or both DDE and GLD is also presented. A skilled artisan used throughout this application is defined as a person who is of skill in this particular field.
[0028] The present invention further provides a kit for the preparation of a molecular structure or an enzyme according to the steps:
i) using capillary electrophoresis to aid in separating out MAO-B proteins; and then ii) detecting the radioactivity by C-labelled precursors to guide a skilled artisan as to which MAO-B protein would bind to either or both DDE and GLD is also presented.
[0031] Yet another embodiment of the present invention provides for a diagnostic use of a PET tracer comprising D-[methyl-11-C]-Deprenyl (“DDE”) or [11C]-GR205171 (“GLD”) for determining WAD.
[0032] Still a further embodiment encompasses a method of use for generating a biological mechanism that is a specific molecular structure which is expressed in the inflammed joint tissue of a patient, wherein the biological mechanism identifies treatment targets according to WADs.
[0033] While still another embodiment entails a method of use for generating a biological mechanism that is an enzyme which is expressed in the inflammed joint tissue of a patient, wherein the biological mechanism identifies treatment targets according to WADs.
[0034] Another embodiment of the present invention entails a method of use for preparing a molecular structure according to the steps:
[0000] i) using capillary electrophoresis to aid in separating out MAO-B proteins; and
then ii) detecting the radioactivity by 11 C-labelled precursors, whereby guiding the MAO-B proteins to either bind to DDE, GLD or both.
[0035] A further embodiment of the present invention encompasses a method of use for preparing an enzyme according to the steps:
[0000] i) using capillary electrophoresis to aid in separating out MAO-B proteins; and then
ii) detecting the radioactivity by 11 C-labelled precursors, whereby guiding the MAO-B proteins to either bind to DDE, GLD or both.
EXAMPLES
[0036] The invention is further described in the following examples which are in no way intended to limit the scope of the invention.
[0037] Uppsala Imanet has developed two tracers which are D-[methyl- 11 C]-deprenyl (DDE) and [11C]-GR205171 (GLD) that are to be used in combination with a Positron Emmison Tomography (PET) scanner, for clinical investigations indicating an inflammatory process such as Whiplash Associated-Disorder (WAD).
[0038] In one experiment, eight patients have been examined and diagnosed with WAD through the use of DDE and PET. In four patients DDE appeared to bind to soft tissue in the neck vertebra. Clinically, those patients with a higher uptake of DDE in the affected joint areas seem to report high pain ratings while being in the scanner.
[0039] Furthermore, when a patient was administered intra-articular injections of gluccorticoids a significant diminishing of the uptake of DDE in the affected area, such as but not limited to the synovial (or diarthrodial) joint or similar joints, was to observed 6-14 days after treatment. The effects are observed with all modes of evaluation. After treatment, the initial thigh uptake of DDE in the affected joint is significantly diminished, indicating a pronounced effect on perfusion.
[0040] In a similar experiment, sixteen patients were investigated using a high resolution PET scanner. It was observed that about 50% of the patients had an increased uptake of DDE in the neck and shoulder areas of the patients. As an example, FIG. 1 shows a PET-imaging picture that depicts an increased DDE uptake in one of the WAD patients.
[0041] In a third experiment eight healthy subjects were investigated using a PET-CT (Computerized Tomography) scanner. PET/CT combines the strengths of two well-established imaging modalities, PET for function and CT for anatomy, into a single imaging device. The subjects were free from pain in the neck and shoulder regions during at least two months and they had not been involved in accidents which could have caused a neck injury. None of the subjects revealed an increased uptake of DDE in the scanned neck and shoulder regions. This indicates that the increased uptake in patients (experiments 1 and 2) are related to their clinical symptoms.
[0042] Furthermore, on-going analysis are being performed through semi-quantitative analysis by comparing the neck and shoulder areas wih an increased DDE uptake to an area of the body without any DDE uptake. Additionally, a control material is planned to compare WAD-patients and healthy volunteers.
[0043] In search for a mechanism of retaining DDE, studies regarding inflamed joints such as synovial (or diarthrodial) were adminstered. The results uncovered a very pronounced uptake and retention on swollen synovial tissue, correlating well with clinical and others signs of active inflammation. In a separate study, an investigation pertaining to the radioactivity concentration in synovial fluid of patients with rheumatoid arthritis given the tracer DDE was adminstered. The synovial fluid had low radioactivity whereas the inflamed tissue as seen in the PET images had very high activity. This activity was reduced by 50% the day after intra-articular administration of glucocorticoid.
[0044] There are various hypothesis as to what biological mechanisms are behind the high uptake of DDE in inflammatory joint tissues of humans. One hypothesis is binding DDE to a specific molecular structure or enzyme which is expressed in the inflamed area. To validate the hypothesis a frozen section autoradiography was performed on various tissues using DDE and thereby demonstrating a much higher binding in inflamed joints than any other tissues. In further determining the character of the binding between DDE and inflammatory joint tissues, it is anticipated that capillary electrophoresis would aid in separating out proteins and the detection of the radioactivity would guide one to know how many and potentially which protein is binding to the tracer.
[0045] In addition, in order to exclude the possibility that the DDE uptake is governed by binding to a monoamine oxidase B (MAO-B), a reexamination of one patient after administration of Eldepryl demonstrated to be sufficient for blocking of an enzyme. In this patient no blocking effect could be seen, only a slightly higher uptake of DDE in the inflamed joint area. In the human brain and pituitary adenomas it has been shown that 11 C-L-deprenyl has a higher binding, whereas DDE is rapidly washed out except in subgroups of non-secreting pituitary adenomas where DDE shows high binding.
[0046] Furthermore, it has been hypothesized that the pharmacological challenge of the binding between DDE and inflammatory joint tissues in patients is when inflamed synovial tissue is incubated with DDE, with or without a range of MAO-B binding proteins or similar compounds which could potentially inhibit the binding. The inhibitors that could be used to potentially inhibit the binding between DDE and inflammatory joint tissue are inhibitors of VAP-1 and other cell surface amino oxidases. Additionally, other molecular entities are searched for which would serve the same task of binding to the identified molecular target.
[0047] In addition, in a small pilot series of experiments in patients with bacterial abscesses, no visible increase of DDE or GLD uptake was found.
[0048] Furthermore, in vitro binding experiments demonstrated very high DDE and GLD tracer binding in inflammatory tissues removed from patients with rheumatoid arthritis. The in vitro binding experiments were performed on thin slices of tissue of about 20 micrometers in rats and in humans. The thin slices of tissues were adhered to gelatinized slide glasses. The tissue adhered to the glass was then incubated in a buffer such as TRIS-HCl containing DDE or GLD at about 2 nM concentration for to about 40 minutes at room temperature. The experimental conditions were varied and the results were not significantly affected. After incubation the slide glasses were washed about 3 times in a buffer, dried, and exposed on phosphor imaging plates for a minimum of 60 minutes.
[0049] In the in vitro binding experiments, local uptake was present in all cases in the parotis and submandibularis glandulae. Differences between patients were found in areas related to the insertion of muscles to the occipital bone, vertebrae and clavicula. In these regions, four of the examined patients showed a visually enhanced uptake in comparison with the rest. In some of these patients an increased uptake was observed in de proximal and distal parts of the muscle sternocleidomastoideus.
[0050] In order to make inter-individual comparisons, it was decided to normalize the uptake in the above-mentioned areas with the uptake of the inferior part of the cerebellum. In the area of insertion of m. rectus capitis posterior major we found bilaterally in 3 patients an increase of 57%-127% in the uptake of DDE compared with the cerebellum. The fourth patient did not show a clear increase, but there was a 40% difference between right and left side of the cerebellum.
[0051] At the level of the cervical vertebrae 2 and 3 (insertion in m. semispinalis capitis) it was found in one case an increase of approximately 70% uptake of DDE and GLD. The other two patients showed lower uptake of these two PET tracers but differences in the patients were found between both sides of the cervical vertebrae in the order of 16-30%. High uptake of DDE and GLD at the level of insertion in the clavicula 70-120% was found in some of these four patients.
SPECIFIC EMBODIMENTS, CITATION OF REFERENCES
[0052] The present invention is not to be limited in scope by specific embodiments described herein. Indeed, various modifications of the inventions in addition to those described herein will become apparent to those skilled in the art from the foregoing description and accompanying figures. Such modifications are intended to fall within the scope of the claims.
[0053] Various publications and patent applications are cited herein, the disclosures of which are incorporated by reference in their entireties.
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Positron Emission Tomography (PET) tracers such as D-[methyl- 11 C]-Deprenyl (DDE) and [ 11 C]-GR205171 (GLD), methods for and methods of preparing biological mechanisms that identify treatment targets in connection with Whiplash-Associated Disorder (WAD) are provided. Associated kits for the evaluation of the biological mechanisms are also provided.
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CROSS REFERENCE TO RELATED PATENTS
[0001] This application claims the benefit of U.S. provisional application No. 60/630,796 filed Nov. 24, 2004, which is herein incorporated in its entirety.
BACKGROUND OF THE INVENTION
[0002] This invention relates generally to methods and apparatus for computed tomography (CT), and more particularly to methods and apparatus that provide for thermal control in CT systems.
[0003] Air cooling of CT systems offers a good combination of simplicity and functionality when the factors of design time, cost and system sitting are considered. One problem with air cooling in a CT system is that there is a local temperature control solution for controlling the photodiode that is dependent and effected by the global system air temperature and flow control. Typical systems simply rely on controlling the bulk air temperature of the gantry (system) air temperature as measured at some convenient location in the gantry. One problem currently being addressed is that with CT system electronic power consumption on the rise it may be no longer feasible to have independent local and global temperature control systems. A further issue for air cooled systems with increased power consumption is to remove audible noise as more power consumption typically uses more and/or larger fans. Lastly, as more fans are added to a higher wattage CT system reliability concerns and field service to replace failed fans or clean air filters become larger more expensive long term problems.
BRIEF DESCRIPTION OF THE INVENTION
[0004] In one aspect, a method of cooling a medical imaging system that includes a gantry is provided. The method includes supplying air to the gantry. The supplied air is conditioned to reduce variation of the temperature within the gantry. After the air is conditioned it is channeled throughout the gantry to a plurality of heat producing electronic devices within the gantry.
[0005] In another aspect, a medical imaging system is provided. The medical imaging system includes a gantry having a controller configured to receive signals indicative of a plurality of temperatures within the gantry. A local thermal control system is further provided to maintain a predetermined temperature at a plurality of electronic devices within the gantry. Finally, a bulk thermal control system is provided to maintain a predetermined temperature within the gantry.
BRIEF DESCRIPTION OF THE DRAWINGS
[0006] FIG. 1 is a pictorial view of a CT imaging system embodiment.
[0007] FIG. 2 is a block schematic diagram of the system illustrated in FIG. 1 .
[0008] FIG. 3 illustrates the allowable temperature variations for the CT system illustrated in FIGS. 1 and 2 .
[0009] FIG. 4 illustrates a system level thermal control system.
[0010] FIG. 5 illustrates a system level thermal control system.
[0011] FIG. 6 illustrates a system level thermal control system.
DETAILED DESCRIPTION OF THE INVENTION
[0012] There are herein provided thermal control methods and apparatus useful for imaging systems such as, for example, but not limited to a Computed Tomography (CT) System. The apparatus and methods are illustrated with reference to the figures wherein similar numbers indicate the same elements in all figures. Such figures are intended to be illustrative rather than limiting and are included herewith to facilitate explanation of an exemplary embodiment of the apparatus and methods of the invention.
[0013] In some known CT imaging system configurations, a radiation source projects a fan-shaped beam which is collimated to lie within an X-Y plane of a Cartesian coordinate system and generally referred to as an “imaging plane”. The radiation beam passes through an object being imaged, such as a patient. The beam, after being attenuated by the object, impinges upon an array of radiation detectors. The intensity of the attenuated radiation beam received at the detector array is dependent upon the attenuation of a radiation beam by the object. Each detector element of the array produces a separate electrical signal that is a measurement of the beam attenuation at the detector location. The attenuation measurements from all the detectors are acquired separately to produce a transmission profile.
[0014] In third generation CT systems, the radiation source and the detector array are rotated with a gantry within the imaging plane and around the object to be imaged such that an angle at which the radiation beam intersects the object constantly changes. A group of radiation attenuation measurements, i.e., projection data, from the detector array at one gantry angle is referred to as a “view”. A “scan” of the object includes a set of views made at different gantry angles, or view angles, during one revolution of the radiation source and detector.
[0015] In an axial scan, the projection data is processed to reconstruct an image that corresponds to a two dimensional slice taken through the object. One method for reconstructing an image from a set of projection data is referred to in the art as the filtered back projection technique. This process converts the attenuation measurements from a scan into integers called “CT numbers” or “Hounsfield units”, which are used to control the brightness of a corresponding pixel on a display device.
[0016] To reduce the total scan time, a “helical” scan may be performed. To perform a “helical” scan, the patient is moved while the data for the prescribed number of slices is acquired. Such a system generates a single helix from a fan beam helical scan. The helix mapped out by the fan beam yields projection data from which images in each prescribed slice may be reconstructed.
[0017] As used herein, an element or step recited in the singular and proceeded with the word “a” or “an” should be understood as not excluding plural said elements or steps, unless such exclusion is explicitly recited. Furthermore, references to “one embodiment” of the present invention are not intended to be interpreted as excluding the existence of additional embodiments that also incorporate the recited features.
[0018] Also as used herein, the phrase “reconstructing an image” is not intended to exclude embodiments of the present invention in which data representing an image is generated but a viewable image is not. Therefore, as used herein the term, “image,” broadly refers to both viewable images and data representing a viewable image. However, many embodiments generate (or are configured to generate) at least one viewable image.
[0019] FIG. 1 is a pictorial view of a CT imaging system 10 . FIG. 2 is a block schematic diagram of system 10 illustrated in FIG. 1 . In the exemplary embodiment, a computed tomography (CT) imaging system 10 is shown as including a gantry 12 representative of a “third generation” CT imaging system. Gantry 12 has a radiation source 14 that projects a cone beam 16 of X-rays toward a detector array 18 on the opposite side of gantry 12 .
[0020] Detector array 18 is formed by a plurality of detector rows (not shown in FIGS. 1 and 2 ) including a plurality of detector elements 20 which together sense the projected X-ray beams that pass through an object, such as a medical patient 22 . Each detector element 20 produces an electrical signal that represents the intensity of an impinging radiation beam and hence the attenuation of the beam as it passes through object or patient 22 . An imaging system 10 having a multislice detector 18 is capable of providing a plurality of images representative of a volume of object 22 . Each image of the plurality of images corresponds to a separate “slice” of the volume. The “thickness” or aperture of the slice is dependent upon the thickness of the detector rows.
[0021] During a scan to acquire radiation projection data, gantry 12 and the components mounted thereon rotate about a center of rotation 24 . FIG. 2 shows only a single row of detector elements 20 (i.e., a detector row). However, multislice detector array 18 includes a plurality of parallel detector rows of detector elements 20 such that projection data corresponding to a plurality of quasi-parallel or parallel slices can be acquired simultaneously during a scan.
[0022] Rotation of gantry 12 and the operation of radiation source 14 are governed by a control mechanism 26 of CT system 10 . Control mechanism 26 includes a radiation controller 28 that provides power and timing signals to radiation source 14 and a gantry motor controller 30 that controls the rotational speed and position of gantry 12 . A data acquisition system (DAS) 32 in control mechanism 26 samples analog data from detector elements 20 and converts the data to digital signals for subsequent processing. An image reconstructor 34 receives sampled and digitized radiation data from DAS 32 and performs high-speed image reconstruction. The reconstructed image is applied as an input to a computer 36 which stores the image in a mass storage device 38 .
[0023] Computer 36 also receives commands and scanning parameters from an operator via a console 40 that has a keyboard. An associated cathode ray tube display 42 allows the operator to observe the reconstructed image and other data from computer 36 . The operator supplied commands and parameters are used by computer 36 to provide control signals and information to DAS 32 , radiation controller 28 , and gantry motor controller 30 . In addition, computer 36 operates a table motor controller 44 which controls a motorized table 46 to position patient 22 in gantry 12 . Particularly, table 46 moves portions of patient 22 through gantry opening 48 .
[0024] In one embodiment, computer 36 includes a device 50 , for example, a floppy disk drive, CD-ROM drive, DVD drive, magnetic optical disk (MOD) device, or any other digital device including a network connecting device such as an Ethernet device for reading instructions and/or data from a computer-readable medium 52 , such as a floppy disk, a CD-ROM, a DVD or an other digital source such as a network or the Internet, as well as yet to be developed digital means. In another embodiment, computer 36 executes instructions stored in firmware (not shown). Generally, a processor in at least one of DAS 32 , reconstructor 34 , and computer 36 shown in FIG. 2 is programmed to execute the processes described below. Of course, the method is not limited to practice in CT system 10 and can be utilized in connection with many other types and variations of imaging systems. In one embodiment, Computer 36 is programmed to perform functions described herein, accordingly, as used herein, the term computer is not limited to just those integrated circuits referred to in the art as computers, but broadly refers to computers, processors, microcontrollers, microcomputers, programmable logic controllers, application specific integrated circuits, and other programmable circuits. Although the herein described methods are described in a medical setting, it is contemplated that the benefits of the invention accrue to non-medical imaging systems such as those systems typically employed in an industrial setting or a transportation setting, such as, for example, but not limited to, a baggage scanning CT system for an airport or other transportation center.
[0025] FIG. 3 illustrates the allowable temperature variations for the CT system illustrated in FIGS. 1 and 2 . FIG. 4 illustrates one thermal control system 100 useable with the system illustrated in FIGS. 1 and 2 and other CT systems and Volume CT systems (VCT). System 100 includes a plurality of rear exhaust fans 102 and a plurality of booster fans 104 . Although illustrated with a particular number of fans, it is contemplated that the benefits of the invention accrue to systems with various fans including a single exhaust fan or a single booster fan. System 100 also includes at least one controller 106 . An analog to digital board (AD Board) 108 is situated in an AD Board plenum 110 and operationally coupled to a detector rail(s) 112 . One controller 106 controls a heater 114 positioned in an inlet blower heater box 116 . A heater 118 may be positioned in a flow path with detector rails 112 and controlled by controller 106 . As illustrated in the figures and as described below a plurality of temperature sensors 120 are situated in various places.
[0026] The herein described methods and apparatus provide, in one embodiment, for an integrated thermal system design which uses variable speed fans with PID (Proportional, Integral, Derivative) feedback control for both local diode temperature control and global system level air temperature and flow control. The local variable speed temperature control system uses the temperature of the digital modules and temperature control of the detector rail to maintain substantially optimal diode temperature control such as is described in co-pending application Ser. No. 10/710,213, filed Jun. 25, 2004, titled Variable Speed Fans for Advanced DAS/Detector Thermal Management, and is hereby incorporated in its entirety. The global thermal control system includes an inlet air blower with heaters used to provide controlled air into the front side of the CT system for consumption by the local digital module control system. Further, the inlet blower heater system provides controlled airflow to provide continuous air mixing. By providing inlet air to the front side of the gantry and the air mixing, the effects of air recirculation from the exhaust of the electronics and tube heat exchanger are minimized. The continuous flow also prevent local pockets of hot air to be trapped and mixing when gantry rotation begins thus preventing temperature spikes during scanning. One effect of the global thermal control system is to reduce the variation in air temperature that is seen by the local digital module temperature control system. FIG. 3 illustrates how the room the temperature control ranges vary from room ambient down to the photo diode of the detector. As can be seen the room ambient graph has the largest temperature range which the global control system reduces to a level that the local system can compensate for to ultimately control the photo diode down to a very narrow range as required for proper performance. A further feature of the herein described methods and apparatus provide substantially optimized audible noise and fan reliability both of which increase with fan speed.
[0027] Thus, by using variable speed fans at the local level, a wider range of inlet air temperatures can be accommodated by modifying air velocity to compensate for temperature difference between cooling air and target electronic components. Similarly, by using variable speed gantry exhaust fans, both a wide variation in room ambient air and gantry rotational speeds can be accommodated. Therefore, by using the inlet air temperature of local temperature control system as feedback to control the gantry exhaust fans the overall system audible noise and fan reliability can be substantially optimized as there will be multiple design points that satisfy the room ambient, system power output, and gantry rotational speed.
[0028] The following equations illustrate relationships.
T plenum-inlet =ƒ( Q AD-Boards ,Q xray-tube ,N gentry ,T ambient ,Q inlet-blower ,N gantry-fans ) (eq 1)
illustrates that the temperature at the plenum inlet (T plenum-inlet ) is a function (f) of heat (Q) produced at the AD-board(s), the x-ray tube, and the inlet blower, the rotation speed of the gantry (N gantry ), the number (N) of gantry fans, and the ambient temperature (T ambient ).
T AD =ƒ( N plenum-fans ,T plenum-inlet ) (eq 2)
illustrates that the temperature at the AD board(s) and/or AD plenum is a function of the plenum inlet temperature and the number of plenum fans.
DB system-fan =ƒ( N plenum-fans ,N gantry-fans ) (eq 3)
illustrates that total noise (DB, decibels) is a function of the number of plenum fans and gantry fans.
Life plenum-fans =ƒ( N plenum-fans ,T plenum-inlet ) (eq 4)
illustrates factors (number of fans and temperature at plenum inlet) that affect plenum fan replacement times.
Life gantry-fans =ƒ( N gantry-fan ,T gantry-exhaust ) (eq 5)
illustrates factors (number of fans and temperature at gantry exhaust) that affect gantry fan replacement times.
[0029] Based on nearly constant electronic power output and the typically low air temperatures encountered in a CT system eq1, 4 and 5 can be simplified to the following.
T plenum-inlet =ƒ( Q xray-tube ,N gantry ,T ambient ,N gantry-fans ) (eq 1a)
Life plenum-fans =ƒ( N plenum-fans ) (eq 4a)
Life gantry-fans =ƒ( N gantry-fans ) (eq 5a)
[0030] Thus, based on the allowable inlet plenum air temperatures that can be accommodated by the local control system variable speed fans, there are multiple possible gantry fan speeds that will give an acceptable AD board temperature to provide the desired diode temperature. This means that the gantry and fan speeds if tied together in a common control system can be optimized or substantially optimized to provide substantially minimum noise and substantially maximum life for any combination of room ambient and x-ray tube output power.
[0031] In one embodiment, the gantry exhaust fans are tied to a PID feedback controller that uses the inlet plenum air temperature as the PID controllers feed back variable. Further, the gantry exhaust fans are broken into banks of fans that can be controlled to run at different speeds to achieve optimal performance. One design of a system level control system is illustrated in FIGS. 4, 5 , and 6 . One embodiment is as illustrated in all of FIGS. 4, 5 , and 6 , while other embodiments utilize just some of the features illustrated in some of FIGS. 4, 5 , and 6 .
[0032] A further feature of the herein described methods and apparatus are the service feedback mechanisms built into the design. Below is a list of the service features enabled by the herein described system level control architecture:
1. Air filter maintenance—The air flow after each air filter is monitored via a velocity sensor (a pressure sensor system can also be used) to send out a message to a service or a user that at least one air filter is critically clogged and need to be cleaned. This will enable pre-emptive maintenance before the filters have clogged to the point of causing system performance degradation. 2. Redundant sensor error handling—Multiple sensors and error trapping are employed to detect a bad sensor and remove it from the feedback loop. By using multiple sensors, an average value can be used for temperature and flow sensing feedback (e.g., as illustrated in FIG. 6 ). When one of the controllers detects a bad sensor the control software removes the sensor from the averaging scheme and sends an error message to field service to replace the sensor at the next available scheduled down time. When any feedback system is down to only 2 working sensors to average a request for immediate service is sent out. 3. Imminent fan failure—The control systems continually monitor for change in current required to run the fans at a given speed compared to baseline current draw (when fans where new). Once a certain level of degradation is seen (e.g., a rise in current required by a fan) an error message is sent to the system warning that a fan is failing and needs to be replaced at the next opportunity.
[0036] Technical effects of the herein described methods and apparatus include a more precise local control while maintaining low audible noise. A further technical effect of an integrated system is the ability to provide preemptive field service data to minimize unscheduled maintenance and eliminate the need for fixed PM schedules. And another technical effect is the ability to optimize against audible noise and fan life to achieve a more robust CT system design.
[0037] Additional methods and apparatus incorporate a system level variable speed fan temperature control system that is tied to the local electronic cooling air temperature. Such a system allows the temperature within a gantry to vary without degrading system performance. A substantially minimization in air recirculation via forced controlled inlet airflow at the front of the gantry is therefore enabled. And a pre-heating of the inlet air enables a reduced sensitivity to low room ambient conditions. In one embodiment, multiple banks of gantry fans phased to provide minimal audible noise and maximum fan life via optimized fan speed set points. In some embodiments, smart service algorithms eliminate the need for fixed maintenance schedules for air filter cleaning or fan replacement, smart service algorithms warn of impending performance degradation due to dirty air filters or imminent fan failure, and/or smart control algorithms that take advantage of multiple redundant sensors that allow for continued operation in the event of a sensor failure.
[0038] Exemplary embodiments are described above in detail. The assemblies and methods are not limited to the specific embodiments described herein, but rather, components of each assembly and/or method may be utilized independently and separately from other components described herein.
[0039] While the invention has been described in terms of various specific embodiments, those skilled in the art will recognize that the invention can be practiced with modification within the spirit and scope of the claims.
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A method of cooling a medical imaging system that includes a gantry is provided. The method includes supplying air to the gantry. The supplied air is conditioned to reduce variation of the temperature within the gantry. After the air is conditioned it is channeled throughout the gantry to a plurality of heat producing electronic devices within the gantry.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority of international application no. PCT/EP2007/003171 filed Apr. 10, 2007, which claims priority of German patent application DE 10 2006 016 497.0 filed Apr. 7, 2006.
FIELD OF THE INVENTION
[0002] The present invention relates to an actuation system for a parking brake of a motor vehicle, particularly to a manually actuated parking brake which acts on the rear wheels.
PRIOR ART
[0003] In motor vehicles, the parking brake usually acts on the rear wheels of the motor vehicle. To this end, brake cables are tightened, which are connected to the brakes of the rear wheels by means of a hand-actuated parking brake unit or a foot-actuated parking brake unit.
[0004] Mechanical parking brake systems have to be arranged within the interior of the motor vehicle, such that the driver may reach them conveniently and can generate the required braking force. Further, the parking brake systems have to maintain the required braking force permanently and have to transmit the braking force securely to the rear wheels.
[0005] Such mechanical systems therefore have to be mounted in an appropriate way to the car body of the motor vehicle and require a certain space due to the required mechanical components for the locking of the hand or foot lever.
[0006] Due to this construction of manual parking brake systems, interior designers of motor vehicles are heavily constrained regarding the arrangement of the hand or foot lever unit.
[0007] Further, electrical parking brakes are known, which provide arbitrary design possibilities for the designer. Such electrical parking brakes, however, are quite expensive and susceptible for mechanical and electrical failures. Therefore, it can happen that the parking brake tightens accidentally due to an electric problem, but without a request of the driver. Further, the parking brake is always tightened with the same force if necessary or not. As a result, the brake cables and the brakes of the vehicle are unnecessarily strained.
[0008] It is therefore the technical problem to provide an actuation system for a parking brake, which can flexibly be arranged within the interior of the motor vehicle, and thereby provides the highest possible freedom of design for the interior designer.
[0009] Further, an actuation system for a parking brake should be provided which can be comfortably operated by the driver, which is more cost-efficient compared to electrical parking brakes, and which provides a high reliability.
SUMMARY OF THE INVENTION
[0010] The above-mentioned problems are solved by an actuation system for a parking brake according to patent claim 1 .
[0011] Particularly, the above-mentioned problems are solved by an actuation system for a parking brake of a motor vehicle comprising a foot or a hand-actuated manual actuation means for tightening of the parking brake, wherein the parking brake is purely mechanically tightened via the actuation means, a locking mechanism for tightening and releasing of the parking brake, wherein the actuation means and the locking mechanism are arranged at different positions of the motor vehicle, respectively.
[0012] Due to the structural separation of manual actuation means and locking mechanism of the actuation system according to the invention, the interior designer has a high flexibility during the arrangement and design of the foot or hand-actuated actuation means. For example, such an actuation means can easily be integrated into the center console or the dashboard of a motor vehicle, since it can be constructed particularly small. Particularly, due to the structural separation, the actuation means can be easily designed mechanically, such that it can be arranged at almost any arbitrary position within the interior of the motor vehicle for the manual actuation by the driver.
[0013] Thereby, the locking mechanism of the actuation system, which comprises the required mechanical components for the locking of the brake, can be arranged at any arbitrary other position within the motor vehicle, where more space is available, for example at the rear area of the motor vehicle.
[0014] Further, the freedom of design is increased, since the actuation means can be designed lighter, since only during actuation of the parking brake a force is applied to the actuation means and the actual load of the parking brake in tightened condition is maintained by the locking mechanism. Therefore, the actuation means in general can be provided smaller and more unconventionally with respect to the materials used and the design.
[0015] Compared to electrical parking brakes the manually tightened parking brake described herein has the advantage that a tightening happens only if the driver for sure wants it. By means of the construction it is excluded that the parking brake accidentally tightens due to an electric problem.
[0016] Further, the driver can determine the force by which the parking brake is tightened. Thereby, over-stressing of the brake cables and the brakes of the vehicle is avoided. In total, thereby, the reliability is increased compared to electrical parking brakes.
[0017] Preferably, the locking mechanism is constructed such that it can be mounted at the area of the rear axle, below the middle tunnel, below the seats or within the engine compartment of the motor vehicle. Preferably, the locking mechanism is arranged where free space is available, preferably near the brakes to be actuated. Thereby, the brake cables, which run from the locking mechanism to the rear wheels, need to be very short, only.
[0018] In a preferred embodiment the actuation means is provided such that it can be arranged in the area of the center console or the dashboard of the motor vehicle for manual actuation by the driver.
[0019] In a preferred embodiment, the actuation means automatically returns into a rest position after the tightening of the parking brake. Thereby, always the same appearance at the interior of the motor vehicle is provided for a released as well as for a tightened parking brake. Particularly, the handbrake lever does not extend into the interior, such that new possibilities of design result. For example, the space between the front seats can be used more efficiently, and overall more space is provided.
[0020] In a further preferred embodiment, the actuation means for applying a braking force is connected with the locking mechanism via a first pulling cable. The transmission of forces from the actuation means to the locking mechanism preferably is done via a pulling cable, since it can be arranged within the motor vehicle almost arbitrarily. However, other possibilities are conceivable to connect the actuation means with the locking mechanism, for example via a linkage, etc.
[0021] In a further preferred embodiment, the locking mechanism comprises locking means to maintain the braking effect of the parking brake, wherein the locking means can mechanically be released by means of a second pulling cable from a remote position to release the brake effect. Thereby, the releasing of the parking brake can be done mechanically independent from the tightening of the parking brake. The actuation element for the releasing of the parking brake therefore can be also be arranged at any arbitrary suitable position within the motor vehicle, since it is connected to the locking mechanism via a second pulling cable. Therefore, huge possibilities of design result for the interior designer.
[0022] In a further preferred embodiment, the locking mechanism comprises of locking means to maintain the locking effect of the motor vehicle, wherein the locking means can be released from a remote position by means of an electric, pneumatic or hydraulic actuator, to release the brake effect. Instead of a mechanical actuation, also an electric, pneumatic or hydraulic actuation of the locking means can be done to release the brake effect. Thereby, again the interior designer has the freedom to choose the design of this actuation means. By means of such an actuator, the release of the parking brake can also be done automatically be means of the board electronics, if for example the driver inserts a gear and presses the accelerator pedal. Thereby, an automatic release of the parking brake is provided, like it is provided by electrical parking brakes, without having to accept the disadvantages described above.
[0023] In a further preferred embodiment, the locking mechanism comprises a follower disk for the actuation of brake cables, which is pivotably supported around a pivot axis, a pivot lever which is pivotably supported around the pivot axis, which is connected with the first pulling cable, wherein the pivot lever comprises a follower bolt, which rotates the follower disk during tightening of the brake, and wherein the pivot lever after the tightening returns to its rest position, independently from the follower disk.
[0024] By means of these elements of the locking mechanism, a simple and robust possibility is provided to tighten the brake cables, wherein the manual actuation means (hand lever or foot pedal) returns to its initial position after the tightening. Therefore, the optical appearance of the interior is the same for the tightened condition of the parking brake as for the released condition.
[0025] According to a further preferred embodiment, the follower bolt extends into a slot within the follower disk. My means of this embodiment, the pivot lever can freely pivot to a certain extent with respect to the follower disk.
[0026] In a further preferred embodiment, the pivot lever is connected with the first pulling cable via a deflection pulley. Therefore, according to the pulley principle a force increase of 2:1 results for the pivot lever with respect to the first pulling cable. Therefore, the pivot lever can be made particularly small and the locking mechanism in total only requires little space. Alternatively, the needed force decreases, which has to be applied by the driver via the actuation means for tightening of the parking brake. Therefore, the actuation means, its support and the first pulling cable can be designed particularly small and lightweight and can be easily integrated into the interior of the vehicle.
[0027] In a further preferred embodiment, the locking mechanism comprises a ratchet-pawl mechanism. A ratchet-pawl mechanism is a particularly simple and reliable possibility to lock the locking mechanism.
[0028] In another preferred embodiment, the locking mechanism comprises a torsion spring clutch, which comprises a rotatably supported cylinder and a torsion spring, which is wound around the cylinder. By means of torsion spring clutch, the locking mechanism can also be locked, wherein during the locking no disturbing noises appear. Additionally, the force, which is required to open the torsion spring, is independent from the braking force. The release force of a ratchet-pawl mechanism, however, is directly dependent from the brake force.
[0029] Therefore, a torsion spring clutch is suitable for an automatic release of the parking brake by means of an actuator.
[0030] In a further preferred embodiment, the follower disk comprises a toothed segment, which is in engagement with a pinion at the cylinder, wherein the pinion comprises a smaller diameter than the toothed segment. By the provision of such a gear drive, the pinion with the torsion spring clutch rotates faster than the follower disk with the toothed segment, during tightening or releasing of the locking mechanism. Therefore, for the locking of the locking mechanism, a smaller force has to be applied to the pinion, compared with the toothed segment. Due to this reason, also the torsion spring clutch, which engages the pinion and locks the pinion, can be provided smaller.
[0031] Further preferred embodiments of the invention result from the subclaims.
SHORT DESCRIPTION OF THE DRAWINGS
[0032] In the following preferred embodiments of the invention are described by means of the figures, in which shows:
[0033] FIG. 1 : a schematic three-dimensional view of a motor vehicle from the bottom to show the arrangement of a locking mechanism according to the invention;
[0034] FIG. 2 : a three-dimensional view of a dashboard of a motor vehicle with an actuation means;
[0035] FIG. 3 : an elongational view of a preferred embodiment of a locking mechanism according to the invention, wherein parts thereof are eliminated to show the inner components in released condition;
[0036] FIG. 4 : an elongational view of a preferred embodiment of a locking mechanism according to the invention, wherein parts thereof are eliminated to show the inner components in tightened condition;
[0037] FIG. 5 : an elongational view of a preferred embodiment of a locking mechanism according to the invention in assembled condition with an element for electrical releasing; and
[0038] FIG. 6 : an elongational view of a preferred embodiment of a locking mechanism according to the invention in assembled condition with an element for mechanical releasing.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0039] In the following, preferred embodiments of the present invention are described with respect to the figures.
[0040] FIG. 1 shows a schematic view of a motor vehicle 1 from the bottom. Usually, the rear wheels of a motor vehicle 1 are mechanically braked while tightening of the parking brake 2 via two brake cables 16 . The brake cables 16 are connected with a locking mechanism 20 for locking and releasing of the parking brake 2 . As shown in FIG. 1 , the locking mechanism 20 is mounted in the area of the rear axle of the motor vehicle 1 .
[0041] The force for the actuation of the locking mechanism 20 is mechanically transmitted via a first pulling cable 12 , which is connected with a mechanical actuation means 10 .
[0042] The actuation means 10 can be a foot lever or a handbrake lever of a conventional kind, wherein, however, no devices for the locking and releasing must be comprised. The actuation means 10 can also be unconventionally designed, as shown in FIG. 2 in the form of a handbrake lever 10 , which comprises a U-shape and which is integrated into the dashboard 4 of the motor vehicle 1 .
[0043] Due to the spacial and functional separation between actuation means 10 and locking mechanism 20 , the interior designer of a motor vehicle 1 need to accept less restrictions with respect to the design of the actuation means 10 , since with the actuation means 10 , only manually a force has to be applied, however, the actuation means 10 itself must not be locked.
[0044] As it is shown in FIG. 2 , the actuation means 10 can for example be integrated flush into the surface of the dashboard 4 .
[0045] Since locking mechanism 20 and actuation means 10 are spacially and functionally separated from each other, it is also possible that the actuation means 10 automatically returns to its rest position, as it is shown for example in FIG. 2 . Thereby, the actuation means 10 does also not extend from the center console 4 in tightened condition of the parking brake 2 .
[0046] In order to signalize the driver if the parking brake is tightened or realized at the actuation means 10 , for example at the shown lever 10 , an optical display can be provided, which signalizes the actual status of the parking brake 2 . For example, a signal lamp 6 can be integrated into the handle of the actuation means 10 , which is enlighted if the parking brake 2 is tightened.
[0047] Additionally or alternatively, the status of the parking brake 2 can for example also be shown via an alphanumeric display. Further, a release knob 8 can be arranged at the actuation means 10 , which releases the parking brake 2 .
[0048] FIG. 3 shows an elongational view of a preferred embodiment of a locking mechanism 20 according to the invention with electrical release. The locking mechanism 20 consists of a frame 22 , which is connected with the car body of the motor vehicle 1 . At the frame 22 , a follower disk 40 is pivotably mounted by means of a pivot axis 42 , wherein at the follower disk 40 an actuation rod 90 is pivotably supported. The actuation rod 90 is connected with an equalizer element 100 , at which brake cables 16 are mounted.
[0049] If the follower disk 40 is pivoted around the pivot axis 42 , as indicated by arrow 41 , the actuation rod 90 moves the equalizer element 100 , and the brake cables 16 are tightened or released.
[0050] The equalizer element 100 is formed in the shaped of a balance and distributes the braking force, which was introduced from the actuation rod 90 equally onto both brake cables 16 for the right and left rear tire.
[0051] The locking mechanism 20 is further provided with a pivot lever 50 , which rotates the follower disk 40 by means of a follower disk bolt 52 during tightening of the parking brake 2 . To this end, the follower bolt 52 extends into a slot 44 which is curved around the pivot axis 52 within the follower disk 40 . The pivot lever 50 can freely rotate around the pivot axis 52 with respect to the follower disk 40 and takes along the follower disk 40 if the follower bolt 52 abuts the end of the slot 44 , as it is shown in FIG. 3 .
[0052] The pivot lever 50 comprises of a deflection pulley 54 at its top end over which the first pulling cable 12 runs. The first pulling cable 12 is mounted at one end at a receptacle 26 of the frame 22 and at its other end at the actuation means 10 . During tightening of the actuation means 10 , the pulling cable 12 is tightened, as indicated by arrow 13 , whereby the pivot lever 50 is pivoted around the pivot axis 42 , as shown in FIG. 4 . Thereby, the follower disk 40 is taken along by the follower bolt 55 and is likewise pivoted and the parking brake 2 is tightened.
[0053] By the deflection of the pulling cable 12 around the deflection pinion 54 , a force transmission according to the pulley principle is provided. Therefore, the deflection pulley 54 does only move half as much as the distance the pulling cable 12 is pulled. Therefore, the force at the pivot lever 50 doubles and it can be provided shorter compared to the condition if the pulling cable 12 would be directly connected to the pivot lever 50 .
[0054] After the tightening, the pivot lever 50 can return in its initial position—as shown in dotted lines in FIG. 4 . This movement is also indicated by arrow 56 . To this end, the pivot lever 50 is biased by means of a spring to its initial position 50 ′.
[0055] Correspondingly, also the actuation means 10 returns to its rest position, wherein the parking brake 2 remains tightened.
[0056] For the locking of the follower disk 40 , i.e. for maintaining the braking effect of the parking brake 2 , the locking mechanism 20 is provided with locking means 40 , 50 , 60 , 70 .
[0057] The locking means may comprise a conventional ratchet-pawl mechanism, as it is known from the prior art of conventional handbrake levers.
[0058] In the shown embodiment, the locking mechanism 20 comprises a torsion spring clutch 60 , 70 which comprises a rotatably supported cylinder 70 and a torsion spring 60 , which is wound around the cylinder 70 . The rotatably supported cylinder 70 is provided with a pinion 72 , which engages the toothed segment 46 of the follower disk 40 .
[0059] The cylinder 70 is rotatably mounted at the frame 22 and is selectively blocked by the torsion spring 60 . To this end, one end 62 of the torsion spring 60 is mounted at the frame 22 . The other end 64 of the torsion spring 60 is connected with a release lever 80 , which likewise is rotatably fixed at the frame 22 . If the release lever 80 is pivoted and thereby also the end 64 of the torsion spring 60 is moved, the diameter of the torsion spring 60 can be increased or decreased.
[0060] The torsion spring clutch 60 , 70 acts for the cylinder 70 as a one-way clutch, i.e. it allows a movement of the cylinder 70 in tightening direction of the parking brake 2 , but blocks a movement in release direction.
[0061] For releasing of the parking brake 2 , the release lever 80 is pivoted to the right, as shown in FIG. 4 by arrow 65 , wherein the diameter of the torsion spring 60 is increased and thereby the cylinder 70 is released, such that is can freely rotate.
[0062] Thereby, also the follower disk 40 can freely rotate and the parking brake 2 is released. If the release lever 80 is not moved, the torsion spring 60 blocks the cylinder 70 in release direction, such that the follower disk 40 cannot return into the position shown in FIG. 3 , and the brake effect of the parking brake 2 is maintained.
[0063] Since the follower disk 40 with respect to the pivot axis 42 comprises a larger diameter in the area of the toothed segment 46 compared to the pinion 72 of the rotatably supported cylinder 70 , the cylinder 70 moves faster than the follower disk 40 during a movement of those parts. Therefore, the torsion spring 60 must only generate a small friction force to lock the cylinder 70 . Therefore, the torsion spring 60 must not be dimensioned very powerful to maintain the brake force.
[0064] Further, the force to open the torsion spring 60 is independent from the braking force, what allows an easy release of the parking brake 2 .
[0065] As indicated, it is necessary to release the follower disk 40 to release the parking brake 2 , which is done by pivoting of the release lever 80 . Such a pivoting of the release lever 80 can be done by means of an electric, pneumatic or hydraulic actuator 30 , like it is shown in FIG. 5 . Preferably, therefore an electric actuator 30 is used, which pulls the release lever 80 in direction of arrow 65 .
[0066] As it is shown in FIG. 6 , however, also a mechanical actuator, like for example a second pulling cable 14 can be used to move the release lever 80 in direction of the arrow 65 , to release the parking brake 2 .
[0067] An electric actuator 30 , however, has the advantage that a release knob for the actuation of the electric actuator 30 can be arbitrarily arranged within the vehicle, for example at the dashboard of the motor vehicle 1 . Further, the electric actuator 30 can also be controlled by the board electronics of the motor vehicle 1 , and for example release the parking brake 2 automatically if the driver inserted a gear and actuates the accelerator pedal. By means of the actuation system according to the invention, therefore automatic release operations of the parking brake 2 are possible, which for example facilitate the starting at a hill.
[0068] Further, the release operation of the parking brake 2 can be controlled such that a release of the parking brake 2 is only possible if particular conditions are met, for example that the motor is running and the driver actuates the vehicle brakes.
[0069] To signalize the board electronics that the parking brakes 2 is tightened, the locking mechanism 20 further comprises a switch 24 , as it is shown in FIGS. 3 and 4 , which is actuated by a stop 48 at the follower disk 40 .
[0070] The locking mechanism 20 further comprises, as shown in FIG. 5 , a cover plate 28 , which supports the inner components and which is connected with the frame 22 .
[0071] The components of the locking mechanism 20 are preferably made of steel, however, fiberglass-reinforced plastic material, particularly PA can also be used for single or for all components. The actuation means 10 is preferably made of a plastic material and consists preferably of a fiberglass-reinforced PA.
[0000]
LIST OF REFERENCE SIGNS
1
motor vehicle
42
pivot axis
2
parking brake
44
slot in follower disk
4
dashboard
46
toothed segment
6
signal lamp
48
stop
8
release knob
50
pivot lever
10
actuation means
52
follower bolt
12
first pulling cable
54
deflection pulley
13
arrow
56
arrow
14
second pulling cable
60
torsion spring
16
brake cables
62
first end
20
locking mechanism
64
second end
22
frame
65
arrow
24
switch
70
cylinder
26
receptacle
72
pinion at the cylinder
28
cover plate
80
release lever
30
actuator
90
actuation rod
40
follower disk
100
equalizer element
41
arrow
|
The present invention relates to an actuation system for a parking brake of a motor vehicle, comprising a foot or a hand-actuated manual actuation means ( 10 ) for tightening of the parking brake, wherein the parking brake is purely mechanically tightened via the actuation means, a locking mechanism ( 20 ) for tightening and releasing of the parking brake, wherein the actuation means ( 10 ) and the locking mechanism ( 20 ) are arranged at different positions of the motor vehicle, respectively.
| 1 |
CROSS-REFERENCE TO RELATED APPLICATION(S)
[0001] This application is based upon and claims the benefit of priority from U.S. Patent Application Ser. No. 61/145,914, filed on Jan. 20, 2009, and from U.S. Patent Application Ser. No. 61/184,180, filed on Jun. 4, 2009, the entire disclosures of which are incorporated herein by reference.
FIELD OF THE DISCLOSURE
[0002] The present disclosure relates to exemplary embodiments of endoscopic biopsy systems that are guided by microscopic image information, and an associated method therefor.
BACKGROUND INFORMATION
[0003] The standard of care for the diagnosis of many epithelial precancerous and early cancer conditions is visual inspection of the patient directly or through an endoscope/laparoscope to identify abnormal tissue. Biopsies can then be obtained from these locations, processed, cut and stained with Hematoxylin and Eosin (H&E), and then observed under a microscope by a pathologist. A pathologist can view the slide at progressively increasing resolutions and renders a diagnosis by comparing its architectural and cellular patterns with his/her knowledge of patterns associated with different disease states.
[0004] For a number of cases, however, metaplasia, dysplasia, and early cancer may not be visually identified. In these situations, the only available option may be to obtain biopsies at random locations which are routinely conducted in the colon, esophagus, prostate, and bladder, among others. When the disease is focal or heterogeneously distributed within a much larger suspect area, a random biopsy procedure may be analogous to “finding a needle in a haystack,” resulting in poor diagnostic yields and uncertain patient management.
[0005] Since random biopsies may only facilitate the assessment of less than 0.1% of the potentially involved tissue, these procedures are usually fraught with significant sampling error and diagnostic uncertainty. Other tasks, such as the delineation of surgical tumor margins, can also be affected by this difficulty, resulting in all too frequent re-excisions or time-consuming frozen section analysis. Thus, there may be a need for providing an apparatus and a method for guiding biopsy that is superior to visual inspection and that can direct the physician to a location that is more likely to harbor the most severe disease.
[0006] Barrett's esophagus is a condition of the tubular esophagus, where the squamous epithelium changes to intestinal epithelium, termed specialized intestinal metaplasia (SIM). Thought to be precipitated by severe or longstanding gastroesophageal reflux disease (GERD), BE can undergo dysplastic progression, leading to esophageal adenocarcinoma. Current management of Barrett's esophagus can include endoscopic surveillance at regular time intervals, consisting of upper endoscopy with 4-quadrant random biopsy, to identify dysplasia or adenocarcinoma at an early stage. This method suffers from a low sensitivity, as it is compromised by the poor ability of endoscopists to identify SIM/dysplasia and the low fractional area of tissue sampled by biopsy.
[0007] In the past, in the field of biomedical optics, imaging methods have been developed to provide improved tissue diagnosis in vivo. These imaging methods can be generally categorized as macroscopic or microscopic techniques.
[0008] Macroscopic, e.g., wide field imaging methods including autofluorescence, fluorescence lifetime imaging, ALA-fluorescence, reflectance and absorption spectroscopic imaging, narrow-band imaging, and chromoendoscopy. These macroscopic methods can be used to quickly evaluate large regions of tissue. While many of these techniques are promising, the information provided is often quite different from that conventionally used in medicine for diagnosis.
[0009] Microscopic imaging, at times referred to as “optical biopsy,” is another approach that enables the visualization of tissues at a resolution scale that is more familiar to physicians and pathologists. In the past, the minimally-invasive endoscopic microscopy techniques that have been developed to visualize the architectural and cellular morphology required for histopathologic diagnosis in vivo facilitate a very small field of view, however, and the probes are usually manually manipulated to obtain images from discrete sites (“point-sampling”). As a result, such techniques suffer from substantially the same sampling limitations as excisional biopsy, and may not be well suited for guiding biopsy.
[0010] One such microscopic imaging technique, reflectance confocal microscopy (RCM), can be suited for non-invasive microscopy in patients as it offers imaging of cellular structures at ˜1 μm resolution, can measure microstructure without tissue contact, and does not require the administration of unapproved exogenous contrast agents.
[0011] RCM can reject or ignore multiply scattered light from tissue, and detects the singly backscattered photons that contain structural information by employing confocal selection of light reflected from a tightly focused beam. Most commonly, RCM can be implemented by rapidly scanning a focused beam in a plane parallel to the tissue surface, resulting in transverse or en face images of tissue. A large numerical aperture (NA) of RCM can yield a very high spatial resolution. Sensitive to the aberrations that arise as light propagates through inhomogeneous tissue; high-resolution imaging with RCM can typically be limited to a depth of 100-200 μm, which is sufficient for most epithelial disorders that manifest near a luminal surface.
[0012] While RCM has been demonstrated in the skin, the development of endoscopic confocal microscopy systems has taken longer due to technical challenges associated with miniaturizing a scanning microscope. One difficulty with such technique is providing a mechanism for rapidly raster-scanning the focused beam at the distal end of a small-diameter, flexible probe. A variety of approaches have been attempted to address this problem, including the use of distal micro electro mechanical systems (MEMS) beam scanning devices, and proximal scanning of single-mode fiber bundles.
[0013] Another challenge can be the miniaturization of high NA objectives used for optical sectioning. Possible solutions employing a gradient-index lens system, dual-axis objectives or custom designs of miniature objectives have been described. First, demonstrations of these technologies in patients are beginning to appear; detailed images of the morphology of cervical epithelium have been obtained in vivo using a fiber optic bundle coupled to a miniature objective lens and fluorescence based images of colorectal and esophageal lesions were shown using commercial instruments.
[0014] Even though endoscopic RCM has been demonstrated in patients, this technique is likely not currently optimized for biopsy guidance. One reason can be that such technique provides microscopic images only at discrete locations, the so-called “point sampling” approach problem mentioned above. Point sampling is inherent to RCM since it has an extremely limited field of view (e.g., 200-500 μm), which is less than that of an excisional biopsy. As a result, endoscopic RCM may likely have the same sampling errors and diagnostic yield limitations as excisional biopsy.
[0015] In order to use endoscopic RCM for biopsy guidance, the imaging paradigm may be shifted away from point sampling to microscopy with extremely large fields of view where every possible location within the tissue of interest is sampled. The output of this paradigm, which can be termed “Comprehensive Volumetric Microscopy (CVM),” can include microscopic images of entire organ or luminal surfaces in three-dimensions.
[0016] For CVM, imaging speeds of current techniques may need to be increased by at least an order of magnitude above video rate, due to the very high bandwidth of the microscopic information and the constraint of obtaining such data in a realistic procedural time (e.g., <20 min). In addition, catheter/endoscope technology can be developed to automatically scan the microscope over these large tissue surface areas rapidly and with a high degree of precision.
[0017] Recently, CVM has been implemented using a second-generation form of optical coherence tomography (OCT), called optical frequency domain imaging (OFDI), and rapid helically scanning catheters. This research has facilitated the acquisition of three-dimensional microscopic images of the entire distal esophagus in a few minutes and long segments of coronary arteries in patients in less than 5 seconds. (See Suter M. J. et al., “Comprehensive microscopy of the esophagus in human patients with optical frequency domain imaging”, Gastrointestinal endoscopy, 2008, Vol. 68(4), pp. 745-53; and Tearney G. J. et al., “Three-dimensional coronary artery microscopy by intracoronary optical frequency domain imaging: First-in-human experience”, Journal of the American College of Cardiology, Imaging, 2008, pp. 1:752-61
[0018] While OFDI shows significant potential for certain clinical applications, its ˜10 μm resolution may not necessarily be sufficient for dysplasia and early cancer diagnosis, which can require knowledge of tissue morphology at both architectural and cellular levels. Thus, there may be a need to provide a new exemplary variant of RCM that is capable of rapidly obtaining high-resolution comprehensive volumetric images through an endoscopic probe.
[0019] One approach is to use spectrally encoded microscopy (“SECM”) technique(s). SECM's rapid imaging rate and its fiber-optic design can enable comprehensive volumetric RCM through an endoscopic probe. An SECM probe has been described which can scan an area equivalent to that of the distal esophagus (about 5.0 cm length, and about 2.5 cm diameter), at a single depth location, in approximately 1 minute. (See, e.g., Yelin D. et al., “Large area confocal microscopy”, Optics Letters, 2007; 32(9):1102-4).
[0020] Spectrally encoded confocal microscopy (“SECM”) is a single fiber-optic confocal microscopy imaging procedure, which uses a broad bandwidth light source and encodes one dimension of spatial information in the optical spectrum (as illustrated in the example of FIG. 1 ). As shown in FIG. 1 , at the distal end of the probe, the output from the core of a single-mode or dual-clad fiber 110 is collimated by a collimation lens 115 and illuminates a transmission diffraction grating 120 . An objective lens 130 focuses each diffracted wavelength to a distinct spatial location 141 , 142 , or 143 within the specimen, producing a transverse line focus 150 where each point on the line has a different wavelength or color. After reflection from the tissue, the light passes back through the lens 130 , is recombined by the grating 120 , and collected by the fiber 110 . The aperture of the fiber 110 provides the spatial filtering mechanism to reject out-of-focus light. Outside the probe (within the system console) the spectrum of the returned light is measured and converted into confocal reflectance as a function of transverse displacement within the sample. Spectral decoding of this line in the image can be performed very rapidly, e.g., at rates of about 70 kHz, which can be approximately 10 times that of video rate confocal microscopy systems and up to about 100 times faster than some endoscopic RCM systems. The other transverse axes of the image can be obtained by relatively slow and straightforward mechanical actuation that may regularly employ for a wide variety of endoscopic probes. Images obtained by SECM demonstrate its capability to image subcellular-level microstructure relevant to the diagnosis of dysplasia and cancer (see FIG. 2 ). FIGS. 2A and 2B show exemplary SECM images of swine duodenum, obtained ex vivo, after compression of the bowel wall, showing the architecture of the duodenal villi and nuclear detail. Illustrated imaging depths are 50 μm and 100 μm shown in FIGS. 2A and 2B , respectively.
[0021] Accordingly, there may be a need to overcome at least some of the above-described issues and/or deficiencies.
SUMMARY OF EXEMPLARY EMBODIMENTS
[0022] Thus, at least some of these issues and/or deficiencies can be addressed with the exemplary embodiments of the apparatus, system and method according to the present disclosure.
[0023] Exemplary embodiments of the present disclosure provides mechanism and a methodology for automatically maintaining the foci at a desired tissue depth while scanning the spectrally encoded line across the sample. This exemplary advancement can compensate for patient motion and enables imaging at multiple depth locations. Further, in one exemplary embodiment, it is possible to conduct a large area confocal microscopy in patients by incorporating these technologies in an endoscopic probe suitable for human use.
[0024] According to another exemplary embodiment of the present disclosure, an apparatus can be provided. The apparatus can comprise at least one dispersive first arrangement which is configured to provide data associated with a signal received from at least one region of the sample(s). The exemplary apparatus can also comprise at least one focusing second arrangement which is configured to control a focal length and/or a focal position associated with first arrangement based on the data. According to an exemplary variant, at least one third arrangement can also be availed which is configured to provide further data associated with a further signal received from at least one further region of at least one sample. The region and the further region can at least partially overlap and/or be located at near one another. The focusing second arrangement(s) can be configured to control the focal length and/or the focal position associated with the first arrangement(s) based on the data and/or the further data. The dispersive and focusing arrangements can be provided in a balloon.
[0025] According to a further exemplary embodiment of the present disclosure, apparatus, method and system can be provided for imaging at least one portion of an anatomical tissue can also be provided. For example, with a dispersive arrangement, it is possible to provide at least one first electromagnetic radiation to the at least one portion to form a sample plane at an angle that is greater than 0 degrees and less than 90 degrees with respect to a plane of a surface of the portion(s). Further, at least one second electromagnetic radiation can be received from the sample plane which is associated with the first electromagnetic radiation(s) to generate information as a function the second electromagnetic radiation(s). A control signal can be generated based on the information so as to further control a location of a focal plane of the first electromagnetic radiation(s), or at least one three-dimensional image of the at least one portion can be generated as a function of the information.
[0026] In one exemplary variant, it is possible to generate the control signal based on a location of a surface of the sample using at least one portion of the at least one first electromagnetic radiation. It is also possible to separate the second electromagnetic radiation(s) into at least one first signal and at least one second signal. Further, the control signal can be generated based on the first signal(s), and at least one image associated with the sample can be generated as a function of the second signal(s).
[0027] In a further exemplary embodiment of the present disclosure, the SECM probe components can be incorporated into a transparent tube, e.g., having about 1.0 cm in diameter, with an approximately 2.5 cm diameter centering balloon and a rapid-exchange guide wire provision. Helical scanning can be accomplished by the use of a rotary junction and a pullback motor connected to the SECM optics via a wound cable through the tube. An exemplary arrangement in which an objective lens is angled relative to the surface of the sample can be used. This angled arrangement can be used to generate a feedback signal for controlling the focal plane of the objective lens and also provide three-dimensional image information through a single helical scan. The transverse resolution of the SECM optics can be, e.g., nominally about 1.6 μm and the autofocus mechanism can function, e.g., over a range of about ±500 μm. The SECM imaging system, operating at a center wavelength of 725 nm and capable of configured to obtain image data at about 70×10 6 pixels per second, can be enclosed in a portable arrangement, e.g., a cart.
[0028] The exemplary system and probe can be configured to comprehensively image the entire human distal esophagus (about 2.5 cm diameter and about 5.0 cm length) at about 10 different focal locations, in approximately 10 minutes. Exemplary software can be provided and stored on a tangible computer-accessible medium (and executed by a processor or other computing arrangement(s)) a for convenient image data acquisition, display, and selection of sites to be marked for biopsy.
[0029] In yet another exemplary embodiments of the present disclosure, a laser marking apparatus, method and system can be provided according to the present disclosure. An approximately 400 mW, 1450 nm laser can be incorporated into the system and coupled into an endoscopic probe to create minute, visible superficial marks on tissue at selected image locations so that they may be subsequently biopsied by the endoscopist. For example, target sites, identified by SECM or OCT, can be marked so that the endoscopist can review and biopsy these locations. An exemplary embodiment of a laser marking apparatus, method and system can be provided for accomplishing this exemplary task. The exemplary laser marking technique can be incorporated into the exemplary embodiment of the apparatus, system and device according to the present disclosure.
[0030] According to one exemplary embodiment of the present disclosure, apparatus, method and system can be provided for determining a position on or in a biological tissue can be provided. For example, using such exemplary embodiment, it is possible (using one or more arrangements) to receive information associated with at least one image of at least one portion of the biological tissue obtained using an optical imaging technique. Further, it is possible to, based on the information, cause a visible change on or in at least location of the portion(s) using at least one electro-magnetic radiation.
[0031] For example, the image(s) can include a volumetric image of the portion(s). The volumetric image can be a cylindrical image having a diameter of between about 10 mm to 100 mm and/or an extension of at most about 1 m. It is also possible (e.g., using a particular arrangement) to receive data associated with the visible change, and guide a visualization to the at least one portion based on the data. Further, it is possible to cause the visible change by ablating the portion(s). The ablation can be performed by irradiating the portion(s) with the electro-magnetic radiation(s).
[0032] In one exemplary embodiment of the present disclosure, the arrangement can be situated in a probe, and an ablation arrangement can be provided in the probe which is controlled by the arrangement to cause the visible change on or in one or more the portions. It is also possible to obtain the information via at least one wave-guiding arrangement, and the ablation arrangement can provides the electro-magnetic radiation(s) via the wave-guiding arrangement(s) to cause the visible change. In addition, the optical imaging technique can include a confocal microscopy technique, and the confocal microscopy technique can be a spectrally-encoded confocal microscopy technique. Further, the optical imaging technique can include an optical coherence tomography.
[0033] These advancements can achieve performance specifications that can be used for endoscopic use in patients. It is also possible to incorporate exemplary embodiments described herein in an endoscope and utilize the targeted biopsy technique, e.g., in clinical studies and in other scenarios.
[0034] The exemplary embodiment of the system and probe according to the present disclosure described herein can be used in patients undergoing upper endoscopy. While the application of the exemplary embodiments can be to a wide variety of epithelial cancers and other clinical applications such as tumor margin detection, one exemplary application can be for Barrett's esophagus (BE), as it is an area where these exemplary embodiments may have a high impact. Because the exemplary comprehensive SECM can sample the entire distal esophagus on a microscopic scale, the exemplary SECM-guided biopsy can yield a significantly higher sensitivity for the detection of dysplasia and early adenocarcinoma.
[0035] According to the exemplary embodiments of the present disclosure, it is possible to screening patients for Barrett's esophagus and improving the diagnostic capabilities of surveillance endoscopy. These advances can decrease the mortality associated with esophageal adenocarcinoma.
[0036] The image-guided biopsy according to the exemplary embodiments of the present disclosure is expected to be safe and well-tolerable, detect previously unattainable subcellular and architectural information over large epithelial surfaces of the esophagus, and provide an effective method for endoscopic biopsy targeting. The impact of these exemplary embodiments can be high, as it can provide clinicians with a powerful tool for improving the management of BE patients. While the broad goal of this invention is focused on reducing the mortality of esophageal adenocarcinoma, the exemplary SECM system and probe represent a new diagnostic platform that can be applied to dysplasia and cancer screening in other internal organ systems. The long term impact of the exemplary embodiments of the present disclosure can also affect treatment as it can enable less invasive surgical techniques such as RF ablation, photodynamic therapy, or endoscopic mucosal resection to be used at an earlier stage of disease progression.
[0037] According to the exemplary embodiments of the present disclosure, it is possible to screening patients for Barrett's esophagus and improving the diagnostic capabilities of surveillance endoscopy. These advances can decrease the mortality associated with esophageal adenocarcinoma.
[0038] To utilize comprehensive SECM to guide biopsy, additional exemplary procedures and/or steps can be taken. As an initial matter, the images are interpreted during the procedure. A comparison of SECM images of biopsy samples to corresponding histology can be performed that can describe an exemplary criteria for SECM diagnosis. Another exemplary embodiment of the system, device and method according to the present invention can be provided for obtaining information that is compatible with current morphologic methods for disease diagnosis. Advantages of this exemplary embodiment can include near-term clinical application and the potential for leveraging a large, existing database of clinic pathologic correlations. Further, it is likely that molecular imaging provide an impact in changing this paradigm in the future.
[0039] These and other objects, features and advantages of the exemplary embodiment of the present disclosure will become apparent upon reading the following detailed description of the exemplary embodiments of the present disclosure, when taken in conjunction with the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0040] Further objects, features and advantages of the present invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the present invention, in which:
[0041] FIG. 1 is a schematic diagram of an exemplary arrangement which utilizes spectrally-encoded confocal microscopy (SECM) techniques;
[0042] FIG. 2A is a SECM image of swine duodenum, obtained ex vivo, after compression of the bowel wall using the exemplary arrangement illustrated in FIG. 1 showing the architecture of the duodenal villi and nuclear detail at an imaging depth of about 50 μm;
[0043] FIG. 2A is another SECM image of swine duodenum, obtained ex vivo, after compression of the bowel wall using the exemplary arrangement illustrated in FIG. 1 showing the architecture of the duodenal villi and nuclear detail at an imaging depth of about 100 μm;
[0044] FIG. 3 is a schematic diagram and a photograph inset of an exemplary SECM arrangement/probe according to an exemplary embodiment of the present disclosure;
[0045] FIG. 4 is a schematic diagram of an exemplary spectrally encoded illumination on tissue using the exemplary embodiment of the arrangement/probe shown in FIG. 3 ;
[0046] FIG. 5A is an exemplary SECM image which can be utilized for focusing by the exemplary embodiment of the arrangement according to the present disclosure;
[0047] FIG. 5B is an exemplary graph of intensity versus pixel coordinate associated with the exemplary SECM image shown in FIG. 5A ;
[0048] FIG. 6A is a cylindrical presentation of an exemplary image of a lens paper phantom obtained by an exemplary SECM bench-top probe without adaptive focusing;
[0049] FIG. 6B is a magnified view of the exemplary image shown in FIG. 6A ;
[0050] FIG. 6C is a cylindrical presentation of an exemplary image of the lens paper phantom obtained by the exemplary SECM bench-top probe with adaptive focusing;
[0051] FIG. 6D is a magnified view of the exemplary image shown in FIG. 6C ;
[0052] FIG. 6E is an illustration of an exemplary stack of SECM images of the lens paper phantom at a region of the sample over the imaging depth of 56 μm;
[0053] FIG. 7 is an exemplary SECM image of a human esophageal biopsy sample showing the gastroesophageal junction, squamous epithelium, and gastric cardia;
[0054] FIG. 8A is an exemplary SECM image of esophageal squamous epithelium showing intraepithelial eosinophils from a patient with presumed eosinophilic esophagitis;
[0055] FIG. 8B is an exemplary SECM image of a gastric body fundic type mucosa from the patient with presumed eosinophilic esophagitis imaged following 0.6% acetic acid;
[0056] FIG. 8C is an exemplary SECM image of Fundic gland polyp with columnar epithelium lining the cyst wall from the patient imaged following 0.6% acetic acid;
[0057] FIG. 9A is an exemplary SECM image of a specialized intestinal metaplasia obtained using the exemplary embodiment of the system and method according to the present disclosure was acquired following application of 0.6% acetic acid;
[0058] FIG. 9B is a magnification view of the image of FIG. 9A showing goblet cells;
[0059] FIG. 9C is an exemplary SECM image of a high grade dysplasia obtained using the exemplary embodiment of the system and method according to the present disclosure;
[0060] FIG. 9D is an exemplary SECM image according to the exemplary embodiments of the present disclosure demonstrating architectural and nuclear atypia;
[0061] FIG. 10 is an exemplary image flow diagram of the comprehensive microscopy guided biopsy platform with laser marking according to an exemplary embodiment of the method of the present disclosure;
[0062] FIG. 11 is an exemplary flow diagram of the SECM-guided biopsy process according to an exemplary embodiment of the present disclosure;
[0063] FIG. 12 is a schematic diagram of a side view of an exemplary SECM arrangement/probe according to an exemplary embodiment of the present disclosure;
[0064] FIG. 13 is a schematic diagram of an exemplary rotary junction of the exemplary embodiment of a system according to the present disclosure;
[0065] FIG. 14 is a schematic diagram of an exemplary SECM system of the exemplary embodiment according to the present disclosure;
[0066] FIG. 15 is a schematic diagram of an exemplary embodiment of an optoelectronic apparatus for generating the auto-focusing feedback signal according to the present disclosure
[0067] Throughout the figures, the same reference numerals and characters, unless otherwise stated, are used to denote like features, elements, components or portions of the illustrated embodiments. Moreover, while the subject disclosure will now be described in detail with reference to the figures, it is done so in connection with the illustrative embodiments. It is intended that changes and modifications can be made to the described exemplary embodiments without departing from the true scope and spirit of the subject disclosure as defined by the appended claims.
DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS
[0068] Exemplary embodiments of the systems, processes and arrangements according to the present disclosure includes, but not limited to (a) a SECM endoscopic probe, (b) diagnosis based on histopathologic features observed in SECM images, and/or (c) an image-guided laser marking system, etc. A description of each of these three exemplary embodiments is described in detail below, along with an exemplary embodiment of a clinically-viable SECM-guided biopsy system/probe according to the present disclosure.
Exemplar), SECM Probe
[0069] Exemplary embodiments of the present disclosure which include certain arrangement/probe components facilitate comprehensive endoscopic SECM imaging of large luminal surfaces can be provided. As shown in the exemplary embodiment illustrated in FIG. 3 , light from a broadband light source 310 (e.g., spectral bandwidth=about 30 nm; central wavelength=about 877 nm) can be coupled into a 50/50 fiber-optic beam splitter 320 . Light from the fiber output port 110 of the beam splitter can be collimated by a collimation lens 115 (e.g., f=about 20 mm), and dispersed by a transmission holographic grating 120 (e.g., about 1700 lines/mm) into e.g., ˜350 resolvable points. The dispersed light can be focused onto the specimen 330 by an objective lens 130 (e.g., aspheric lens: f=about 4.5 mm; effective NA=about 0.53) through a thin-walled balloon 328 (e.g., diameter=about 20 mm; thickness=about 50 μm). The objective lens 130 can be angled so that the axial positions of the focused spots vary by e.g., about 50 μm across the imaging bandwidth. Helical scanning can be accomplished by rotating and translating the probe housing 320 by a motor 326 and a translation stage 327 . A photo of the exemplary embodiment of the SECM probe is shown in the inset of FIG. 3 . The size of the exemplary probe can be about 10 mm (W)×39 mm (L)×13 mm (H). The reflected light can be coupled back into the beam splitter and directed to a spectrometer comprising a collimation lens 341 (f=about 44 mm), a grating 342 (about 1800 lines/mm), a focusing lens 343 (f=about 200 mm), and a line scan camera 344 (e.g., Basler Sprint; pixel size=about 10 μm; 2048 pixels). The exemplary spectral resolution of the spectrometer can be about 0.04 nm.
[0070] To generate depth-resolved optical sections, each digitized spectrally-encoded line can be divided into, e.g., 8 segments where each segment corresponds to image information obtained at a different depth level. Exemplary image segments from the same depth level can be connected together to create a large-area optical section at each depth. In order to keep the focus of the high NA objective lens 130 within the sample 330 , the objective lens 130 can also be scanned along the axial direction by a focusing mechanism 325 , which can include a miniature linear guide and a piezoelectric transducer (PZT) actuator.
[0071] FIG. 4 shows a schematic diagram of the illumination beam from the objective lens 130 on the sample 330 through the balloon 328 . Since the objective lens 130 is angled, each wavelength can image at a different depth of the sample 330 . A spectral band 450 that images the balloon region 328 at a line scan can be used to locate the balloon surface in the field of view, which can be used to generate a feedback signal to control the focusing mechanism 325 . for example, the remaining spectral band 440 , together with the spectral band 450 , can be used to generate line image of the sample 330 . FIG. 5A shows an exemplary image that can be generated by the exemplary embodiment of the SECM arrangement/probe according to the present disclosure as shown in FIGS. 3 and 4 . For example, the portion that visualizes the balloon 328 has higher signal level than that for the sample 330 . The line profile along a line 530 (shown in FIG. 5B ) illustrates a high intensity peak 540 at the balloon location, and such peak location can be used as a reference point to control the focusing mechanism (e.g., using a processing or computing device or arrangement).
Exemplary Experimental Results
[0072] The transverse resolution of the exemplary embodiment of the SECM arrangement/probe according to the present disclosure, measured by imaging the edge response function from bars on a 1951 USAF resolution chart, ranged from 1.25±0.13 μm to 1.45±0.33 um, from the center to the edges of the spectral field of view, respectively. The axial resolution of the exemplary embodiment of the SECM arrangement/probe, obtained by z-scanning a mirror through the focus, was measured to be 10 μm and 4.4 μm for the edge and the center of the spectral FOV's, respectively. The adaptive focusing mechanism in the exemplary embodiment of the SECM arrangement/probe accurately tracked the sinusoidal motion of a moving mirror at rate of 1 Hz with displacement amplitude of about 250 μm. The exemplary mechanical design of the probe head and the software procedure used in this exemplary embodiment of the arrangement/probe was somewhat limited the speed and range of the adaptive focusing mechanism. It is possible to generate the feedback signal using a separate opto-electronic apparatus and it is possible to modify the probe housing, which can increase the response speed of the feedback loop and the focal range, respectively.
[0073] FIGS. 6A-6E show exemplary SECM images and data for a substantially complete exemplary pullback image of, e.g., a 2.0 cm phantom without adaptive focusing (see FIGS. 6A and 6B ) and with adaptive focusing (see FIGS. 6C and 6D ). The exemplary phantom consists of lens paper affixed to the outer surface of the balloon (diameter=about 20 mm). The exemplary embodiment of the SECM arrangement/probe according to the present disclosure was scanned using a rotation rate of about 20 rpm; a total of about 400 circumferential scans were acquired in 20 minutes, limited primarily by the speed of the method used to generate the control signal. Since the length of a single spectrally-encoded line was 400 μm, the longitudinal step size of 50 μm provided 8 different depth levels. At low magnification (shown in FIGS. 6A and 6C ), the macroscopic structure of the paper, including folds and voids, can be visualized. When regions of this data set are shown at higher magnifications, individual fibers and fiber microstructure can be clearly resolved (as shown in FIGS. 6 B and 6 D—see inset).
[0074] By utilizing the automatic focusing mechanism (the image produced by which is shown in FIGS. 6C and 6D ), the entire dataset remained in focus and information can be acquired from all optical sections within the approximately 50 μm range, even when the exemplary arrangement/probe was not centered. In contrast, when the focusing mechanism was off, only small portions of the phantom were in focus and visible (as shown in FIGS. 6A and 6B ). A stack of exemplary SECM images at a region of the sample through different imaging depths is shown in FIG. 6E . This exemplary image stack provides three-dimensional information over the depth of about 56 μm at 8 different focal planes. Feature changes are well noticed between the images from the different imaging planes including the white dotted circular region. These exemplary results demonstrate the technical feasibility of comprehensive exemplary SECM for luminal organs.
Histopathologic Features Visualized by Exemplary SECM Techniques
[0075] An exemplary SECM system with similar optical specifications as that described herein above for the exemplary embodiment of the endoscopic SECM probe can be utilized, e.g., to image entire human biopsy samples (as described in, e.g., Kang D. et al., “Comprehensive imaging of gastroesophageal biopsy samples by spectrally encoded confocal microscopy”, Gastrointest Endosc. 2009). This exemplary SECM system can utilize a wavelength-swept source (e.g., central wavelength=1320 nm; bandwidth=70 nm; repetition rate=5 kHz) and a 0.7 NA objective lens. A single-mode illumination and multi-mode detection imaging configuration can be used to reduce laser speckle noise, a method that can also be employed in the exemplary arrangement/probe described herein above. The resolutions of such exemplary SECM system can be, e.g., 2.3 μm and 9.7 μm along the transverse and axial directions, respectively. FIG. 7 shows an exemplary image of one of the first data sets that have been acquired from an exemplary biopsy study, demonstrating the architectural morphology of, e.g., a normal gastroesophageal junction.
[0076] Exemplary SECM images of other esophageal tissue types can also be obtained, including squamous mucosa with scattered eosinophils gastric fundic body type mucosa and a fundic gland polyp (see FIGS. 8A , 8 B and 8 C). Images of Barrett's esophagus (see FIGS. 9A and 9B ) appear to be distinct from gastric cardia (as shown in FIG. 7 ) and high-grade dysplasia (as shown in FIG. 9C ). For example, an application of 0.6% acetic acid (vinegar) for enhancing nuclear contrast can be performed on, e.g., the majority of the biopsy samples. Further clinical study of SECM imaging on a larger set of biopsy samples can deliver diagnostic criteria of SECM imaging and evaluate its accuracy. The diagnostic criteria can be used in the SECM-guided biopsy to identify and locate diseased regions automatically or manually by clinicians or image readers.
Exemplary Laser Marking for Guiding Biopsy
[0077] To utilize endoscopic microscopy techniques to guide biopsy, regions of dysplasia and early carcinoma identified by the imaging system can be marked so that they can be visible by traditional endoscopy.
[0078] FIG. 10 shows an image progress diagram of an exemplary embodiment of a method of image-guided biopsy that uses laser marking of the superficial esophageal mucosa according to the present disclosure. To demonstrate the feasibility of laser marking targeted biopsy, this exemplary technique has been tested in swine in vivo (n=4) through a balloon catheter with OFDI imaging modality. For each animal, the balloon catheter and inner optical imaging probe were positioned within the esophagus. A 400 mW, 1450 nm laser was used to mark the esophagus through a fiber-optic probe, focused to a spot diameter of approximately 30 μm. A total of 68 randomly located 8-second targets 1021 were created in the swine esophagus. A comprehensive microscopy dataset 1010 of the distal 5.0 cm of the esophagus was then obtained and used 1020 to locate the targets 1021 . After locating a target on the endoscopic microscopy image, smaller 2-second laser marks 1041 were made on either side of the target to serve as a guide for biopsy 1030 (see FIG. 10 ). Following laser marking, the balloon catheter was removed and the esophagus was visualized by conventional endoscopy 1040 . An inspection of the esophagus 1040 revealed that both marks surrounding 1041 each target 1021 were visible by endoscopy for about 97% of the targets. Histopathological analysis 1050 of the marks showed that both the 8- and 2-second marks caused only minor injury to the mucosa, extending to the superficial submucosa, which healed after two days. These exemplary results demonstrate that laser marking is a viable approach for facilitating biopsy guided by endoscopic microscopy. Although OFDI imaging modality was used for this experiment, SECM can also be utilized through a balloon catheter to guide biopsy.
[0079] For various internal organ systems, random biopsy can be the standard of care for the diagnosis of epithelial metaplasia, dysplasia, and early cancer. SECM-guided biopsy can change this paradigm and improve outcomes for patients who undergo regular surveillance for these conditions. SECM may be capable of identifying architectural and cellular microstructure relevant to esophageal diagnosis. Certain exemplary technical components can be preferred for implementing SECM-guided biopsy in an endoscopic probe. It is possible to provide an exemplary embodiment of a clinically viable SECM system and endoscopic probe. The exemplary system/device can obtain RCM data at multiple depths over the entire distal esophagus, and can facilitate the physician to identify and mark suspect locations in the tissue so that they can be subsequently biopsied.
Exemplary SECM-Guided Biopsy
[0080] FIG. 11 illustrates a flow diagram of exemplary embodiment of the procedures according to the present disclosure for conducting the exemplary SECM-guided biopsy. For example, a centering balloon probe can be inserted over a guide wire (block 1120 ) that has been previously placed endoscopically (block 1110 ). When the balloon probe is in place, the balloon can be inflated in block 1130 , and comprehensive SECM can be performed using a helical scan pattern in block 1140 . In the endoscopic suite, the exemplary SECM dataset can be analyzed, and biopsy targets may be selected on the image in block 1150 . The SECM probe can then automatically return to those locations in the patient and can place laser marks on either side of the targets in block 1160 . Following such exemplary laser marking, the balloon can be deflated and removed in block 1170 . The endoscopist can then obtain biopsies from the marked sites in block 1180 . Although SECM is used in the exemplary procedures shown in FIG. 11 , other microscopic imaging technologies including OCT can be also used to guide the biopsy.
Exemplary Endoscopic Probe
[0081] A clinical exemplary SECM-guided biopsy device can comprise, e.g., three components: a) the probe, b) the probe-console interface, and c) the console. An exemplary schematic diagram of an exemplary embodiment of the SECM arrangement/probe is shown in
[0082] FIG. 12 . The exemplary SECM arrangement/probe can comprise a double-clad fiber (DCF) 1211 which can transceive the imaging light, and also transmit the laser marking beam. To reduce speckle noise, imaging can be accomplished by illuminating the sample through the core of the DCF, and by receiving the light remitted from the sample through both the core and inner cladding. The fiber can be contained within a wound cable 1212 that rotates, and can translate within a transparent 1.0 cm diameter sheath 1232 .
[0083] Rotating and translating the wound cable at its proximal end can facilitate an exemplary helical imaging to take place over the entire extent of the balloon 328 . During imaging, a control signal, derived from the reflection from the balloon surface (see FIGS. 4 and 5 ), can be used to generate an input to the focusing mechanism 325 to adaptively change the focal location. The wound cable 1212 and DCF 1211 can be attached to the housing 320 of the exemplary SECM arrangement/probe, which can contain a collimation lens 115 , a grating 120 , an objective lens 130 , and the focusing mechanism 325 . A 6.0 cm long, 2.5 cm diameter transparent centering balloon 328 , can be affixed to the transparent sheath 1232 . The distal end of the exemplary arrangement/probe can be terminated by a guide wire provision 1231 .
[0084] Exemplary Probe Optics. It is possible to reduce the size of the exemplary arrangement/probe further by developing customized optical and mechanical components. In order to minimize or reduce the rigid length, the collimation lens 115 can be fabricated to decrease the distance between the DCF 1211 and the lens 115 . The grating 120 (e.g., Holographix, Hudson, Mass.) can be provided to have, e.g., maximum diffraction efficiency for the 2 nd order at 725 nm and for the 1 st order at about 1450 nm. The exemplary objective lens 130 (e.g., NA=0.4) can be provided (e.g., ZEMAX, Bellevue, Wash.) and produced (e.g., Optimax Systems Inc., Ontario) to have diffraction-limited performance throughout the optical sectioning depth range of about 100 μm in tissue. The objective lens 130 can be achromatic at 725 nm and 1450 nm, and can have a cylindrical surface to compensate for the astigmatism induced by the transparent catheter's sheath 1232 .
[0085] Exemplary Wound Cable. It is possible to utilize exemplary multi-layer wound drive shafts to scan distal optics within the patient for other imaging modalities. A custom wound cable 1212 can be fabricated (e.g., Asahi Intec, USA) and tested for the motion transduction accuracy and repeatability through the catheter.
[0086] Exemplary Balloon-Centering Catheter. An exemplary balloon-centering catheter utilizing a transparent polycarbonate sheath 1232 (e.g., diameter=about 10 mm) and a transparent plastic balloon 328 (e.g., Advanced Polymers, Salem, N.H.; inflated diameter=about 25 mm) can be provided to house the probe optics and wound cable (e.g., Device company; Innovative Medical Design, Tyngsboro, Mass.). The exemplary catheter can be tested for transparency, flexibility, and trackability to ensure that it is suitable for intraesophageal imaging.
Exemplary Probe-Console Interface
[0087] An exemplary rotary junction (shown in an exemplary embodiment of the arrangement of FIG. 13 ) can be provided to couple light from the console to/from the probe and rotate the exemplary SECM arrangement/probe within the transparent sheath. In contrast to the exemplary OCT rotary junctions, the exemplary SECM optical rotary junction can transmit the imaging light from the light source 310 into the core 1351 of a double clad fiber (“DCF”). The inner cladding 1352 of the DCF can transmit laser marking light 1380 , and can deliver imaging light returned from the sample to a spectrometer 1370 .
[0088] To accomplish a separation of single- from multi-mode light, the exemplary rotary junction can contain two focusing lenses 1320 , 1360 and a single-mode/multi-mode splitter, e.g., comprise a mirror 1330 with a central transparent aperture and a relay lens 1340 (see FIG. 13 ). The exemplary rotary junction can rotate the wound cable 1212 at 70 rpm. In addition to coupling light from a static system to rotating catheter optics, the exemplary rotary junction can also transmit low electrical current to control the focusing mechanism. Further, the entire exemplary rotary junction can be affixed to a linearly scanning pullback stage, translating at a rate of about 0.1 mm/s, to enable helical scanning of the SECM probe optics. Motor encoder output from both rotational and linear motors can be digitized synchronously with the image signal to facilitate the exemplary SECM probe to return to any given image location in the patient for laser marking.
[0089] The exemplary optical rotary junction can be provided in Solid Works and simulated in ZEMAX. Exemplary design(s) can be optimized for maximum throughput and ease of manufacturing and tolerancing. The exemplary design(s) can be custom-machined, assembled and tested for single and double-passed throughput and rotational uniformity. The exemplary rotary junction can additionally be designed to fit within the standard motorized pull back trays.
Exemplary Console
[0090] An exemplary console (an example of a schematic diagram of which is shown in FIG. 14 ) can comprise the light sources and detectors used to image, mark, and can also be used to generate a feedback signal to control the focal location of the probe's objective lens. For imaging, light from a broadband light source 310 (e.g., Fianium SC450-6) can be filtered by a filter 1411 to have a broadband NIR spectrum 1421 of 725±30 nm. This exemplary wavelength range can be chosen so as to provide an appropriate compromise between resolution, penetration depth, and detector sensitivity. In addition, the center wavelength can be half that of the wavelength of the laser marking beam 1448 (e.g., about 1450 nm) from the high power laser 1380 . By diffracting the imaging beam through the grating of the probe's second order and the marking laser through the first order, both can illuminate the same location on the sample.
[0091] Optical components, including the dichroic mirror 1441 and the mirror 1442 in the console, can route the single-mode imaging laser and multi-mode marking laser to the exemplary SECM probe 1430 through the rotary junction 1420 . Remitted confocal light from the rotary junction 1420 can be divided by a dichroic mirror 1443 into two beams; the imaging beam 1446 that is directed to a spectrometer 1370 and the focusing beam 1447 that can be coupled to an optoelectronic apparatus 1460 for generating the auto-focusing feedback signal. The imaging beam 1446 and the focusing beam 1447 can cover different spectral regions. Each line in the image can be detected using a line-scan camera (e.g., SPL2048-140k, Basler) in the spectrometer 1380 ; exemplary digital image data can be transferred to the computer 1480 at a line rate of about 70 kHz and saved to a data recording system (e.g., Signatec DR-400) in real-time. The computer generates the control signal for the focusing mechanism in the SECM probe 1430 .
[0092] Exemplary Adaptive Focusing Optoelectronics. An exemplary optoelectronic apparatus for generating the adaptive focus feedback signal according to the present disclosure can be provided (an exemplary diagram of which is shown in FIG. 15 ). As shown in FIG. 15 , the focusing beam 1447 from the exemplary SECM probe (shown in FIG. 5 ) can be optically separated from the imaging beam 1446 (as shown in the diagram of FIG. 14 ), and a grating 1520 can be used to disperse its spectrum onto a position-sensitive detector 1530 (PSD; e.g., quadrant photodetector). The electrical signals from the individual cells in the PSD 1530 can be algebraically or mathematically processed (e.g., using a computing or processing arrangement) to provide the peak wavelength, which can correspond to the position of the inner surface of the balloon.
[0093] The balloon surface position can then be converted into a control signal that can drive the focusing mechanism and move the objective lens in the SECM probe. The output signal 1540 from the PSD 1530 can be fed to an analogue electric feedback circuit that controls the focusing mechanism directly or can be routed to the computer 1540 to be used for control purpose. By making this feedback/control independent of the imaging data acquisition, its response time can be much faster than that of the exemplary SECM arrangement/probe described herein above with reference to FIG. 3 , resulting in an increase in imaging speed by more than a factor of, e.g., 4.
[0094] Exemplary Laser Marking for Guided Biopsy. For example, two exemplary diode lasers (e.g., wavelength=about 1450 nm, power=about 200 mW each) can be polarization-multiplexed and integrated into the SECM system to create marks for guiding biopsy. Light from the diode lasers can be transmitted through a shutter and coupled into the inner cladding of the SECM probe through the rotary junction. A computer or other processing device(s) can control the intensities and exposure durations of the diode lasers. For safety reasons, e.g., the laser shutter can be configured to only allow a maximum of, e.g., about 10 seconds per exposure at any given site.
[0095] Exemplary System Integration. Exemplary imaging and marking lasers can be tested for power and spatial coherence. Some or all optics can be tested for throughput and efficiency. The optical layout can be assembled on a small breadboard for incorporation into the cart. The imaging spectrometer can be fabricated and its spectral resolution and light throughput can be tested using standard techniques. Following assembly of the exemplary individual components, the exemplary system can be integrated into a portable, medical-grade cart. Software can be provided to control the rotary junction, the adaptive focusing mechanism, and the marking lasers using one or more computers. Existing software to facilitate the navigation of the image in a manner similar to that done with Google™ Earth, where pan and zoom quickly enable the viewer to focus on a precisely located area of interest, can be adapted for SECM datasets. Additional software user-interface inputs can be provided to allow the observer to quickly switch between different optical sections, delineate the target sites, and initiate laser marking.
Exemplary Specifications and Performance Expectations
[0096] Table 1 depicts the exemplary specifications and objective performance targets (OPT) for the exemplary SECM arrangement/probe and system according to the present disclosure. The exemplary OPTs can be based on the preferences of comprehensive endoscopic confocal microscopy and prior experience with centering-balloon imaging of the esophagus.
[0097] Meeting such exemplary OPTs can furthermore provide beneficial imaging performance. The exemplary arrangement/probe can have a deflated diameter of about 1.0 cm and a rigid length of about 4.5 cm—specifications that match that of commercially available, over-the-wire endoscopic ultrasound devices. Transverse and axial resolutions, governed by the number of modes transmitted through the inner cladding of the DCF can be better than critically sampled in the circumferential direction and Nyquist sampled along the longitudinal dimension. The longitudinal interval of about 72 μm between neighboring circumferential scans can provide optical sections at about 10 discrete depth locations and up to about 100 μm beyond the surface of the balloon. The exemplary marking beam can have a spot size of about 30 μm on the sample, which is sufficient for producing endoscopically visible marks on the esophageal surface in, e.g., about 2 seconds.
[0098] The image-guided biopsy according to the exemplary embodiments of the present disclosure is expected to be safe and well-tolerable, detect previously unattainable subcellular and architectural information over large epithelial surfaces of the esophagus, and provide an effective method for endoscopic biopsy targeting. The long term impact of the exemplary embodiments of the present disclosure can also affect treatment as it can enable less invasive surgical techniques such as RF ablation, photodynamic therapy, or endoscopic mucosal resection to be used at an earlier stage of disease progression.
[0099] The foregoing merely illustrates the principles of the invention. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. Indeed, the arrangements, systems and methods according to the exemplary embodiments of the present invention can be used with imaging systems, and for example with those described in International Patent Publication WO 2005/047813 published May 26, 2005, U.S. Patent Publication No. 2006/0093276, published May 4, 2006, U.S. Patent Publication No. 2005/0018201, published Jan. 27, 2005 and U.S. Patent Publication No. 2002/0122246, published May 9, 2002, the disclosures of which are incorporated by reference herein in their entireties. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements and methods which, although not explicitly shown or described herein, embody the principles of the invention and are thus within the spirit and scope of the present invention. In addition, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it is explicitly being incorporated herein in its entirety. All publications referenced herein above are incorporated herein by reference in their entireties.
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Exemplary embodiments of apparatus, method and system for determining a position on or in a biological tissue can be provided. For example, using such exemplary embodiment, it is possible to control the focus of an optical imaging probe. In another exemplary embodiment, it is possible to implement a marking apparatus together with or into an optical imaging probe. According to one exemplary embodiment, it is possible (using one or more arrangements) to receive information associated with at least one image of at least one portion of the biological tissue obtained using an optical imaging technique. Further, it is possible to, based on the information, cause a visible change on or in at least location of the portion(s) using at least one electro-magnetic radiation.
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RELATED APPLICATION
This application claims priority to U.S. Provisional Patent Application Ser. No. 60/080,196 entitled Methods and Apparatus for Percutaneous In Situ Coronary Artery Bypass, filed Mar. 31,1998.
FIELD OF THE INVENTION
The present invention relates generally to medical devices and methods, and more particularly to catheter devices and methods that are useable to form channels (e.g., penetration tracts) between vessels such as arteries and veins as well as between vessels and other anatomical structures, in furtherance of a therapeutic purpose such as bypassing an arterial blockage, delivering therapuetic agents, or performing other interventional procedures.
BACKGROUND OF THE INVENTION
Applicant has invented several new interventional procedures wherein channels (e.g., bloodflow passageway(s)) are formed between blood vessels, and between blood vessels and other target structures, using transluminally advanceable catheters. These new procedures include novel percutaneous, transluminal techniques for bypassing obstructions in coronary or peripheral arteries through the use of the adjacent vein(s) as in situ bypass conduit(s), and other means of revascularizing oxygen starved tissues or delivering therapuetic substances to vessels, tissue and other organs. These procedures are fully described in U.S. Pat. No. 5,830,222 and in U.S. patent application Ser. Nos. 08/730,496, 09/048,147 and 09/048,147. Some of these procedures may be performed by a venous approach, such as vein-to-artery wherein a tissue penetrating catheter is inserted into a vein and the desired arterio-venous passageway is initially formed by passing a tissue penetrating element (e.g., a flow of energy or an elongate penetration member) from a catheter, through the wall of the vein in which the catheter is positioned, and into the lumen of an adjacent artery. Alternatively, some of these procedures may be performed by an artery-to-vein approach wherein the catheter is inserted into an artery and the desired arterio-venous passageway is initially formed by passing a tissue penetrating element (e.g., a flow of energy or elongate penetration member) from the catheter, through the wall of the artery in which the catheter is positioned, and into the lumen of an adjacent vein. Both approaches have been previously described in U.S. patent application Ser. No. 08/730,327. In addition, it may be advantageous to direct a penetrating element directly into other anatomical structures such as the myocardium, pericardium, chamber of the heart or other organs as described in U.S. patent application Ser. No. 09/048,147.
Different considerations and limitations may apply, depending upon which of these approaches (the vein-to-artery approach, the “artery-to-vein” approach, or vessel to other anatomical structure) is being used or, more generally, the size and contour of the blood vessel lumen in which the operative catheters are to be placed, and the distance and/or angle between the vessels or other target. This is due in part to the fact that, in the heart as well as in other areas of the body, adjacent arteries and veins may be of significantly different diameter and significantly different dilatory capability. In addition, depending on the procedure to be performed, for example, such as the desired angle of channel creation between blood vessels, one approach may be preferred over the other, to promote, among other things, blood flow channels that encourage non-turbulent blood flow. Also, the consequences associated with causing temporary complete obstruction of a vein may be significantly less than the consequences of causing temporary complete obstruction of an artery. Thus, it is desirable to devise tissue penetrating catheters of the above-described type that are sized, configured and/or equipped differently for use in blood vessels of different sizes, shapes and in connection with different types of pathology.
Moreover, it is desirable for tissue penetrating catheters of the abovedescribed type to be constructed and equipped for precise aiming and control of the tissue penetrating element as the tissue penetrating element passes from the catheter, through at least the wall of the blood vessel in which the catheter is located, and to the target location. Such aiming and control of the tissue penetrating element ensures that it will create the desired penetration tract at the intended location with minimal or no damage to surrounding tissues or other structures.
SUMMARY OF THE INVENTION
The present invention provides methods and apparatus for performing the percutaneous in situ coronary arterio-venous bypass procedures generally described in U.S. Pat. No. 5,830,222 and U.S. patent application Ser. No. 08/730,327, and other procedures requiring the use of accurately placed catheter elements.
A. Devices and System:
In accordance with the invention, there is provided a system for forming an initial penetration tract from the lumen of a blood vessel in which the catheter is positioned to a target location (such as another blood vessel, organ or myocardial tissue). This system generally comprises:
a) a coronary sinus guide catheter which is insertable within the venous system of the body and into the coronary sinus of the heart;
b) a tissue penetrating catheter which is advanceable to a position within a coronary vein, such tissue-penetrating catheter comprising i) a flexible catheter body, ii) a tissue penetrating element (e.g., a needle member, electrode or flow of energy) which is passable from the catheter body, through the wall of the coronary vein in which the catheter body is positioned and into the lumen of an adjacent coronary artery, or other targeted structure, iii) an imaging lumen through which an imaging catheter (e.g., an intravascular ultrasound imaging (IVUS) catheter) may be passed; and,
c) a separate imaging catheter (e.g., an intravascular ultrasound (IVUS) catheter) that is advanceable through the imaging lumen of the tissue-penetrating catheter.
In addition to components a-c above, this catheter system may include a subselective sheath and introducer. The subselective sheath comprises a flexible tubular sheath that has a proximal end, a distal end and a lumen extending therethrough. The introducer is insertable through the lumen of the sheath and has a tapered, non-traumatizing distal portion that protrudes out of and beyond the distal end of the sheath as well as a guidewire lumen extending longitudinally therethrough. The tapered, non-traumatic distal portion of the introducer serves to dilate the blood vessel lumens or openings through which the sheath is inserted, thereby facilitating advancement and positioning of the sheath at a desired location within the body. After the sheath has been advanced to its desired position within the body, the introducer is extracted and various channel modifying catheters, connector delivery catheters and/or blocker delivery catheters may be advanced through the subselective sheath.
The coronary sinus guide catheter may incorporate a hemostatic valve to prevent backflow or leakage of blood from the proximal end thereof. Also, the coronary sinus guide catheter may include an introducer that is initially insertable through the guide catheter lumen. This introducer has a tapered, non-traumatizing distal portion that protrudes out of and beyond the distal end of the guide catheter, and a guidewire lumen extending longitudinally therethrough. The tapered, non-traumatizing distal portion of the introducer served to dilate the blood vessel lumens through which the guide catheter is inserted, thereby facilitating advancement and positioning of the coronary sinus guide catheter within the coronary venous sinus.
The tissue-penetrating catheter may incorporate one or more of the following elements to facilitate precise aiming and control of the tissue-penetration element and the formation of the passageway at the desired location:
a) Orientation Structure: An orientation structure may be positioned or formed on the distal end of the tissue penetrating catheter. This orientation structure has i) a hollow cavity or space formed therewithin in alignment with the catheter's imaging lumen and ii) a marker member positioned in direct alignment with the opening in the catheter through which the tissue penetrating element emerges (or otherwise in some known spacial relationship to the path that will be followed by the tissue penetrating element as it passes from the tissue penetrating catheter). The separate imaging catheter may be advanced through the tissue penetrating catheter's imaging lumen and into the receiving space of the orientation structure. Thereafter, the imaging catheter is useable to image the target location as well as the marker. The image of the marker provides a path indication that is indicative of the path that will be followed by the tissue penetrating element as it passes from the tissue penetrating catheter. The operator may then adjust the rotational orientation of the tissue penetrating catheter as necessary to cause the path indication to be aligned with or aimed at the target location, thereby indicating that when the tissue penetrating member is subsequently passed from the catheter body, it will advance into the target location and not to some other location. In this manner the imaging lumen, separate imaging catheter and orientation structure that are incorporated into the catheter system of this invention operate, in combination with each other, to facilitate precise rotational orientation of the tissue penetrating catheter and aiming of the tissue penetrating element before the tissue penetrating element is advanced, thereby ensuring that the tissue penetrating element will enter the desired target at the desired location. In particular, the orientation structure may comprise a plurality (e.g., three) of longitudinal struts, such longitudinal struts being disposed about a central space into which the IVUS catheter may be advanced. One of such longitudinal struts may be aligned or specifically positioned in relation to the path that will be followed by the tissue penetrating element as it passes from the catheter, thereby providing on the display of the image received from the IVUS catheter, an artifact of other indication delineating the path or direction in which the tissue penetrating element will pass. The tissue-penetrating catheter may then be selectively rotated to aim the tissue penetrating element into the lumen of the artery or other target anatomical structure into which it is intended to pass.
b) Soft Distal Tip Member: The catheter may incorporate a soft distal tip member that is formed or mounted on the distal end of the tissue-penetrating catheter (e.g., on the distal aspect of the above-described orientation structure). Such soft tip member is preferably formed of material which is soft enough to avoid trauma to the walls of the blood vessels through which the tissue-penetrating catheter is passed. A lumen may extend longitudinally through the soft tip member, to allow the operator to selectively advance the IVUS catheter or other device beyond the distal end of the tissue-penetrating catheter when it is desired to image blood vessels or other structures located distal to the then-current position of the tissue-penetrating catheter or perform other diagnostic functions with said IVUS catheter or other device.
c) Tissue Penetrating Member Stabilizer: In embodiments wherein the tissue penetrating element is a needle or other elongate member that is advanceable laterally from the catheter body, the tissue penetrating catheter may incorporate a stabilizer to prevent or deter the tissue penetrating member from rotating or deviating from a predetermined acceptable penetration zone (APZ) (hereinafter sometimes referred to as the “stabilizer”). As used herein, the term stabilizer shall mean any structural or functional attributes of the catheter and/or tissue penetrating member that deter or prevent the tissue penetrating member from rotating or otherwise deviating from its intended path of advancement within a predetermined acceptable penetration zone (APZ). Examples of such structural and/or functional attributes include but are not limited to; curved distal housing formed to mirror the curve or form of the tissue penetrating element, engagement projections or elements for frictional engagement between the tissue penetrating member and the catheter body, bushings or narrowed/reduced diameter regions of the tissue penetration member lumen that serve to constrain the tissue penetrating member preventing side-to side play or movement thereof, permanent magnets or electromagnets that create a magnetic field that prevents or deters lateral or rotational movement of the tissue penetrating member, etc. More specifically, for example, this stabilizer may comprise one or more of the following:
i) a curved needle housing which mates (i.e. has the same direction of curvature) with a preformed curvature formed in the needle. This mating of the curvatures of the needle and needle housing serves to deter unwanted rotation and resultant lateral deviation (flopping or wagging) of the portion of the needle which extends out of the catheter body;
ii) frictionally engaged surfaces formed on the needle member and surrounding catheter body (e.g., the wall of the lumen in which the needle member is disposed) to lock or deter rotation of the needle member relative to the catheter body;
iii) a steering mechanism for causing the distal portion of the catheter body to become curved in the direction in which the needle member is intended to advance so as to cause the preformed curve of the needle member to mate with the induced curvature of the surrounding catheter body; and,
iv) A laterally deployable needle guide member (e.g., a balloon or rigid annular structure) that is deployable from side of the tissue penetrating catheter adjacent to the outlet opening through which the tissue penetrating member passes to support and prevent unwanted lateral “play” or movement of the tissue penetrating member as it is advanced from the catheter. This outwardly deployable needle guide member is initially disposed in a “stowed” position wherein it does not protrude (or only minimally protrudes) from the catheter body, and is subsequently deployable to an “active” position wherein it protrudes laterally from the catheter body, in the area of the needle outlet aperture, to provide support and/or guidance for the advancing tissue penetrating element (e.g., needle member or flow of energy) as the tissue penetrating element passes from the catheter body to the target location. This laterally deployable needle guide member may comprise a tubular cuff that has a lumen. The lumen of such tubular cuff may form, in combination with the catheter lumen in which the tissue penetrating element is positioned, a curvature that mates with or conforms to the preformed or intended curvature of the path of the tissue penetrating element as it passes from the catheter to the target location. In cases where the tissue penetrating element is a curved needle, the curvature of the laterally deployable needle guide member and/or catheter lumen may mate with or be the same as the curvature of the needle member.
d) Needle Member Locking Apparatus: The tissue penetrating catheter may incorporate an apparatus that prevents or deters rotation of the tissue penetration member within the catheter body prior to its advancement out of the catheter. Such rotational locking of the tissue penetrating member while it is in its retracted position serves i) to maintain the desired rotational orientation of the needle member and ii) to enhance or couple the transfer of torque from the proximal end of the catheter to the distal end of the needle, without the addition of mass or cross-sectional dimension to the catheter body.
e) Catheter Body Construction: The tissue penetrating device may comprise an elongate catheter body 12 with proximal, medial and distal segments of varying flexibility and torque strength as described more fully in U.S. patent application Ser. No. 08/837,294, incorporated herein by reference. Said catheter body may incorporate reinforcement members such as a reinforcement braid member which imparts structural integrity/stability as well as enhancing the ability of the catheter body to transmit torque along its length. In addition, it may be important for said reinforcement member to maintain the longitudinal integrity of said catheter body, and to minimize any variability of the catheter components during operation in the body.
B. Methods:
Further in accordance with the invention, there are provided methods for using the above-summarized catheter system to bypass an obstruction in a coronary artery by forming one or more arterio-venous passageways. Examples of these methods are the Percutaneous In Situ Coronary Artery Bypass (PICAB), as well as the Percutaneous Coronary Venous Arterialization (PICVA). It is understood that the same orientation steps and procedures may be used to access various targets and anatomical structures from placement of a tissue penetrating catheter within a blood vessel and orienting said catheter in accordance with this invention.
i. Percutaneous In Situ Coronary Artery Bypass (PICAB)
The PICAB procedure generally comprises the following steps:
1. Introduce a coronary sinus guide catheter into the coronary sinus;
2. Pass a tissue-penetrating catheter of the above-described type through the guide catheter and into the coronary vein;
3. Position an IVUS catheter or ultrasound transducer within the orientation structure of the tissue-penetrating catheter, and utilize the IVUS catheter or ultrasound transducer to view the artery into which the arteriovenous passageway is to extend as well as the marker that denotes the path that will be followed by the tissue penetrating member as it is advanced from the catheter body;
4. Rotate or move the tissue-penetrating catheter, as necessary, to cause the needle path indicator generated by the marker to become aligned with the lumen of the artery; and,
5. Pass the tissue penetrating element from the catheter, through the wall of the vein in which the catheter is positioned, and into the lumen of the artery, thereby forming an initial arterio-venous passageway distal to the arterial obstruction. In some embodiments, the tissue penetrating element has a lumen extending longitudinally therethrough for passage of a guidewire from vessel to vessel.
6. Move the catheter to a second location and repeat steps 4-6 to form an initial arterio-venous passageway proximal to the arterial obstruction.
7. Enlarge the proximal and distal arterio-venous passageways, if necessary, to permit the desired volume of blood flow through such passageways.
8. Place connector(s), stent(s), liner(s) or other stenting or connecting devices within the proximal and/or distal passageways, if necessary, to maintain the patency of the passageways; and,
9. Optionally, if necessary, place one or more blocker(s) within the coronary vein, or otherwise fully or partially block blood flow through the coronary vein, at location(s) that urge arterial blood to flow from the artery, through the first passageway and into the vein, through a segment of the vein, through the second passageway, and back into the artery (downstream of the blockage), thereby restoring arterial blood flow to the ischemic myocardium.
ii. Percutaneous Coronary Venous Arterialization (PICVA)
Further, in accordance with the present invention, there is provided a method for Percutaneous In Situ Coronary Venous Arterialization (PICVA) procedure, using a catheter system of the foregoing character. This preferred PICVA procedure generally comprises the steps of:
1. Introduce a coronary sinus guide catheter into the coronary sinus;
2. Pass a tissue-penetrating catheter of the above-described type through the guide catheter and into the coronary vein;
3. Position an IVUS catheter or ultrasound transducer within the orientation structure of the tissue-penetrating catheter, and utilize the IVUS catheter or ultrasound transducer to view the artery into which the arterio-venous passageway is to extend as well as the marker that denotes the path that will be followed by the tissue penetrating member as it is advanced from the catheter body;
4. Rotate or move the tissue-penetrating catheter, as necessary, to cause the needle path indicator generated by the marker to become aligned with the lumen of the artery; and,
5. Pass the tissue penetrating element from the catheter, through the wall of the vein in which the catheter is positioned, and into the lumen of the artery, thereby forming an initial arterio-venous passageway distal to the arterial obstruction.
In some embodiments, the tissue penetrating element has a lumen extending longitudinally therethrough for passage of a guidewire from vessel to vessel.
6. Enlarge the initial arterio-venous passageways, if necessary, to permit the desired volume of blood flow through such passageway.
7. Place connector(s), stent(s), liner(s) or other stenting or connecting devices within the arterio-venous passageway, if necessary, to maintain the patency of the passageway; and,
8. Optionally, if necessary, place one or more blocker(s) within the coronary vein, or otherwise fully or partially block blood flow through the coronary vein, at location(s) that urge arterial blood to flow from the artery, through the arterio-venous passageway and into the vein, such that the arterial blood will flow through the vein in a direction opposite normal venous flow, thereby retro-perfusing the ischemic myocardium by arteralization of the coronary vein.
Further aspects and advantages of the present invention will become apparent to those of skill in the art upon reading and understanding the detailed description of preferred embodiments set forth herebelow and the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic showing of a human being having a tissue-penetrating catheter system of the present invention percutaneously inserted via a femoral entry site.
FIG. 1 a is a broken, side elevational view of a first embodiment of a tissue-penetrating catheter of the present invention.
FIG. 1 b is an enlarged view of the distal end of the catheter of FIG. 1 a.
FIG. 1 b ′ is a broken, side view of the catheter body construction of the catheter shaft of a tissue penetrating catheter of the present invention.
FIG. 1 b ″ is a detailed view of the braided construction of the catheter shaft of FIG. 1 b′.
FIG. 1 c is a cross sectional view through line 1 c— 1 c of FIG. 1 a.
FIG. 1 d is a cross sectional view through line 1 d— 1 d of FIG. 1 a.
FIG. 1 e is an enlarged, side elevational view of the needle housing/stabilizer assembly of the catheter of FIG. 1 a.
FIG. 1 f is a cross sectional view through line 1 f— 1 f of FIG. 1 e.
FIG. 1 f ′ is a cross sectional view through line 1 f ′— 1 f ′ of FIG. 1 f.
FIG. 2 is a representation of the intravascular ultrasound image that is obtained when the tissue-penetrating catheter of FIG. 1 a is positioned within a coronary vein and properly oriented/aimed such that deployment of its tissue penetrating member will form a penetration tract (i.e., a passageway) from the coronary vein to an adjacent coronary artery.
FIG. 3 is a representation of the intravascular ultrasound image which is obtained when the tissue-penetrating catheter of FIG. 1 a is positioned within coronary vein and improperly oriented/aimed such that deployment of its tissue penetrating member will not form a passageway from the coronary vein to the adjacent coronary artery.
FIG. 4 is a side elevational view of a subselective sheath and accompanying introducer that are useable in combination with the tissue-penetrating catheter of the present invention.
FIG. 4 a is a side elevational view of a dilator that is insertable through and useable in conjunction with the subselective sheath of FIG. 4 .
FIG. 5 is a partial longitudinal sectional view of the subselective sheath of FIG. 4 having the dilator of FIG. 4 a operatively inserted therein.
FIG. 5 a is an enlarged, cross sectional view through line 5 a— 5 a of FIG. 5 .
FIG. 6 is an enlarged, longitudinal sectional view of the distal portion of the subselective sheath of FIG. 4 .
FIG. 7 is a side elevational view of the tissue puncturing needle member of the tissue-penetrating catheter of FIG. 1 a.
FIG. 8 a is an enlarged, side elevational view of the distal end of the needle member of FIG. 7 .
FIG. 8 b is an enlarged top view of the of the distal end of the needle member of FIG. 7 .
FIGS. 9 & 9 a show the hand piece/needle controller and distal end, respectively, of tissue-penetrating catheter of FIG. 1 a with its tissue penetrating needle member in its retracted position.
FIGS. 10 & 10 a show the handpiece/needle controller and distal end, respectively, of tissue-penetrating catheter of FIG. 1 a with its tissue penetrating needle member in its fully advanced position.
FIG. 10 d is a side elevational view of an optional rotation-inhibiting key insert and corresponding keyed needle member which may be incorporated into the tissue-penetrating catheters of the present invention to prevent the tissue-penetrating needle member from rotating relative to the body of the catheter.
FIG. 10 d ′ is a cross sectional view through line 10 d′— 10 d ′ of FIG. 10 d.
FIG. 10 d ″ is a cross sectional view through line 10 d″— 10 d ″ of FIG. 10 d.
FIG. 10 e is a side elevational view of an optional rotation-inhibiting oval insert and corresponding oval shaped needle member which may be incorporated into the tissue-penetrating catheters of the present invention to prevent the tissue-penetrating needle member from rotating relative to the body of the catheter.
FIG. 10 e ′ is a cross sectional view through line 10 e ′— 10 e ′ of FIG. 10 e.
FIG. 10 e ″ is a cross sectional view through line 10 e″ - 10 e ″ of FIG. 10 e.
FIG. 10 f is a partial longitudinal sectional view of a tissue-penetrating catheter device of the present invention incorporating an optional locking collar apparatus for preventing the tissue penetrating needle member from rotating relative to the catheter body when the needle member is in its retracted position.
FIG. 10 f ′ is an enlarged view of region 10 f ′ of FIG. 10 f.
FIG. 10 g is a side elevational view of a tissue-penetrating catheter of the present invention having a laterally deployable needle stabilizer disposed in its “stowed” position.
FIG. 10 g ′ is a side elevational view of a tissue-penetrating catheter of the present invention having a laterally deployable needle stabilizer disposed in its “active” position.
FIG. 11 is a side elevational view of a coronary sinus guide catheter/introducer assembly of the present invention.
FIG. 11 a is a cross-sectional view through line 11 a — 11 a of FIG. 11 .
FIG. 11 b is an enlarged, longitudinal sectional view of the proximal end/hemostatic valve of the coronary sinus guide catheter shown in FIG. 11 .
FIG. 11 c is broken, side elevational view of the introducer of the coronary sinus guide catheter/introducer assembly.
FIG. 12 is an enlarged, cross-sectional view through a coronary artery and adjacent coronary vein, showing the typical difference in diameter of the artery and vein, and delineating a preferred Acceptable penetration zone (APZ) wherein the arterio-venous bloodflow passageways of the present invention are formed.
FIGS. 13 a - 13 x are schematic, step-by-step showings of a preferred method for performing a percutaneous, in situ coronary arterio-venous bypass (PICAB) procedure to bypass a blockage in the proximal Left Anterior Descending coronary artery, using a a vein-to-artery approach.
FIGS. 14 a - 14 m are schematic, step-by-step showings of a preferred method for performing a percutaneous coronary venous arterialization (PICVA) procedure to provide retrograde arterial bloodflow through a coronary vein.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following detailed description, and the drawings to which it refers, are provided for the purpose of describing and illustrating certain preferred embodiments or examples of the invention only, and no attempt has been made to exhaustively describe all possible embodiments or examples of the invention. For example, the tissue penetrating catheter of this invention may be utilized is numerous locations in the body to reliably access organs, tissue or other structures to deliver therapeutic substances or procedures. Thus, the following detailed description and the accompanying drawings are not intended to limit, in any way, the scope of the claims recited in this patent application and any patent(s) issuing therefrom.
A. The Catheter System
Referring generally to FIGS. 1-12, a presently preferred catheter system of the present invention generally comprises i) a tissue-penetrating catheter component 10 (FIGS. 1-3 and 7 - 10 a ), ii) a subselective sheath/introducer component 100 (FIGS. 4-6) and iii) a coronary sinus guide catheter/introducer component 200 (FIGS. 11-11 c ). Each of these components is described in substantial detail herebelow. These components of the catheter system may be packaged together in a single kit, or may be provided in separate packages to permit the operator to mix and match component sizes in accordance with the particular anatomy of the patient, the size of the channels to be formed, the types of connectors and/or stents and/or blockers to be used, etc.
I. The Tissue-Penetrating Catheter Component of the Catheter System
Referring to FIGS. 1-3 and 7 - 10 there is shown a tissue-penetrating catheter device 10 which is insertable into the vasculature of a mammalian patient and useable to form passageways (e.g., puncture tracts) between the blood vessel in which the distal end of the catheter device 10 is situated and another blood vessel or other anatomical structure. This catheter device 10 generally comprises an elongate, flexible catheter body 12 having a proximal portion 12 P of a first diameter D 1 and a distal portion 12 D of a second diameter D 2 which is smaller than the first diameter D 1 . The catheter body 12 has two (2) lumens 14 , 16 which extend longitudinally therethrough. The first lumen 14 is sized and configured to permit a standard commercially available IVUS catheter (e.g., those available from Endosonics of Rancho Cordova, Calif.; CVIS of Natick, Mass. or Hewlett-Packard of Andover, Mass.) to be inserted therethrough and slidably disposed therewith. The second lumen 16 is sized and configured to house a tissue penetrating needle member 30 (see FIGS. 7, 9 and 10 ) which is alternately moveable between i) a retracted position (FIGS. 9-9 a ) wherein the distal end DE of the needle member 30 is contained within the catheter body 12 , and ii) an extended position (FIGS. 10-10 a ) wherein the needle member 30 is advanced out of the catheter body 12 so as to penetrate through the walls of the blood vessels and through any intervening tissue located between the blood vessels.
a. Orientation Structure
An orientation structure 36 and tip member 38 are formed integrally with or mounted on the distal end of the catheter body 12 , as shown in FIGS. 1 b, 9 a and 10 a. The orientation cage 36 comprises first 40 , second 42 and third 44 strut members which extend longitudinally between the distal end of the catheter body 12 and the proximal end of the distal tip member 38 . The first strut member 40 is in direct longitudinal alignment with a needle outlet opening 46 formed in the side of the catheter body 12 through which the tissue penetrating needle member 30 is advanced. The second and third strut members 42 , 44 are located at equally spaced distances from the first strut member 40 , while the distance between the second and third strut members 42 , 44 is less than the distance between either of those second and third strut members 42 , 44 and the first strut member 40 . Such disparate (e.g., unequal) radial spacing of these strut members 40 , 44 and 46 allows the operator to easily identify and distinguish the first strut member 40 from the other two strut members 42 , 44 by way of the image received from an IVUS catheter positioned within the orientation structure 36 . Thus, in this manner, the operator may selectively rotate the catheter body 12 until the first strut member 40 is directly aligned or juxtapositioned with the target blood vessel into which the needle member 30 is to be advanced. An illustration of this technique is shown in FIGS. 2 and 3. FIG. 2 shows the IVUS image which is obtained when the tissue-penetrating catheter 10 is properly rotated such that the first strut member 40 is aligned with the target artery A and the needle member 30 will advance into such target artery A. FIG. 3 shows another situation where the tissue-penetrating catheter 10 is not properly rotated, the first strut member 40 is not aligned with the target artery A and the needle member 30 , if advanced, would not enter the target artery A.
It will be appreciated that the disparate distancing of the strut members 40 , 42 , 44 is only one possible way of rendering the first strut member 40 distinguishable from the other two strut members 42 , 44 . Alternatively, the size or configuration of the first strut member could be different so as to produce a distinguishable ultrasound image or the material or surface characteristics of the first strut member 40 could be made different from the other two strut members 42 , 44 such that the first strut member 40 would reflect more or less ultrasound than the other two strut members 42 , 44 thus producing an ultrasound image which is distinguishable from the images produced by the other two strut members 42 , 44 . It will also be appreciated that only one strut member may be required to provide a distinguishable element to aid catheter orientation, or alternatively two strut members may be positioned to delineate a zone within which the tissue penetrating member may be deployed, or other procedure conducted.
b. Distal Tip Member
The distal tip member 38 is preferably of blunt tipped configuration and is formed of smooth soft material (e.g., PEBAX having a durometer hardness of 35 D) so as to minimize trauma to the vasculature as the tissue-penetrating catheter device 10 is advanced or otherwise manipulated about. A hollow lumen 39 may extend longitudinally through the tip member 38 , in alignment with the first lumen 14 of the catheter body 12 , such that an IVUS catheter or other device such as a guidewire may be advanced from the first lumen 14 , through the orientation structure 36 , through the distal tip lumen 38 and distally beyond the catheter device 10 . This permits the operator to use the IVUS catheter to explore areas which are ahead of the distal end of the tissue-penetrating catheter without having to advance the tissue-penetrating catheter from its then-present position. It also permits the catheter device 10 to be introduced to the vasculature in the preferred “over the wire” manner.
c. Tissue Penetrating Needle Member
The tissue penetrating element of the tissue penetrating catheter may comprise a sharp tipped needle 30 as shown in FIGS. 7, 8 a and 8 b. This needle 30 includes a proximal shaft 30 p formed of stainless steel hypotubing and a resilient, curved distal portion 30 d formed of a resilient material or, more preferably, a material such as NiTi alloy. Preferably a lumen 31 extends longitudinally through the proximal shaft 30 p and the curved distal portion 30 d.
The particular radius of curvature of the curved distal portion 30 d may be an important factor in determining the trajectory and path of the needle tip as it advances and the point at which the needle tip will stop when in its fully advanced position.
The distal tip of the needle member 30 is preferably sharpened so as to easily penetrate through the walls of the blood vessels and any intervening tissue located therebetween. One preferred needle tip configuration is the lancet type bevel 36 shown in FIGS. 8 a and 8 b. This lancet type bevel comprises a first radial surface 36 a and a second radial surface 36 b. Such lancet type tip 36 provides excellent tissue-penetrability and retains its sharpness after multiple retractions into/advancements from the catheter. In practice it may be important for the material surrounding the lumen of the needle, particularly at the distal tip of the needle, and particularly the heel of the needle lumen 36 c, to be smooth and free of rough edges or burrs. This allows smooth passage of devices, such as guidewires, through the needle lumen.
In many applications, the controllability and aiming of the needle member 30 may be enhanced by constraining the needle member 30 such that it will remain in a preferred plane or acceptable penetration zone APZ as shown in FIG. 12, as it is advanced from the catheter. In embodiments where a curved needle member 30 is advanced out of a side aperture in the catheter ( e.g., the embodiment shown in FIG. 10 a ), any rotation of the needle member 30 prior to, during or after advancement of the needle member 30 can cause the distal end of the curved needle member to deviate from or move out of the intended plane or acceptable penetration zone APZ. In this regard, the potential for such unwanted lateral movement of the distal end of the needle member 30 may be prevented or substantially limited by providing a stabilizer to prevent or substantially limit the amount of rotation that the needle member 30 may undergo relative to the catheter body 12 or to otherwise prevent or deter the needle member from deviating from a predetermined acceptable acceptable penetration zone APZ (FIG. 12) as it is advanced from the catheter 10 . In particular, by preventing or limiting the rotation of the needle member 30 within the needle lumen 16 , the curved distal portion of the needle member will be deterred from deviating from its intended path of advancement as it is extended laterally from the catheter body 12 (see FIG. 10 a ). Such prevention or limitation of the potential for rotation or lateral movement of the needle member 30 may be accomplished in any suitable way. As described in detail herebelow, specific apparatus which may be incorporated into the catheter device 10 to prevent or deter rotation or lateral movement (i.e., “wagging” or “flopping”) of the needle member 30 during or after its advancement from the catheter body 12 , include:
a) a curved needle housing 60 which has a curve at its distal end which mates with the preformed curvature of the needle member 30 to deter rotation (see FIGS. 9-10 f );
b) engaged surfaces 76 , 77 formed on the needle member 30 and surrounding catheter body 12 to lock or deter rotation of the needle member 30 , examples of such engaged surfaces 76 , 77 including but not necessarily being limited to i) a tongue in groove or key in key-way arrangement (see FIGS. 10 d - 10 d ″) or ii) an oval to oval arrangement (see FIGS. 10 e - 10 ″), etc;
c) a steering mechanism for causing the distal portion of the catheter body 12 to curve in the lateral direction in which the needle member 30 is intended to advance so as to cause the preformed curve of the needle member 30 to mate with the induced curvature of the catheter body 12 ; and,
d) a needle guide member 500 which is laterally projectable from the catheter body 12 in the area of the needle outlet aperture 46 to support the needle member 30 and/or to form a lateral extension of the needle lumen 16 so as to create a lateral curve in the needle lumen which mates with the preformed curvature of the needle member 30 (see FIG. 10 g ).
i. Curved Needle Housing to Deter Rotation/Lateral Deviation of Extended Needle
An example of a preferred curved needle housing 60 mountable within the needle lumen 16 is specifically shown in FIGS. 1 b - 1 f. Such needle housing 60 comprises a curved, rigid tube. A tubular liner 61 may be disposed within, and may extend from either end of, the curved needle housing 60 . Such tubular liner 61 may be formed of a three-layer composite wherein the inner layer is a lubricious polymer material (e.g., polytetrafluoroethylene (PTFE)), the middle layer is a structural polymer material (e.g., polyimide) and the outer layer is an adhesive material which will bond to the inner surface of the curved needle housing 60 and to the inner surface of the needle lumen 16 at either end of the housing 60 (e.g., polyurethane adhesive). When the needle member 30 is in its retracted position (FIGS. 9 and 9 a ), and during advancement, the portion of the needle member which resides within the needle housing 60 will remain in a slightly curved state in conformance to the slightly curved configuration of the needle housing 60 . This serves to deter the needle member 30 from rotating relative to the catheter body 12 and/or from undergoing uncontrolled movement (i.e., “flopping”) out of the intended acceptable penetration zone APZ, during or after advancement from the catheter. This prevention or deterrence from rotation of the needle member 60 allows the operator to control the orientation of the lancet type or other bevel formed in the needle tip, and also enhances the operator's ability to predict the precise position of the needle tip by eliminating or minimizing the uncontrolled side-to-side movement of the needle. To facilitate the desired positioning and orientation of the curved needle housing 60 during manufacture of the catheter 10 , a locator member 62 may be attached to the needle housing 60 and incorporated into the catheter body 12 as shown in FIGS. 1 b, 1 e, 1 f, 1 f ′, 9 a and 10 a. This locator member 62 comprises a rigid disc 64 which is transversely positionable within the catheter body, having a first bore 66 and a second bore 68 extending longitudinally therethrough. A chamfered edge 69 is formed about the proximal end of the first bore 66 , as shown in FIGS. 1 f and 1 f ′. During manufacture of the catheter body 12 , a rod or mandrel is inserted through the first bore 66 of the locator and into the first lumen 14 of the proximal catheter body portion 12 P and the curved needle housing 60 having a tubular liner 61 extending therethrough and protruding for either end, are inserted through the second bore 68 and into the second lumen 16 of the proximal catheter body portion 12 P . Thereafter, a distal plastic tube is advanced about the locator, a tubular polymer skin 73 is applied, and the composite is then heated to form the distal portion of the catheter body 12 , as shown.
ii. Frictionally Engaged Surfaces of Needle Member and Catheter to Deter Rotation/Lateral Deviation of Extended Needle:
As an alternative to, or in addition to, the use of the curved needle housing 60 as a means for preventing rotation of the needle member 30 and for providing more accurate and stable deployment of the needle member 30 , the needle member 30 and at least a portion of the second lumen 14 may incorporate engaged surfaces which are frictionally engaged to one another so as to prevent or deter rotation of the needle member 30 within the needle lumen 16 . Examples of such engaged surfaces 76 , 77 include a key/key-way design shown in FIGS. 10 d - 10 d ″ or an oval/oval design such as that depicted in FIGS. 10 e - 10 e″.
With specific reference to the showings of FIGS. 10 d - 10 d″, the key/keyway method of preventing independent rotation of the needle member 30 may be effected by use of a key-way element 76 in combination with a keyed needle 30 key . The key-way element 76 comprises a tubular member which has a key-way shaped lumen 77 with a key portion 79 extending longitudinally therethrough. The keyed needle 30 key comprises a hollow needle of the type described hereabove and shown in FIGS. 7-8 b having a longitudinally extending rail or key member 33 formed upon a segment thereof. The key member 33 may be formed as a portion of the needle wall or may alternatively comprise a separate member, such as a section of hypotube, affixed to the side of the needle wall. The keyed needle 30 key is sized and configured to be advanced and retracted through the lumen 77 of the key-way housing, with the key member 31 being disposed within the key portion 79 of the lumen 77 . In this manner the keyed needle member 30 key is longitudinally advanceable and retractable, but can not be rotated within the lumen 77 due to the engagement of the needle key member 31 with the key portion 79 of the lumen 77 . The key-way element 76 is provided with a stabilizer 78 which is substantially the same as the needle housing stabilizer 62 described above and shown in FIGS. 1 e - 1 f ′, and the key-way element 76 /stabilizer 78 assembly may be installed and mounted within the catheter body at the time of manufacture in the same manner as described hereabove with respect to the needle housing 60 /stabilizer 62 assembly shown in FIGS. 1 e - 1 f ′. This key-way element 76 /stabilizer 78 assembly is typically installed and mounted in the catheter body 12 proximal to the location of the needle housing 60 /locator 62 assembly shown in FIGS. 1 e - 1 f ′ but near enough to the distal end of the catheter device 10 to prevent the portion of the needle adjacent its distal end from undergoing untoward rotation within the catheter body 12 during the catheter insertion procedure.
With specific reference to the oval/oval arrangement shown in FIGS. 10 e - 10 e″, the device 10 may incorporate an oval shaped needle housing 76 alt in combination with an oval shaped needle 30 ov . The oval shaped needle housing 76 alt comprises a tubular member positioned within the needle lumen 16 and having an oval shaped lumen 77 alt extending longitudinally therethrough. The oval shaped needle 30 ov comprises a hollow needle of the type described hereabove and shown in FIGS. 7-8 b having an oval, ovoid or other non-round cross-sectional configuration. The oval shaped needle 30 ov is sized and configured to be advanced and retracted through the lumen 77 alt of the oval shaped needle housing 76 alt , but can not be rotated within the lumen 77 alt due to the engagement of the oval shaped needle member 30 ov with the oval shaped wall of the housing lumen 77 alt . The oval shaped needle housing 76 alt is provided with a locator 78 which is substantially the same as the needle housing locator 62 described above and shown in FIGS. 1 e - 1 f ′, and the oval shaped needle housing 76 alt /locator 78 assembly may be installed and mounted within the catheter body 12 at the time of manufacture, in the same manner as described hereabove with respect to the needle housing 60 /locator 62 assembly shown in FIGS. 1 e - 1 f ′. This oval shaped needle housing 76 alt /locator 78 assembly will typically be installed and mounted in the catheter body 12 proximal to the location of the needle housing 60 /locator 62 assembly shown in FIGS. 1 e - 1 f ′, but near enough to the distal end of the catheter device 10 to prevent the portion of the needle 30 ov adjacent its distal end from undergoing untoward rotation within the catheter body 12 during the catheter insertion procedure.
iii. Laterally Deployable Needle Guide to Deter Rotation/Lateral Deviation of Extended Needle:
FIGS. 10 g and 10 g ′ show an example of a needle guide member 500 which may be caused to project or extend laterally from the catheter body 12 in the area of the needle outlet aperture 46 to stabilize and guide the advancing needle member, thereby deterring lateral or side-to-side movement of the needle member 30 and further constraining the path which will be followed by the advancing needle. The deployment of such needle guide member 500 may also give rise to a lateral extension of the needle lumen 16 which mates with the preformed curve of the needle member 30 to prevent rotation of the needle member 30 in essentially the same manner as the curved needle housing 60 described above.
The particular laterally deployable guide member 500 shown in FIGS. 10 g and 10 g ′ is an inflatable annular member that is connected to an inflation fluid lumen 502 that extends through the catheter body 12 to permit inflation fluid to be infused and withdrawn from the inflatable guide member 500 . When deflated (FIG. 10 g ) the guide member 500 will nest within a depression or cut out region in the catheter's outer wall thereby assuming a configuration that is substantially flush with the outer surface 504 of the catheter body 12 . When inflated (FIG. 10 g ′) the guide member 500 will form an annular support collar around the tissue penetrating member 30 as it advances laterally from the catheter body. The surface(s) of the inflatable guide member 500 that may be brushed against or contacted by the tip of the tissue penetrating member as it advances out of the outlet opening 46 may be armored or coated with a metal foil or other material that will resist puncture by the tip of the tissue penetrating member 30 .
iv. Steerable Catheter Body to Deter Rotation/Lateral Deviation of the Extended Needle Member:
The catheter body 12 may be provided with a mechanism for inducing a curve or bend in the region of the catheter body 12 proximal to the needle outlet aperture 46 to cause the portion of the needle lumen 16 proximal to the outlet aperture 46 to assume a curvature which mates with the curved shape to which the needle member 30 is biased, thereby deterring rotation of the needle member 30 within the catheter in the same manner described above with respect to the curved needle housing 60 . The mechanism by which the catheter body 16 may be induced to curve may be any suitable catheter steering apparatus known in the art, such as an internal pull wire or spine member formed on shape memory alloy which is alternately transitionable between a straight configuration and a curved configuration.
v. Rotational Locking of Needle Member When Retracted to Maintain Correct Orientation and Enhance Torque Transfer:
It is desirable for the proximal shaft of the tissue-penetrating catheter 10 to be endowed with enough structural integrity to transmit torque to the distal end of the catheter, as necessary for precise rotational orientation and aiming of the catheter device 10 before advancement of the needle member 30 therefrom. Also, in many applications, it is desirable for the needle member 30 to be maintained in a predetermined rotational orientation within the catheter body 12 prior to advancement of the needle member 30 from the catheter 10 (i.e., while the needle member 30 is still in its retracted state). In many applications, it is also desirable to minimize the diameter of the catheter body 12 to allow it to pass through small blood vessel lumens. Each of these three (3) objectives may be achieved by rotational locking of the needle member 30 within the catheter body prior to its advancement from the catheter, as such rotational locking i) prevents unwanted needle rotation, ii) enhances the efficiency of torque transfer to the distal end of the catheter body 12 and thereby the needle, and iii) does not add any mass or additional diameter to the catheter body 12 .
FIGS. 10 f - 10 f ′ show a needle locking collar assembly 520 , which comprises an enlarged region 522 formed within the needle lumen 16 , wherein a first locking collar member 524 and second locking collar member 526 are located. The first locking collar member 524 is stationarily affixed to the catheter body 12 and has cavities or grooves 528 formed in the distal surface thereof and a central aperture through which the needle member 30 col may be advanced and retracted. The second locking collar member 526 is affixed to the needle member 30 col and has projections 530 extending from the proximal surface thereof. The projections 530 are sized, located and configured to be received within the grooves 528 of the first collar member 524 when the needle member 30 col is in its retracted position, thereby frictionally locking the needle member 30 col to prevent its rotation relative to the catheter body 12 . However, when the needle member 30 col is in its extended position, the projections 530 will not be inserted within the grooves 528 , and the collar assembly 520 will not prevent the needle member 30 col from rotating within the catheter body 12 . It will be appreciated that these stabilizing devices may be employed at various points along the length of the catheter body, including the proximal, medial, distal or needle housing portion.
d. Handpiece/Needle Controller
A handpiece/needle controller 15 is mounted on the proximal end of the Catheter body 12 , and is useable to control the rotational orientation of the catheter body 12 and the advancement/retraction of the needle member 30 .
Also this handpiece/needle controller 15 has a proximal port 27 formed on its proximal end through which a small guidewire (e.g., a 0.0010-0.016 inch diameter wire) may be advanced through the lumen 31 of the needle member 30 , a first side port 21 through which a large guidewire (e.g., a 0.030-0.040 inch diameter wire) may be advanced through the first lumen 14 when that first lumen 14 is not occupied by an IVUS catheter, and a second side port 23 through which a flush solution may be infused into the catheter's second lumen 16 outside of the needle member 30 disposed therein.
e. Catheter Body
The catheter body 12 includes a relatively stiff proximal section 12 a, a medial section 12 b, and a distal section 12 c shown in FIGS. 1A and 1B. The catheter body exhibits varying flexibility and torque strength along its length, and may incorporate reinforcement members such as a reinforcement braid member which imparts structural integrity as well as enhancing the ability of the catheter body to transmit torque. A hand piece 15 is attached to the proximal end of the proximal section 12 a, as shown. In the preferred embodiment the hand piece 15 and proximal section 12 a are approximately 115 cm in length. The medial section extends approximately 25 cm terminating approximately 2 cm from the distal section 12 c. The proximal and medial sections of the catheter contain a braided component 50 as shown in FIGS. 1 B′ and 1 B″, encased in a polymer material (e.g. Pebax, nylon, polyurethane, polyester or PVC) extruded to form the inner lumen 50 b and out jacket 50 a of catheter body 12 .
It has been determined that material expansion and changes in the physical properties of certain materials may occur after the catheter 10 is inserted into the patient's body and warmed from room temperature to body temperature. This material expansion and changes in the physical properties of certain materials can result in variation in the tolerances and sizing of the catheter 10 (e.g. elongation or shrinking) and can thus give rise to an unwanted modification of the position of the tissue penetrating member 30 . This could, in at least some cases, interfere with the precise aiming and advancement of the tissue penetrating member as desired. FIG. 1 B″ illustrates the braid angle A and pick count PC of the catheter braid 50 . The “pick count” PC of the braid is, as is well known in the art, a function of the braid angle A (i.e., the greater the braid angle the more picks per inch).
Also, the torque transmission and stiffness of the braided section 50 is a function of the braid angle (i.e., a braid angle of 90 degrees provides maximum torque transfer and a braid angel of 0 degrees provides minimum torque transfer). Catheters used in the present invention that have exhibited this phenomenon have braid angles A that result in a pick count of 50-70 picks per inch. However, applicant has determined that by decreasing the braid angle A of the braid 50 within the proximal and medial sections of the catheter 10 to result in a pick count of 20-30 picks per inch, it is possible to minimize or eliminate the unwanted longitudinal expansion of the catheter 10 and/or its components, while retaining sufficient torque transmission and acceptable stiffness to accomplish the procedures for which the catheter 10 is intended (examples of such procedures are illustrated in FIGS. 13 a - 14 m herebelow). This variation in braid angle or picks per inch may vary depending on the material of construction of the catheter and/or the braid fiber, and the diameter of the catheter body.
II. The Coronary Sinus Guide Component of the Catheter System:
FIGS. 11-11 c show a preferred coronary sinus guide catheter/introducer assembly 200 , which comprises a) a flexible coronary sinus guide catheter 203 that has a curved distal portion 204 , a proximal assembly 214 mounted on the proximal end of the flexible catheter body 203 , and a hollow lumen 202 extending longitudinally therethrough and b) an introducer 213 that has a tapered, soft distal portion 213 d that protrudes out of and beyond the distal end DE of the guide catheter 203 and a guidewire lumen 215 that extends longitudinally through the introducer 213 to permit the guide catheter/introducer assembly to be advanced over a guidewire GW as described more fully herebelow in connection with a preferred method of using the catheter system 10 .
A reinforcement braid 212 , such as a wire braid, is formed within a portion of the catheter body 203 but terminates approximately 2 to 5 centimeters from the distal end DE. In this manner, the reinforcement braid 212 will prevent kinking and improve torque strength of the proximal portion of the catheter body 203 , and the curved portion thereof, up to a location at about 2 to 5 centimeters from its distal end DE.
The proximal assembly comprises a rigid body 248 through which the lumen 202 extends, and upon which a proximal port 250 is formed to permit the guide introducer 213 , subselective sheath 100 (FIGS. 4 - 6 ), tissue-penetrating catheter device 10 (FIGS. 1 and 9 - 10 ), or other catheters, guidewires and/or devices (e.g., blocker delivery catheter, channel connector delivery catheter, channel enlarging device, etc. . . . ) to be inserted through the lumen 202 of the coronary sinus guide catheter 200 . A hemostatic valve 244 , such as a cross-cut resilient membrane, a slit-cut resilient membrane, or a flapper valve) is positioned transversely within the lumen 202 of the proximal assembly 214 to prevent blood from backflowing out of the proximal port 250 when no catheter or other device is inserted therethrough and to prevent or minimize the amount of blood which may leak out of the proximal port 250 when a catheter or other device is inserted therethrough. A side port 246 is formed on the proximal assembly 214 to permit preparation fluid to be infused or injected into or through the lumen 202 . A plurality of side apertures 210 are formed in the wall of the catheter body 203 near its distal end to allow pressure relief in the event that a radiographic contrast medium or other fluid is injected.
III. The Subselective Sheath Component of the Catheter System
As shown in FIGS. 4-6, a preferred subselective sheath 100 of the present invention comprises a flexible sheath body 102 having a proximal hub 104 and a lumen 106 extending longitudinally therethrough. A reinforcement braid 108 is formed within the catheter body 102 to prevent kinking and improve torque strength. Such reinforcement braid terminates distally at 0.1-1.0 centimeter from the distal end of the catheter body 102 . A gradual taper 110 is formed about the distal end of the sheath body's outer surface to such that the sheath 100 will taper to a flush transition with the distally protruding portion 111 d of its introducer 111 . The lumen 202 has an inner diameter D 1 which is substantially the same as the outer diameter of the introducer 111 that is initially inserted through the lumen 106 . The introducer 111 has a guidewire lumen 109 that extends longitudinally therethrough to permit the subselective sheath/introducer assembly to be advanced over a previously inserted guidewire GW (e.g., a 0.035 inch guidewire). The outer diameter of the sheath 100 is sized to be advanced and retracted through the lumen 202 of the coronary sinus guide catheter 200 (FIGS. 11-11 b ). The preferred method of using this subselective sheath 100 and introducer 111 are described in detail herebelow with respect to the methods of the present invention.
B. Preferred Methods for Using the Catheter System
The present invention also includes methods for using this catheter system described hereabove (or any other catheter system or devices that may be suitable to carry out the desired purpose), in conjunction with other apparatus such as guidewires, channel enlarging catheters/devices, channel connecting catheters/devices and vessel blocking catheters/devices to perform percutaneous, in situ coronary arterio-venous bypass procedures by way of a vein-to-artery approach, such method being fully described herebelow and shown in step-by-step fashion in FIGS. 13 a - 13 x and 14 a - 14 m.
The catheter system described hereabove and shown in FIGS. 1-11 b is useable in conjunction with a fluoroscope, an IVUS imaging catheter, a coronary sinus access catheter (e.g., a standard angiographic catheter), a channel-enlarging catheter device, lumen-blocking device(s), a 0.035 inch diameter guidewire, and one or more 0.014 inch diameter guidewire(s) to perform various revascularization procedures including, as described in detail herebelow, a Percutaneous In Situ Coronary Artery Bypass (PICAB) procedure as well as a Percutaneous In Situ Coronary Venous Arterialization (PICVA) procedure. It will be appreciated that, in addition to the particular PICAB and PICVA examples described in detail herebelow, the catheter system of the present invention may also be useable to perform various other procedures such as directed drug delivery procedures of the type described in co-pending U.S. patent application Ser. No. 09/048,147 and other revascularization procedures.
I. A Preferred Method for Performing the PICAB Procedure:
FIGS. 13 a - 13 x show, in step-by-step fashion, an example of a PICAB procedure wherein the catheter system 10 of the present invention is used for the purpose of bypassing a blockage located in the proximal portion of the Anterior Descending Coronary Artery (LAD) of a human patient. In this PICAB procedure, a coronary sinus access catheter (e.g., a standard angiographic catheter such as the modified Simmons-type angiographic catheter available from Cook Cardiology, Bloomington, Ind.) is initially inserted through a femoral vein or external jugular vein approach, using standard percutaneous catheter insertion technique. After such initial percutaneous catheter insertion has been accomplished, the PICAB procedure proceeds as follows:
First Step: Coronary Sinus Access/Introduction of First Guidewire:
As shown in FIG. 13 a, an arterial blockage AB to be bypassed is located in the left anterior descending coronary artery (LAD). The coronary sinus access catheter 500 is advanced into the coronary sinus CS, as shown in FIG. 13 b, to assist in the placement of a 0.035 inch diameter guidewire GW 1 into the great cardiac vein (GCV) and anterior interventricular vein (AIV). This guidewire GW 1 can be pre-loaded in the lumen of the coronary sinus access catheter 500 or can be advanced through the lumen of the coronary sinus access catheter 500 after it has been positioned inj the coronary sinus, as a separate step. Thereafter, the coronary sinus access catheter 500 is removed, leaving the 0.035 inch guidewire GW 1 in place.
Second Step: Introducton of Coronary Sinus Guide Catheter/AIV Access:
As shown in FIGS. 13 c - 13 d, the coronary sinus guide catheter 200 with introducer sheath 100 disposed within or through its lumen 202 , is advanced over the 0.035 inch guidewire GW 1 until the tip of the coronary sinus guide catheter 200 is past the “mouth” of the coronary sinus. The introducer sheath 100 is then removed, leaving the coronary sinus guide catheter 200 in place, in the manner shown in FIG. 13 d.
Third Step: Introduction & Aiming of Tissue-penetrating Catheter
As shown in FIG. 13 e, the tissue-penetrating catheter 10 is then inserted over the pre-positioned 0.035 inch guidewire GW 1 , through the lumen 202 of the coronary sinus guide catheter 200 , and is advanced using fluoroscopy to a position distal to the arterial blockage AB being bypassed. The 0.035 inch guidewire GW 1 is then extracted and removed from the first lumen 14 of the tissue-penetrating catheter 10 and an IVUS imaging catheter (not shown) is then advanced through that first lumen 14 until the IVUS transducer resides within the hollow interior space of the orientation structure 36 . The IVUS catheter is then used to receive a 360 degree ultrasound image from a vantage point within the interior space of the orientation structure 36 . Such image enables the operator to see both the resident vessel (the AIV) and the target vessel (the LAD), as well as the reflections or artifacts from the three strut members 40 , 42 & 44 of the orientation structure 36 . Because of the disparate distancing between the strut members 40 , 42 & 44 , the reflections or artifacts produced by the strut members will form a generally “Y” shaped image as illustrated in FIGS. 2 and 3 of this patent application. The reflection 40 Ref produced by the first strut member 40 is clearly distinguishable from the reflections 42 Ref , 44 Ref produced by the second and third strut members 42 , 43 , and provides an indication of the particular direction in which the needle member 30 will travel when advanced from the needle outlet opening 46 in the side of the catheter body 12 . Thus, if the first strut member reflection 40 Ref observed on the IVUS image does not extend directly toward or into the lumen of the LAD (as illustrated in FIG. 3 ), the operator will rotate the tissue-penetrating catheter 10 until such first strut member reflection 40 Ref observed on the IVUS image does extend directly toward or into the lumen of the LAD (as illustrated in FIG. 2 ). This will ensure that the needle member 30 is properly aimed to enter the LAD when advanced.
Fourth Step: Formation of Initial Arterio-Venous Penetration Tract Distal to Blockage:
As shown in FIGS. 13 f - 13 h, the tissue penetrating needle member 30 is then advanced in the distal direction to its extended position such that it punctures through the wall of the resident vessel (the AIV), through any tissue which may exist between the resident vessel (the AIV) and the target vessel (the LAD) and into the lumen of the target vessel (the LAD) at a location downstream of the arterial blockage AB. This maneuver results in the formation of an initial arterio-venous penetration tract PT. With the needle member 30 in its extended position and its distal tip in the lumen of the target vessel (the LAD), a 0.014 inch diameter guidewire GW 2 is inserted through the proximal port 27 of the tissue-penetrating catheter handpiece/needle controller 15 and advanced through the lumen 31 of the needle member 30 into the target vessel (the LAD), as shown in FIG. 14 h. After the 0.014 inch diameter guidewire GW 2 has been introduced into the target vessel (the LAD) the needle member 30 is withdrawn to its retracted position, leaving the 0.014 inch diameter guidewire GW 2 extending through the initially formed interstitial passageway into the target vessel (the LAD) as shown in FIG. 14 h. After the needle member 30 is withdrawn to its retracted position, the tissue-penetrating catheter 10 is withdrawn and removed, leaving the 0.014 inch guidewire in place (i.e., extending through the newly formed arterio-venous penetration tract PT).
Fifth Step: Deployment of Blocker into Vein Lumen Distal to Blockage:
As shown in FIGS. 13 i-k, the subselective sheath 100 with its introducer 111 inserted therethrough is advanced through the coronary sinus guide 200 over the large guide wire GW 1 . Thereafter, the introducer 111 and guidewire GW 1 are removed and one or more embolic blocker members BM are introduced into the proximal end of the subselective sheath, pushed through the lumen of the subselective sheath 100 using a pusher rod (not shown) and expelled into the lumen of the coronary vein (the AIV) where such embolic blocker(s) expand and engage the wall of the vein to cause substantial occlusion and blockage of bloodflw through the vein ath that location. Examples of such blocker members BM and their methods of implantation are described in U.S. patent application Ser. No. 09/117,156. The 0.035 inch diameter guidewire GW 1 is then removed, and an embolic blocker member BM is inserted into the proximal end of the subselective sheath. A push rod is then advanced through the lumen of the subselective sheath to push the embolic blocker member BM out of the distal end of the subselective sheath and into its desired position within the lumen of the coronary vein (the AIV). It is to be noted that this blocker deployment step may be performed at this point in the procedure, or alternatively may be delayed until a later time in the procedure. After the distal blocker member BM has been implanted at its desired location, the 0.035 inch diameter guidewire GW 1 is reinserted through the subselective sheath 100 and the subselective sheath 100 is then withdrawn and removed as shown in FIG. 13 k.
Sixth Step: Formation of Initial Arterio-Venous Penetration Tract Proximal to Blockage:
As shown in FIGS. 13 l - 13 n, the tissue-penetrating catheter 10 is then once again advanced over the 0.035 inch diameter guidewire GW 1 , under fluoroscopy, to a position that is proximal to the previously-formed distal penetration tract PT. The above-described fourth step is then repeated to form another initial arterio-venous penetration tract PT proximal to the blockage, and to pass a second 0.014 inch guidewire GW 3 through that second arterio-venous penetration tract PT. The tissue-penetrating catheter 10 is then withdrawn and removed, leaving both 0.014 inch guidewires GW 1 and GW 3 in place, in the manner shown in FIG. 13 n.
Seventh Step: Enlargement of Distal Penetration Tract to Form Arterio-Venous Bloodflow Passageway:
As shown in FIG. 13 o, the subselective sheath 100 and its introducer 111 are advanced through the guide catheter 203 , over the second guidewire GW 2 to a location where the distal end of the subselective sheath 100 is within the AIV immediately adjacent the distal penetration tract PT. Thereafter, the introducer 111 is withdrawn and a channel enlarging catheter device CEC, of the type described in U.S. patent application Ser. No. 09/056,589, now allowed, is advanced over the 0.014 inch guidewire GW 2 which extends through the distal arterio-venous penetration tract PT, thereby the dilating or enlarging that tract to form an arterio-venous bloodflow passageway PW. This step of the procedure provides control over the diameter or size of the arterio-venous bloodflow passageways PW and helps to ensure that the passageways PW will remain patent and functional following completion of the procedure. After such enlargement of the penetration tract to form the intended passageway PW, the channel enlarging catheter device CEC is withdrawn and removed along with the subselective sheath 100 , leaving both 0.014 inch guidewires GW 1 and GW 3 in place, in the manner shown in FIG. 13 p.
Eighth Step: Placement of Connector Device in Distal Arterio-Venous Bloodflow Passageway:
As an optional step, a connection device may be deployed in the passageway PW. As shown in FIGS. 13 q - 13 s, the subselective sheath 100 and its introducer 111 are then advanced over the distal channel guidewire GW 2 to a position where the distal end of the subselective sheath 100 is in the AIV immediately adjuacent the distal bloodflow passageway PW. Thereafter, the introducer 111 is removed and a connector device delivery catheter CDC, of the type described in U.S. patent application Ser. No. 08/970,694, now U.S. Pat. No. 6,432,127, is advanced over through the subselective sheath 100 and over the 0.014 inch guidewire GW 2 which extends through the distal arterio-venous passageway PW, to implant a connector device CD within that passageway PW. The connector delivery catheter device CDC is then removed, along with the subselective sheath 100 and the distal 0.014 inch guidewire GW 2 that had extended through the distal arterio-venous passageway PW, leaving the distal connector device CD in place within the distal arterio-venous passageway PW in the manner shown in FIG. 13 s.
Ninth Step: Enlargement of Proximal Penetration Tract to form the Proximal Arterio-Venous Bloodflow Passageway:
As shown in FIGS. 13 t - 13 u, the subselective sheath 100 and its introducer 111 are then advanced over the distal channel guidewire GW 2 to a position where the distal end of the subselective sheath 100 is in the AIV immediately adjuacent the distal bloodflow passageway PW. Thereafter, the introducer 111 is removed and a and a channel enlarging catheter device CEC, of the type described in U.S. patent application Ser. No. 09/056,589, now allowed, is advanced over the 0.014 inch guidewire GW 3 that extends through the proximal arterio-venous penetration tract PT, thereby the dilating or enlarging that tract to form a proximal arterio-venous bloodflow passageway PW. This step of the procedure provides control over the diameter or size of the arterio-venous bloodflow passageways PW and helps to ensure that the passageways PW will remain patent and functional following completion of the procedure. After such enlargement of the proximal penetration tract to form the intended passageway PW, the channel enlarging catheter device CEC is withdrawn and removed leaving the subselective sheath 100 and proximal 0.014 inch guidewire GW 3 in place, as shown in FIG. 13 u.
Tenth Step: Placement of Connector Device in Proximal Arterio-Venous Passageway:
As an optional step, a connection device may be deployed in the passageway PW. As shown in FIG. 13 v, a connector device delivery catheter CDC, of the type described in U.S. patent application Ser. No. 08/970,694, (U.S. Pat. No. 6,432,127) is then advanced through the subselective sheath 100 and over the 0.014 inch guidewire GW 3 which extends through the proximal arterio-venous passageway PW, to implant a connector device CD within that passageway PW. The connector delivery catheter device is then removed, and the subselective sheath 100 and 0.014 inch guidewire GW 3 are then retracted to a position within the Great Cardiac Vein GCV, proximal to the proximal passageway PW, as shown in FIG. 13 w, leaving the proximal connector device CD in place within the proximal arterio-venous passageway.
Eleventh Step: Deployment of Blocker into Vein Lumen Proximal to Blockage:
As shown in FIG. 13 w, the above-described fifth step is then repeated to implant a second blocker device BD within the lumen of the Great Cardiac Vein (GCV), proximal to the proximal arterio-venous passageway PW. This completes the procedure, and results in the flow of arterial blood from the Circumflex Artery (CX), through the proximal arteriovenous passageway PW, through the Great Cardiac Vein GCV and Anterior Interventricular Vein in the retrograde direction, through the distal arterio-venous passageway PW, and into the Left Anterior Descending coronary artery LAD, downstream of the blockage AB, as illustrated by the flow-indicating arrows on FIG. 13 x.
II. A Preferred Method for Performing the PICVA Procedure:
FIGS. 14 a - 14 m show, in step-by-step fashion, an example of a PICVA procedure wherein the catheter system 10 of the present invention is used for the purpose causing arterial blood to be rerouted into the Anterior Interventricular Vein and caused to subsequently flow through the AIV in retrograde fashion (i.e., in a direction opposite normal venous return) thereby bypassing an extensive blockage within the patient's Anterior Descending Coronary Artery (LAD) and perfusing the region of myocardium that had been rendered ischemic due to the extensive blockage in the LAD. In this PIVA procedure, a coronary sinus access catheter (e.g., a standard angiographic catheter such as the modified Simmons-type angiographic catheter available from Cook Cardiology, Bloomington, Ind.) is initially inserted through a femoral vein or external jugular vein approach, using standard percutaneous catheter insertion technique. After such initial percutaneous catheter insertion has been accomplished, the PICAB procedure proceeds as follows:
First Step: Coronary Sinus Access/Introduction of First Guidewire:
As shown in FIG. 14 a, an extensive arterial blockage AB extends though substantially the entire length of the left anterior descending coronary artery (LAD), thereby rendering this patient an unlikely candidate for the above-described PICAB procedure because no patent distal portion of the LAD remains available to receive the bypass arterial bloodflow. It is appreciated that in cases where the disease AB does not extend into the proximal portion of the LAD, a connection may be established between the LAD and the AIV proximal to the blockage, but there would be no opportunity to make a distal connection as required by the PICAB procedure. As shown in FIG. 14 b, a coronary sinus access catheter 500 is advanced into the coronary sinus CS to assist in the placement of a 0.035 inch diameter guidewire GW 1 into the great cardiac vein (GCV). This guidewire GW 1 can be pre-loaded in the lumen of the coronary sinus access catheter 500 or can be advanced through the lumen of the coronary sinus access catheter 500 after it has been positioned in the coronary sinus, as a separate step. Thereafter, the coronary sinus access catheter 500 is removed, leaving the 0.035 inch guidewire GW1 in place.
Second Step: Introduction of Coronary Sinus Guide Catheter/AIV Access:
As shown in FIGS. 14 c - 14 d, the coronary sinus guide catheter 200 with introducer sheath 100 disposed within or through its lumen 202 , is advanced over the 0.035 inch guidewire GW 1 until the tip of the coronary sinus guide catheter 200 is past the “mouth” of the coronary sinus. The introducer sheath 100 is then removed, leaving the coronary sinus guide catheter 200 in place, in the manner shown in FIG. 14 d.
Third Sten: Introduction & Aiming of Tissue-penetrating Catheter:
As shown in FIG. 14 e, the tissue-penetrating catheter 10 is then inserted over the pre-positioned 0.035 inch guidewire GW 1 , through the lumen 202 of the coronary sinus guide catheter 200 , and is advanced using fluoroscopy to a position proximal to the arterial blockage AB being bypassed. The 0.035 inch guidewire GW 1 is then extracted and removed from the first lumen 14 of the tissue-penetrating catheter 10 and an IVUS imaging catheter (not shown) is then advanced through that first lumen 14 until the IVUS transducer resides within the imaging catheter-receiving space of the orientation structure 36 . The IVUS catheter is then used to receive a 360 degree ultrasound image from a vantage point within the interior space of the orientation structure 36 . Such image enables the operator to see both the resident vessel (the GCV) and the target vessel (the CX), as well as the reflections or artifacts from the three strut members 40 , 42 & 44 of the orientation structure 36 . Because of the disparate distancing between the strut members 40 , 42 & 44 , the reflections or artifacts produced by the strut members will form a generally “Y” shaped image as illustrated in FIGS. 2 and 3 of this patent application. The reflection 40 Ref produced by the first strut member 40 is clearly distinguishable from the reflections 42 Ref , 44 Ref produced by the second and third strut members 42 , 43 , and provides an indication of the particular direction in which the needle member 30 will travel when advanced from the needle outlet opening 46 in the side of the catheter body 12 . Thus, if the first strut member reflection 40 Ref observed on the IVUS image does not extend directly toward or into the lumen of the CX (as illustrated in FIG. 3 ), the operator will rotate the tissue-penetrating catheter 10 until such first strut member reflection 40 Ref observed on the IVUS image does extend directly toward or into the lumen of the CX (as illustrated in FIG. 2 ). This will ensure that the needle member 30 is properly aimed to enter the CX when advanced.
Fourth Step: Formation of Initial Arterio-Venous Penetration Tract Distal to Blockage:
As shown in FIGS. 14 f - 14 h, the tissue penetrating needle member 30 is then advanced in the distal direction to its extended position such that it punctures through the wall of the resident vessel (the GCV), through any tissue which may exist between the resident vessel (the GCV) and the target vessel (the CX) and into the lumen of the target vessel (the CX) at a location downstream of the arterial blockage AB. This maneuver results in the formation of an initial arterio-venous penetration tract PT. With the needle member 30 in its extended position and its distal tip in the lumen of the target vessel (the CX), a 0.014 inch diameter guidewire GW 2 is inserted through the proximal port 27 of the tissue-penetrating catheter handpiece/needle controller 15 and advanced through the lumen 31 of the needle member 30 into the target vessel (the CX), as shown in FIG. 14 h. After the 0.014 inch diameter guidewire GW 2 has been introduced into the target vessel (the LAD) the needle member 30 is withdrawn to its retracted position, leaving the 0.014 inch diameter guidewire GW 2 extending through the initially formed interstitial passageway into the target vessel (the CX) as shown in FIG. 14 h. Thereafter, the needle member 30 is withdrawn to its retracted position and the tissue-penetrating catheter 10 is withdrawn and removed, leaving the 0.014 inch guidewire in place (i.e., extending through the newly formed arterio-venous penetration tract PT), as shown in FIG. 14 h.
Fifth Step: Enlargement of Penetration Tract to Form Arterio-Venous Bloodflow Passageway:
As shown in FIG. 14 i, the subselective sheath 100 and its introducer 111 are advanced through the guide catheter 203 , over the second guidewire GW 2 to a location where the distal end of the subselective sheath 100 is within the AIV immediately adjacent the distal penetration tract PT. Thereafter, the intoducer 111 is withdrawn and a channel enlarging catheter device CEC, of the type described in U.S. patent application Ser. No. 09/056,589, is advanced over the 0.014 inch guidewire GW 2 which extends through the arterio-venous penetration tract PT, thereby the dilating or enlarging that tract to form an arterio-venous bloodflow passageway PW. This step of the procedure provides control over the diameter or size of the arterio-venous bloodflow passageways PW and helps to ensure that the passageways PW will remain patent and functional following completion of the procedure. After such enlargement of the penetration tract to form the intended passageway PW, the channel enlarging catheter device CEC is withdrawn and removed, leaving the subselective sheath 100 and second guidewire GW 2 in place.
Sixth Step: Placement of Connector Device in Arterio-Venous Bloodflow Passageway:
It may be desirable, in an optional step as shown in FIGS. 14 j - 14 k, to place a connector device within the passageway PW. A connector device delivery catheter CDC, of the type described in U.S. patent application Ser. No. 08/970,694, is advanced over through the subselective sheath 100 and over the 0.014 inch guidewire GW 2 which extends through the arterio-venous passageway PW, to implant a connector device CD within that passageway PW. The connector delivery catheter device CDC is then removed, and the subselective sheath 100 and the 0.014 inch guidewire GW 2 that had extended through the distal arterio-venous passageway PW are then retracted to a position proximal to the passageway PW.
Seventh Step: Deployment of Blocker into Vein Lumen Proximal to Blockage:
As shown in FIGS. 14 l - 14 m, the guidewire GW 2 is then removed and one or more embolic blocker members BM are introduced into the proximal end of the subselective sheath 100 , pushed through the lumen of the subselective sheath 100 using a pusher rod (not shown) and expelled into the lumen of the Great Cardiac Vein (GCV) proximal to the bloodflow passageway PW where such embolic blocker(s) expand and engage the wall of the vein to cause substantial occlusion and blockage of bloodflow through the vein at that location. Examples of such blocker members BM and their methods of implantation are described in U.S. patent application Ser. No. 09/117,516. The 0.035 inch diameter guidewire GW 1 is then removed, and an embolic blocker member BM is inserted into the proximal end of the subselective sheath. A push rod is then advanced through the lumen of the blocker delivery catheter to push the embolic blocker member BM out of the distal end of the subselective sheathand into its desired position within the lumen of the coronary vein (the GCV). It is to be noted that this blocker deployment step may be performed at this point in the procedure, or alternatively may be delayed until a later time in the procedure. This completes the procedure, and results in the flow of arterial blood from the Circumflex Artery (CX), through the arterio-venous passageway PW, through the Great Cardiac Vein GCV and Anterior Interventricular Vein in the retrograde direction so as to perfuse the myicardium that has been rendered ischemic due to the blockage of the Left Anterior Decending coronary arter (LAD) as illustrated by the flow indicating arrows on FIG. 14 m.
It is to be understood and appreciated that the invention has been described herein with reference to certain presently preferred embodiments and examples only, and no effort has been made to exhaustively describe all possible embodiments and examples of the invention. Indeed, as those killed in the art will appreciate, various additions, deletions, modifications and variations may be made to the particular embodiments and examples described hereabove without departing from the intended spirit and scope of the invention. For example, where this patent application has listed the steps of a method or procedure in a specific order, it may be possible (or even expedient in certain circumstances) to change the order in which some steps are performed, and it is intended that the particular steps of the method or procedure claims set forth herebelow not be construed as being order-specific unless such order specificity is expressly stated in the claim. Another example is that, although the specific procedures described in detail in this application involve penetrating through tissue located within an “acceptable penetration zone,” such acceptable penetration zone need not be occupied by tissue but rather such acceptable penetration zone may fully or partially comprise an open space such as a body cavity or void. Accordingly, it is intended that all such additions, deletions, modifications and variations be included within the scope of the following claims.
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A system of catheter devices and methods for forming channels or passageways between a luminal anatomical structure (e.g., a blood vessel) and a target location (e.g., another blood vessel, an organ, a mass of tissue, etc.) for the purpose of rerouting blood flow or for delivering a substance or instrument, etc. to the target location.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application claims priority from U.S. Provisional Patent Application No. 61/148,947 filed Jan. 31, 2009. The contents of U.S. Provisional Patent Application 61/148,947 are incorporated herein by reference.
FIELD OF THE INVENTION
This present invention relates to a strapping system for securing motorcycle or similar vehicle in an upright position for transport.
BACKGROUND OF THE INVENTION
Motorcycles are two wheeled vehicles that vary in size and shape depending on the model. However, there is general similarity in the shape of motorcycles, which allows embodiments of the present invention to be applicable to different models of motorcycles and other vehicles of similar shape.
During transport of a motorcycle the forces incurred vary greatly, both in severity and direction, depending upon various factors. These include road conditions, driving habits, construction and condition of the vehicle used for transport, and the user's understanding of the various methods of securing a motorcycle for transport.
One of the present strapping systems includes tying a motorcycle down with two separate ropes, one from each handlebar, which cause excessive wearing of motorcycle parts such as handlebar covering and gas tank paint. This method is also inherently difficult as it requires balancing the tension equally on the different tie downs.
Another strapping system includes two interconnected straps with soft cuffs engaging the grips of the handlebar. This method reduces the damage to the handlebar covering and gas tank paint. However, the soft cuff design of the system allows handlebar grips to be exposed to a lateral pull that sometimes resulted in an inward “bunching” of the grips if the grips are not sufficiently glued to the throttle tube (on the right side) and handlebar (on the left side). In addition, under certain conditions this strapping system would contact with switch gear (horn, turn signal, and start buttons) causing unnecessary wearing of motorcycle parts.
Yet another strapping system includes hard cuffs that are susceptible to failure due to exposure from the elements. The new improved motorcycle tie down system and method for transport of motorcycles provides solutions to these problems inherent in the related art.
SUMMARY OF THE INVENTION
The present invention provides a new and improved strapping system for securing motorcycles for transport in a vertical upright position, which also reduces damage during the transport and provides greater motorcycle stability. Embodiments of the present invention overcome certain undesirable properties inherent in the related art, while providing better overall results.
The embodiment of the invention comprises two identical securing straps that are connected to a cuff on one end and have a sewn loop on the other end. The sewn loop is useful for attaching the hook of a tie-down strap which is then attached to the towing or hauling vehicle. Two straps can be interconnected in such a way that they represent mirror images of one another.
This invention uses a molded cuff (rather than a soft cuff sewn from fabric as in known designs). The molded cuff incorporates a closed end which acts as a “stop” to prevent the cuff from migrating inward under tension and either “bunching” the grips or contacting any switchgear. The molded cuff can also incorporate “ribs” that reinforce the closed end of the cuff. This provides added strength to the cuff and helps keep the cuff intact. It can also further prevent “bunching” of the grips.
Each cuff contains a strap attachment housing that allows engagement of securing straps. The strap attachment housing provides a reinforced attachment device for one strap and provides a pathway between the strap attachment housing and the cylindrical portion of the cuff through which the second strap may pass. The orientation of the cuffs in use on a vehicle allows one end of a securing strap to be attached to the housing portion of the cuff and the other end of the strap passes through the slot in the opposing cuff (between the housing and cylindrical body).
The cuff also incorporates a support ring that at least partially is embedded into the cylindrical body of the cuff and the body of the strap attachment housing. The support ring does not have to be contained solely within the raised boss sections of the cylindrical cup and the strap attachment housing. The position of the support ring with respect to the strap attachment housing and cylindrical cup is unique. In addition, the latest technologies in plastics are being incorporated in the design of the molded cuffs to ensure resistance to breakage, distortion, and UV degradation to improve the quality of service and extend the service life of this securing strap system. The support ring is typically made of metal but is not limited to a metallic composition.
BRIEF DESCRIPTION OF DRAWINGS
The invention is illustrated in the following drawings.
FIG. 1 schematically shows a single molded grip cuff with an opening at one end.
FIG. 2 is a section view of a cuff showing the metal ring imbedded into the cylindrical body of the cuff and the cuff strap attachment housing.
FIG. 3 is a schematic view of two grip cuffs incorporated into the motorcycle tie-down system of the present invention.
FIG. 4 presents a view of a grip cuff from the open end of the cuff.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIG. 1 , which shows the general features of a preferred embodiment of the invention, the grip cuff 10 is comprised of a cylindrical cup 12 and a strap attachment housing 14 . The strap attachment housing includes a raised boss section 15 . The cylindrical body also includes a raised boss section 13 .
FIG. 2 is a cutaway section view that shows the open end 16 of the cuff cylinder and the closed end 18 . A metal ring 20 is encased within the grip cuff structure as shown.
FIG. 3 shows a strapping system in accordance with present invention. A first grip cuff 22 is shown interconnected with a second grip cuff 24 . The strapping system includes a first securing strap 26 that passes through the aperture in the first grip cuff 22 and is connected to the strap attachment housing of the second grip cuff 24 . Both securing straps pass through an anti-chaffing guard 30 that is a padded tube that protects against chaffing damage. In operation, both grip cuffs will have the same orientation with the cylindrical cup on the top and the strap attachment housing underneath. Strap crossing can occur within the anti-chaffing guard.
FIG. 4 is a view of a grip cuff from the open end 16 of the cylinder. The interior of the closed end of the cylinder can contain reinforcing ribs 32 to keep the closed end intact. The support ring 20 is visible at several cutout sections 38 of the device. These exposed sections of the support ring are typically coated for protection. The dotted lines represent the approximate position of the support ring 20 within the grip cuff. There is adequate cuff material between the inside edge 34 of the ring and the inside edge of the cylindrical cup as well as between the inside edge of the ring and the inside edge of the strap attachment housing 14 .
Similarly there is adequate and substantial cuff material between the outside edge 36 of the support ring and the outside edge of the cylindrical body and the strap attachment housing with the exception of the small cutaway areas 38 . The raised sections of the cylinder and strap attachment housing in the vicinity of the support ring are referred to as the boss area(s) and are clearly shown in the drawings. The cylindrical cup boss section 13 and the strap attachment housing boss section 15 are shown in FIGS. 1 and 4 . Cutouts 38 in the boss sections provide view sites for verification of the existence of the support ring 20 .
CONCLUSIONS, OTHER EMBODIMENTS, AND SCOPE OF INVENTION
The support ring is typically made of metal but non-metallic support rings may be applicable. When metal support rings are utilized, sections of the support rings that are not enclosed by the cuff can be protected by a coating of suitable material. The tie-down cuffs are made from suitable moldable materials. If raised boss sections are utilized on the strap attachment housing and cylindrical body components, breaks in the boss section are typically included.
The above description presents the best mode contemplated in carrying out my invention. However, it is susceptible to modifications and alternate constructions from the embodiments shown in the drawings and accompanying description. Consequently it is not intended that the invention be limited to the particular embodiments disclosed. On the contrary, the invention is intended to cover all modifications, sizes and alternate constructions falling within the spirit and scope of the claimed invention or the equivalents thereof.
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A strapping system for positioning and transporting a motorcycle or similar vehicle in an upright position include two interconnected straps with reinforced cuffs. The cuffs have a cylindrical body and strap attachment housing contiguously formed and a reinforcement ring substantially enclosed within the walls of the cylindrical body and strap attachment housing.
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RELATED APPLICATIONS
[0001] This application claims priority to U.S. patent application 60/568,756, filed May 6, 2004, entitled “USE OF INDUCED OSCILLATIONS TO ACHIEVE HIGH EFFICIENCY TRANSFORMATION OF DIFFICULT TO TRANSFORM BACTERIA” the disclosure of which is incorporated herein by reference.
US GOVERNMENT RIGHTS
[0002] The United States Government has certain rights in this invention pursuant to contract Phase I SBIR DE-FG02-03ER83593 awarded by the Department of Energy.
FIELD OF THE INVENTION
[0003] The present document relates to methods and apparatus for engineering genomes of microorganisms. In particular, the present document relates to transformation of bacteria by driving DNA segments across a bacterial cell membrane with an electric field.
BACKGROUND OF THE INVENTION
Engineering Bacterial Genomes
[0004] Bacteria typically have genomes including one or a few chromosomal strands of Deoxyribose Nucleic Acid (DNA) having thousands of segments known as genes. Each gene includes a sequence of nucleotides that code for one or more peptides, or proteins, together with regulatory nucleotide sequences such as promoters, start codons, and stop codons. Bacteria may also incorporate shorter DNA segments such as plasmids and dormant bacteriophages, which may also contain genes and which may reside in the cytoplasm alone or be incorporated into the bacterial genome.
[0005] Typical bacterial species encode proteins that have evolved according to the needs of the species in the environment it normally inhabits. These proteins typically include proteins for reproduction of the bacterial cell, for energy production, for producing fundamental building blocks of the cell like nucleotides, for producing motility structures like flagella, and for toxins that give that species a survival advantage over other species in the same environment.
[0006] Bacteria have been engineered to produce proteins unnecessary for survival of that species, but of interest to humans. This has been done by isolating or creating a new segment of DNA encoding a desired protein and inserting the new segment into the bacterial genome; once inserted the new segment reproduces with the bacteria and, if properly designed and inserted, may produce the desired protein. The process of inserting the new DNA segment is known as transformation.
[0007] Similarly, transformation can be used to disable selected genes normally present in the bacterial genome, or to increase production of preferred products.
[0008] Alteration of bacterial genomes can be of use in adapting an organism to survive in a different environment, or to modify the organism's metabolic pathways to produce non-protein metabolic products of interest to humans.
Electroporation
[0009] Electroporation is a term describing transport of hydrophilic molecules across a hydrophobic membrane via electrically formed pores (electropores).
[0010] While some bacteria can be transformed simply by adding a solution of new DNA to culture media; most bacteria require further manipulation to transport the new DNA across the bacteria's cell wall and membrane into the interior of the bacterial cell. One such technique is Electroporation.
[0011] DNA generally has a negative charge in aqueous solution; DNA is an acid and liberates hydrogen ion in solution at physiological pH. DNA therefore tends to move towards a positively charged electrode when an electric field is applied to a DNA solution, a phenomenon known as electrophoresis.
[0012] A desired new DNA plasmid is prepared in aqueous solution of low ionic strength, and added to bacterial cells suspended in an electroporation buffer. The mixture is typically kept on ice to prevent DNA degradation and to avoid overheating the bacteria during electroporation. Electroporation is performed by exposing the mixture of DNA solution and suspended bacteria to a high-intensity, brief, electric field. The intense field carries DNA molecules across the hydrophilic cell wall by electrophoresis. The intense field also carries DNA molecules through a temporary electropore in the hydrophobic cell membrane into some, but far from all, of the bacteria.
[0013] The desired new DNA plasmid may include sequences homologous to portions of the bacterial chromosome at which they can insert into the bacterial chromosome. The new plasmid may alternatively include portions that code for integrases that incorporate portions of the plasmid into the bacterial chromosome. The new plasmid may be capable of surviving and replicating within the bacteria.
[0014] The bacteria are then cultured under conditions favorable to growth of bacteria incorporating the desired new DNA. Typically a gene encoding for resistance to an antibiotic is included in the new DNA, and that same antibiotic is included in a post-electroporation culture media. Transformed bacteria are selected for because they have a survival advantage over untransformed bacteria in this media.
[0015] Typically, electroporation is performed by placing the bacterial suspension and the transforming DNA between electrodes of a chilled electroporation cuvette and applying an electric pulse to the cuvette. A high, DC, or RF modulated DC voltage pulse is applied to the electrodes for a preset time typically up to several dozen milliseconds.
Difficult to Transform Bacteria.
[0016] Some bacteria with complex intracellular morphology and/or complex cell development cycle are known as “difficult to electrotransform”. When transforming these bacteria, it is important to identify the right growth medium, specific growth stage of the culture, and some other biological conditions, such that the cells become as “electrocompetent” as possible before performing electroporation.
[0017] When bacteria of some species are subjected to stressful conditions, they may form hardy endospores. Endospores are generally smaller than normal vegetative cells, and much more resistant to chemical, thermal, dessication, and other environmental hazards than normal vegetative cells. Electroporation may provide sufficient chemical, electrical, and thermal stress to trigger spore formation in some bacteria. As spores form, much of the cellular contents, often including the newly inserted and desired DNA plasmid if sporulation occurs immediately after electroporation, is excluded from the spore. Spore forming bacteria with complex lifecycles therefore are often difficult to transform.
[0018] Some bacteria, such as Acinetobacter species, have intracellular granules or vesicles that can block inserted DNA plasmids from the nucleoid region of the cell where the genome and DNA replication enzymes are located. These bacteria can also be difficult to transform because only DNA inserted into the proper part of the cell is likely to be expressed, and because these granules and vesicles may block plasmids from reaching the proper part of the cell.
[0019] Clostridium is a genus of Gram-positive, spore-forming, anaerobic, bacteria, including several species that are difficult to transform, typically derive energy through fermentation and for which free oxygen is toxic. Example members of the genus include Clostridium perfringens, pathogenic in animals and man; Clostridium botulinum , noted for production of potent toxins; as well as Clostridium thermocellum , capable of fermenting cellulose at 60° C.
[0020] Prior techniques for transformation of difficult-to-transform bacteria have included modifying the bacterial cell walls by growing the bacteria in media containing ingredients that damage developing cell walls, or by partially digesting the cell walls. The weakened cell walls then allow desired DNA plasmids to reach the cell membrane more rapidly, so that plasmids are more likely to pass through electropores into the cells. It has been found that weakening cell walls often adversely affect viability of the bacteria, viability is often so poor that electroporation yield remains unacceptably low.
[0021] It is desirable to improve transformation yield of difficult-to-transform bacteria to expedite research performed with such bacteria.
Selection of Transformed Bacteria
[0022] Once electroporation is performed, transformed bacteria may be selected by culturing the bacteria in a selective media. Selective medium contains at least one antibiotic for which a gene of resistance is included in the desired DNA plasmid. In such media, only transformed bacteria thrive.
[0023] Alternatively, electroporated bacteria may be cultured into colonies on an agar plate and bacterial products blotted onto a membrane. The membrane can then be stained with fluorescent antibodies to proteins encoded on the desired DNA plasmid. Colonies expressing those proteins will then have associated fluorescent marks on the membrane, thereby allowing identification of colonies that express those proteins.
[0000] Modified Clostridium thermocellum May Help Produce Biofuels
[0024] Most plants produce sugars by photosynthesis in abundance. Typical plants process most of the sugars they produce into cellulose, forming much of the cell wall and supporting fiber of angiosperms. Only a small proportion of sugars become starches in seed.
[0025] There are many uses for the seed of corn, wheat, oats, or other grains, both for food, animal feed, and for fermentation into alcohols. Many organisms, including humans, produce amylase enzymes capable of hydrolyzing starch.
[0026] Mammals, yeast, and other eukaryotic organisms lack enzymes for hydrolyzing cellulose; sugars linked with beta-glucoside bonds in cellulose are not well used and often become waste. Grass, wood, agricultural residues (including cornstalks, wheat and oat straw, and manure), and municipal solid waste (paper) have high cellulose content.
[0027] Clostridium thermocellum has the ability to hydrolyze cellulose, it ferments the resulting sugars into a mixture of alcohols and organic acids, including acetic acid.
[0028] It has been proposed that a strain of Clostridium thermocellum suitable for use in industrial production of ethanol from cellulose can be more easily engineered if this organism's resistance to transformation by electroporation can be overcome since multiple, substantial, modifications of its genome are required. In particular, it is desirable to decrease organic acid production and increase both ethanol production and ethanol tolerance.
SUMMARY
[0029] A method of electroporation includes placing a mixture of bacterial suspension and transforming DNA into an electroporation cuvette. The resulting sample is subjected through a current-limiting resistor to a complex waveform including a burst of high-voltage radio-frequency current, which in some embodiments is superimposed on a biphasic high-voltage DC pulse. The total waveform has at least an initial portion greater than eleven thousand volts per centimeter of electrode spacing. In some embodiments the waveform in a later portion is reduced to between ten and thirty percent of the magnitude of the initial portion. Transformed bacteria are selected by culture in selective medium.
BRIEF DESCRIPTION OF THE FIGURES
[0030] FIG. 1 is a block diagram of a prior-art electroporation apparatus.
[0031] FIG. 2 illustrates the principle of electroporation.
[0032] FIG. 3 is a block diagram of the present electroporation apparatus.
[0033] FIG. 4 is an illustration of DC and AC components of the high-voltage burst.
[0034] FIG. 5 is an illustration of DC and AC components of an alternative high-voltage burst.
[0035] FIG. 6 is an abbreviated flow chart of a method of bacterial transformation.
[0036] FIG. 7 is an illustration of DC and AC components of an alternative high-voltage burst.
[0037] FIG. 8 is an illustration of a composite-AC high-voltage burst.
DETAILED DESCRIPTION OF THE EMBODIMENTS
[0038] FIG. 1 illustrates prior-art electroporation apparatus similar to that described in Tyurin M. V., Padda R., Ke-xue Huang, Wardwell S., Caprette D., Bennett G. N. (2000): Electrotransformation of Clostridium acetobutylicum ATCC 824 Using High - Voltage Radio Frequency Modulated Square Pulses //Journal of Applied Microbiology. 88(2): 220-227 (hereinafter Tyurin, 2000), the text of which is hereby incorporated by reference. A suspension of cultured bacteria in a solution 102 of desired-sequence DNA is placed in an electroporation cuvette 104 . Care is taken to ensure that the solution 102 is as free of salt as possible, nonionic solutes are used to provide appropriate osmolarity. The cuvette 104 has a first electrode 106 and a second electrode 108 spaced both exposed to the solution 102 but electrically insulated by a polypropylene microcentrifuge tube 110 from a surrounding ice block 112 . When working with anaerobic bacteria, the entire cuvette 104 and ice-block 112 are placed in an oxygen-free glovebox 114 . The first 106 and second 108 electrodes are connected to the output of a high-voltage electrical function generator 120 , or operating under control of pulse timing circuits 122 .
[0039] Reported apparatus includes high-voltage electrical function generators 120 having direct current DC output, and high-voltage electrical function generators having a one-hundred kilohertz AC burst superimposed on a DC pulse. In particular, Tyurin 2000 in his FIG. 3 taught that better results were obtained with one-hundred kilohertz AC superimposed on a DC pulse than with higher frequencies in the range one hundred fifty to three hundred fifty kilohertz.
[0040] When the prior apparatus of FIG. 1 is used, the operator triggers the pulse timing circuits 122 , and the pulse generator provides either a square pulse as indicated 124 , an exponentially decaying pulse, or a superposition of a high-voltage DC pulse with one hundred kilohertz AC of amplitude one-tenth to one-third the magnitude of the DC pulse between the first 106 and second 108 electrodes of the cuvette. While DC pulses are standard in the art, Tyurin 2000 disclosed transformation of Clostridium species using a pulse having an AC signal of 100 kHz superimposed on a DC pulse. High-voltage pulses above one kilovolt are typically used.
[0041] The high-voltage electric field applied between the electrodes 106 , 108 , causes current to flow through the solution 102 of desired DNA plasmids 202 ( FIG. 2 ) with suspended bacteria 204 . DNA plasmids 202 are typically circular of DNA with a replication initiation site. The current, which readily flows through the saline intracellular fluid, burns minute holes in the bacterial cell walls 206 , and electrophoretically shifts DNA molecules in the solution, through the cell walls, and some molecules may shift through the minute holes. After the high-voltage current pulse, some desired DNA molecules 210 end up inside transformed 212 bacteria, where the desired DNA molecules 210 may be expressed and further incorporate into the bacterial genome.
[0042] In the present electroporation apparatus as illustrated in FIG. 3 , a suspension of cultured bacteria in a solution of desired-sequence DNA is placed in an electroporation cuvette 302 . The desired-sequence DNA is preferably in the form of a plasmid. The cuvette has first 304 and second 306 polished parallel-plate stainless-steel electrodes spaced approximately two millimeters (distance D) apart in a two-milliliter polypropylene disposable centrifuge tube 307 , and both the electrodes and cuvette contents are electrically insulated from, but thermally coupled to, a surrounding ice block 308 . In doing so, part of the tube 307 is placed within a cavity in the ice block 308 . When working with anaerobic bacteria such as Clostridium thermocellum , the cuvette 302 and icewater bath 308 are kept in an oxygen-free glovebox 310 . The cuvette's electrodes 304 , 306 are connected to a high-voltage burst generator 312 , controlled by a pulse generator 314 .
[0043] When the present electroporation apparatus is operated, an operator triggers the pulse generator 314 to fire the high-voltage burst generator 312 . The high-voltage burst generator then provides a high-voltage burst 316 through a current limiting resistor 318 .
[0044] The high-voltage burst 316 can be described as illustrated in FIG. 4 as the superposition of a high-voltage Initial Spike of Direct Current (DC) pulse having a DC component amplitude 402 with a superimposed sinusoidal high radio-frequency Alternating Current (AC) peak-to-peak amplitude 404 such that the Initial Spike Total Amplitude 406 is in the range of from 12 to 25 kilovolts per centimeter of electrode spacing D. The electroporation pulse has an initial spike pulsewidth 408 between approximately five and twenty percent, and in an embodiment is about ten percent of the total pulsewidth 410 of initial spike and plateau; the total pulsewidth 410 ranges from three to twenty-five milliseconds, and is preferably from eight to ten milliseconds. The plateau therefore is greater in length than half of the total pulsewidth 410 . The plateau continues the radio-frequency alternating current at approximately the same peak-to-peak amplitude 404 as during the initial spike, and has a plateau DC component 412 that is between ten and thirty percent of the initial spike DC component, and has magnitude greater than half of the AC peak-to-peak amplitude. The total magnitude 414 of the plateau of the voltage burst is the sum of the DC component 412 plus half the AC peak-to-peak amplitude 404 . The sinusoidal AC component has a frequency of between 3 and 125 MHz, being preferably within twenty percent of 24 MHz, and has peak-to-peak magnitude greater than six and a half percent of the initial spike total amplitude 406 . The high-voltage burst may be of either polarity, since relative voltages between the electrodes 304 , 306 induce current flow in the electroporation cell. The composite of AC and DC components is known herein as a high-voltage burst.
[0045] Since in the embodiment of FIG. 4 , the AC component begins with the initial spike, the AC component overlaps the initial spike.
[0046] It is believed that the initial spike serves to create pores in the bacterial cell membrane and start discharge through the cuvette, while the plateau portion serves to electrophorese the desired DNA plasmid through cell wall and through the pores into cells. It is also believed that the AC component causes current paths through the bacterial sample to vary, such that cell damage is spread out and not focused on any one portion of the cell.
[0047] Pulses approximating that described in FIG. 4 , such as those with a rapid exponential decay from the initial spike DC component to the plateau level, are expected to produce similar results.
[0048] It is expected that with certain bacteria, especially difficult to transform members of genus Clostridium , the present electroporator using the waveform of FIG. 4 will give substantially better yields of transformed bacteria than achieved by other workers and with other apparatus. It was also found that a greater percentage of bacteria appeared largely intact after electroporation than with conventional electroporation.
[0049] The present electroporator is also expected to be successful with bacterial strains from species of Thermoanaerobacterium and Thermoanaerbacter , and other bacteria having characteristics resembling those of Clostridium species. It is also expected that the present electroporator will be successful with Acinetobacter.
[0050] Experiments where the AC component was lacking show significantly reduced transformation efficiency.
[0051] An alternative high-voltage burst is illustrated in FIG. 5 as the superposition of a high-voltage Initial Spike of Direct Current (DC) pulse having a DC component amplitude 502 in the range of from 12 to 24 kilovolts per centimeter of electrode spacing D, or 2400 to 4800 volts for electrodes spaced two millimeters apart. The electroporation pulse has an initial spike pulsewidth 504 approximately ten percent of the total pulsewidth 506 of initial spike and plateau; the total pulsewidth 506 ranges from three to twenty-five milliseconds, and is preferably from eight to ten milliseconds. The plateau has superimposed a sinusoidal radio-frequency alternating current (AC) 508 component, and has a plateau DC component 510 that is between ten and thirty percent of the initial spike DC component, and has magnitude greater than half of the AC peak-to-peak amplitude 508 . The total magnitude 512 of the voltage burst is the sum of the DC component 510 plus half the AC peak-to-peak amplitude 508 . The AC component has a frequency of between 3 and 125 MHz, being preferably about 24 MHz, and has a peak-to-peak magnitude greater than six and a half percent of the peak amplitude of the initial spike 502 .
[0052] In the embodiment of FIG. 5 , the AC component begins as the initial spike ends.
[0053] In summary, the process of generating transformed bacteria begins by purifying a culture of bacteria 602 to remove most contaminating salts from the culture media. A solution of desired DNA plasmids is prepared 604 , this is combined 606 with the purified bacteria to produce a suspension of bacteria in a solution of DNA plasmids. The bacteria may be suspended in salt-free solvent and DNA solution added, or the bacteria may be suspended directly in the DNA solution.
[0054] The suspension of bacteria in DNA solution is placed 608 in the electroporation cuvette 302 such that the electrodes 304 , 306 make contact with the solution. A burst as described above with reference to FIG. 4 or FIG. 5 is applied 610 to the suspension. Surviving bacteria are cultured 612 and selected 614 to provide a culture of transformed bacteria.
[0055] The culturing 612 and selection 614 are in a first embodiment performed by including an antibiotic resistance gene in the DNA plasmids, and including the related antibiotic in culture media in which surviving bacteria are cultured 612 .
[0056] In an alternate embodiment selection 614 is performed by blotting.
[0057] FIG. 7 illustrates an alternative burst that has been successfully used to transform Clostridium thermocellum bacteria. The burst is essentially the superposition of a square DC pulse represented as DC component 702 having a pulsewidth 704 of between three and twenty-five milliseconds, in an embodiment the pulsewidth is between eight and twelve milliseconds. The DC component 702 is superimposed on an AC component 706 having peak-to-peak magnitude greater than six and a half percent of the magnitude of the DC component 702 , and in an embodiment a frequency of twenty-four megahertz. A total magnitude 710 of the voltage burst is the sum of the DC component 702 plus half the AC peak-to-peak amplitude 706 . The AC component has a frequency of between 3 and 125 MHz, being preferably within twenty percent of 24 MHz. The burst of FIG. 7 has total magnitude 710 in the range of between eleven kilovolts and twenty-four kilovolts per centimeter of electrode spacing in the electroporation cuvette.
[0058] It was found that, with difficult to transform members of genus Clostridium , the present electroporator using the waveform of FIG. 7 gave better yields of transformed bacteria than achieved by other workers and with other apparatus. It was also found that a greater percentage of bacteria appeared largely intact after electroporation than with conventional electroporation.
[0059] In an alternative embodiment, illustrated in FIG. 8 , a burst having a first and a second superimposed AC signals with combined zero-to-peak magnitude 802 reaching between eleven kilovolts and twenty-four kilovolts per centimeter of spacing between electrodes in the electroporation cuvette. The first AC signal has a frequency of between twenty and five hundred kilohertz, and preferably about one hundred kilohertz, the second AC signal has a frequency of between three and one hundred twenty-five, and preferably about twenty-four, megahertz. The second AC signal has a magnitude between six and thirty percent of the magnitude of the first AC signal. The burst has a width 804 of between three and twenty-five milliseconds, in an embodiment the width is between eight and twelve milliseconds.
[0060] In yet another alternative embodiment, illustrated in FIG. 9 , a damped AC burst having a center frequency of between three and one hundred twenty-five, and preferably about twenty-four, megahertz. The damped burst has an initial zero-to-peak magnitude 902 reaching between eleven kilovolts and twenty-four kilovolts per centimeter of spacing between electrodes in the electroporation cuvette. The burst tapers in amplitude to a level approximately ten percent of the initial magnitude over a width 904 of between three and twenty-five milliseconds, in an embodiment the width is between eight and twelve milliseconds.
[0061] It is anticipated that the current limiting resistor 318 may be replaced by other forms of current limiting devices appropriate for the waveform applied. In particular, it is expected that a reactive component such as an inductor, or a reactive network incorporating one or more inductors, resistors, and capacitors, are particularly suitable for use as a current limiting device with waveforms incorporating the AC components herein described. In some embodiments, current sensing with current limiting through active feedback may also be used.
[0062] With the use of substantial AC components in the transforming pulse as herein described, it is anticipated that some embodiments may embed the current limiting device into an RF or pulse transformer that serves to increase voltage between the burst generator and the cuvette.
[0063] While the invention has been particularly shown and described with reference to a preferred embodiment thereof, it will be understood by those skilled in the art that various other changes in the form and details may be made without departing from the spirit and scope of the invention. It is to be understood that various changes may be made in adapting the invention to different embodiments without departing from the broader inventive concepts disclosed herein and comprehended by the claims that follow.
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A method and apparatus for electroporation includes placing a mixture of bacterial suspension and transforming DNA into an electroporation cuvette. The resulting sample is subjected through a current-limiting device to a complex 5 waveform including a burst of high-voltage radio-frequency current, which in some embodiments is superimposed on a biphasic high-voltage DC pulse, and in other embodiments on a high-voltage lower-frequency AC burst. The total waveform has at least an initial portion greater than eleven thousand volts per centimeter of electrode spacing, and a later portion in some embodiments is reduced to less than thirty percent 10 of magnitude of the initial portion. Transformed bacteria are selected by culture in selective medium in an embodiment. The high-voltage radio-frequency current is between 3 and 125 MHz, and in an embodiment is 24 MHz.
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RELATED APPLICATION
This application is a continuation-in-part of my U.S. patent application Ser. No. 08/276,418, filed Jul. 18, 1994, now U.S. Pat. No. 5,764,776 and which is, in turn, a continuation-in-part of U.S. patent application Ser. No. 143,981 filed Nov. 4, 1993 entitled "System for Delivering Sound to and Monitoring Effects on a Fetus" now U.S. Pat. No. 5,491,756, dated Feb. 13, 1996).
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates in general to certain new and useful improvements in systems for generating and delivering various types of sensory effects to a fetal child through a mother's abdomen and more particularly, to a system of the type stated which also allows for the generation of the sensory effect and transmission across the abdomen wall, as well as means for monitoring for the effects on the fetal child.
2. Brief Description of the Related Art
There have been numerous attempts to impart sounds, such as music and the like to a fetus during gestation. Prior art attempts to impart any type of sensory excitation to the fetus were usually rudimentary and unsophisticated.
In U.S. Pat. No. 5,109,421, dated Apr. 28, 1992, entitled "Fetal Speaker System And Support Belt For Maternal Wear" there is provided a more sophisticated system for generating and imparting sound to a fetus. In this prior art device, a belt is provided and supports speakers for imparting sound through the abdomen wall to the fetal child. While this device is effective, it has been found to be lacking in certain respects, not the least of which is the fact that the belt itself did not provide sufficient support to hold transducers, sound generators and the like.
It has also been recognized that there is a possibility that other forms of sensory excitation can be generated and transmitted to the fetus through the wall of the abdomen of the mother. However, there are no effective techniques for applying other types of sensory effects.
It is believed that imparting of various types of sensory effects to the fetus can be effective in creating a bond between the fetus and the mother. The sound, if properly selected, can provide a soothing effect to the fetus. For that matter, a light of a selected proper frequency, capable of at least some transmission across the abdomen wall, may also have a desirable effect on the fetus. In addition, the fetus may also find vibration effects imparted across the abdomen wall to be desirable. Not only does this create a more pleasurable gestation period for the fetus, but it also helps to create a bond between the mother and the fetus.
It has also been recognized in the art that applications of radiation, as well as physical actions such as vibration, for example, of various types across the abdomen of a mother can be and is received by the fetus and has a sensory type effect on the fetus. Moreover, the fetus can and frequently does respond to the application of the sensory effects. Thus, a type of communication is achieved between the mother and the fetus when these sensory effects are transmitted to the fetus. The fetus can express its pleasure or displeasure at the type of sensory effects by the physical movement of the fetus within the mother's abdomen.
The applicant has now discovered that it is possible to apply certain types of electromagnetic radiation, such as light, magnetic effects and the like across the abdomen wall to the fetus from a harness-type device which can be worn by the mother and which is essentially portable in construction.
The applicant has also discovered that various types of light effects clearly have an effect upon the fetus. It has now been established that laser light, for example, is one form of light to which the fetus is clearly sensitive. The laser light, in particular, is collimated and can, when of sufficient intensity, does impact on the fetus. The applicant has theorized and believes that the pineal gland of the fetus, even though in a developmental stage, will respond to this light energy much in the same manner as a pineal gland of a living individual is effected by the presence of light or lack of light on an individual, even when that individual is sleeping.
It has been found that in all cases, it is desirable to also provide for monitoring the effects of any type of sensory excitation on the fetus. It is possible to determine if the fetus reacts negatively to one form of sensory excitation or favorably to another form of excitation. In this way, the mother can selectively apply that excitation form favorable to the fetus.
In addition, it is recognized that many mothers find pregnancy to be uncomfortable, if not painful, due to the fact that they are carrying a substantial additional amount of weight in their abdomen. This almost necessarily creates strains on the back, as well as other parts of the skeletal muscular system. While there is no effective way to reduce the extra weight being carried by the mother, the deleterious effects can be mitigated to some extent by applying sensory effects to the mother. Vibration, and/or heat are oftentimes effective for this purpose. Thus, in any device in which sensory effects are imparted to a fetus, it may also be desirable to impart certain sensory effects to the mother.
OBJECTS OF THE INVENTION
It is, therefore, one of the primary objects of the present invention to provide a system for generating and imparting sensory effects to a fetus through a mother's abdomen and which also allows for monitoring of the effects on the fetus.
It is another object of the present invention to provide a system of the type stated which is capable of generating and imparting various types of sensory effects, such as light effects, magnetic effects, vibrational effects or the like, all of which can be imparted to the fetus cross the abdomen wall of the mother.
It is a further object of the present invention to provide a system of the type stated which can be adapted so as to interchangeably provide different types of transducers for generating different type of effects to be transmitted to the fetus.
It is still another object of the present invention to provide a light source of desired intensity, color and wavelength which can be transmitted across a mother's abdomen to a fetus in order to create a desired sensory effect on the fetus.
It is also an object of the present invention to provide a system for generating and imparting sensory effects to the fetus and which is highly reliable in its operation and highly effective in creating a desired effect on the fetus.
It is an additional object of the present invention to provide a system for generating and imparting sensory effects to a fetus and also for generating and providing sensory effects to a mother to aid the mother during the gestation period.
It is yet another object of the present invention to provide a system of the type stated which can be manufactured at a relatively low unit cost and which is highly reliable in operation.
With the above and other objects in view, my invention resides in the novel features of form, construction, arrangement and combination of parts presently described and pointed out in the claims.
BRIEF SUMMARY OF THE DISCLOSURE
Generally speaking, the present invention relates to a system for generating and imparting various types of sensory effects, and particularly electromagnetic radiation-type sensory effects to a fetus (often referred to as a "fetal child") through the mother's abdomen wall and which also allows for monitoring of the effects on the fetal child. The system of the invention also is effective for providing various sensory effects to the mother in order to aid in overcoming some of the discomforts associated with pregnancy.
The system for generating and imparting sensory effects of the present invention adopts some of the basic principles utilized in U.S. Pat. No. 5,109,421, but constitutes a significant advance thereover in that it not only solves many of the problems which had arisen in prior art sound systems, but also allows for transmitting of other types of sensory effects. Furthermore, the system of the present invention also allows for the important aspect of monitoring the effects on the fetus.
The system for generating and imparting various types of sensory effects comprises a belt sized for wearing disposition about the waist of a woman user. That belt may adopt the form of belt which is now described and claimed in my previously identified U.S. Patent Applications. That belt typically is designed with an enlarged frontal portion which extends over a substantial surface area of the lower abdomen of the woman user and provides greater support for the transducers and sensory effect generators, as well as the monitoring equipment.
In one of the preferred embodiments, sound generation is usually employed. In this case, at least one speaker is carried by and mounted on the belt. Preferably, a pair of spaced-apart speakers are mounted on and carried by the belt and located in juxtaposition to the abdomen and in proximity to the fetal child. Thus, sound can be imparted to the fetal child across the wall of the abdomen.
The sound generator may adopt any form of the type described in my aforesaid co-pending patent application. As a simple example, a radio, a tape player or compact disc player or a so-called "Walkman" unit may be mounted in and carried by the belt. This sound generator is capable of generating sounds of the type to be imparted to the fetal child and has one or more outputs connected to the one or more speakers.
Speakers may also be located for external transmission of sound, if desired. However, in accordance with the invention, the primary focus is upon the transmission of sensory effects to the fetus.
In one embodiment of the invention, the system is designed to generate light of various intensities and/or frequencies for imparting across the wall of the abdomen to the fetus. While the fetus itself may not have yet developed sight capability, the applicant has, nevertheless, determined that light radiation does, in fact, have some effect on the fetus. This is particularly the case when the frequency, and hence color, of the light changes and when the intensity of the light changes. For example, it is possible to provide a type of strobing effect which allows the light to be rapidly turned on and off. In other cases, it is possible to change the frequency, and hence the color, of the light.
In accordance with the present invention, the applicant has now been able to define various types of light sources which are effective in creating desired sensory effects on the fetus and in generating responses from the fetus. In particular, one of these light sources relies upon the use of laser light. Moreover, and in each case, the applicant has developed a means to enable generation of the light from a light generator carried on the belt or other harness arrangement which is worn by the mother. In particular, one form of carbon dioxide laser light source has been developed for generating of laser light across the abdomen of the mother and directed to the fetus.
The applicant has also found in accordance with the present invention that the light which is generated is not necessarily limited to the visible light frequency spectrum. Thus, for example, both ultraviolet light and infrared light at opposite ends of the visible frequency spectrum also have an effect on the fetus. For some reason, and even though the fetus may not actually observe the non-visible light energy, as such, the pineal gland of the fetus, and even though in the development stage, nevertheless responds to that light.
In another embodiment of the invention, the invention relies upon the use of magnetic effects which are generated and imparted across the wall of the abdomen to the fetus. These magnetic effects can be either generated by permanent magnets or by electromagnets. In the case of permanent magnets, the magnets, such as alnico magnets, are mounted on and contained within pockets in the belt. The magnetic effects are normally created by the magnet and the effects thereof are imparted to the fetus through the abdomen wall.
Where stronger magnetic effects are desired, electromagnetic effects can be generated by use of a simple electromagnetic transducer. A battery source of power may be carried by the belt and the electromagnetic transducers are connected to the battery source of power. A switch means is also provided for energizing and de-energizing the electromagnetic transducers.
In still another embodiment of the invention, vibrational effects can be created and transmitted across the abdomen wall to the fetus. In this case, the vibrational effects would be created by some type of vibration-generating device as, for example, a conventional massage unit. Electric power is again provided by a battery unit or battery pack carried on the belt which is worn by the mother and is conducted to the vibration generator through electrical conductors.
In one of the important aspects of the invention, the effects of these various types of sensory excitations are monitored. For this purpose, a conventional stethoscope can be used. A suitable stethoscope sensor may be mounted in and carried by the belt to be located in juxtaposition to the mother's abdomen. The stethoscope sensor would, of course, be located in proximity to the fetal child to enable listening to the sounds generated by the fetal child in the mother's abdomen.
In a preferred embodiment, a sound conductor extends from the stethoscope sensor and has a connector for coupling to a stethoscope earpiece, so that the mother can monitor the effects of the sound on the fetal child. In this case, the stethoscope earpiece would be worn by the mother or other user of the system for listening to the sounds generated by the fetal child.
The present invention also envisions the use of other types of monitoring equipment. As a simple example, a heart rate monitor can be mounted on the belt with a sensor similarly located adjacent the abdomen of the mother and in proximity to the fetal child.
It is believed that in accordance with the present invention, the heart rate of the fetus may be a function of the effects which are imparted to the fetus. For example, where the fetus responds more favorably to soft music or to certain types of vibration or to a certain type of heat, these conditions can be noted and reapplied to the fetus at a later date. Otherwise, if the fetus responds negatively to certain types of sensory excitation, then the mother can avoid the imparting of that sensory excitation in the future.
It has also been established that the physical activity of the fetal child, as, for example, kicking, may be a result of the application of various sensory effects across the fetus and imparted to the fetal child. This is, again, another parameter for determining the effects of the sensory excitations upon the fetal child.
To the extent that any of the monitoring equipment requires electrical power, this equipment can be powered from the same source of electrical power, such as the batteries which are mounted on or carried by the belt.
The belt or other harness used in accordance with the present invention can also be provided with the devices for applying certain excitations to the mother. Thus, for example, a heating element can be mounted in the belt and located in juxtaposition to either the abdomen or the back of the mother. In like manner, vibratory mechanisms may also be mounted in the belt to literally apply vibration to the back of the mother and aid in overcoming back pain as a result of carrying the fetus.
This invention possesses many other advantages and has other purposes which will be made more fully apparent from a consideration from a consideration of the forms in which it may be embodied. These forms are show in the drawings forming part of and accompanying the present specification. They will now be described in detail for purposes of illustrating the general principles of the invention, but it is to be understood that the detailed description and the accompanying drawings are not to be taken in a limiting sense.
BRIEF DESCRIPTION OF THE DRAWINGS
Having thus described the invention in general terms, reference will now be made to the accompanying drawings in which:
FIG. 1 is a perspective view of a system for generating and imparting sensory excitations across the abdomen wall of a mother to a fetus and showing a harness-type arrangement along with transducers for generating and imparting sensory effects;
FIG. 2 is a front perspective view of the system of FIG. 1 and specifically showing details of the harness-type arrangement;
FIG. 3 is a side elevational view of the harness-type arrangement forming part of a slightly modified form of system of the invention on the abdomen of a pregnant woman;
FIG. 4 is a front elevational view of the belt forming part of the harness-type arrangement and showing the use of sound sensory excitation;
FIG. 5 is a fragmentary plan view, partially in section of the embodiment of the invention of FIG. 4;
FIG. 6 is a fragmentary perspective view, partially in section, and showing connections of lighting devices to a control unit and a battery source of power;
FIG. 7 is a perspective view of the opposite side of the belt showing the control unit and battery of FIG. 6;
FIG. 8 is a front elevational view of the belt forming part of the harness of the invention utilizing light sensory excitation;
FIG. 9 is a schematic electrical view showing a portion of the electrical components used in fetal monitoring forming part of the system of the present invention;
FIG. 10 is a sectional view taken through the belt and showing the use of a vibrator mechanism;
FIG. 11 is a fragmentary perspective view, partially in section, of the system of FIG. 10;
FIG. 12 is a schematic electrical circuit view showing the components used with vibrators as the means for generating excess sensory excitation;
FIG. 13 is a perspective view of another modified form the belt using heating elements therein;
FIG. 14 is a schematic view showing some of the electrical circuitry used in operating heating elements forming part of the system of the invention;
FIG. 15 is a fragmentary perspective view in partially exploded form and showing a portion of the components and a means for mounting in a belt of the present invention;
FIG. 16 is a perspective view showing a large number of the sensory excitation devices mounted in a belt forming part of the harness-type arrangement;
FIG. 17 is a electrical circuit schematic view showing electrical connection of some of the components forming part of the present invention;
FIG. 18 is a perspective view, partially in schematic form, and showing one form of laser light generating device which can be used for causing sensory excitation upon a fetus;
FIG. 19 is a fragmentary perspective view showing the embodiment of FIG. 18 on a belt arrangement;
FIG. 20 is a schematic top plan view showing a redirecting of a laser light through a light directing mechanism to a fetus;
FIG. 21 is a sectional view through the light generating device of FIG. 18 showing a folded wave path;
FIG. 22 is a schematic view showing an arrangement of mirrors forming part of the folded light path used in FIG. 21;
FIG. 23 is a fragmentary perspective view showing one means for measuring information about a fetus or a mother and transmitting the same;
FIG. 24 is a schematic view showing one form of information transmitting system for purposes of transmitting information initially measured in acoustic form; and
FIG. 25 is a schematic view showing another form of information transmitting system for transmitting information in digital electrical format.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Referring now in more detail and by reference characters to the drawings which illustrate several practical embodiments of the present invention, 10 designates a system for generating and imparting sensory excitation to a fetus or so-called "fetal child" through the abdomen wall of the mother. The system 10 comprises a harness arrangement 12 which includes a belt 14 sized to extend around the abdomen of the mother. The belt 14 is constructed so that it has an enlarged frontal section 16 and an enlarged rear section 18.
By reference to FIG. 2, it can be observed that the enlarged frontal section 16 and, for that matter, the enlarged rear section 18, are both enlarged in the sense that they have a greater overall vertical dimension. In this way, it has been found that a belt with non-constant vertical dimension, particularly in the front and rear portions thereof, tends to provide a greater support to the mother who is wearing the harness 12 of the invention. In this case, it has been found that little support is actually provided on the sides and therefore, the sides are of reduced thickness.
In order to facilitate ease of wearing, the belt 14 is provided with a terminal end section 17 which fits within a belt buckle 19. Furthermore, it has been found in connection with the present invention that the terminal section 17 and the buckle 19 should be located at the rear portion of the belt in order to allow for some expansion of the belt as the fetus grows and the mother's abdomen expands. For this purpose, elastic strips 21 may also be formed on the sides of the belt in order to provide some degree of expansion. It should also be understood that other means for adjustably sizing the belt, such as the use of Velcro strips or the like could also be employed. The elastic strips 21 are preferably positioned toward the side of the belt so that they are, in effect, rearward of the speakers and other transducers. In this way, expansion of the mother's abdomen will not result in a changing of the position of the sensory transducers (hereinafter described) with respect to the fetal child.
In addition to the foregoing, and in order to provide greater support for the mother wearing this harness 12, the harness 12 is provided with a pair of suspender straps 20, as also best illustrated in FIGS. 1 and 2. The suspender straps 20 are also provided with buckles 22 for adjustably sizing the overall length of each of the suspender straps 20. Furthermore, if desired, these suspender straps 20 could be provided with elastic portions 24. These elastic portions 24 also allow for some individual stretching when the mother changes her position.
The suspender straps 20 should be connected to the belt so that they are adjustably securable to the belt at selected positions along the length of the belt. Thus, as the mother's abdomen expands, the belt is opened to a larger loop and the suspender straps can be moved outwardly. For this purpose, a series of buttons or other fasteners (not shown) may be provided on the belt for releasably securing the lower end of the suspender straps.
The underside of the suspender straps 20, particularly in the shoulder regions, are provided with soft pads 26 in order to provide wearing comfort to the mother. These shoulder pads 26 may be formed of a soft felt-like material so as to reduce the abrasive effect of a conventional pair of straps.
The belt 14 is preferably formed of a leather material, although any other type of material, such as a woven fabric or the like, could be used. Various rubber materials or foam materials could be used. A preferred rubber material which can be used is a neoprene rubber. However, leather is preferred inasmuch as it has some structural integrity and also provides for the necessary rigidity to hold speakers and a sound generator, as hereinafter described. The suspender straps 20 may also be formed of leather although, again, other materials may similarly be employed.
The belt 14 is provided with the buckle 19 for opening and closing the belt 14 in order to position the belt 14 around the waist of the user as also shown in FIGS. 1 and 2. Further, the belt 14 and the buckles 19 may be cooperatively designed so as to be adjustable in position.
The belt 14 is designed to carry one or more transducers and power sources, as may be required, at the option of the user. In this respect, the belt 14 could be provided with available pockets or the like in order to receive and hold one or more of the transducers. In this way, the user of the system can add the selected type of transducer at will. Otherwise, the belt 14 could be constructed to hold only a pre-selected number of transducers and perhaps, monitors.
In essentially all embodiments of the sensory excitation system, sound generating equipment will probably be used, since this is an important type of sensory effect to be provided to the fetal child. In the sound generating system there will be speakers 30 for imparting sound to the child fetus. The exact means for mounting the speakers 30 within the belt 14 is not critical and any conventional mechanism for mounting the speakers 30 may be employed. In the case of the present invention, the speakers 30 are fitted within recesses formed in the belt 14 and project to and through the interior surface of the belt 14. However, the outer surface of the speakers 30 is at least flush with the inner surface of the belt 14. In this way, the speakers 30 will be juxtaposed to the wall of the abdomen of the mother when the system 10 is worn.
The speakers 30 are connected to a sound generator 34, such as a conventional radio and tape player combination. The sound generator 34 could also adopt the form only of a tape player, a radio or the like. The sound generator could adopt any conventional form of sound generator and may be of the type described in my copending application Ser. No. 143,981, filed Nov. 11, 1993. The sound generator 34 may be any conventional type sound generator, as aforesaid, and may be fitted within a pocket 32 located on the belt 14 in the manner as shown. Otherwise, sound generators of this type may be conventionally provided with clips for clipping onto the belt 14.
Electrical conductors 36 are used to connect the speakers to the sound generator 34. However, when the sound generator is removed, it is necessary to disconnect the conductors 36. For this purpose, the conductors 36 exit the belt 14 at an exit port 37 and are provided with plugs 40 which literally plug into conventional sockets provided on the radio tape recorder unit. Thus, the sound generator 34 can be removed from the belt 14 and used for other purposes. Inasmuch as the details relating to the use of the invention for imparting sound have been described in my aforesaid co-pending application, those details may be incorporated herein by reference. Accordingly, they will be neither illustrated nor described in any further detail herein.
FIGS. 6-8 illustrate an embodiment of the invention which is used for the transmission of light radiation to the fetus. In many cases, if the light is of sufficient intensity, the light can penetrate, to some degree, the wall of the abdomen and even the uterus, to some degree. However, it has nevertheless been found that the light does have effects on the fetus.
One of the preferred forms of light sources which has been found to be effective for creating effects on the fetus are laser light sources. To some extent, this may be a result of the intensity of laser light sources, as well as a function of the wave length. As a simple example, with laser light, the beams of light are parallel much in the same manner as sunlight. Consequently, intensity can be quite substantial. Furthermore, even though the light is somewhat collimated, the light beam still does not carry a substantial amount of heat and, therefore, there is little or no damage to the abdomen tissue of the mother.
Some of the laser lights which can be used include the helium-neon lasers, and the helium-cadmium lasers. Also effective are many of the noble gas lasers and carbon dioxide lasers. Some laser mechanisms which could be used, but which have certain limitations because of power requirements, size and the like, include various chemical lasers, copper and gold vapor lasers, excimer lasers, far infrared gas lasers, and other commercial gas lasers. For that matter, some of the semi-conductor diode lasers, such as the short wavelength diode lasers and the long wavelength III-V semiconductor diode lasers can be used.
It has been recognized that digestion and assimilation by animals and humans are effected by light energy. Indeed, Albert Szent-Gyorgyi, Nobel prize winner and discoverer of vitamin C, has reported and recognized the effects of both light and even the color of light on the human body. Mr. Szent-Gyorgyi discovered that many enzymes and hormones of the body are involved in the processing of light energy and are sensitive to both the color and the intensity of light. These enzymes and hormones are actually stimulated by selected colors of light and undergo molecular changes which alter their original colors, and thereby cause dynamic reactions within the body. See Introduction to Sub-Molecular Biology, New York Academic Press 1960 by Albert Szent-Gyorgyi.
Although a fetus may not directly observe light, as such, because of the tissue between the source of light and the fetus, and also because of the fact that the eyesight of the fetus is not well developed, it has been recognized that the fetus will nevertheless detect the presence of light. The pineal gland apparently is sensitive to incidence of light on the body and acts as a type of light meter. Thus, it is established that the fetus is sensitive to incidence of light. It is for this reason that the pineal gland is often referred to as "the third eye".
Until recently, there was some scientific controversy over the effects of light on the human body, although science did recognize the effects of x-rays, ultraviolet rays and microwaves on the human body. However, the visible light differs from x-rays and other types of radiation only in wavelength range. Indeed, the various colors of light differ from one another only in wavelength range. It is now recognized that not only do the non-visible portions of the spectrum have effects on the human health, but also visible light has effects on the human health.
It is now known that lighting which simulates sunlight creates little or no stress on an individual and, moreover, it improves behavior and academic achievement. See H. Wohlfarth, et al. "The Effective of Color Pysicodynamic Environmental Modification Upon Physiological and Behavioral Reactions of Severely Handicapped Children" as reported in the International Journal of Biosocial Research, No. 3 (1982), pages 10-38. There are numerous reported cases where light has been used to cure mal-development or disease. Consequently, the applicant has recognized that light may have a very significant effect on the fetus.
In the present invention, a plurality of light sources 40. e.g. lights, are mounted on the interior face of the belt 14, as shown in FIGS. 4 and 8. These lights 40 may be any conventional type of incandescent light, although incandescent lights are not preferred due to the fact that they generate heat, if there is sufficient wattage for the required purpose. Fluorescent and neon lights are therefore preferred for this purpose and also they are more desirable since they consume less power for the same amount of light generation than do incandescent lights.
In the case of the present invention, the light sources may be within the visible wave length range. However, in some embodiments, the light sources may also be beyond the red or the violet light ranges, such as into the infrared or ultraviolet light ranges.
The light sources 40 are internally connected through electrical conductors 42 located within a plural ply-belt structure and with the wires connecting the light sources 40 extending between the plies of the belt, as hereinafter described in more detail. The conductors 42 exit the belt as shown in FIG. 8 and are connected to a suitable control unit 44 which is provided with control switches 46. The control unit may suitably contain conventional sequencers of the type which would cause a sequencing or strobing of the light to be imparted to the fetus. Otherwise, the control unit 44 may contain light-intensity controls and typical on/off controls.
It is has now been found that the noble gas lasers and carbon dioxide lasers are highly effective in creating the desired laser light. Moreover, the generators for producing this laser light can be made sufficiently small so as to be carried on a belt. Admittedly, energy level is still somewhat of a problem, although with a small rechargeable battery pack carried on the belt, effective laser operation can be achieved.
One preferred form of laser light which can be used in accordance with the present invention is that noble gas laser and which, in this case, uses a small metal-ceramic or ceramic tube. The current densities required for excitation calls for the discharge to be applied along the length of the laser tube and confined to a very narrow bore of 1-3 mm in diameter. A discharge current passes from the cathode in the tube along the narrow bore and collected at the anode. A linerally polarized light escapes without loss and serves as an optical path. In the case of the present invention, cooling, if needed, can be achieved by airflow. Moreover, a magnet which creates a magnetic field parallel to the bore axis may be used to help confine the discharge current to the center of the bore, thereby increasing the ion density.
Some of the noble gas lasers which can be used in accordance with the invention are the Crypton lasers and Argon lasers. Another laser which can be used in accordance with the present invention is a solid tube laser utilizing carbon dioxide. The tube is usually filled with carbon dioxide, helium and nitrogen and mirrors forming a resonate cavity are placed at the ends of the tube. Electrodes are located near the ends of the tube and the tube is filled with a proper gas and sealed. The voltage as applied to the electrodes causes a discharge through the gas. Again, air cooling is applied for dissipation of the generated heat.
One of the preferred light sources used in accordance with the present invention is the carbon dioxide laser light. It is a highly versatile type of light and emits infrared radiation between 9 and 11 micrometers and even at a single line which may be selected by the user. Moreover, it can be adapted to provide a continuous light output or a pulsed light output.
The laser used in accordance with the present invention is a sealed tube laser. In the embodiment as shown, the laser light employed uses a discharge tube 250 along with mirrors 252 at each of the opposite ends of the discharge tube 250. Connected to the discharge tube 250 is a relatively small gas supply reservoir 254 and a pump 256. The pump 256 can actually adopt the form of a fan. The gas supply reservoir 254 is provided with a fitting 258 for refilling the gas in the reservoir 254. Moreover, the entire assembly can be mounted in an outer housing 260 on the belt 16, as shown in FIG. 19.
In order to redirect any generated beam to the proper direction, a redirecting lens mechanism 262 is located at one end of the laser light housing 260. In this case, a pair of mirrors 252 in the redirecting mechanism 262 are shown in schematic form. In this way, a beam of light from an end of the housing would be redirected in a generally perpendicular path. However, any redirection mechanism could be employed for this purpose.
In addition to the foregoing, the discharge tube 250 is provided with a plurality of flutes or ribs 268 on its exterior surface. This enables some cooling to take place from the discharge tube.
In the preferred embodiment of the present invention, one of the mirrors 252 is a total reflecting mirror and the other of the mirrors 252 is a partially transparent mirror. The mirror close to the bean redirecting mechanism 262 is the partially transparent mirror, as shown in FIG. 20. The mirrors preferably are formed of silicon with a highly reflective coating, such as molybdenum and copper. Due to the fact that the gain is high in its carbon dioxide layer, the beam transmitted is higher than in the lower gain lasers, such as helium-neon.
The laser generated light unit is highly effective in that it can be packaged in a small compact unit and literally worn on a belt of a mother. This type of laser has been found to operate at room temperature and can function well in moderately clean environments. They are compact and the heads on the laser tube are only about one kilogram in weight. This type of laser light source is highly durable and generally fail proof in operation.
In order to achieve compactness, the discharge tube 250 could be constructed with a folded optic arrangement, as schematically shown in FIG. 21 of the drawings. In this case, an outer housing 280 is provided with longitudinal baffles 282 located therein. The baffles create a plurality of individual channels 284, including an upper channel and a lower channel, as shown. The mirror arrangements 286 are located at each of the ends of the channels, as shown. In this case, each mirror arrangement comprises a first mirror 288 located at approximately a 45° angle with respect to the light beam and which receives the light beam. A second mirror 290 receives the beam from the mirror 288 and is reflected to a generally reflecting mirror 292 to again redirect the light beam in a generally columnar path in the individual channels 284.
A generally first reflecting mirror 298 is located at one end of the upper channel and a partially reflecting and partially transparent mirror 294 is located adjacent the lower channel 284, as best shown in FIG. 21. The remaining construction of the laser, as shown in FIG. 21, is similar to that shown in FIG. 18. Again, it should be recognized that the outer housing 280 would also be provided with cooling fins or the like.
The control unit 44 is connected to a battery 48, through conductors 50, as also shown in FIGS. 6-8 of the drawings. In this way, electrical power is provided to the control unit 44 and hence, to the individual light sources 40. The control unit 44 is removably located within a suitable pocket 52 formed on the exterior surface of the belt, as best shown in FIGS. 7 and 8 of the drawings. In like manner, the conventional battery 48 is located within a pocket 54 also formed on the exterior of the belt 14, in the manner as shown in FIGS. 7 and 8 of the drawings. Preferably, the pocket 54 is closely located with respect to the pocket 52 so that conductors 50 extending between the battery 48 and the control unit 44 are relatively short in length. In accordance with the above-identified construction, both the control unit 44 and the battery 48 can be removed periodically for maintenance, recharging or for cleaning.
The battery 48 may be of a rechargeable type and for this purpose, it may be necessary to remove the battery 48 from the pocket 54. In like manner, the batteries may be replaceable batteries. If the batteries employed are small-sized dry cell batteries, then a casing inside the pocket 54 would be provided with an exterior plug for connection to the control unit 44. The conductors 50 are external conductors in the manner as shown. However, it should be understood that these conductors could extend within the belt and terminate with connectors inside of the respective pockets 52 and 54. The conductors 42 which exit the belt for connection to the control unit 44 are shown as being partially external. In like manner, they could exit the belt at the interior of the pocket 52 and also be provided with connectors for connection to the control unit 44.
As indicated previously, the various conductors could terminate inside of the pockets 52 and 54. In the same way, all conductors could have terminal connectors located within the pockets so that there are, in effect, no electrical conductors extending externally of the belt. In this way, the belt would provide a clean and attractive appearance and avoid the cumbersome problem of dealing with externally extending wires.
In the invention as illustrated thus far, the lights 40 have been shown as being mounted in a different belt than the sound generator and the speakers. In some embodiments of the invention, the lights may be provided without the speakers and sound generator and for this reason, have been illustrated in a separate belt. However, and in such cases, the sound generating system may be coupled with other sensory effects and, for that matter, the lights may be coupled with other sensory effects. Further, and more preferred embodiments, the lights will be included within the same belt as the sound generating equipment.
Also mounted in a pocket on the interior surface of the belt 14 is a sensor 64 which functions as a stethoscope sensor. Here again, the stethoscope sensor 64 is located close to the interior surface so that it is also disposed in juxtaposed relation to the wall of the abdomen of the mother. Further, a conductor 66 extends from the sensor 64 through the plies forming the belt 14 and terminates in a socket 68, as shown. The present invention provides a conventional stethoscope headset 70 for the mother to place in a position where the earpieces 72 are disposed in the ears of the mother. A cable 74 extends from the headset 70 and terminates in a plug 76 which is adapted for detachable connection to the socket 68.
In accordance with the above-identified construction, it can be observed that a user of this system can insert the earpieces 72 of the stethoscope 64 in her ear and connect the plug 76 to the socket 68. In this way, the headset 70 will be in sound conductive relationship with the stethoscope sensor 64.
When the mother desires to monitor the effect of sensory excitations, such as sound or light, on the fetal child, the mother can listen to the sounds from the abdomen itself. In this case, the mother may readily hear the heartbeat of the fetal child or otherwise, any physical activity such as kicking and the like. The mother is then in an excellent position to determine the effect of one type of light effect or sound effect upon the fetal child, compared to others. Thus, the mother can obtain that sound or light or other audio effects which are most soothing or enjoyable to the fetal child.
The embodiment of the system which utilizes sound is effective and relatively inexpensive, since it can use a conventional sound generator 34 and a conventional associated stethoscope arrangement as described in the aforesaid co-pending patent application. The embodiment of the invention which utilizes light is also highly effective and relative inexpensive, since it may also use conventional light sources and conventional batteries. The control unit 44 is generally made of conventional components, since off/on switches are well known and available as are sequencers and other elements which may be used to control the light. Consequently, there is no need to engage in expensive or elaborate modification of existing components. The systems, as described herein, are highly effective and achieve the desired results.
FIG. 9 illustrates an embodiment of the invention which uses a small electrical amplification system 80 for amplifying or otherwise attenuating the sounds generated by the stethoscope sensor. In this case, a stethoscope sensor 82, substantially identical to the previously described sensor 64, is mounted on the belt in substantially in the same position as the sensor 64. The output of the sensor 64 is introduced into a pizzo-electric crystal 84 for converting into an equivalent electrical signal. This electrical signal is then introduced into an operational amplifier 86 where the signal is amplified. In this respect, it should be understood that filters could also be employed for otherwise enhancing the sounds generated by the stethoscope sensor, if desired.
The output of the amplifier 86 is again introduced into another pizzo-electric crystal 88 for conversion back into sound. In this case, the output of the crystal 88, or similar electrical-sound converter, is connected to a coupling 90. The coupling 90 receives a plug 92 and which is connected through a sound tube 94 to a stethoscope headset 96. Thus, amplified sound is delivered directly to the stethoscope headset 96.
The sound amplification system, as illustrated in FIG. 9, is relatively simple, but is effective in amplifying the sounds of the fetus so that they can be more readily understood and heard by a mother who is relatively unexperienced with stethoscope sounds. The amplification system can be in the form of a small chip which can be mounted directly to the belt or otherwise, it can be included in a small compact unit which is affixed to the belt or retained in a pocket on the belt.
FIGS. 10 and 11 illustrate an embodiment of the invention which utilizes vibrators. In this case, conventional vibrators 100, such as the type used in hand-held vibration devices are mounted in the belt 14, as shown. The vibrator includes an outer plate 102 which is disposed against the abdomen wall of the mother, as well as motorized vibration generating mechanism, including a coil 104. The coil is connected through a pair of electrical conductors 106 to a battery source of power, such as the battery 48. In FIG. 10, a motor 110 is mounted on the exterior face of the belt 14 for operating the plate 102 of the vibrator. In this case, the motor 110 would be connected across the conductors 106, as shown. The vibrators, such as the vibrators 100, would also be connected to a control unit, such as the control unit 44. In this case, the control unit 44 would control the intensity of the vibration or the frequency of the vibration. Furthermore, the control unit 44 could be provided with individual controls to selective control any one or more of the individual vibrators.
FIG. 12 illustrates an embodiment in which magnets 120 may be mounted on the belt in place of the light sources 40 or in addition to the light sources. In this case, the magnets could be permanent magnets, although for purposes of control by the mother, they are preferably electromagnets. Since electromagnets are well known in the art, the operation of the electromagnets, per se, is not described in any further detail herein.
The electromagnets 120 are connected across a pair of conductors 122, as shown and which are in turn connected to a control unit 124. The control unit 124 could individually control the selected magnets which are to be energized or, for that matter, the intensity of the magnetic field which is generated. For this purpose, and when the magnets are electromagnets, a battery source of power 126, similar to the previously-described battery source of power 48, may be employed. The battery source of power 126 is connected to the control until 124 through conventional conductors 128.
If desired, and in order to create a magnetic field entirely across the abdomen of the mother, a metal plate 130 could be disposed behind the mother. This metal plate could be formed in the belt itself so as to couple magnetically with the magnets across the mother.
FIGS. 13 and 14 illustrate an embodiment of the invention in which heating plates 134 and 136 may be mounted within the belt 14, as shown. In FIG. 13, the plate 134 is located at the rear of the belt and in this case, is preferably designed to provide heat for purposes of relieving some of the back pain and tension encountered by the mother during the pregnancy. The forward heating plate 136 is either provided for the benefit of the mother or for the fetus, or both. In the embodiment as shown in FIG. 13, a pair of individual heating plates 136' and 136" are shown. It can be seen that these heating plates are mounted directly within the belt itself, and may extend to the surface of the belt. However, it is preferable to mount the heating plates in the belt with only a thin film of the leather, or other material forming the belt, extending over the heating plate to prevent direct contact of the heating plate with the skin of the mother. In this way, overheating or even burning to the mother's skin could be avoided.
Again, as with the other forms of sensory excitation, a heating unit is connected directly to a control unit 138 mounted within a pocket 140 retained on the belt. Again, for battery source of power, the control unit is connected to a battery 142 retained in a pocket 144 also mounted on the belt.
It should be understood that the light, sound, magnetic fields, vibration and heat are only some of the forms of sensory excitation which can be imparted to a fetus. Other forms could also be employed and with the proper transducer mounted directly on the belt 14. However, in all cases, the system of the invention is highly effective in that it allows the mother to easily monitor the effects of the sensory excitations on the fetus.
FIG. 15 illustrates an embodiment showing the belt 14 with speakers 30, lights 40 and vibrators 100 mounted within the belt, as shown. In addition, heating elements 136 are also shown as being mounted in the belt. In this embodiment, positional relationship of each of these aforesaid components for causing sensory excitation is actually shown where they may be mounted.
Also in the embodiment of the invention, as shown in FIG. 15, there is a single control unit 150 mounted within a pocket 152. The components are operated through the control unit utilizing power from a battery 154 also contained in a pocket 156 mounted on the battery. In this case, it can be seen that the control unit 150 is located at the side of the user and the battery pack could be moved slightly toward the back where it is somewhat in an out-of-the-way position.
These various components are relatively simple and utilize electrical conductors which are trained through the interior of the belt itself. Referring to FIG. 16, it can be seen that the speakers 30 are electrically connected by conductors 156 directly to a sound generator 158, such as a radio or tape player, or the like. The stethoscope sensor 64 is connected directly to the stethoscope tube, 66 as shown. The vibrators 100 and the lights 40 are both connected to a common pair of electrical conductors 160. These conductors are connected directly to the control unit 150 which is again, in turn, connected to the battery source of power 154, as shown. Thus, a simple pair of electrical conductors trained through the belt can operate the vibrators and lights, if both are employed. A separate pair of conductors trained through the belt will be connected to the sound generating unit. In like manner, if heating elements are employed, they could also be connected across the conductors 160. The same holds true of electromagnets and the like.
The actual belt may be provided with only a pair of pockets, one for the battery and one for the control unit, or it might be provided with a plurality of other pockets for holding additional control units or other equipment. The belt itself could also be constructed with a plurality of spaces for the addition of sensory excitation components. Thus, the user of the belt system could purchase an individual belt or harness arrangement and thereafter, at will, select additional components for use. The belt itself may be normally provided with internal conductors having leads terminating at pockets where the various sensory excitation transducers would be used. Thus, it would be a relatively simple procedure to install additional transducers if desired, or the additional equipment used to operate the transducers.
Also shown in FIG. 16 is an additional transducer 161 which is capable of monitoring another activity of the fetus, as for example, heart rate activity. Thus, the transducer 161 could function as a heart rate monitor. In this case, the transducer could also be connected across the conductors 160 if needed. A small chip which primarily functions as an amplifier 162 is connected to the transducer 161 and has an output conductor 164 connected to a jack terminal 166. In this way, the jack terminal 166 could be connected to a modem for transmitting fetal information directly to a physician or other attendant.
FIG. 17 illustrates one form of belt construction which may be used in the present invention. In this embodiment, the belt 14 is comprised of a pair of plies 170 and 172. Ply 170 is of a thicker cross-sectional construction than the ply 172 and is provided along a portion of its length with an interior cavity 174. This cavity is also provided with openings 176 to receive, for example, the speakers 30 and cavities 180 to receive the lights 40. It can be seen that the conductors, such as the electrical conductors 156, are trained right through the cavity 174. In like manner, the electrical conductors, such as the conductors 160 for operating lights and other equipment, are also located right in the cavity. In this way, simple cutout openings can be used to receive the transducers and with the conductors laid directly in the cavity 170. The second ply 172 can thereafter be secured to the interiorly presented face 182 of the ply 170.
In some cases the ply 172 can be releasably attached to the ply 170 so that the belt can be opened for the insertion of additional transducers or like equipment, or additional conductors In other cases, the plies could be permanently secured with conductors already laid in the cavity 174 and provided with terminal ends which can be grasped at the openings for connection to additional transducers.
As indicated previously, the system of the present invention also is capable of providing a sensory feedback and other types of feedback. In connection with the embodiment of the invention, as illustrated in FIG. 17, there was provided a built-in transducer 161 of the type which could function as a heart rate monitor and which had ultimately terminated with a jack terminal 166 for transmitting information via a modem.
FIG. 23 illustrates an embodiment of the invention utilizing the belt 14 and which also employs a transducer 190 connected to the belt through a conductor 192. In this case, the transducer 190 may be mounted on the belt or removably located in a pocket located within the belt but is removable therefrom. Thus, the transducer 190 could be located at various positions on the mother's abdomen in order to obtain fetal information or, for that matter, information about the mother.
The transducer 190 could adopt various forms as, for example, one which is capable of detecting acoustic information and immediately converting it into electrical signal form. Otherwise, the transducer 190 may be used as an acoustic transducer as, for example, in ultrasonic measurement and used for transmitting the acoustic information. Thus, the mother could obtain ultrasonic information about the fetus and ultimately transmit that information to a doctor or other practitioner who is capable of analyzing the information.
In FIG. 23, the cable 192 is shown as being extended through the belt 14 in the interior thereof as, for example, at reference numeral 194. This conductor is then connected to a suitable signal processing unit 196 located in a pocket 198 formed on the belt 14. Another conductor 200 terminating in a jack 202 for connection to a modem would be used for ultimately transmitting the measured information.
FIG. 24 illustrates an embodiment of the invention in which the transducer is capable of measuring data in acoustic format. For this purpose, the transducer 190 may adopt the form of an ultrasonic transducer. The cable 192 would also adopt the form of a cable capable of transmitting acoustic information as, for example, the type of cable used in a stethoscope. This sonic or ultrasonic information is then introduced into a filter 204 for filtering any extraneous signal or information which might have been detected during measurement.
The information, measured by the transducer 190, can be acoustically transmitted over a telephone link 206 comprised of a transmitting telephone 208 and a receiving telephone 210 via a telephone line 212. The information at the receiving telephone 210 is then ultimately converted by means of a suitable converter 214 into electrical format, much in the same manner as ultrasonic information is converted into an equivalent digital electrical format. This information is then capable of being stored in a computer 216 for processing or storage or display through a computer terminal 218.
The ultrasonic information which would normally be contained in a physician's office or in a hospital environment can be obtained directly from the mother and automatically processed for transmission via a telephone link to a physician's office or other attendant who would examine the received data. Thus, the belt of the present invention can become a much more sophisticated device for not only generating sensory effects for delivery to a fetus, but can also be used for measuring information about the fetus or about the mother and transmitting same for ultimate examination by an expert capable of analyzing the information.
FIG. 25 illustrates an embodiment of the invention in which information from the transducer 190 is used in electrical form. Thus, if the transducer 190 were capable of measuring data and providing an electrical signal representative of that data or, otherwise, provided with means for converting the data, that electrical data would first be amplified in an amplifier 224, as shown in FIG. 20 and thereafter transmitted to a conventional signal processing unit 226. The signal processing unit 226 can adopt a variety of forms, depending upon the actual type of signal which is to be processed and the required processing. For example, the signal may be in a wave form pattern which is to be rectified and consequently, the signal processing unit 226 would contain a suitable rectifier or the like. The signal processing unit may also include wave form clipping or the like.
The information from the signal processing unit 226 could be delivered to a modem 228 for transmission via a telephone link 230 comprised of a transmitting telephone 232, a receiving telephone 234 and a telephone line 236. Otherwise, a computer, or at least a signal display unit 238, may be interposed between the signal processing unit 226 and the modem 228. In this case, the computer 238 is shown as being provided with a display 240. Thus, the mother or other party at the location of the mother can also examine the data which is to be transmitted via the telephone link 230 by their own monitor 240.
The information which is transmitted from the modem 238 across the telephone link 230 would then be received by a remote modem 242 and then ultimately introduced into the storage of a computer 244. In this case, the computer 244 would similarly operate as a means for displaying the information on a computer display 246, or further processing the data or merely storing same.
In either of the aforesaid embodiments, as illustrated in FIGS. 24 and 25, it can be observed that the system of the present invention is also highly effective in measuring information about either the fetus or the mother, or both, and transmitting that information to a location where the information is to be analyzed. Consequently, and as indicated previously, the harness system, and particularly the belt 14, is not limited to mere generation of sensory excitation for delivery to a fetus or to a mother. The belt can also be used solely for the purpose of measuring and transmitting information, or may be used as a combination of both generating sensory excitation for the mother or fetus, or both, and for measuring data and transmitting the same.
Thus, there has been illustrated and described a unique and novel system for generating sensory excitations which can be imparted to a fetal child through a mother's abdomen and which thereby fulfills all of the objects and advantages which have been sought. It should be understood that many changes, modifications, variations and other uses and applications will become apparent to those skilled in the art after considering this specification and the accompanying drawings. Therefore, any and all such changes, modifications, variations and other uses and applications which do not depart form the spirit and scope of the invention are deemed to be covered by the invention.
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A system for generating and delivering various types of sensory effects to a fetus or so-called "fetal child" through a mother's abdomen and simultaneously allowing for the monitoring of the effects on the fetus. In a preferred embodiment, the system relies upon the generation of light of various intensities, wavelengths or color to provide certain types of stimulation to the fetus. Vibrations or magnetic effects can also be transmitted across the abdomen wall of the mother to the fetus. The system utilizes a belt which is worn about the abdomen of the mother and includes transducers located in the region of the fetal child for imparting the desired sensory effect. A stethoscope or like device can be mounted in and carried by the belt and is designed for juxtaposition to the abdomen and in proximity to the fetus. The stethoscope head piece can be worn by the mother to determine the effects of the stimulus on the fetus.
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BACKGROUND OF THE INVENTION
[0001] This invention relates forming elements or parts and, more particularly, to a method of removing power from parts formed by electron beam melting.
[0002] Powder bed fusion (PBF) methods use either a laser or electron beam to melt and fuse material powder together. Electron beam melting (EBM) is a particular example of a PDF method and is a type of additive manufacturing (AM) for metal parts. In particular, it is a powder bed fusion technique process where an electron beam is used to melting metal powder layer by layer in a vacuum to form a product. One unique aspect of EBM additive manufacturing is that non-melted particles, i.e. those particles not utilized in the final part, are sintered together. The sintering process binds the non-melted particles together providing additional mechanical strength during the build process. The sintered particle is very difficult to remove from more complex structures, particularly those that contain internal features such passages or blind holes. Another type of PDF utilizes a laser. Powder is not sintered but complex geometries may still exist that include powder.
BRIEF DESCRIPTION OF THE INVENTION
[0003] According to one aspect of the invention, a method for forming a part is disclosed. The method includes: forming a first portion of the part at a first level; forming a second portion of the part at a second level; wherein forming the first and second portions includes exposing the first and second levels to a sintering process and portions of the first and second levels to an electron beam; forming a wire in the passage formed inside the first and second portions by exposing a portion of the passage to the electron beam; applying a signal to the wire to break up sintered material in the passage; and removing the wire.
[0004] According to some aspects of the invention, a method for forming a part includes: forming a first portion of the part at a first level; forming a second portion of the part at a second level; wherein the first and second portions are formed by exposing, respectively, by exposing some of the first level and some of the second level to a laser beam; forming a wire in the passage formed inside the first and second portions by exposing a portion of the passage to the laser beam; applying a signal to the wire to break up sintered material in the passage; and removing the wire.
BRIEF DESCRIPTION OF THE DRAWINGS
[0005] The subject matter which is regarded as the invention is particularly pointed out and distinctly claimed in the claims at the conclusion of the specification. The foregoing and other features, and advantages of the invention are apparent from the following detailed description taken in conjunction with the accompanying drawings in which:
[0006] FIG. 1 is a cut-away side view of a part including powder and a removal wire;
[0007] FIG. 2 is a top view of the part of FIG. 1 taken along line A-A;
[0008] FIG. 3 depicts one example of a passage with multiple wires formed therein;
[0009] FIG. 4 depicts another embodiment of a wire including a cleaning attachment;
[0010] FIG. 5 shows an alternative embodiment that includes multiple wires and cleaning elements in combination; and
[0011] FIG. 6 is a flow chart of one method of removing powder.
DETAILED DESCRIPTION OF THE INVENTION
[0012] As briefly described above, it is very difficult to remove the dense, sintered powder after completion of the build. Parts with internal features such as passages within a housing have to be specially processed in order to remove dense powder. Powder removal is a step that, for complex parts, will add cost to an additively built part. Embodiments disclosed herein may provide a more efficient or economical solution to removing the dense power.
[0013] The methods disclosed herein may expedite and minimize the amount of time required for powder removal from PBF (including EBM and laser PBF) manufactured parts. In one embodiment, the removal element is formed as a portion of the part itself, used to remove the powder and then discarded. The methods disclosed herein may be especially useful in removing hardened powered in internal surfaces of a part.
[0014] FIG. 1 is an example of part 100 that is formed by PBF shown in a cut-away side view. While the following describes an EBM process, the removal methods are applicable to all PBF created pieces where powder needs to be removed from internal passages. The part 100 includes first and second portions 102 , 104 separated by an internal passage 106 . As the part 100 is formed, metallic power is first layered down and then sintered. The portions of the part 100 that are to become part of the final product are then exposed to an electron beam to convert the sintered powder to a hard metal object. However, the portions of the part that are not exposed to the electron beam are still sintered, just not fully hardened by the electron beam.
[0015] In the example in FIG. 1 , the passage 106 may be filled with sintered material 108 . That is, the portions 102 , 104 are metal pieces formed by exposing the sintered powder to an electron beam to form the fully hardened metal. Portions that are not exposed remain as partially hardened sintered material as illustrated by sintered material 108 . Removal of this material to open, for example, passage 106 may be difficult, especially when the passage is not a straight or varies in size. According to one embodiment, as the part 100 is being formed, a wire 110 is formed through the passage 106 . The wire 110 is formed in the same manner as the portions 102 , 104 . That is, as each level of the part 100 is formed, a small portion of the otherwise sintered only section (e.g., material 108 ) is exposed to the electron beam to form a continuous wire 110 through it.
[0016] FIG. 2 shows a top view of the part taken along line A-A from FIG. 1 . The portions 102 , 104 have been exposed to the electron beam to fully harden them. So too has the wire 110 . Thus, portions 102 , 104 and wire 110 are in the same state of processing and are fully hardened metal. The passage 106 is shown as including sintered material 108 that has not been exposed to an electron beam. This is the material that needs to be removed in order to allow material to pass through passage 106 . For example, if the part 100 is a manifold, passage 106 would need material 108 removed in order to allow fluids to pass through it.
[0017] With reference to both FIGS. 1 and 2 , in one embodiment, the wire 110 may be coupled to a transducer 112 . The transducer 112 is an ultrasonic transducer in one embodiment. In one embodiment, the transducer 112 provides an ultrasonic input to the wire 100 which causes the sintered material 110 to more easily be removed.
[0018] FIG. 3 shows an alternative embodiment. Again, a passage 106 is formed that includes sintered material (not shown). Portions of sintered material are exposed to form multiple sinusoidal wires 110 a, 110 b, 110 c. The number of wires can be varied from 1 to any number and the wires can be either straight or sinusoidal. Using sinusoidal wire shapes may allow for more ultrasonic energy from the transducer 112 to be contact the sintered material in the passage 106 . Further, as the wires 110 are pulled out (for example, in direction C) the increased surface area of additional wires may remove more powder.
[0019] FIG. 4 shows yet another embodiment. In this embodiment, the passage 106 is formed to include wire 110 a cleaning element 120 . The cleaning element 120 is formed of the same material as the wire in one embodiment. As the wire 100 is removed (direction C) the cleaning element 120 may aid in powder removal. The particular shape of the cleaning element 120 may be varied from that shown in FIG. 4 . Also, more cleaning elements 120 may be provided. In general, the cleaning element 120 has a larger cross-section than the wire 110 . In another embodiment, one or more optional additional cleaning elements 140 may be added to the wire 110 . One or more of the additional elements 140 may be of a different size or shape than cleaning element 120 .
[0020] In yet another embodiment, nested cleaning elements 220 may be provided. Each element (e.g., 220 a, 220 b ) may be attached to an individual wire 110 a, 110 b, respectively. As illustrated, a first cleaning element 220 a is attached to a first wire 110 a and a second cleaning element 220 b is attached to a second cleaning element 220 b. In this configuration, the first wire 110 a passes through a hole or other passage way (e.g., notch 240 ) formed in the second cleaning element 220 b. This allows the second cleaning element 220 b to be removed before the first cleaning element 220 a. In this manner, a first amount of powder may be removed and then a second amount (assuming that the second cleaning element 220 b is smaller than the first cleaning element 220 a ). In on embodiment, the wires 110 a. 110 b may run through different channels to allow them both to work in the illustrated channel 106 and then to work in different channels as they are removed.
[0021] FIG. 6 shows a method according to one embodiment. The method includes several optional steps that may or may not be needed depending on the particular wire/cleaning element combination chosen.
[0022] At block 600 a plan for part is received. The plan may, for example, be a representation of the part or it may be CAD model of the part. One or more wires are added to the plan at block 602 . The added wires are added such that they will be formed in an interior passage(s) of the part. At block 604 optional cleaning elements are added to the plan. At block 606 the part, including the wire(s)/optional cleaning element(s), is formed. The part and the wires are formed using electron beam manufacturing as described above. At block 608 a signal is applied to the wires. This signal causes sintered powder to break up or otherwise become easier to remove. The signal is an ultrasonic signal in one embodiment. At block 610 the wire (or wires) is removed.
[0023] While the invention has been described in detail in connection with only a limited number of embodiments, it should be readily understood that the invention is not limited to such disclosed embodiments. Rather, the invention can be modified to incorporate any number of variations, alterations, substitutions or equivalent arrangements not heretofore described, but which are commensurate with the spirit and scope of the invention. Additionally, while various embodiments of the invention have been described, it is to be understood that aspects of the invention may include only some of the described embodiments. Accordingly, the invention is not to be seen as limited by the foregoing description, but is only limited by the scope of the appended claims.
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A method for forming a part. The method includes: forming a first portion of the part at a first level; forming a second portion of the part at a second level; wherein forming the first and second portions includes exposing the first and second levels to a sintering process and portions of the first and second levels to an electron beam; forming a wire in the passage formed inside the first and second portions by exposing a portion of the passage to the electron beam; applying a signal to the wire to break up sintered material in the passage; and removing the wire.
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CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] The present application claims priority to U.S. Ser. No. 61/153,079, filed Feb. 17, 2006, herein incorporated by reference in their entirety.
FIELD OF THE INVENTION
[0002] The present invention relates to the use of Granulocyte Colony Stimulating Factor (G-CSF) polypeptide in the prevention of neuronal cell death in the infarct penumbra after acute stroke. More particularly, the invention provides methods of enhancing the therapeutic window for thrombolytic treatment after acute stroke by the preceding administration of G-CSF polypeptide in conjunction with a subsequent thrombolytic therapy.
BACKGROUND OF THE INVENTION
[0003] Granulocyte colony stimulating factor (G-CSF) was originally identified as a hematopoietic factor in the myeloid lineage responsible for the generation of neutrophilic granulocytes. Recently, the presence and activity of this factor in the central nervous system was identified G-CSF and its receptor are up-regulated after cerebral ischemia, G-CSF acts anti-apoptotically on neurons, passes the intact blood-brain barrier, and reduces infarct size in experimental stroke models (Schneider et al., J Clin Invest. 2005, 115:2083; Zhao et al., Exp Neurol. 2007, 204:569; Schabitz et al., Stroke 2003, 34:745; Six et al., Eur J Pharmacol. 2003, 458:327; Shyu et al., Circulation 2004, 110:1847; Gibson et al., 2005, 25:431; Komine-Kobayashi et al., J Cereb Blood Flow Metab. 2006, 26:402; Schneider et al., BMC Biol. 2006, 4:36). This has led to a number of smaller clinical trials in acute ischemic stroke patients (reviewed in Schabitz et al., Stroke 2006, 37:1654; Schabitz et al., Trends Pharmacol Sci. 2007, 28:157). However, although meta-analysis of published data supports the broad basis for efficacy of this factor in experimental stroke models (Minnerup et al., Stroke 2008, 39:1856), the majority of experiments were done using transient ischemic models. In particular, no published data exist on embolic models.
[0004] Thrombolysis with recombinant tissue plasminogen activator (rt-PA) remains the only approved acute stroke therapy until now. Unfortunately, the use of rt-PA is limited by a relatively narrow time window. Efficacy was recently demonstrated up to 4.5 h following onset of stroke symptoms, but efficacy decline rapidly over time (Hacke et al., Lancet 2004, 363:768; Hacke et al., N Engl J Med. 2008, 359:1317). The biological reason for the reduced therapeutic efficiency over time likely lies in the progressing deterioration of cell viability with ongoing ischemia/hypoxia in hypoperfused brain areas. This may be paired with generation of free radicals during reperfusion (i.e., reperfusion injury). Clinically, this concept is supported by data that suggest that the presence of a perfusion/diffusion (PWI/DWI) mismatch on MRI identifies patients where thrombolysis may be efficacious later in the therapeutic time window (Fisher et al. Cerebrovasc Dis. 2006, 21 Suppl 2:64).
[0005] A strategy to extend the time window for thrombolysis may be to protect tissue at risk identified as the PWI/DWI mismatch region. Proof-of-concept for this hypothesis has been demonstrated with normobaric hyperoxia treatment (Henninger et al. J Cerb Blood Flow Metab. 2007, 27:1632) and stimulation of the sphenopalatine ganglion (Henninger and Fisher Stroke 2007, 38:2779).
BRIEF SUMMARY OF THE INVENTION
[0006] Cerebral infarcts caused by stroke comprise the infarct core (already irreversibly injured tissue) and the penumbra (tissue at risk but still salvageable). Thrombolysis, particularly with tissue plasminogen activator (t-PA), is known as an effective treatment of acute ischemic stroke but only if therapy is initiated within a short time period (therapeutic window) after the onset of stroke. The volume of salvageable penumbra tissues decreases strongly continuously over timewithin the first hours of cerebral ischemia. Thereafter, the thrombolytic establishment of reperfusion is ineffective in preventing further neuronal cell death and ameliorating the clinical outcome or is even harmful. t-PA has to be administered within the first 4.5 h preferably 3 h, after stroke onset, whereas this time period is sometimes extended up to a total of 6 h by the physicians.
[0007] For this reason, early thrombolytic intervention is usually desired. On the other hand however, thrombolytic intervention may have severe hemorrhagic adverse side effects which worsen the clinical outcome of the stroke patient. Therefore, thrombolytic treatment requires neuroimaging to exclude a hemorrhage and assessment of basic coagulation parameters prior to administration of the thrombolytic agent. During that time however, neuronal cell death in the infarct penumbra continues and the therapeutic window for thrombolysis might close.
[0008] There is a need for a method or an agent capable to halt the neuronal cell death in the penumbra (“penumbra freezing”) soon after the onset of the stroke and, thereby, extending the therapeutic window for later thrombolytic treatment which allows for the necessary careful diagnostic examinations and treatment decisions.
[0009] The inventors found that G-CSF when administered in a stroke model is capable to preserve the penumbra region and, thereby, prevent further extension of the infarct size. It is well accepted in the art that the extent of preserved penumbra tissue is crucial for the beneficial effect of a thrombolytic reperfusion. Since G-CSF is safe in acute ischemic stroke patients, and at least in animal models there is no indication that it might cause intracerebral hemorrhage, or increase the risk of systemic bleeding, it can be administrated to the stroke patient immediately with the begin of the intensive care and without extensive prior diagnostic examinations and even before admission in or transport to the hospital given by paramedicals or other qualified health professionals. G-CSF can be considered as an emergency drug that could be given in the ambulance to prolong the time-window for, and possibly improve outcome after thrombolysis, e.g by t-PA.
[0010] The present invention relates to the use of G-CSF for extending the therapeutic window of subsequent thrombolytic treatment of acute stroke, allowing the necessary pre-thrombolysis diagnostic examinations.
[0011] One aspect are methods of treating a patient suffering from acute stroke, comprising initial G-CSF administration, followed by diagnostic examinations, whereas said examinations allows the decision if a thrombolytic therapy is suitable to the patient, and, optionally, based on the results of the diagnostic examination, followed by a thrombolytic treatment. Such diagnostic examinations can be e.g. the exclusion of a hemorrhagic stroke, which is a contra-indication for a thrombolytic therapy.
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIG. 1 : Infarct volume at 24 h after induction of an embolic ischemia by single clot injection. Shown are edema corrected volumes obtained from TTC-stained sections. Rats were treated with G-CSF at 1 h post clot injection (intravenously) and 4 h post clot injection (intraperitoneal), 120 μg/kg body weight each. G-CSF treatment resulted in significantly smaller infarcts compared to the vehicle group (p<0.05).
[0013] FIG. 2 : Spatiotemporal evolution of diffusion-weighted lesion within sMCAO model. Rats were subjected to permanent filament occlusion of the MCA, and monitored for 3 h after occlusion for the evolution of the diffusion-weighted lesion. G-CSF orvehicle solution were given at 60 min and at 4 h after occlusion onset. The 60 min dose was started before image acquisition at the 60 min time point. There were no statistical between- or within-group differences in CBF deficit. CBF was significantly larger than ADC at all time points except for 120 and 180 min in the vehicle group. The G-CSF group showed significantly smaller ADC volumes than the vehicle group starting at 90 min. Final infarct volume was also significantly smaller in the G-CSF group compared to the vehicle group (p=0.007). Shown are means+/−SEM; *: p<0.05; PWI volume (A), DWI and final infarct (B), absolute (C) and relative mismatch (D).
[0014] FIG. 3 : Alignment of G-CSF peptide sequences of various species (human (SEQ ID NO: 6), mouse (SEQ ID NO: 11), rat (SEQ ID NO: 12), feline (SEQ ID NO: 13), bovine (SEQ ID NO: 14), and pig (SEQ ID NO: 15)) shows the position of strongly and less conserved amino acids. Evolutionary strongly conserved amino acids are generally thought to be of major importance for the structure and function of the protein.
DETAILED DESCRIPTION OF THE INVENTION
[0015] The inventors describe a finding that makes G-CSF ideally suited as a time-window extender in stroke treatment for any further therapy, preferably, thrombolytic stroke therapy (e.g. with rt-PA).
[0016] This is a very useful application, as a major issue that limits the usefulness of thrombolytic stroke therapy, e.g. rt-PA therapy is the limited time window due to loss of efficacy with time. rt-PA has to be administered usually during the initial 3 to 4.5 h after onset of the stroke based on clinical studies. Occasionally, it might be given by some physicians within up to 6 h. Since the possibility of hemorrhagic side effects of rt-PA has to be excluded for the individual patient to avoid worsening of the situation, it is often difficult to enable a safe thrombolytic therapy during this time-window. G-CSF could be given very soon after the suspicion of a cerebral insult has occurred, as it does not complicate a possible hemorrhagic stroke and as it is well-tolerated even in high doses.
[0017] The finding relates to the fact that in an animal model of stroke, permanent filament occlusion, G-CSF keeps the diffusion-weighted deficit stable in the presence of an ongoing ischemia. Such an effect is also known as “penumbra freezing”. This means that damage to brain tissue can be delayed until a thrombolytic therapy can be applied to reopen the occluded vessels. In the cases where G-CSF alone might be not sufficient to enable complete recovery from the stroke, the unexpected finding according to the invention enables a combinational or consecutive therapy comprising an initial step of G-CSF administration to the subject and a later step of administration of an thrombolytic agent, e.g. rt-PA. The earlier G-CSF administration allows for a postponed onset of thrombolytic therapy within the first several days, preferably within the first 24 h, more preferably within the first 12 h after onset of the stroke. This allows for a closer diagnostic examination of the patient after stroke or after suspicion of stroke to ensure a safe and effective additional thrombolytic therapy. The advantage of such a combination of an early G-CSF administration and a postponed thrombolytic therapy (e.g. rt-PA administration) is to the inventors knowledge not disclosed previously.
[0018] Unexpectedly, G-CSF was effective in preserving the penumbra tissue even during the time the vessel was occluded.
[0019] According to the invention, G-CSF administration is started during the first 12 h, preferably during the first 6 h, and more preferably during the first 3 h after onset of the stroke. Preferred uses of G-CSF could be up to a time window of 24 h in doses of at least 10 μg/kg body weight, at least 90 μg/kg body weight, or at least 130 μg/kg body weight given intravenously (i.v.) or subcutaneously (s.c.) over 1-24 h.
[0020] According to the invention, it is included that the administration of G-CSF may either be completed before the administration of the thrombolytic agent or may be continued after the administration of the thrombolytic agent. Furthermore, it is also included within the present invention that G-CSF may be administered only once. Alternatively, G-CSF may also be administered in at least two separate steps.
[0021] Preferably human recombinant G-CSF, such as Filgrastim, is used according to the invention. Also functional G-CSF derivatives which are know to the person skilled in the art can be used according to the invention.
[0022] The method according to the invention is suitable for the therapy of mammals, preferably of humans suffering from stroke or give reason to suspect a stroke.
[0023] As one aspect of the invention, a method is provided for treating stroke of a mammalian subject, comprising the steps (a) starting the administration of G-CSF or a functionally active G-CSF derivative in a therapeutically active amount to the subject, and subsequently (b) administering to the subject a thrombolytic agent in a therapeutically active amount.
[0024] As another aspect of the invention, a method is provided for treating stroke of a mammalian subject, comprising the steps (a) administering to a subject G-CSF or a functionally active G-CSF derivative in a therapeutically active amount, and subsequently (b) administering to the subject a thrombolytic agent in a therapeutically active amount.
[0025] The mammalian subject can be a human being.
[0026] As one embodiment of the invention, a method as mentioned above is provided, wherein the subject undergoes after step (a) and before step (b) a diagnostic examination to exclude the risk of hemorrhagic or other adverse side effects during step (b).
[0027] The “thrombolytic agent” of above mentioned step (b) is meant to refer to any agent capable of dissolving at least partially a fibrin-platelet clot. Examples of thrombolytic agents include streptokinase, prourokinase, urokinase, desmoteplase and tissue-type plasminogen activator (t-PA). Although natural t-PA may be employed, it is preferable to employ recombinant t-PA (rt-PA, e.g. Alteplase). The invention may additionally employ hybrids, physiologically active fragments or mutant forms of the above thrombolytic agents. The term “tissue-type plasminogen activator” as used herein is intended to include such hybrids, fragments and mutants, as well as both naturally derived and recombinantly derived tissue-type plasminogen activator.
[0028] As a further embodiment of the invention, a method as mentioned above is provided, wherein administration of said G-CSF or functionally active G-CSF derivative of step (a) starts within the first 6 h after onset of the stroke and/or administration of said thrombolytic agent of step (b) starts within the first 24 h after onset of the stroke or in the time period between 4.5 h and 24 h after onset of the stroke or between 6 h and 24 h after stroke.
[0029] As a still further embodiment of the invention, a method as mentioned above is provided, wherein G-CSF or functionally active G-CSF derivative of step (a) is administered to the subject within the first 6 h, the first 4.5 h, or the first 3 h after onset of the stroke and/or administration of said thrombolytic agent of step (b) starts within the first 24 h after onset of the stroke or in the time period between 4.5 h and 24 h after onset of the stroke or between 6 h and 24 h after stroke.
[0030] As one embodiment of the invention, a method as mentioned above is provided, wherein there is a time period of at least 0.5 h, at least 1.5 h, or at least 3 h between the administration, the start of the administration, or the end of the administration of G-CSF or functionally active G-CSF derivative of step (a) and the start of the administration of said thrombolytic agent of step (b). Preferably, this time period is used for diagnostic examination of the subject, assessing the risk of hemorrhagic or other adverse side effects of the thrombolytic therapy.
[0031] As a further aspect of the invention, a method is provided of treating a mammalian subject suffering from acute stroke, comprising an initial G-CSF administration or a start of a initial G-CSF administration, followed by diagnostic examinations, whereas said examinations assess the risk of a thrombolytic therapy for the subject, and, optionally, based on the results of the diagnostic examination, followed by a thrombolytic treatment. Such diagnostic examinations can be e.g. the exclusion of a hemorrhagic stroke, which is a counter-indication for a thrombolytic therapy.
[0032] As another embodiment of the invention, a method as mentioned above is provided, wherein said G-CSF of step (a) is given intravenously or subcutaneously in doses of at least 10 μg/kg body weight, at least 90 μg/kg body weight, or at least 130 μg/kg body weight.
[0033] As a further aspect of the invention, G-CSF or functionally active derivative thereof is provided for the preparation of a pharmaceutical composition for treating a mammalian subject suffering from acute stroke, wherein the subject is admitted to a stroke unit or a clinic within the initial 6 h after stroke onset or within the time period of 3 to 6 h after stroke onset or within the time period of 4.5 to 6 h after stroke onset, and wherein the expenditure of time for the diagnostic examination necessary to assess the subject's risk of hemorrhagic or other sever adverse side effects of a thrombolytic treatment would otherwise cause the expiration of the therapeutic window for thrombolytic treatment. The thrombolytic treatment in this context can be e.g. the administration of t-PA, such as rt-PA. The therapeutic window for thrombolytic treatment in this context can be within 3 h, within 4.5 h, or within 6 h after stroke onset. The diagnostic examination in this context can last at least 0.5 h, at least 1.5 h, or at least 3 h. The mammalian subject in this context can receive the G-CSF or functionally active derivative thereof immediately after admittance to the stroke unit or clinic, or within the first 6 h, within the first 4.5, or within the first 3 h after stroke onset. Further, the mammalian subject in this context can receive subsequently the thrombolytic treatment if the diagnostic examination permits such a treatment. The mammalian subject in this context can be a human being. The G-CSF in this context can be human G-CSF, preferably, Filgrastim.
[0034] The diagnostic examination of above described embodiments is meant to refer to any examination of the mammalian patient suffering from acute stroke which allows, improves, or supports the decision, whether a thrombolytic treatment, particularly thrombolytic treatment with t-PA, of the patient is indicated or contra-indicated. Such diagnostic examinations can be e.g., but without any claim of completeness: Medical imaging such as magnetic resonance imaging (MRI), analysis of blood parameters such as coagulation factors, or also survey of the patients anamnesis. Since patients suffering from acute stroke are frequently unconscious or confused, a survey of the patients anamnesis can be time consuming. Contraindications for thrombolytic treatment of acute stroke, particularly for t-PA treatment, which should be excluded by diagnostic examinations prior starting the treatment are e.g., but without any claim of completeness: Active internal bleeding, history of cerebrovascular accident, recent intracranial or intraspinal surgery or trauma, Intracranial neoplasm, arteriovenous malformation, or aneurysm, bleeding diathesis (including but not limited to current use of oral anticoagulants (e.g., warfarin sodium), an International Normalized Ratio (INR) >1.7, a prothrombin time (PT) >15 seconds, administration of heparin within 48 hours preceding the onset of stroke and elevated activated partial thromboplastin time (aPTT) at presentation, or platelet count <100,000/mm 3 ), uncontrolled hypertension at time of treatment (e.g., >185 mm Hg systolic or >110 mm Hg diastolic), intracranial hemorrhage, subarachnoid hemorrhage, recent (within 3 months) intracranial or intraspinal surgery, serious head trauma, previous stroke, history of intracranial hemorrhage, seizure at the onset of stroke
[0035] Granulocyte-colony stimulating factor (G-CSF) is a well known growth factor. The G-CSF that can be employed in the inventive methods described herein are human G-CSF (pro-form, short splice variant (SEQ ID NO: 2), mature form, short splice variant (SEQ ID NO: 4), pro-form, long splice variant (SEQ ID NO: 6), mature form, long splice variant (SEQ ID NO: 8), Filgrastim (SEQ ID NO: 10)) or various functional variants, muteins, and mimetics that are known and available. In the discussion that follows these are referred to as G-CSF derivatives.
[0036] Said G-CSF derivatives which can be employed in the present invention are proteins that are at least 70%, preferably at least 80%, more preferably at least 90% identical to human G-CSF amino acid sequences described herein. In another embodiment, the G-CSF that can be used are those that are encoded by polynucleotide sequence with at least 70%, preferably 80%, more preferably at least 90%, 95%, and 97% identity to the human G-CSF coding sequence (pro-form, short splice variant (SEQ ID NO: 1), mature form, short splice variant (SEQ ID NO: 3), pro-form, long splice variant (SEQ ID NO: 5), mature form, long splice variant (SEQ ID NO: 7), Filgrastim (SEQ ID NO: 9)), these polynucleotides will hybridize under stringent conditions to the coding polynucleotide sequence of the human G-CSF coding sequence. The terms “stringent conditions” or “stringent hybridization conditions” includes reference to conditions under which a polynucleotide will hybridize to its target sequence, to a detectably greater degree than other sequences (e.g., at least 2-fold over background). Stringent conditions will be those in which the salt concentration is less than about 1.5 M Na ion, typically about 0.01 to 1.0 M Na ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30° C. for short probes (e.g., 10 to 50 nucleotides) and at least about 60° C. for long probes (e.g., greater than 50 nucleotides), for example, high stringency conditions include hybridization in 50% formamide, 1 M NaCl, 1 SDS at 37° C., and a wash in 0.1×SSC at 60 to 65° C. (see Tijssen, Laboratory Techniques in Biochemistry and Molecular Biology-Hybridization with Nucleic Acid Probes, Part I, Chapter 2 “Overview of principles of hybridization and the strategy of nucleic acid probe assays”, Elsevier, New York (1993); and Current Protocols in Molecular Biology, Chapter 2, Ausubel, et al., Eds., Greene Publishing and Wiley-Interscience, New York (1995)). Amino acid and polynucleotide identity, homology and/or similarity can be determined using the ClustalW algorithm, MEGALIGN™, Lasergene, Wis.)
[0037] Examples of the various G-CSF functional variants, muteins, and mimetics include functional fragments and variants (e.g., structurally and biologically similar to the wild-type protein and having at least one biologically equivalent domain), chemical derivatives of G-CSF (e.g., containing additional chemical moieties, such as polyethyleneglycol and polyethyleneglycol derivatives thereof, and/or glycosylated forms such as Lenogastrim™), and peptidomimetics of G-CSF (e.g., a low molecular weight compound that mimics a peptide in structure and/or function (see, e.g., Abell, Advances in Amino Acid Mimetics and Peptidomimetics, London: JAI Press (1997); Gante, Angew Chem. 1994, 106:1780; Olson et al., J Med Chem. 1993, 36:3039).
[0038] Additional examples of G-CSF derivatives include a fusion protein of albumin and G-CSF (Albugranin™), or other fusion modifications such as those disclosed in U.S. Pat No. 6,261,250; PEG-G-CSF conjugates and other PEGylated forms; those described in WO 00/44785 and Viens et al., J Clin Oncology 2002, 6:24; norleucine analogues of G-CSF, those described in U.S. Pat. No. 5,599,690; G-CSF mimetics, such as those described in WO 99/61445, WO 99/61446, and Tian et al., Science 1998, 281:257; G-CSF muteins, where single or multiple amino acids have been modified, deleted or inserted, as described in U.S. Pat. Nos. 5,214,132 and 5,218,092; those G-CSF derivatives described in U.S. Pat. No. 6,261,550 and U.S. Pat. No. 4,810,643; and chimeric molecules, which contain the full sequence or a portion of G-CSF in combination with other sequence fragments, e.g. Leridistim—see, for example, Streeter et al., Exp Hematol. 2001, 29:41, Monahan et al., Exp Hematol. 2001, 29:416, Hood et al., Biochemistry 2001, 40:13598, Farese et al., Stem Cells 2001, 19:514, Farese et al., Stem Cells 2001, 19:522, MacVittie et al., Blood 2000, 95:837. Additionally, the G-CSF derivatives include those with the cysteines at positions 17, 36, 42, 64, and 74 of SEQ ID NO: 4 or analogously of SEQ ID NO: 10, substituted with another amino acid, (such as serine) as described in U.S. Pat. No. 6,004,548, G-CSF with an alanine in the first (N-terminal) position; the modification of at least one amino group in a polypeptide having G-CSF activity as described in EP 0 335 423; G-CSF derivatives having an amino acid substituted or deleted in the N-terminal region of the protein as described in EP 0 272 703; derivatives of naturally occurring G-CSF having at least one of the biological properties of naturally occurring G-CSF and a solution stability of at least 35% at 5 mg/ml in which the derivative has at least Cys 17 of the native sequence replaced by a Ser 17 residue and Asp 27 of the native sequence replaced by a Ser 27 residue as described in EP 0 459 630; a modified DNA sequence encoding G-CSF where the N-terminus is modified for enhanced expression of protein in recombinant host cells, without changing the amino acid sequence of the protein as described in EP 0 459 630; a G-CSF which is modified by inactivating at least one yeast KEX2 protease processing site for increased yield in recombinant production using yeast as described in EP 0 243 153; lysine altered proteins as described in U.S. Pat. No. 4,904,584; cysteine altered variants of proteins as described in WO 90/12874 (U.S. Pat. No. 5,166,322); the addition of amino acids to either terminus of a G-CSF molecule for the purpose of aiding in the folding of the molecule after prokaryotic expression as described in AU-A-10948/92; substituting the sequence Leu-Gly-His-Ser-Leu-Gly-Ile (SEQ ID NO: 16) at position 50-56 of G-CSF of SEQ ID NO: 4 and position 53 to 59 of the G-CSF of SEQ ID No: 8 or/and at least one of the four histedine residues at positions 43, 79,156 and 170 of the mature G-CSF of SEQ ID NO: xx (174 form) or at positions 46, 82, 159, or 173 of the mature G-CSF of SEQ ID NO: 8 as described in AU-A-763 80/91; and a synthetic G-CSF-encoding nucleic acid sequence incorporating restriction sites to facilitate the cassette mutagenesis of selected regions and flanking restriction sites to facilitate the incorporation of the gene into a desired expression system as described in GB 2 213 821. Further examples of G-CSF analogs include SEQ ID NO: 17) and others described in U.S. Pat. No. 6,632,426. The contents of the above are incorporated herein by reference.
[0039] The various functional derivatives, variants, muteins and/or mimetics of G-CSF preferably retain at least 20%, preferably 50%, more preferably at least 75% and/or most preferably at least 90% of the biological activity of wild-type mammalian G-CSF activity—the amount of biological activity include 25%, 30%, 35%, 40%, 45%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 95%; and all values and subranges there between. Furthermore, the functional derivatives, variants, muteins and/or mimetics of G-CSF can also have 100% or more of the biological activity relative to wild-type mammalian G-CSF activity—the amount of biological activity including at least 105%, at least 110%), at least 125%, at least 150%, and at least 200%.
[0040] To measure the biological activity of G-CSF, several known assays can be employed singularly or in combination. One example of determining G-CSF function is illustrated in Example 1. Other methods for determining G-CSF function are known and include a colony formation assay employing murine bone marrow cells; stimulation of proliferation of bone marrow cells induced by G-CSF; specific bioassays with cells lines that depend on G-CSF for growth or that respond to G-CSF (e.g., AML-193; 32D; BaF3; GNFS-60; HL-60; Ml; NFS-60; OCl/AMLIa; and WEHI-3B). These and other assays are described in Braman et al., Am J Hematology 1992, 39:194; Clogston et al., Anal Biochem. 1992, 202:375; Hattori et al., Blood 1990, 75:1228; Kuwabara et al., J Pharmacobiodyn. 1992, 15:121; Motojima et al., J Immunological Methods 1989, 118:187; Sallerfors and Olofsson, Eur J Haematology 1992, 49:199; Shorter et al., Immunology 1992, 75:468; Tanaka and Kaneko, J Pharmacobiodyn. 1992, 15:359; Tie et al., J Immunological Methods 1992, 149:115; Watanabe et al., Anal Biochem. 1991, 195:38.
[0041] In one embodiment, the G-CSF is modified or formulated, or is present as a G-CSF mimetic that increases its ability to cross the blood-brain barrier, or shift its distribution coefficient towards brain tissue. An example of such a modification is the addition of PTD or TAT sequences (Cao et al., J Neurosci. 2002, 22:5423; Mi et al., Mol Ther. 2000, 2:339; Morris et al., Nat Biotechnol. 2001, 19:1173; Park et al., J Gen Virol. 2002, 83:1173). These sequences can also be used in mutated forms, and added with additional amino acids at the amino- or carboxy-terminus of proteins. Also, adding bradykinin, or analogous substances to an intravenous application of any G-CSF preparation will support its delivery to the brain, or spinal cord (Emerich et al., Clin Pharmacokinet. 2001, 40:105; Siegal et al., Clin Pharmacokinet. 2002, 41:171).
[0042] In one embodiment the biological activity of G-CSF is enhanced by fusion to another hematopoietic factor. The enhanced activity can be measured in a biological activity assay as described above. Such a preferred modification or formulation of G-CSF leads to an increased antiapoptotic effect and/or an increase in neurogenesis. An example for such a modification is Myelopoietin-1, a G-CSF/IL-3 fusion protein (McCubrey et al., Leukemia 2001, 15:1203) or Progenipoietin-1 (ProGP-1) is a fusion protein that binds to the human fetal liver tyrosine kinase flt-3 and the G-CSF receptor.
EXAMPLES
Example 1
[0043] G-CSF Decreases Infarct Size within Embolic Model
[0044] Embolic models of cerebral ischemia possibly present a stroke model that is closer to the human situation compared to the filament model. So far, efficacy of G-CSF has not been shown in embolic models. Here, embolic stroke was modeled by injection of a preformed blood clot into the internal carotid artery of rats.
[0045] Male Wistar rats (n=20) weighing approximately 320 g were anesthetized with isoflurane (5% for induction, 2% for surgery, 1.2% for maintenance). PE-50 polyethylene tubing was inserted into the femoral artery for monitoring of mean arterial blood pressure (MABP) and for obtaining blood samples to measure blood gases (pH, PaO 2 , PaCO 2 ), electrolytes (Na + , K + , Ca 2+ ), and plasma glucose. Body temperature was monitored continuously with a rectal probe and maintained at 37.0+/−0.3° C. with a thermostatically controlled heating lamp. For embolic stroke (ES) one red blood clot (diameter=0.35 mm, length=18 mm) was injected into the internal caroted artery (ICA) of 20 animals over approx. 1 s at the bifurcation of the pterygopalatanine artery (PPA) and ICA. Laser Doppler Flowmetry was used to monitor occlusion success.
[0046] Verum (G-CSF, Filgrastim (SEQ ID NO: 10)) and vehicle (buffer solution (250 mM Sorbitol, 0.004% Tween-80, and 10 mM sodium-acetate buffer (pH 4)) groups received two injections: an intravenous infusion (120 μg/kg body weight over 30 min) at 1 h after clot injection, and an intraperitoneal bolus (120 μg/kg body weight) at 4h after clot injection. At 24 h animals were neurologically scored as previously described (rating scale: 0: no deficit, 1: failure to extend the left forepaw, 2: decreased grip strength of left forepaw, 3: circling to paretic side by pulling the tail, 4: spontaneous contralateral circling, and 5:death; Menzies et al., Neurosurgery 1992, 31:100) and sacrificed to determine infarct volumes by 2,3,5-triphenyltetrazolium chloride (TTC) staining with edema correction (Meng et al., Ann Neurol. 2004, 55:207).
[0047] Physiological parameters (blood pH, partial pressure of blood gases (PaCO 2 , PaO 2 ), plasma concentrations of electrolytes (Na + , K + , CA 2+ ) and of glucose) were not significantly changed by treatment. Also, MABP was not influenced by treatment (p>0.05 by repeated measures ANOVA), however there was a significant group-independent drop in MABP at 30 min, after which the blood pressure rose again.
[0048] 12 of 20 animals died prematurely between 16 and 24 h post ES and were therefore included in the TTC analyses. Infarct volumes determined by postmortem TTC staining were 295+/−20 mm 3 (vehicle) vs. 206+/−16 mm 3 (G-CSF, means+/−SEM; P=0.003) ( FIG. 1 ). This considerable decrease in infarct size was however not reflected in the neuroscore at 24 h, which did not show any difference between treatments (vehicle: 4.0+/−1.33; G-CSF: 4.2+/−1.32), likely reflecting the insensitivity of that scale for larger infarcts.
Example 2
[0049] G-CSF Halts the Evolution of a DWI Lesion in the Presence of a Permanent Perfusion Deficit
[0050] Permanent filament occlusion of the MCA was performed as previously described using 4-0 silicone-coated nylon filament sutures (suture occlusion of the right middle cerebral (sMCAO; Bouley et al., Neurosci Lett. 2007, 412:185). Wistar rats (n=15) weighing 320+/−19 g were anesthetized with isoflurane (5% for induction, 2% for surgery, 1.2% for maintenance) in room air. PE-50 polyethylene tubing was inserted into the femoral artery for monitoring of mean arterial blood pressure (MABP) and for obtaining blood samples to measure blood gases (pH, PaO 2 , PaCO 2 ), electrolytes (Na + , K + , Ca 2+ ), and plasma glucose at prior to as well as 30, 60, 90, 120, 180 min after middle cerebral artery occlusion (MCAO). Body temperature was monitored continuously with a rectal probe and maintained at 37.0+/−0.3° C. with a thermostatically controlled heating lamp.
[0051] The perfusion deficit and DWI lesion was monitored over a time period of 180 min by MRI measurements. These MRI experiments were performed on a 4.7 T/40 cm horizontal magnet equipped with a Biospec Bruker console (Billerica, Mass., USA), and a 20 G/cm gradient insert (ID=12 cm, 120 ps rise time). A surface coil (ID=2.3 cm) was used for brain imaging and an actively decoupled neck coil for perfusion labelling (Meng et al., Ann Neurol. 2004, 55:207). Animals were imaged at 25, 45, 60, 90, 120, 150 and 180 min post-sMCAO. Three ADC maps were separately acquired with diffusion-sensitive gradients applied along the x, y, or z direction. Single shot, echo-planar images (EPI) were acquired over 3 min with matrix=64×64, spectral width=200 kHz, TR=2 s (90° flipangle), TE=37.5 ms, b=8 and 1,300 s/mm 2 , Δ=24 ms, δ=4.75 ms, field of view (FOV)=2.56×2.56 cm, seven 1.5 mm slices, and 16 averages. Quantitative CBF measurements were made using the continuous arterial spin-labeling technique with single-shot, gradient-echo, EPI acquisition. Sixty paired images (for signal averaging) were acquired over 4 min, alternately, one with arterial spin labeling and the other (control) without spin-labeling preparation. The MRI parameters were similar to ADC measurements except TE=13.5 milliseconds. Arterial spin labeling utilized a 1.78-second, square radiofrequency pulse in the presence of 1.0 Gauss/cm gradient along the flow direction. The sign of the frequency offset was switched for nonlabeled images.
[0052] Final infarct volumes were determined at 24 h after onset of occlusion, whereas brains were removed and sectioned coronally into seven 1.5 mm-thick slices corresponding to the MR slices and stained with TTC.
[0053] Rats were treated with vehicle (buffer solution (250 mM Sorbitol, 0.004% Tween-80, and 10 mM sodium-acetate buffer (pH 4)), n=5) or G-CSF (Filgrastim, SEQ ID NO: 10; n=10) at 1 h after occlusion (intravenously; 120 μg/kg body weight over 30 min) and 4 h after occlusion (intraperitoneally; 120 μg/kg body weight as bolus).
[0054] Animals surviving for more than 16 hours were prespecified to be included in the study while those dying before 16 hours were excluded. Effects of G-CSF on apparent diffusion coefficient (ADC) and cerebral blood flow (CBF) characteristics as well as the spatiotemporal evolution of the ischemic lesion were evaluated.
[0055] Blood gases, electrolytes, pH, and blood glucose levels did not differ between the two groups. MABP was also not significantly different between treatment groups in both experiments (p>>0.05 by repeated measures ANOVA), however there was a group-independent significant rise over the course of the experiment (p<0.05 for factor time by repeated measures ANOVA). 2 of 15 animals died between 16 to 24 h.
[0056] Images were analyzed using Quickvol II (Schmidt et al., J Neurooncol. 2004, 68:207). Quantitative CBF and ADC maps and their corresponding threshold-derived lesion volumes were calculated as described previously (Meng et al., Ann Neurol. 2004, 55:207). The thresholds used to define abnormal DWI and PWI regions were a reduction to 0.53×10 −3 mm 2 /s for ADC and 0.3 mL/g/min for CBF as previously validated (Meng et al., Ann Neurol. 2004, 55:207). FIG. 2 summarizes the spatiotemporal evolution of threshold-derived ADC and CBF lesion volumes. The CBF lesion volume did not differ between groups (vehicle and G-CSF) and remained relatively constant over time at about 230 mm 3 ( FIG. 2A ).
[0057] The ADC-derived lesion in the vehicle-treated animals increased with time in a linear fashion until 120 min, when the curve flattened. The final infarct volume determined at 24 h by the TTC method lay slightly above the last DWI volume measured at 180 min post occlusion. In G-CSF-treated animals, the DWI lesion grew from 25 min to 45 min post occlusion identical to the vehicle situation. However, when the MRI data were obtained at the 60 min time point after application of G-CSF, the increase seemed to begin to reverse. At 90 min, the DWI lesion in the G-CSF-treated animals became significantly smaller compared to the vehicle-treated rats (repeated measures ANOVA: p<0.0001 for the interaction treatment-time followed by Tukey-Kramer post-hoc test). For the following time points measured, the lesion remained stable until the end of the MRI data acquisition at 180 min, and resulted in a final infarct at 24 h of approximately the same size ( FIG. 2B ).
[0058] The TTC-defined infarct volumes were significantly different between the treatment groups (223+/−7 mm 3 (vehicle) vs. 124+/−19 mm 3 (G-CSF; p=0.007), and correspond well to the 3 h ADC lesion volumes in both groups and to the 3 h CBF in the vehicle group ( FIGS. 2B and 2A ).
[0059] FIGS. 2C and 2D show the absolute and relative mismatch between CBF and ADC derived volumes. All two measures also became significantly different at 90 min following occlusion (p<0.05; repeated measures ANOVA followed by Tukey Kramer post hoc test). Employing an alternative statistical approach and comparing DWI volume behaviour over time relative to PWI volume and treatment by a multiple linear regression model (factors: PWI, ANIMAL (random factor), TREATMENT, TIME, TIME×TREATMENT interaction) showed the treatment effect to become significant at 84 min post sMCAO. The present experiment shows that the action of G-CSF must be immediate to allow for a significant effect on the DWI deficit volume at least at 90 min post onset of occlusion. Induction of anti-apoptotic cascades in vitro is immediate, with phosphorylation and activation of Akt within 5 min after addition of G-CSF to the neurons 9. In contrast, an indirect effect mediated by bone-marrow derived cells would require release of those cells from the bone marrow into the bloodstream, passage of the blood-brain barrier, and tissue invasion, possibly followed by release of protective factors. This is unlikely to be rapid enough for the effect observed in the current experiment.
[0060] Significant between-group differences were not detected in Menzies neurological scores at 4 and 24 h, respectively, likely reflecting the insensitivity of that scale for larger infarcts.
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The present invention relates to the use of G-CSF and derivatives thereof for extending the therapeutic window of subsequent thrombolytic treatment of acute stroke, and thereby, allowing the diagnostic examinations which are necessary prior to the thrombolytic treatment in order to avoid hemorrhagic and other severe adverse side effects of the thrombolysis.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority from U.S. Provisional Application Ser. No. 62/036,347, filed Aug. 12, 2014, the disclosure of which is incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Technical Field
[0003] The present invention relates generally to a hub and brake rotor assembly such as used for a wheel assembly of a wheeled vehicle. More particularly, the invention relates to corrosion resistance of such an assembly by use of cathodic protection.
[0004] 2. Background Information
[0005] Corrosion of hub and brake rotor assemblies is well known, and is especially problematic in coastal areas due to the salt water. Coatings of various sorts have been applied to hubs and rotors in an attempt to prevent or minimize such corrosion. While such coatings have been used with various degrees of success, there is still a need in the art for better protection. The present invention addresses this and other problems in the art.
SUMMARY
[0006] In one aspect, the invention may provide an apparatus comprising: at least one of a wheel hub and a brake rotor; and a first sacrificial anode secured to the at least one of the wheel hub and brake rotor.
[0007] In another aspect, the invention may provide a method comprising the steps of: providing an assembly comprising at least one of a wheel hub and a brake rotor; and securing a sacrificial anode to the at least one of the wheel hub and brake rotor.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0008] A sample embodiment of the invention is set forth in the following description, is shown in the drawings and is particularly and distinctly pointed out and set forth in the appended claims.
[0009] FIG. 1 is an outboard end elevation view of the hub and brake rotor assembly.
[0010] FIG. 2 is a sectional view taken on line 2 - 2 of FIG. 1 .
[0011] FIG. 3 is a sectional view taken on line 3 - 3 of FIG. 1 .
[0012] FIG. 4 is a sectional view taken on line 4 - 4 of FIG. 1 .
[0013] FIG. 5 is a perspective view of one of the sacrificial anodes.
[0014] FIG. 6 is an elevation view of the anode of FIG. 5 .
[0015] Similar numbers refer to similar parts throughout the drawings.
DETAILED DESCRIPTION
[0016] FIGS. 1-3 show a hub and brake rotor assembly 1 which may include a hub 2 , a brake rotor 4 , a plurality of wheel bolts or studs 6 , a bearing protector assembly 8 having a bearing protector or sleeve 10 and dust cap 12 , a plurality of galvanic or sacrificial anodes 14 A-D, 15 A-D and 16 A-B. Sleeve 10 may also serve as a galvanic or sacrificial anode. Hub 2 and brake rotor 4 are formed of metal, typically cast iron or ductile iron, and less commonly a steel which may be a stainless steel. The figures show hub 2 and rotor 4 as individual pieces which are secured to one another by bolts 6 . However, the figures also may represent that hub 2 and rotor 4 are formed as an integral hub and rotor which is a single unitary piece. Wheel bolts 6 are formed of a suitable metal such as steel, as known in the art. Sleeve 10 when serving as a sacrificial anode, and sacrificial anodes 14 , 15 and 16 are formed of a suitable metal which will serve as a sacrificial anode for hub 2 and/or rotor 4 . These anodes are typically formed of aluminum or an aluminum base alloy, zinc or a zinc base alloy, or magnesium or a magnesium base alloy. One example of a suitable aluminum alloy for use as a sacrificial anode is military specification MIL-A-24779, which is roughly about 95% aluminum and about 5% zinc plus or minus about 1% or 2% of either element. This is but one example, and many other alloys may be suitable for the present purpose.
[0017] Assembly 1 has an inboard end 18 and an outboard end 20 and has a central axis X which extends from inboard end 18 to outboard end 20 and about which assembly 1 is rotatable such as it is when a wheel assembly (tire and rim) is mounted thereon and assembly 1 is mounted on a spindle assembly of a wheeled vehicle. Assembly 1 is essentially radially symmetrical about axis X. Assembly 1 has an axial direction extending generally in the direction of axis X. Assembly 1 has an inboard direction (Arrow A) which is generally in the axial direction toward the inboard end 18 and away from outboard end 20 , and an outboard direction (Arrow B) which is generally in the axial direction toward the outboard end 20 and away from inboard end 18 .
[0018] Hub 2 includes a generally cylindrical hub sleeve 22 and an annular wheel flange 24 which is rigidly secured to and extends radially outwardly from hub sleeve 22 (away from axis X). Flange 24 defines a plurality of wheel bolt holes 26 for receiving therein bolts 6 respectively. Flange 24 has inboard and outboard surfaces 25 and 27 which face away from one another and respectively are inboard-facing and outboard-facing surfaces. Each of holes 26 extends from inboard surface 25 to outboard surface 27 . In the exemplary embodiment, there are five holes 26 which are equally circumferentially spaced from one another and equidistant from axis X, for receiving the corresponding five bolts 6 therein. Flange 24 may define a plurality of anode receiving holes 31 which may be threaded holes in which anodes 16 A and 16 B are respectively received and mounted on flange 24 of hub 2 . Holes 31 typically extend in the outboard direction from inboard surface 25 and may extend to outboard surface 27 . A pair of holes 31 is typically diametrically opposed such that each hole of the pair is directly on the opposite side of axis X from the other and equidistant from axis X. Each of holes 31 is typically substantially identical. Each hole 31 is disposed circumferentially intermediate an adjacent pair of holes 26 and corresponding adjacent pair of bolts 6 . Given the use of five holes 26 and five bolts 6 , as well as the diametrically opposed configuration of holes 31 , each hole 31 may be closer to one of the holes 26 and bolts 6 than the other of the holes 26 and bolts 6 of the adjacent pair between which the given hole 31 is circumferentially disposed.
[0019] Hub sleeve 22 has inboard and outboard ends 28 and 30 which serve as the inboard and outboard ends of hub 2 . Sleeve 22 has a sleeve inboard section 32 and a sleeve outboard section 34 such that inboard section 32 extends in the inboard direction to inboard end 28 , and outboard section 34 extends in the outboard direction from flange 24 to outboard end 30 . Sleeve 22 defines a through passage 36 which serves as a spindle receiving passage for receiving a spindle of a wheeled vehicle for rotatably mounting assembly 1 and a rim and tire thereon. Passage 36 extends from inboard end 28 to outer end 30 and is defined by an inner perimeter or surface 38 which is circular as viewed in the axial direction. Inner perimeter or surface 38 includes an outboard bearing seat 40 which is typically cylindrical and extends inwardly from inboard end 28 to a shoulder 46 which extends radially inwardly from the inboard end of seat 40 . Perimeter 38 also includes an inboard bearing seat 42 and seal seat 44 . Seal seat 44 is typically cylindrical and extends in the outboard direction from adjacent inboard end 28 to a shoulder 48 at the outboard end of seat 44 . Inboard bearing seat 42 is typically cylindrical and extends in the outboard direction from adjacent shoulder 48 to a shoulder 50 which extends radially inwardly from the outboard end of seat 42 . Shoulder 48 extends radially inwardly from seal seat 44 to inboard bearing seat 42 . Seat 40 is configured to receive therein an outboard bearing which id mounted on and circumscribes a spindle when assembly 1 is mounted on said spindle. Similarly, seat 42 is configured to receive therein an inboard bearing which also circumscribes the spindle when mounted thereon. Seat 44 is configured to receive a seal bearing which also circumscribes the spindle when mounted thereon.
[0020] Brake rotor 4 includes a hat or hat section 52 and a friction section or disc section 54 which is rigidly secured to and extends radially outwardly from hat 52 . Hat 52 includes an annular wheel bolt flange 56 which is typically a circular annular plate which may extend perpendicular to axis X. Hat 52 also includes a circular annular sidewall 58 which extends in the inboard direction from flange 56 . Sidewall 58 may extend parallel to axis X. Flange 56 has a circular inner perimeter 60 which is adjacent and spaced radially outwardly from the outer perimeter of sleeve outboard section 34 adjacent the inboard end of section 34 and outboard surface 27 of flange 56 . Flange 56 has an outer perimeter 62 , and inboard and outboard surfaces 64 and 66 which extend radially outwardly from adjacent inner perimeter 60 to adjacent outer perimeter 62 and which may be perpendicular to axis X. Sidewall 58 has inner and outer perimeters 68 and 70 which are circular and concentric about axis X and which may be cylindrical. Sidewall 58 has inboard and outboard ends 72 and 74 such that inner and outer perimeters 66 and 68 extend from adjacent end 72 to adjacent end 74 . Outboard end 74 is rigidly secured to flange 56 adjacent outer perimeter 62 thereof and extends in the inboard direction therefrom to inboard end 72 .
[0021] Bolt flange 56 defines therein a plurality of bolt holes 65 which are typically threaded and threadingly engage the externally threaded portions of bolts 6 to secure hub 2 to rotor 4 . In the sample embodiment, there are five bolt holes 65 which are respectively aligned with holes 26 in flange 24 such that bolts 6 extend through a given pair of aligned holes 26 and 65 such that a threaded section of each bolt or stud 6 extends in the outboard direction beyond outboard surface 66 to provide sufficient space for mounting the rim of a wheel thereon with lug nuts threaded onto bolts 6 . Flange 24 may also define a plurality of anode receiving holes 67 which may be threaded holes and which may be aligned with holes 31 respectively. In this case, holes 67 are likewise diametrically opposed and have a similar position with respect to holes 26 and bolts 6 as do holes 31 . Where such holes are used, holes 67 may extend in the outward direction from inboard surface 64 and may extend to outboard surface 66 .
[0022] Disc section 54 has a circular annular configuration with inner and outer perimeters 76 and 78 which are circular and concentric about axis X. Section 54 also has inboard and outboard surfaces 80 and 82 which extend radially outwardly from adjacent inner perimeter 76 to adjacent outer perimeter 78 and which are typically perpendicular to axis X. Surfaces 80 and 82 serve as friction surfaces or braking surfaces which are engaged by brake pads of a brake caliper when assembly 1 is mounted with a brake system including such a caliper. As is well known in the art, disc section 54 may be formed of a single plate which defines the friction surfaces analogous to surfaces 80 and 82 . In the sample embodiment, the brake rotor is a vented rotor which includes a circular annular inboard plate or disc 84 , a circular annular outboard plate or disc 86 and a plurality of vanes 88 which are rigidly secured to and extend between plates 84 and 86 such that the plates are axially spaced from one another and such that vanes 88 are circumferentially spaced from one another. There are typically multiple vanes which are spaced circumferentially from one another all the way around discs 84 and 86 extending between the inner and outer perimeters 76 and 78 . For example, there may be at least 20 , 25 , 30 , 35 , or 40 or more vanes. When there are two plates or discs 84 and 86 , surfaces 80 and 82 respectively serve as the inboard surface of plate 84 and the outboard surface of plate 86 . Plates 84 and 86 respectively include an inboard surface 90 and an outboard surface 92 which face one another and define therebetween an annular circular space 94 in which vanes 88 are disposed. Each adjacent pair of vanes 88 defines therebetween a vent passage 96 such that there are multiple vent passages 96 along the circumference of the discs between inner and outer perimeters 76 and 78 . As known in the art, vent passages 96 are provided to facilitate the flow of air therethrough to facilitate dissipation of the heat created in rotor 4 during the braking process.
[0023] One or both of the inboard and outboard plates 84 and 86 may define a plurality of anode receiving holes such as holes 95 which are shown formed in inboard plate 84 . Holes 95 may be threaded holes and in the sample embodiment extend from outboard surface 80 to outboard surface 92 of plate 84 . In the sample embodiment, four holes 95 are shown in FIG. 1 such that one pair of the holes is diametrically opposed on opposite sides of axis X and another pair is likewise diametrically opposed on opposite sides of axis X and such that each pair of diametrically opposed holes is formed at a 90 degree angle with respect to the other pair of diametrically opposed holes as viewed along axis X. Each pair of diametrically opposed holes is preferably equidistant from axis X and typically all of holes 95 are equidistant from axis X.
[0024] Sleeve or anode 10 has an inboard end 98 , an outboard end 100 and inner and outer perimeters 99 and 101 extending from adjacent end 98 to adjacent end 100 . Sleeve 10 includes a wider segment 102 and a narrower segment 104 separated by a shoulder 106 . More particularly, the wider section 102 has a greater outer diameter of outer perimeter 101 than does narrower segment 104 . Shoulder 106 extends radially inwardly from the inboard end of segment 102 to the outboard end of segment 104 and serves as a stop which may abut the outboard end 30 of hub 2 to limit the depth of insertion of the insertion portion or segment 104 into passage 36 when sleeve 10 is mounted on hub 2 . Wider segment 102 includes an internally threaded section 108 of inner perimeter 99 adjacent outboard end 100 . When sleeve 10 is mounted on hub 2 , the insert segment 104 is inserted into or received within passage 36 adjacent outboard end 30 and adjacent or within bearing seat 40 such that shoulder 106 may engage outboard end 30 of hub 2 . Wider segment 102 is external to passage 36 and extends in the outboard direction from the outboard end of passage 36 and outboard end 30 .
[0025] Dust cap 12 includes a generally cylindrical sidewall 110 which is essentially concentric about axis X, and a flat circular cap wall 112 which is rigidly secured to and extends radially inward from the outboard end of sidewall 110 . Sidewall 110 includes an externally threaded segment 114 which threadedly engages threaded segment 108 of sleeve 10 to removably secure dust cap 12 to sleeve 10 . Sidewall 110 may include a shoulder 116 which faces in the inboard direction outboard and threaded segment 114 such that shoulder 116 may engage outboard end 100 of sleeve 10 when dust cap 12 is secured to sleeve 10 by the threaded engagement between segments 114 and 108 . Dust cap 12 may thus easily be secured to sleeve 10 by threading dust cap 12 onto sleeve 10 and removed therefrom by unthreading the dust cap. An annular seal 118 such as a gasket or a compressible O-ring may be disposed outboard of threaded segment 114 and inboard of shoulder 116 to provide a seal between the outer perimeter of sidewall 110 and the inner perimeter 99 of sleeve 10 .
[0026] Each of anodes 14 has an inboard end 120 and an outboard end 122 , a first segment 124 which may be a threaded segment, a second segment 126 which may be an unthreaded segment and a tool engaging hole 128 which may for example be a hexagonal hole for receiving therein a hex wrench although various other shapes may be used. In the sample embodiment, segment 124 extends in the outboard direction from adjacent inboard end 120 about halfway to end 122 , and segment 126 extends from the outboard end of segment 124 to outboard end 122 . First segment 124 is disposed within one of holes 95 while second segment 126 is disposed in or extends within one of passages 96 . Inboard end 120 may be flush with or recessed from surface 80 , while outboard end 122 may be within the given passage 96 and may abut inboard surface 90 . In the sample embodiment, segment 124 may be externally threaded and thereby threadedly engage the internally threaded hole 95 to form a threaded connection which secures anode 14 to plate 84 . In the sample embodiment, anode 14 is in direct contact with plate 84 and plate 86 , thereby providing direct electrical communication or contact between the given anode 14 and both plates 84 and 86 . While the sample embodiment provides a threaded engagement between the given anode 14 and plate 84 within hole 95 , anodes 14 may also be press fit into holes 95 and thus secured by a press fit connection without the use of a threaded segment or threaded engagement between the anode and plate. Holes may also be formed in plate 86 which are aligned with holes 95 such that each anode 14 may extend into such holes in plate 86 with or without a threaded connection therein. Inasmuch as anodes 14 are disposed within holes 95 , anodes 14 are thus positioned relative to one another in the same manner as holes 95 are positioned relative to one another as described in greater detail further above. Thus, anodes 14 A and 14 C are a pair of diametrically opposed anodes which are equidistant from axis X. Likewise, anodes 14 B and 14 D are a pair of diametrically opposed anodes which are equidistant from axis X. Each pair of diametrically opposed anodes 14 A and 14 C is formed at a 90 degree angle with respect to the other pair of diametrically opposed anodes 14 B and 14 D as viewed along axis X. Typically, all of anodes 14 are equidistant from axis X. In the sample embodiment, all of anodes 14 have the same dimensions and weight and are essentially identical whereby their positioning ensures that assembly 1 is weight balanced during rotation about axis X.
[0027] Each anode 15 may essentially be a block and have a box shape or parallelepiped configuration. In the sample embodiment, anode 15 has flat inboard and outboard surfaces 130 and 132 which are parallel, radial inner and outer ends or surfaces 134 and 136 which are parallel to one another and perpendicular to surfaces 130 and 132 , and circumferential ends or surfaces 138 and 140 which are parallel to one another and perpendicular to surfaces 130 and 32 and ends or surfaces 134 and 136 . Anode 15 may define a plurality of slots 142 . In the sample embodiment, four slots 142 are formed in anode 15 , with two of slots 142 extending inwardly from circumferential end 138 toward end 140 , and two of slots 142 extending inwardly from end 140 toward end 138 . Thus, two of the slots are open ended at end or surface 138 and the other two slots 142 are open ended at end or surface 140 . Each of the slots 142 also extends from inboard surface 130 to outboard surface 132 and thus is open ended at both these surfaces as well. Each slot 142 extends inwardly into anode 15 to a closed end.
[0028] A plurality of connectors 144 are secured to anode 15 and extend outwardly therefrom such that portions of connectors 144 extend outwardly in the inboard direction beyond inward surface 130 and other portions of connectors 144 extend in the outboard direction beyond outboard surface 132 . In the sample embodiment, connectors 144 are springs formed of spring steel which have opposed ends 146 . The body of each spring 144 is received in a given slot 142 such that each spring 144 is secured to anode 15 . The inboard end 146 of a given spring 144 extends outwardly out of a given slot 142 beyond inboard surface 130 in the inboard direction, while the outboard end 146 of a given spring extends out of a given slot 142 beyond outboard surface 132 in the outboard direction. Each spring 144 is curved such that ends 146 extend or are angled toward the radial outer end 136 of anode 15 .
[0029] Anode 15 is secured to brake rotor 4 by inserting the given anode 15 with connectors 144 secured thereto into one of vent passages 96 in a radial inward direction from the outer perimeter 78 toward the inner perimeter 76 and toward axis X. During insertion of anode 15 into the given passage 96 , ends 46 slidably engage surfaces 90 and 92 of plates 86 and 84 respectively. Once anode 15 is mounted within passage 96 , the inboard ends 146 of springs 144 engage outboard surface 92 and the outboard ends 146 engage inboard surface 90 , thus providing a press fit or interference fit between the ends of the springs and surfaces 90 and 92 to secure anode 15 to discs 84 and 86 . In this secured position, ends 146 extend or are angled radially outwardly away from axis X and inner perimeter 76 and toward outer perimeter 78 . Inboard surface 130 is adjacent and faces outboard surface 92 , while outboard surface 132 is adjacent and faces inboard surface 90 . Surfaces 130 , 132 , 90 , and 92 may be parallel. Radial inner end or surface 134 faces radially inwardly toward axis X, while radial outer end or surface 136 faces radially outwardly away from axis X. Anode 15 is in electrical communication with plates 84 and 86 via connectors 144 . More particularly, each anode 15 is in direct electrical communication or contact with connectors 144 , which are in turn in direct electrical communication or contact with plates 84 and 86 via contact between ends 146 and the respective surfaces 90 and 92 .
[0030] As shown in FIG. 1 , anodes 15 A-D are arranged in a pattern similar to that of anodes 14 A-D. Thus, anodes 15 A and 15 C are a pair of diametrically opposed anodes which are equidistant from axis X. Likewise, anodes 15 B and 15 D are a pair of diametrically opposed anodes which are equidistant from axis X. Each pair of diametrically opposed anodes 15 A and 15 C is formed at a 90 degree angle with respect to the other pair of diametrically opposed anodes 15 B and 15 D as viewed along axis X. Typically, all of anodes 15 are equidistant from axis X. In the sample embodiment, all of anodes 15 have the same dimensions and weight and are essentially identical whereby their positioning ensures that assembly 1 is weight balanced during rotation about axis X.
[0031] Anodes 16 each have an inboard end 148 and an outboard end 150 . Each anode 16 includes a first segment 152 which may be a threaded segment, and may also include a second segment 154 (shown in dashed lines in FIG. 3 ). Segment 152 may define a tool engaging hole 128 such as a hexagonal hole or other shape as discussed previously. Each anode 16 is received within a respective hole 31 and may also extend into a hole 67 aligned with hole 31 . In the sample embodiment, anode 16 in solid lines is shown only within hole 31 with outboard surface 150 in contact with inboard surface 64 of flange 56 . If segment 152 is threaded, there may be a threaded engagement or connection between the externally threaded segment 152 and internally threaded hole 31 to secure anode 16 to flange 24 of hub 2 . In the sample embodiment, anode 16 is thus in direct electrical communication or contact with flange 24 and flange 56 .
[0032] As with the other anodes, anodes 16 A and 16 B are typically diametrically opposed and equidistant from axis X, and are essentially identical and have the same weight so that assembly 1 is weight balanced during rotation about axis X. It is noted that anodes such as anodes 14 , 15 and 16 may be positioned other than in the diametrically opposed configuration while still maintaining the weight balance of assembly 1 . For instance, three anodes which are essentially identical may be circumferentially spaced about axis X (120 degrees apart) such that they are equidistant from axis X and equidistant from one another. Other weight balanced configurations will be understood by one skilled in the art.
[0033] In the foregoing description, certain terms have been used for brevity, clearness, and understanding. No unnecessary limitations are to be implied therefrom beyond the requirement of the prior art because such terms are used for descriptive purposes and are intended to be broadly construed.
[0034] Moreover, the description and illustration set out herein are an example and the invention is not limited to the exact details shown or described.
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A wheel hub and brake rotor assembly is disclosed which is resistant to corrosion via cathodic protection. One or more sacrificial anodes may be mounted on the hub and/or the rotor.
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TECHNICAL FIELD
[0001] The present application generally relates to a method and a device for producing plastic containers.
BACKGROUND
[0002] Methods for producing plastic containers have been known from the prior art for a long time. In this connection it is known that preforms are first heated by means of an oven and are then expanded into plastic containers using a blow moulding unit. After that, these containers are filled with a liquid such as, for example, a beverage and are finally closed with closures. For this purpose, plastic closures are usually also used as closures, which plastic closures are fed to a closing unit and are subsequently attached to the containers.
[0003] From DE 197 37 697 A1 an injection blow moulding machine is known, wherein the plastic blanks are initially moulded in injection moulding cavities and are then transferred by a transfer unit from the injection moulding cavities into a blow moulding unit. Thus, also the plastic performs are produced within the context of the production of the plastic containers and are subsequently expanded into containers.
[0004] From DE 198 19 731 A1 a method and a device for producing labelled plastic bottles are known. Here, the bottles are labelled in a continuous flow immediately upon leaving a blowing machine, and in this way labels can be reliably affixed at a high speed.
[0005] EP 0 794 903 B1 describes a system and a method for packaging beverages in a sterile way. In this method, too, the preforms are first produced within a sterile room and are subsequently expanded into containers. Further, also a sterilisation unit for the closure caps is provided, which is also disposed within said sterile room.
SUMMARY
[0006] It is the object of the present application to provide devices and methods for producing plastic containers, which allow the production process thereof to be rationalised even further.
[0007] In a method for producing plastic containers, plastic performs are first fed to a moulding unit. Thereafter, the plastic performs are moulded into plastic containers. In a further method step, the plastic containers are filled with a liquid and are finally closed with plastic closures. In the course of this process, the plastic closures are preferably produced from a plastics material and are heated during this production process.
[0008] It is therefore proposed that not only the containers themselves are produced by moulding, but also the plastic closures which subsequently close the containers are produced within the context of this process. In this way, the method can in its entirety be designed to be economical. By contrast, in the prior art the plastic closures are produced in an entirely separate process and in particular in different production systems. In the prior art, the closures thus produced are joined with the containers and/or screwed onto these. In the prior art therefore the closures used also have to be sterilised.
[0009] The production rate of the closures is preferably adapted to the production rate of the moulded or blown containers. In this way, a continuous production process for the containers provided with closures is achieved. In the case of a failure occurring, for example in the blow moulding unit, a control unit preferably causes the closure production process to be stopped or slowed down. Thus, a higher level control unit is preferably provided which controls the entire production process, i.e. in particular also the production of the closures.
[0010] Due to the heating of the plastic closure, the need for a sterilisation of said closure may at least partly be eliminated. In this way, too, the expenditure for the corresponding process is reduced. The moulding of the plastic performs is carried out here, as is known from the prior art, by a blow moulding process wherein the plastic preforms are expanded into the containers using pressurised air. In this way, a centralised (in particular single step) packaging process of a liquid into a container as well as the production thereof and preferably also the labelling and sterilisation thereof as well as the filling and closing thereof under particularly sterile conditions is suggested.
[0011] In a preferred method, the closure blank is moulded into the plastic closure by way of a microwave-based heating process. Here, the moulding process may for example be carried out by press forming. The high material temperatures which are necessary or advantageous for this cause at the same time the closure to be sterilised. It is to be noted here that due to several protrusions such as for example the internal thread of the closure, the sterilisation of the closure often is a complex process.
[0012] In a further advantageous process, the production of the plastic closure is carried out at least at times at temperatures which cause the plastic closure to be sterilised. Thus, it would advantageously also be possible to use slightly higher temperatures for the production of the plastic closures than for the actual moulding of the material, in order to achieve or promote the desired sterilisation effect.
[0013] In a further advantageous process, the plastic preforms are produced prior to being fed into the moulding unit. This means that not only the closures but also the containers or the preforms themselves are produced directly in the course of this process. In this way, a further simplification of the process is achieved. More specifically, it is possible in this connection to produce a preform from known materials such as for example PET, PP and the like in a continuously operating rotary injection moulding machine, which machine feeds these preforms (correctly tempered) preferably directly to a in a conventional stretch blow moulding process a blow moulding machine for further processing.
[0014] Thus, the plastic preforms are preferably heated within the context of their production process in such a way that they can be fed to a moulding unit immediately after the production thereof. In this way, any heating devices as used in the prior art for heating preforms may be dispensed with. In this case, too, it is possible for the preforms to be produced, if necessary, at higher temperatures than this would normally be necessary for the production thereof, in order to be able to eliminate the need for any downstream heating units for the preforms.
[0015] Further, owing to said production process it is also possible to dispense with any other sterilisation steps that might otherwise be necessary.
[0016] In a further preferred process, the plastic containers are labelled and are sterilised during this labelling process. Preferably, as mentioned above, the container is first generated from the preform in a usual stretch blow moulding process. After that, as mentioned above, labelling, for example by means of neck handling systems, and at the same time sterilising of the container in its empty condition may be carried out.
[0017] The advantage of this method consists in the fact that the containers are dry after the blow moulding process and in this dry condition they are suitable for the labelling process. Thus, it is possible here as well on the one hand to affix the label (to an outer wall of the container) and at the same time to sterilise the container (on the inner wall thereof). For the sterilisation process, an electron beam device such as a beam finger may be used, which is inserted into the container and is moved relative to the container during the sterilisation process. In this process it is both possible to move the beam finger and to move the container itself in its longitudinal direction. These simultaneous labelling and sterilisation processes, too, allow the number of components used to be reduced. However, it would also be possible to carry out the labelling process not until after the containers have been closed.
[0018] In a further preferred process, the closures are produced in a clean room. In this way it can be avoided that the produced closures are immediately contaminated again. Preferably, also the labelling process is carried out in a clean room, in particular in the case of those processes where the containers are labelled and sterilised at the same time.
[0019] After sterilisation of the empty containers, said containers are preferably filled with a (sterile) liquid and finally the containers are closed with a closure (which is preferably also sterile), which closure, as mentioned above, is produced in a parallel production process and is fed directly to the filled containers in order to subsequently close these (in a sterile manner).
[0020] Advantageously, the closures are produced using a pressing process. To this end, a plastics composition or a core can be inserted into a press mould and can then be moulded by a punch. After that, a cutting tool may be used to provide a thread. It would also be possible to additionally sterilise the closures during this forming operation, for example by means of hydrogen peroxide gas.
[0021] The present invention further relates to a device for producing plastic containers. This device includes a moulding unit which moulds plastic preforms into plastic containers. In addition, the device includes a filling unit disposed downstream of the moulding unit in the transport direction of the containers, which filling unit fills the plastic containers with a liquid, as well as a closing unit which closes the filled plastic containers with closures.
[0022] According to the invention, the device includes a closure production unit which produces the plastic closures from a plastics material. This closure production unit is preferably designed in such a way that it produces the plastic closures whilst heating the same.
[0023] In a further advantageous embodiment, the closure production unit includes a microwave-based heating unit which heats the plastic closures.
[0024] In a further advantageous embodiment, the device includes a first sterilisation unit that sterilises the plastic preforms. In this connection it is possible for this sterilisation to be carried out immediately after the production of the plastic preforms, i.e. even prior to the blow moulding operation. A further sterilisation process may be carried out after the production of the plastic containers or during the moulding process.
[0025] The device further includes a labelling unit which labels the plastic containers. This labelling unit can, as mentioned above, be implemented here together with a sterilisation unit. Thus, the containers may be transported for example by their necks using gripping claws and may be externally labelled and internally sterilised in the process. In doing so it is possible to rotate the containers about their own axis both for the purpose of sterilising and for the purpose of labelling them.
[0026] In a further advantageous embodiment, the device includes a preform production unit that produces the preforms from a plastics material.
[0027] In a further advantageous embodiment, the device includes a sterile room, within which at least the filling unit, the closing unit and the closure production unit are arranged. Preferably, also a unit for producing the preforms as well as one or more sterilisation units are arranged within the sterile room.
[0028] In one aspect, a method for producing plastic containers, comprises the following steps: feeding plastic preforms ( 10 ) to a blowing ( 4 ) for moulding plastic preforms unit; moulding said plastic preforms ( 10 ) into plastic containers ( 20 ) by a blowing unit ( 4 ); filling the plastic containers ( 20 ) with a liquid; closing the plastic containers ( 20 ) with plastic closures ( 15 ); characterised in that the plastic closures are produced from a plastics material and are heated during this production process, wherein at least a filling unit ( 8 ), a closing unit ( 12 ) and a closure production unit ( 3 ) are arranged in a clean room ( 25 ) and wherein a production rate of the closures is adapted to a production rate of the moulded or blown containers.
[0029] In some embodiments, the method is characterised in that a closure blank is moulded into the plastic closure ( 15 ) by way of a microwave-based heating process.
[0030] In some embodiments, the method is characterised in that the production of the plastic closure is carried out at least at times at temperatures which cause the plastic closure to be sterilised.
[0031] In some embodiments, the method is characterised in that the plastic preforms are produced prior to being fed into the blowing unit ( 4 ).
[0032] In some embodiments, the method is characterised in that the plastic preforms ( 10 ) are heated within the context of the production process thereof in such a way that they can be fed to a blowing unit ( 4 ) immediately after the production thereof.
[0033] In some embodiments, the method is characterised in that the plastic containers ( 20 ) are labelled and are sterilised during this labelling process.
[0034] In some embodiments, the method is characterised in that the production of the closures ( 15 ) is carried out in a clean room ( 25 ).
[0035] In some embodiments, the method is characterised in that the closures ( 15 ) are produced by way of a pressing process.
[0036] In another aspect, a device for producing plastic containers, comprises a blowing unit ( 4 ) which moulds plastic preforms ( 10 ) into plastic containers ( 20 ), a filling unit ( 8 ) disposed downstream of the blowing unit ( 4 ) in a transport direction of the plastic containers ( 20 ), which filling unit ( 20 ) fills the plastic containers ( 20 ) for example with a liquid, and a closing unit ( 12 ) which closes the filled plastic containers ( 20 ) with closures ( 15 ), characterised in that the device includes a closure production unit ( 30 ) which produces the plastic closures ( 15 ) from a plastics material and includes a clean room ( 25 ) within which at least the filling unit ( 8 ), the closing unit ( 12 ) and the closure production unit ( 30 ) are arranged, wherein a production rate of the closures is adaptable to a production rate of the blown containers.
[0037] In some embodiments, the device is characterised in that the closure production device ( 30 ) includes a microwave-based heating unit ( 32 ) which heats the plastic closures ( 15 ).
[0038] In some embodiments, the device is characterised in that the device includes a first sterilisation unit ( 5 ) which sterilises the plastic preforms ( 10 ).
[0039] In some embodiments, the device is characterised in that the device includes a labelling unit ( 18 ) that labels the plastic containers ( 20 ).
[0040] In some embodiments, the device is characterised in that the device includes a preform production unit ( 3 ) that produces the preforms ( 10 ) from a plastics material.
[0041] In another aspect, a method for producing plastic containers, comprises the steps of: (a) feeding plastic preforms to a blow moulding unit; (b) moulding the plastic preforms into plastic containers at the blow moulding unit; (c) filling the plastic containers with a liquid at a filling unit; and (d) closing the plastic containers with plastic closures at a closing unit, wherein the plastic closures are produced from a plastics material and are heated during steps (a) through (d) at a closure production unit, wherein the filling unit, the closing unit and the closure production unit are arranged in a clean room, and wherein a production rate of the closures is adapted to a production rate of the moulded containers.
[0042] In some embodiments, producing the plastic closures includes moulding closure blanks into the plastic closures by way of a microwave-based heating process.
[0043] In some embodiments, producing the plastic closures is carried out at times and temperatures which cause the plastic closures to be sterilised.
[0044] In some embodiments, the method further comprises producing the plastic preforms from a supply of plastics material prior to feeding the plastic preforms to the blow moulding unit.
[0045] In some embodiments, during producing the plastic preforms, the plastic preforms are heated to a temperature such that the plastic preforms are fed directly to the blow moulding unit immediately after the production of the plastic preforms.
[0046] In some embodiments, the method further comprises the step of: (e) labelling the plastic containers, wherein the plastic containers are sterilised during step (e).
[0047] In some embodiments, the closures are produced by way of a pressing process.
[0048] In some embodiments, the production rate of the closures is synchronized with the production rate of the moulded containers.
[0049] In another aspect, a device for producing plastic containers, comprises: a blow moulding unit that moulds plastic preforms into plastic containers; a filling unit disposed downstream of the blow moulding unit in a transport direction of the plastic containers, the filling unit configured to fill the plastic containers with a liquid; a closing unit that closes the filled plastic containers with closures; and a closure production unit that produces the plastic closures from a plastics material, wherein the filling unit, the closing unit and the closure production unit are configured to be placed in a same clean room, and wherein a production rate of the closures is adaptable to a production rate of the plastic containers.
[0050] In some embodiments, the closure production unit includes a microwave-based heating unit that is constructed and arranged to heat the plastic closures.
[0051] In some embodiments, the device further comprises a first sterilisation unit that sterilises the plastic preforms.
[0052] In some embodiments, the device further comprises a labelling unit that is configured to label the plastic containers.
[0053] In some embodiments, the device further comprises a preform production unit that is constructed and arranged to produce the preforms from a plastics material. In some embodiments, the filling unit, the closing unit and the closure production unit are arranged in the same clean room.
BRIEF DESCRIPTION OF THE DRAWINGS
[0054] Further advantages and embodiments will become evident from the attached drawings, wherein:
[0055] FIG. 1 shows a block diagram illustrating a first embodiment of a device; and
[0056] FIG. 2 shows a block diagram illustrating a second embodiment of a device.
DESCRIPTION
[0057] FIG. 1 shows a block diagram of a first embodiment of a device 1 . Here, reference numeral 3 identifies a unit for producing plastic preforms. In this connection it is possible that that unit for producing plastic preforms 3 includes a rotary injection moulding machine, into which plastics material is introduced, from which it produces preforms 10 . The preforms 10 produced in this way may be passed on to a blow moulding unit 4 , where they may be expanded into plastic containers 20 in the blow moulding unit 4 . Reference numeral 5 relates here to a sterilisation unit that sterilises the plastic preforms 10 produced, and in particular may sterilize an interior of the plastic preforms 10 . The sterilisation unit 5 may use electron beams or UV radiation for sterilising the walls of the plastic preforms 10 . In this manner, the unit for producing plastic preforms 3 may deliver the produced plastic preforms 10 immediately to the blow moulding unit 4 .
[0058] Reference numeral 40 refers to a supply for a plastics material that is introduced into the production unit 3 . In the embodiment shown in FIG. 1 , the containers 20 produced in this way may be then transferred to a labelling unit 18 and may be provided with labels on the outside thereof. In the same section of the machine, a sterilisation unit 7 may also be provided, which can sterilises the interior of the containers 10 . In this way it is possible to label the containers and at the same time to sterilise the interior thereof in the area of the two system sections 18 and 7 . Further, a heating unit may also be provided between the production unit 3 and the blow moulding unit 4 , which heating unit tempers the preforms so as to facilitate in this way the actual blow moulding process. However, it is also possible for the production unit 3 itself to generate an appropriate temperature for the preforms, so that these can be directly transferred to the moulding process in the blow moulding unit 4 .
[0059] In this connection it is possible that the blow moulding unit 4 , too, includes a transport carousel and the preforms are transferred directly from the production unit 2 to the blow moulding unit 4 . However, it is also possible that a further conditioning circuit in which, as mentioned above, the containers are for example heat treated, is provided between the production unit 3 and the blow moulding unit 4 .
[0060] The labelling and sterilisation units 18 and 7 are followed by a filling unit 8 for filling the containers, in which the filling unit 8 may fill the containers 20 with a liquid and in particular with a beverage. This beverage is here preferably also sterile. Subsequently, the containers 20 are closed in a closing unit 12 and may be finally passed on to a packaging unit 38 , in which the containers 20 are packaged together to form larger groups.
[0061] Reference numeral 36 relates to a supply for a plastics material to be used for producing the closures 15 . Reference numeral 30 refers to a corresponding closure production unit in which closures 15 are produced from the material. This closure production unit may include a heating unit 32 that heats the closures 15 . The closures 15 produced are preferably heated in such a way that additional sterilisation thereof is no longer necessary. However, a further sterilisation unit 34 , which may additionally sterilise the closures 15 may also be provided.
[0062] Moreover, sterilisation units could also be provided between the sterilisation unit 7 and the filling unit 8 . Reference numeral 25 relates to a sterile room in which in the embodiment shown in FIG. 1 , both the labelling unit 18 and the sterilisation unit 7 and the filling unit 8 as well as the closing unit 12 are arranged. The individual machines 3 , 4 , 18 , 7 , 8 , 12 are preferably interlocked and/or synchronised with each other as indicated by box 35 . Apart from that it would also be possible to create further sterile rooms, for example with a higher degree of sterilisation, within the sterile room 25 shown, in order to run some sub-processes of the production in this higher degree of sterilisation, such as for example the filling process.
[0063] The device preferably includes a plurality of transfer or transport stars which transport the containers between the individual units 3 , 4 , 18 , 8 . In this way, the containers 10 , 20 are passed individually or one by one through the entire device 1 . The closures 15 may also be conveyed one after the other, e.g. in an accumulation or feeding section.
[0064] FIG. 2 shows a further embodiment of a device 1 . The difference in comparison with the embodiment shown in FIG. 1 is in the arrangement of the individual treatment units. In the embodiment shown in FIG. 2 , first preforms 10 and then containers 20 are produced, which are subsequently filled and closed and are not labelled until in a subsequent step. In this connection, a sterilisation unit 39 is provided between the blow moulding machine 4 and the filling unit 8 .
[0065] However, here too the closures 15 may be produced in a sterile room 25 , but unlike in the embodiment shown in FIG. 1 , the labelling process of the (filled) containers is here carried out outside of the sterile room 25 and thus on containers that have already been filled and/or closed. However, also in the case of the embodiment shown in FIG. 2 , the containers 20 are finally packaged. In the case of the embodiment shown in FIG. 2 , the synchronisation corresponds to the variant shown in FIG. 1 . Here, too, it would be conceivable that only the preforms 10 and possibly the produced containers 20 are sterilised, which is advantageous in so far as the preforms have a smaller surface area than the containers 20 .
[0066] While the present inventive concepts have been particularly shown and described above with reference to exemplary embodiments thereof, it will be understood by those of ordinary skill in the art, that various changes in form and detail can be made without departing from the spirit and scope of the present inventive concepts described and defined by the following claims.
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A method for producing plastic containers includes feeding plastic preforms to a shaping unit, shaping the plastic preforms to plastic containers, and filling the plastic containers with a liquid. The method further includes closing the plastic containers with plastic closures, wherein the plastic closures are produced of a plastic material and are heated during the manufacturing process.
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FIELD OF THE INVENTION
The present invention relates to interferon α-2a modified by Y-shaped branched polyethylene glycol (PEG) at a single amino acid residue and the preparation thereof, as well as the use of the prepared PEGylated IFN-α2a at a single amino acid residue in pharmaceutical field.
BACKGROUND OF THE INVENTION
Interferons (IFNs) are a family of small molecule proteins or glycoproteins produced by eukaryotic cells in response to viral infection and other antigenic stimuli, which display broad-spectrum antiviral, antiproliferative and immunomodulatory effects. IFNs have been widely applied in the treatment of various conditions and diseases, such as viral infections, e.g. hepatitis B, hepatitis C and HIV; inflammatory disorders and diseases, e.g. multiple sclerosis, arthritis, asthma, cystic fibrosis and interstitial lung disease; and tumors e.g. myelomas, lymphomas, liver cancer, lung cancer, hairy-cell leukemia, and so on (Kenji Oritani, Paul W Kincade, et al. Type I interferon and limitin: a comparison of structures, receptors, and functions. Cytokine and Growth Factor Reviews, 12, 337-348, 2001; Yu-Sen Wang, Stephen Youngster, et al. Structural and biological characterization of PEGylated recombinant interferon alpha-2b and its therapeutic implications. Advance Drug Delivery Reviews, 54, 547-570, 2002).
IFNs are classified into four types according to their differences in chemical, immunological, and biological properties: interferon-α, β, γ and ε. Interferon-α (IFN-α) is secreted by leukocytes. Human IFNs-α are encoded by a multigene family consisting of about 20 genes, the encoded proteins sharing up to about 90% amino acid sequence homology (Henco K., Brosius F. J., et al. J. Mol. Biol., 185, 227-260, 1985). Human IFN-α2a is one of the subtypes of the α2 subfamily of human IFN-α family, and is a single chain protein with various biological activities. The single chain protein consists of 165 amino acid residues, as shown in SEQ ID No.1, in which the N-terminal amino acid is Cys with one free α-NH 2 group, and the residues in positions 23, 31, 49, 70, 83, 112, 121, 131, 133, 134 and 164 of the amino acid sequence are Lys, each of which contains one free ε-NH 2 group.
IFNs are usually administered parenterally in clinical treatments. The short in vivo half-life (2-4 h) and strong immunogenicity of IFNs result in a shorter dosing interval and a higher dosing frequency. As the generated antibodies significantly decrease the therapeutic efficacy, it is difficult to achieve ideal clinical efficacy. The polyethylene glycol (PEG) modification technology developed in recent years has provided a possible solution to the above problems.
PEG is an inert, nontoxic and biodegradable organic polymer, and is important in the fields of both biotechnology and pharmaceutics. PEG modification technique is to link PEG to an active protein via covalent bond. After the PEGylation, the properties of the protein can be significantly improved, e.g. the prolongation of drug metabolic half-life, the reduction of immunogenicity, the increase of safety, the improvement of therapeutic efficacy, the decrease of dosing frequency, the increase of drug solubility/water solubility, the increase of resistance against proteolysis, the facilitation of drug controlled release and so on. For further details please refer to Inada et al. J. Bioact. and Compatible Polymers, 5, 343, 1990, Delgado et al. Critical Reviews in Therapeutic Drug Carrier Systems, 9, 249, 1992, Katre. Advanced Drug Delivery Systems, 10, 91, 1993, and U.S. patent publication U.S. Pat. No. 4,179,337.
It is disclosed in U.S. Pat. No. 4,179,337, after linking PEG to an enzyme or insulin, the immunogenicity of the protein was reduced, while simultaneously the activities of the protein were reduced as well. This was also found in G-CSF (Satake-Ishikawa et al. Cell Structure and Function, 17, 157-160, 1992), IL-2 (Katre et al. Proc. Natl. Acad. Sci. USA, 84, 1487, 1987), TNF-α (Tsutsumi et al. Jpn. J. Cancer Res., 85, 9, 1994), IL-6 (Inoue et al. J. Lab. Clin. Med., 124, 529, 1994) and CD4-IgG (Chamow et al. Bioconj. Chem., 5, 133, 1994).
Currently many kinds of PEGylated proteins have been applied clinically. In 1990, the PEGylated-bovine adenosine deaminase (Adagen) produced by ENZON Inc. was approved by FDA, and used to treat severe combined immunodeficiency disease (pegfamg013102LB). In 1994, another PEG-modified protein for treating acute lymphoblastic leukemia, the PEGylated asparaginase (pegaspargase, Oncaspar), was also marketed in US (103411s5052lbl). The PEG modified interferon-α2b (PEG IFN-α2b, PEG-Intron) developed by Schering-Plough was approved by FDA for marketing in 2000 and the PEGylated interferon-α (PEG IFN-α2a, Pegasys) produced by Hoffman-la Roche Ltd. was also approved for marketing in 2002, both of which are used to treat hepatitis (103964s5037lbl, pegsche011901LB). In 2002, the PEG modified human granulocyte colony-stimulating factor produced by Amgen Inc. (PEG-filgrastim, Neulasta) was also approved by FDA, which is used to treat metastatic breast cancer (pegfamg013102LB). The FDA also accepted the application for PEGylated human growth factor antagonist developed by Pharmacia. The PEG combined TNF-α antibody fragment from Celltech and the PEG-TNF receptor from Amgen are tested in the advanced clinical trials. The first PEG-organic molecule conjugate, PEGylated camptothecin, has also entered phase II of clinical trial. In 2004, the PEG modified oligonucleotide (Pegaptanib, Macugen™) was approved by FDA. The in vivo metabolism of the PEG in the drug (or PEG itself) has already been clearly understood, and PEG has been proven to be a good and safe drug modifier without any adverse effect.
Generally, a PEG molecule modifies a protein by linking itself to the N-terminal α-amino group or ε-amino group of an internal Lys residue in the protein molecule. There are normally three types of PEGs for protein modification: a linear chain molecule (EP 0593868), an U-shaped branched molecule (EP 0809996) and an Y-shaped branched molecule (CN1243779C). Up to now, there are still no reports about the preparation of Y-shaped branched PEG-modified IFN-α2a and the separation of different IFNs-α2a with a single PEG molecule modification at different amino acid positions. It was reported that the branched PEG-modified protein displayed better pH tolerance, thermo-stability and resistance against proteolysis than linear chain PEG-modified proteins (Monfardini et al. Bioconjugate Chem., 6, 62, 1995).
The PEGs that can be linked to a protein drug normally need to derivatized, so that one or two terminal groups of the ends of PEGs can be chemically activated to possess a proper functional group which displays activity, and thus can form a stable covalent bond with, at least one functional group of the drug to be linked. For example, PEGs can be linked to ε-NH 2 of a Lys residue within the protein peptide chain, or to α-NH 2 of the N-terminal amino acid residue of the protein peptide chain. In the PEGylation of IFN-α described in European patent EP0809996, PEG-NHS is linked through nucleophilic substitution to α-NH 2 of the N-terminal amino acid or ε-NH 2 of Lys in IFN-α. The PEG-NHS mentioned in the above patent is a U-shaped branched PEG derivative (PEG 2 -NHS), the molecular formula thereof as below:
wherein, R and R′ are independently a low molecular weight alkyl group, n and n′ are from 600 to 1500, and the average molecular weight of the PEGs is from 26 KD to 66 KD. The molecular formula of the PEG 2 -NHS-modified IFN-α is as below:
Where one or more PEG 2 -NHS molecules are linked to α-NH 2 of the N-terminal amino acid or ε-NH 2 of Lys in IFN-α, the obtained products are a mixture of non-PEGylated IFN-α, PEGylated IFNs-α at a single amino acid residue, and PEGylated IFNs-α at multiple amino acid residues. The PEGylated IFN-α at a single amino acid residue can be isolated from the obtained products by an appropriate purification means. IFN-α has one N-terminal amino acid and more than one Lys residues, namely several reactive sites for PEG 2 -NHS, so the isolated PEGylated IFNs-α at a single amino acid residue are a mixture of the isomers of the PEGylated IFNs-α at different single amino acid residues.
In European patent EP 0593868, linear-chain PEG is used to modify IFN, the molecular formula of the modified product as below:
wherein R is a low molecular weight alkyl group; R 1 , R 2 , R 3 and R 4 are H or low molecular weight alkyl groups; m is from 1 to the number of possible PEG modification positions in IFN; W is O or NH; x is from 1 to 1000, y and z are from 0 to 1000, x+y+z is from 3 to 1000; and at least one of R 1 , R 2 , R 3 and R 4 is a low molecular weight alkyl group, Yu-Sen Wang et al (Yu-Sen Wang et al, Advanced Drug Delivery Reviews, 54: 547-570, 2002. Yu-Sen Wang et al, Biochemistry, 39, 10634-10640, 2000.) have reported the modification of rIFN-α2b with 12 KD linear monomethoxy-PEG (Peg-Intron) and shown that the products analyzed by HPLC-IE are a mixture of more than 14 isomers modified by PEG at different single amino acid residues. The molecular formula of the linear PEG used by Yu-Sen Wang et al is shown below:
wherein the average molecular weight of the PEG is 12 KD.
SUMMARY OF THE INVENTION
The PEG derivatives used in the present invention are novel branched, Y-shaped branched PEG derivatives, and their structures are different from those of the U-shaped branched PEGs. The biggest difference between these two kinds of PEGs is that: two-branch PEG chains of the Y-shaped PEG derivatives according to the present invention are connected together through N atom, while the two-branch PEG chains of the U-shaped PEG derivatives in EP0809996 are connected together through C atom. The molecular composition of the Y-shaped PEG derivatives according to the present invention is shown as below:
wherein, P a and P b are same or different PEGs; j is an integer from 1 to 12; R i is H, a substituted or unsubstituted C1-C12 alkyl group, a substituted aryl, an aralkyl or a heteroalkyl; X 1 and X 2 are independently linking groups, wherein X 1 is (CH 2 ) n , and X 2 is selected from the group consisting of (CH 2 ) n , (CH 2 ) n OCO, (CH 2 ) n NHCO, and (CH 2 ) n CO; n is an integer from 1 to 10; and F is a terminal group selected from the group consisting of a hydroxyl group, a carboxyl group, an ester group, acyl chloride, hydrazide, maleimide, pyridine disulfide, capable of reacting with an amino group, a hydroxyl group or a mercapto group of a therapeutic agent or a substrate to form covalent bond. In one preferred embodiment of the present invention, the Y-shaped PEG derivative molecule is shown as below:
wherein, R and R′ are independently a C1-C4 alkyl group, preferably methyl; m and m′ denote the degree of polymerization and can be any integer; m+m′ is preferably from 600 to 1500; R i is H, a substituted or unsubstituted C1-C12 alkyl, a substituted aryl, an aralkyl, or a heteroalkyl group; j is an integer from 1 to 12; and F is a terminal group selected from the group consisting of a hydroxyl group, a carboxyl group, an ester group, carboxylic acid chloride, hydrazide, maleimide, pyridine disulfide, capable of reacting with an amino group, a hydroxyl group or a mercapto group of a therapeutic agent or a substrate to form a covalent bond. Preferably, the average total molecular weight of the PEG is from about 10000 to about 60000 Dalton, most preferably about 40000 Dalton.
In one preferred embodiment of the present invention, a possible structural formula of the Y-shaped PEG derivative molecule is shown as formula (I):
wherein R and R′ are independently a C1-C4 alkyl group, preferably methyl; m and m′ denote the degree of polymerization and can be any integer; m+m′ is preferably from 600 to 1500; j is an integer from 1 to 12; and the average total molecular weight of the PEG is about 40000 Dalton.
The present inventors used Y-shaped branched PEG derivatives (YPEG) to modify interferon-α2a (IFN-α2a), and isolated the YPEG-IFNs-α2a, modified by YPEG at a single amino acid residue, by Q-Sepharose FF ion-exchange chromatography. Moreover, the isolated YPEG-IFNs-α2a modified at a single amino acid residue were further separated by SP-Sepharose FF chromatography to obtain YPEG-IFN-α2a wherein the YPEG is principally linked to the side chain ε-NH 2 of Lys at position 134 in SEQ ID NO.1, which is called YPEG-IFN-α2a(134). After measurement, it is found that the in vitro activity of the YPEG-IFN-α2a(134) is significantly higher than that of the YPEG-IFN-α2a in which the YPEG is linked to another amino acid position, and the half-life of the YPEG-IFN-α2a(134) in serum is significantly longer than that of the unmodified IFN-α2a.
Therefore, the present invention provides PEGylated IFNs-α2a at a single amino acid residue, the structure of which is as below:
wherein P a and P b are same or different PEGs; j is an integer from 1 to 12; R i is H, a substituted or unsubstituted C1-C12 alkyl group, a substituted aryl, an aralkyl, or a heteroalkyl group; X 1 and X 2 are independently linking groups, wherein X 1 is (CH 2 ) n , and X 2 is selected from the group consisting of (CH 2 ) n , (CH 2 ) n OCO, (CH 2 ) n NHCO and (CH 2 ) n CO, wherein n is an integer from 1 to 10.
In one preferred embodiment of the present invention, the structural formula of the PEGylated IFN-α2a of the present invention is as below:
wherein R and R′ are independently a C1-C4 alkyl group, preferably methyl; j is an integer from 1 to 12; m and m′ denote the degree of polymerization and can be any same or different integers; m+m′ is preferably from 600 to 1500. In this structure, a Y-shaped branched PEG molecule is linked to an IFN-α2a molecule via one single amino acid residue. The average molecular weight of the YPEG-IFNs-α2a in formula (II) depends principally on the degree of polymerization, m and m′. Where m+m′ is preferably from 600 to 1500, the corresponding average molecular weight of the YPEG is from about 26000 to about 66000 Dalton. Where m+m′ is preferably from 795 to 1030, the corresponding average molecular weight of the YPEG is from about 35000 to about 45000 Dalton. Where m+m′ is preferably from 885 to 1030, the corresponding average molecular weight of the YPEG is from about 39000 to about 45000 Dalton. Where m+m′ is most preferably 910, the corresponding average molecular weight of the YPEG is 40000 Dalton. The ratio of m and m′ can be in a range from 0.5 to 1.5, preferably from 0.8 to 1.2.
In one preferred embodiment, in the PEGylated IFN-α2a of the present invention, a PEG molecule is linked to IFN-α2a via an amido bond formed by α-amino group of the N-terminal amino acid or the side chain ε-amino group of Lys residue of IFN-α2a corresponding to position 23, 31, 49, 70, 83, 112, 121, 131, 133, 134, or 164 as shown in SEQ ID No.1.
In a further preferred embodiment, in the PEGylated IFN-α2a of the present invention, a PEG molecule is linked to IFN-α2a via an amido bond principally formed by the side chain ε-amino group of Lys residue of IFN-α2a corresponding to position 134 as shown in SEQ ID No. 1.
Optionally, the IFN-α2a of the present invention can be extracted from natural sources or obtained by the recombinant biotechnology. Preferably, the IFN-α2a is human IFN-α2a (hIFN-α2a) having the amino acid sequence of SEQ ID No.1, which is extracted from natural sources or obtained by the recombinant biotechnology. More preferably, the human IFN-α2a is recombinant human IFN-α2a (rhIFN-α2a). The rhIFN-α2a can be artificially synthesized, or be expressed from prokaryotic expression systems such as E. coli , or be expressed from eukaryotic yeast expression systems such as Pichia , or be expressed from insect cell expression systems or mammalian cell expression systems such as CHO. The preparation methods of the natural or recombinant IFN-α2a and the activity tests of IFN-α2a and YPEG modified IFN-α2a are known in prior art.
Similar to IFN-α2a, the YPEG-IFN-α2a of the present invention can also be used clinically to treat tumors and viral infections, such as hepatitis, hairy-cell leukemia, cell-mediated lympholysis, Kaposi's sarcoma and so on. In clinical, the YPEG-IFN-α2a of the present invention is clearly improved, as compared to IFN-α2a, in stability, solubility, half-life in serum and clinical therapeutic efficacy. For the mode of administration, the YPEG-IFN-α2a of the present invention can be administered to the patients in the form of a composition comprising a pharmaceutically effective amount of the YPEG-IFN-β2a and a pharmaceutically acceptable carrier or excipient. Hence, the present invention, in another aspect, also provides a composition comprising a pharmaceutically effective amount of the PEGylated IFN-α2a of the present invention and a pharmaceutically acceptable carrier or excipient. Preferably, the composition comprises mannitol, an amino acid, sodium chloride and sodium acetate, wherein the amino acid is preferably selected from the group consisting of aspartic acid, asparagine and glycine.
In another aspect, the present invention also provides the use of the PEGylated IFN-α2a of the invention or the composition comprising the PEGylated IFN-α2a of the invention in the preparation of a medicament for treating a disease in need of IFN-α2a treatment. Preferably, the disease in need of IFN-α2a treatment is selected from the group consisting of viral infections e.g. hepatitis B, hepatitis C, hepatitis D and condyloma acuminatum, tumors e.g. hairy-cell leukemia, chronic myeloid leukemia, low-grade malignant non Hodgkin's leukemia, cell-mediated lympholysis, Kaposi's sarcoma, multiple myeloma, malignant melanoma, cutaneous T-cell lymphoma, laryngeal papilloma, recurrent or metastatic renal cell carcinoma, inflammatory disorders and diseases e.g. multiple sclerosis, arthritis, asthma, cystic fibrosis and interstitial lung disease, and myeloproliferative diseases related thrombocythemia.
In order to obtain the YPEG modified IFN-α2a, in one embodiment of the present invention, initially the PEG moiety of activated YPEG derivatives such as PEG N-hydroxyl succinimidyl ester (YPEG-NHS) is covalently linked to an amino (—NH 2 ) group of the protein through nucleophilic substitution, wherein the amino group includes N-terminal α-amino group and an ε-amino group of Lys residue of the protein. The reaction equation for the generation of YPEG-IFN-α2a from IFN-α2a and YPEG is as below:
The reaction conditions are mild, the pH is in a range from 4.5 to 9.5, the temperature is between 0-25° C., and stirring or other blending measures are necessary. For detailed conditions please refer to the Examples in DETAILED DESCRIPTION OF THE INVENTION. All YPEGs with different molecular weights can be linked to IFN-α2a using the above method. The products include IFNs-α2a modified at a single amino acid residue (YPEG-IFN-α2a), IFNs-α2a modified at two amino acid residues (YPEG 2 -IFN-α2a) and IFNs-α2a modified at multiple amino acid residues (YPEG n -IFN-α2a), wherein the products modified at a single amino acid residue can be the predominant products by adjusting the reaction condition.
Subsequently, the YPEG-IFNs-α2a, modified by PEG at a single amino acid residue, can be isolated from the mixture of all kinds of the YPEG modified IFNs-α2a using a method such as cation exchange chromatography, anion exchange chromatography, or exclusion chromatography, and then the IFNs-α2a modified by PEG at different single amino acid residues can be further resolved to obtain the YPEG-IFN-α2a in which the YPEG is linked at a specific position. Conventional purification methods include cation exchange chromatography, anion exchange chromatography, hydrophobic interaction chromatography and exclusion chromatography. Characteristic analysis can be performed by a known method in the art, e.g. the mass spectroscopy, the polyacrylamide gel electrophoresis and the high-performance liquid exclusion chromatography can be used to analyze the molecular weight of the products, so as to distinguish the products modified by PEG at a single amino acid residue from those modified by PEG at two or multiple amino acid residues and unmodified IFN-α2a. The above mentioned purification methods can also be used to further resolve the products modified by PEG at a single amino acid residue to obtain different isomers with the PEG modification at different single positions. The in vitro biological activities of all kinds of the PEG modified products can be measured according to any known assay for IFN-activity, e.g. cytopathic effect inhibition. For IFNs modified by PEG at a single amino acid residue, the PEG moieties in the different isomers have different effects on maintaining the active domains of IFNs, resulting in the great differences in the biological activities of different isomers. Generally speaking, the in vitro activities of IFNs are remarkably decreased after PEG modification. However, according to the present invention, the in vitro specific activity of the isolates of three peaks obtained by ion exchange chromatography have been measured, and the results indicate that the isolate of peak 3 (SP2) has significantly higher specific activity than the isolates of other peaks and PEGASYS (Hoffmann-La Roche, Basel, Switzerland), and has significantly longer half-life in serum than unmodified IFN-α2a.
In a further embodiment, the Y-branched PEG-linked peptide of the SP2 was sequenced using Edman degradation, and the results showed that the primary component of SP2 was YPEG-IFN-α2a(134).
Hence, in another aspect, the present invention also provides the preparation and purification methods for YPEG-IFN-α2a, comprising:
(a) under an alkaline condition, preferably at pH 9.0, allowing Y-shaped branched PEG as shown in formula (I) below to react with IFN-α2a, and obtaining PEGylated IFN-α2a;
wherein R and R′ are independently a C1-C4 alkyl group, preferably methyl; j is an integer from 1 to 12; m and m′ denote the degree of polymerization and can be any integer; and m+m′ is preferably from 600 to 1500;
(b) capturing the reaction products in step (a) with an anion exchange resin, preferably Q Sepharose FF, and eluting the products in an anion gradient, preferably in a chloride ion gradient, to obtain modified products;
(c) eluting the reaction products captured in step (b) with a cation exchange resin, preferably SP Sepharose FF, in a cation gradient, preferably in a sodium ion gradient, and collecting each peak separately:
(d) determining the activity of the product from each peak, and selecting the peak corresponding to the reaction product with the highest activity.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 : SDS-PAGE of 3 batches of IFN-α2a modified with YPEG (40 KD). The concentration of the separation gel was 12%, and Coomassie brilliant blue R-250 was used as staining dye. Lanes 1-2: 20060804; Lanes 3-4: 20060807-1; Lanes 5-6: 20060807-2.
FIG. 2 : The resolving profile of YPEG-IFN-α2a modification isomers by SP-Sepharose FF.
FIG. 3 : Silver-stained SDS-PAGE (12%) of the YPEG-IFN-α2a samples purified through SP-Sepharose FF. Lanel: molecular weight marker; Lanes 2, 4, 6, 8, blank; Lanes 3, 5, 7, 9, corresponding respectively to peaks 1 to 4 in the elution profile.
FIG. 4 : Apparent molecular weights of the YPEG-IFN-α2a modification isomers in silver-stained SDS-PAGE. Lane 1: molecular weight marker (GE Lifesciences); Lane 2: YPEG-IFN-α2a SP3, 0.4 μg; Lane 3: YPEG-IFN-α2a SP2, 0.4 μg; Lane 4. YPEG-IFN-α2a SP1, 0.4 μg.
FIG. 5 : The molecular weights of the YPEG-IFN-α2a samples purified through SP-Sepharose FF by MALDI-TOF MS. YPEG-IFN-α2a SP1 corresponds to the sample in lane 4 of FIG. 4 , YPEG-IFN-α2a SP2 corresponds to the sample in lane 3 of FIG. 4 , and YPEG-IFN-α2a SP3 corresponds to the sample in lane 2 of FIG. 4 .
FIG. 6 : The molecular weight of YPEG-NHS (40 KD) by MALDI-TOF MS.
FIG. 7 : The serum concentration of the drug and 2′, 5′-A concentration after a single s.c. injection of 30 μg·kg −1 YPEG-rhIFN-α2a SP2 into Crab-eating Macaque ( Macaca fascicularis ).
FIG. 8 : The analysis of Trypsinase Peptide Mapping of the trypsin digested (Oh) YPEG-IFN-α2a SP2 sample by HPLC-RP C 18 . The retention time of YPEG-IFN-α2a SP2 was 62.105 min, the elution peak at 71.882 min was the solvent background, and elution peaks at 2-3 min were trypsin.
FIG. 9 : The analysis of Trypsinase Peptide Mapping of the trypsin digested (48 h) YPEG-IFN-α2a SP2 sample by HPLC-RP C 18 . Solvent peak at 71.581 min was detected, corresponding to the solvent peak at 71.882 min in the trypsin digested (Oh) sample. No substrate protein peak (62.105 min) was detected between 59.5 min and 62.5 min, demonstrating the sample was substantially completely digested.
FIG. 10 : Sephacryl S-100 HR separation profile of the YPEG modified peptides from the trypsin completely digested YPEG-IFN-α2a SP2 sample.
DETAILED DESCRIPTION OF THE INVENTION
The present invention will be further described by the following examples, but any example or the combination thereof should not be understood as limiting the scope or embodiment of the invention. The scope of the invention is limited only by the appended claims. In combination with the description and prior art, skilled persons in the art would clearly understand the scope limited by the claims.
Example 1
Preparation of Y-Shaped Branched Peg Modified Recombinant Human IFN-α2a
(1) Small-Scale Preparation of Y-Shaped Branched Peg Modified Recombinant human IFN-α2a
166.3 mg of YPEG (formula (I), average molecular weight 40 KD, equal-arm, lot number RD010P041, Beijing JenKem Technology Co., Ltd.) was weighted and dissolved in 1 ml of 2 mM HCl (Guangdong Guanghua Chemical Factory Co., Ltd.). 40 mg of IFN-α2a (Xiamen Amoytop Biotech Co., Ltd.) and 50 mM of boric acid-borax buffer (pH 9.0, Sinopharm Shanghai Chemical Reagent Co., Ltd.) were added to a final reaction volume of 10 ml. In this reaction system, the final concentration of IFN-α2a was 4 mg/ml, and the reaction molar ratio of IFN-α2a and YPEG was 1:2. The reaction system was kept under 0-25° C. for 2 h with stirring. The PEGylated IFNs-α2a were then generated, and the reaction was stopped by adding glacial acetic acid (Shantou Xilong Chemical Co., Ltd.) to make pH<4.0. A sample was subjected for SDS-PAGE. The reaction system was diluted 50 times with water and then 0.2 μm filtered before stored at 4° C. for further use.
Q-Sepharose FF Chromatography was used to separate the remaining PEG and PEG hydrolates, IFNs-α2a modified by YPEG at multiple amino acid residues, IFNs-α2a modified by YPEG at a single amino acid residue and the unmodified IFN-α2a. Q-Sepharose FF (GE Healthcare) column (Φ12 mm×90 mm, 1 CV=10 ml) was regenerated with 3 column volume (CV) of 20 mM boric acid/borax buffer (pH9.0)-1M NaCl (BBI), and then equilibrated with 5 CV of 20 mM boric acid/borax buffer (pH9.0). UV detection wavelength was set at 280 nm. The entire sample stored at 4° C. was loaded. After loading, the column was equilibrated with 3 CV of boric acid/borax buffer (pH9.0), and then 20 mM boric acid/borax buffer (pH9.0)-12 mM NaCl was used for elution until the first peak was completely eluted, which peak was the remaining PEG. 20 mM boric acid/borax buffer (pH9.0)-60 mM NaCl was then used for elution, and the sample collected in this elution peak was primarily the YPEG-IFNs-α2a, modified by PEG at a single amino acid residue. And then 20 mM boric acid/borax buffer (pH9.0)-500 mM NaCl was used for elution and the elution peak was the unmodified IFN-α2a.
The target products were primarily the products modified by PEG at a single amino acid residue, YPEG-IFNs-α2a, with a yield rate of 20-40%.
(2) Large-Scale Preparation of Y-Shaped Branched Peg Modified Recombinant Human IFN-α2a
4989.6 mg of YPEG (formula (I), average molecular weight 40 KD, equal-arm, lot number RD010P041, Beijing JenKem Technology Co., Ltd.) was weighted and dissolved in 25 ml of 2 mM HCl. And 1200 mg of IFN-α2a and 50 mM boric acid/borax buffer (pH 9.0) were added to a final reaction volume of 200 ml. In this reaction system, the final reaction concentration of IFN-α2a was 6 mg/ml, and the reaction molar ratio of IFN-α2a and YPEG was 1:2. The reaction system was kept under 0-25° C. for 2 h with stirring. The reaction was stopped by adding glacial acetic acid to make pH<4.0. A sample was subjected for SDS-PAGE. The reaction system was diluted 50 times with water and then 0.2 μm filtered before stored at 4° C. for further use.
Q-Sepharose FF Chromatography was used to separate the remaining PEG and PEG hydrolates, IFNs-α2a modified by YPEG at multiple amino acid residues, IFNs-α2a modified by YPEG at a single amino acid residue and the unmodified IFN-α2a. Q-Sepharose FF (GE Healthcare) column (Φ38 mm×265 mm, 1 CV=300 ml) was regenerated with 3 CV of 20 mM boric acid/borax buffer (pH9.0)-1M NaCl, and then equilibrated with 5 CV of 20 mM boric acid/borax buffer (pH9.0). UV detection wavelength was set at 280 nm. The entire sample stored at 4° C. was loaded. After loading, the column was equilibrated with 3 CV of 20 mM boric acid/borax buffer (pH9.0), and then 20 mM boric acid/borax buffer (pH9.0)-12 mM NaCl was used for elution until the first peak was completely eluted, which peak was the remaining PEG 20 mM boric acid/borax buffer (pH9.0)-60 mM NaCl was then used for elution, and the sample collected in this elution peak was primarily the YPEG-IFNs-α2a, modified by PEG at a single amino acid residue. And then 20 mM boric acid/borax buffer (pH9.0)-500 mM NaCl was used for elution and the elution peak was the unmodified IFN-α2a.
The target products were primarily the products modified by PEG at a single amino acid residue, YPEG-IFNs-α2a, with a yield rate of 35-50%.
FIG. 1 shows SDS-PAGE results for 3 batches of IFNs-α2a modified with YPEG (40 KD). It can be seen from FIG. 1 that under the condition, the PEG modification rate of rhIFN-α2a was between 35-50% and remained stable. The primary modified products were modified by PEG at a single amino acid residue, and there were also some products modified by PEG at multiple amino acid residues.
Example 2
Resolving YPEG-IFNs-α2a by SP-Sepharose FF
The Q-Sepharose FF captured YPEG-IFN-α2a sample was adjusted to pH 5.0 with 20% acetic acid, then diluted 15 times with 5 mM NaAc/HAc (pH5.0, Shantou Xilong Chemical Co., Ltd.). The sample was loaded at 0.5 mg/ml loading capacity to SP-Sepharose FF 100 ml (GE Healthcare) column (Φ18 mm×394 mm). The column was equilibrated with 3 CV of 5 mM NaAc/HAc (pH5.0), and then eluted with 2.5 CV of the gradient of 0%-30% 5 mM NaAc/HAc-70 mM NaCl (pH5.0), following with 50 CV of the gradient of 30%-100% 5 mM NaAc/HAc-70 mM NaCl (pH5.0). YPEG-IFN-α2a was resolved as 4 elution peaks by SP-Sepharose FF 100 ml. The samples were collected according to these peaks and then tested by SDS-PAGE with silver staining respectively. According to the SDS-PAGE results, it can be seen that peak 1 resolved by SP-Sepharose FF was primarily the products modified by YPEG at multiple amino acid residues (YPEG n -IFN-α2a). Peak 2 by SP-Sepharose FF was primarily the products modified by PEG at a single amino acid residue (YPEG-IFN-α2a), and also contained some products modified by PEG at multiple amino acid residues. Peak 3 and peak 4 by SP-Sepharose FF were both the products modified by PEG at a single amino acid residue. Peaks 2-4 resolved by SP-Sepharose FF were isomers modified with YPEG at different single positions, and were named respectively as YPEG-IFN-α2a SP1, YPEG-IFN-α2a SP2 and YPEG-IFN-α2a SP3. The resolution profile and silver-stained SAD-PAGE results were shown in FIG. 2 and FIG. 3 respectively.
Every sample of YPEG-IFN-α2a SP1-3 was supplemented with sodium chloride, sodium acetate, mannitol, aspartic acid and was sterilized with 0.22 μm filter before stored at 4° C. for further use.
Example 3
Characteristic Analysis of YPEG-IFN-α2a Modification Isomers
(1) Protein Concentration by Kjeldahl Method
The concentrations of YPEG-IFN-α2a modification isomers were determined by Kjeldahl method.
(2) Protein Apparent Molecular Weight
The apparent molecular weights of YPEG-IFN-α2a modification isomers were determined by SDS-PAGE. The method was according to Laemmli et al (Nature 227: 680, 1970). The concentration of the gel was 7.5%, and the gel was visualized by silver staining. The apparent molecular weights of YPEG-IFN-α2a modification isomers were almost the same, about 120 KD ( FIG. 4 ).
(3) Molecular Weight Determined by MALDI-TOF MS
MALDI-TOF MS (Autoflex TOF/TOF system, Bruker Daltonics, Germany) was used to determine the molecular weights of YPEG-rHuIFN-α2a modification isomers. Sinapinic acid (SA, C 11 H 12 O 5 , M.W. 224.22, lot number: 2006 236870 002, Bruker Daltonics, Germany) was used as matrix. Protein Calibration Standard II (Part No. 207234, Bruker Daltonics, Germany) was used as protein molecular weight standard, and the software for data analysis was FlexAnalysis Ver.3.0.54.0. The MS molecular weights of YPEG-IFN-α2a modification isomers were almost the same, about 59000 Dalton ( FIG. 5 ).
(4) Protein Purity
The purity of YPEG-IFN-α2a modification isomers was determined by HPLC-SE. HPLC column was TSK G4000 SW XL (Φ7.8 mm×300 mm, TOSOH), the sample loading volume was 20 μl (about 10 μg protein), the mobile phase was 0.1M PBNa-0.1M NaCl (pH7), the flow rate was 0.8 ml/min, and the detection wavelength was set at 280 nm. The YPEG-IFN-α2a SP2 was a single main peak, with a purity more than 99%.
(5) Endotoxin Content Test
Based on limulus assay ( Pharmacopoeia of the People's Republic of China, 2005, Volume 3, Appendix X C), the endotoxin content of every YPEG-IFN-α2a sample was less than 5.0 EU/mg.
(6) In Vivo Activity and Pharmacokinetics of YPEG-IFN-α2a SP2 in Animal.
{circle around (1)} In vivo activity of YPEG-IFN-α2a SP2 in animal.
The action mechanism of IFN is partially to induce the production of 2′,5′-AS (2′,5′-oligoadenylate synthetase), which in turn exerts its antiviral effects. Using 125 I as tracer, the pharmacodynamic parameters of IFN are reflected by the in vivo 2′,5′-AS activity. 2′,5′-AS catalyzes the synthesis of 2′,5′-A (2′,5′-oligoadenylate) from ATP in the presence of Poly(I)·Poly(C) agar (The activity of 2′,5′-AS can be represented by the concentration of the synthesized 2′,5′-A). First, 2′,5′-AS in the samples are absorbed and activated by Poly(I)·Poly(C) agarose, then catalyzes the substrate ATP to generate 2′,5′-A. A mixture of 125 I labeled 2′,5′-A, anti-2′,5′-A serum and secondary antibody is added into the sample which then is incubated and centrifugated to separate the mixture. The supernatant is discarded and a Gamma Counter is used to measure the radioactivity of the sediment. The binding rate of the initially added 125 I labeled 2′,5′-A is calculated. Four-parameter Logistic regression is used to generate standard curve, and then the concentration of the 2′,5′-AS-induced 2′,5′-A product in an unknown sample could be estimated.
Using the above mentioned 2′,5′-A method, the results in Table 1 and FIG. 7 showed the serum 2′,5′-A concentration after a single s.c. injection of 30 μg·kg −1 YPEG-rhIFN-α2a SP2 into Crab-eating Macaque ( Macaca fascicularis ) (15 Crab-eating Macaques, 7 female and 8 male. Laboratory Animal Center of the Academy of Military Medical Sciences, Certification No. SCXK-(MIL)2002-001. Body weight 2.5-3.7 kg, raised in separate cages, fed with standard monkey feed, drink freely). It can be seen from FIG. 5 , after administration, the activity of 2′,5′-AS in serum was clearly increased, and the time-to-peak of 2′,5′-A in serum was delayed than that of YPEG-IFN-α2a SP2. The average time-to-peak was 24±18.33 h, and the concentration to peak was 104.31±56.39 Pmol·dL −1 .
TABLE 1 The serum 2′,5′-A concentrations over time, after a single s.c. injection of 30 μg·kg −1 YPEG-rhIFN-α2a SP2 into Crab-eating Macaque. (Pmol · dL −1 ) No. of crab-eating Macaque Time (h) 1 2 3 Mean SD 0 16.08 19.01 42.91 26.00 ± 14.72 1 39.04 — 16.19 27.61 ± 16.16 2 48.21 16.90 20.20 28.44 ± 17.21 4 55.22 36.09 74.16 55.15 ± 19.04 8 32.04 59.69 99.52 63.75 ± 33.92 10 13.52 41.21 51.85 35.53 ± 19.79 12 37.35 53.32 119.76 70.14 ± 43.71 24 58.29 167.22 87.42 104.31 ± 56.39 48 77.50 160.67 71.41 103.19 ± 49.87 72 62.88 165.97 58.52 95.79 ± 60.82 96 73.53 119.79 90.85 94.72 ± 23.37 168 45.41 135.26 68.92 83.20 ± 46.60 240 48.14 102.61 73.97 74.90 ± 27.25 312 93.23 21.69 62.84 59.26 ± 35.90
{circle around (2)} Pharmacokinetics of YPEG-IFN-α2a SP2 and rhIFN-α2a in Crab-eating Macaque
A single s.c. injection of 7.5, 30 or 120 μg·kg −1 YPEG-IFN-α2a SP2 was given to Crab-eating Macaque. For the administration group, 1 ml of venous blood was taken from the hind leg opposite to the injected side at the time before, 1 h, 2 h, 4 h, 8 h, 10 h, 12 h, 24 h, 48 h, 72 h, 96 h, 168 h, 240 h, and 312 h after administration. For the group with a single s.c. injection of rhIFN-α2a (7.5 μg·kg −1 ), 1 ml of blood was taken at the time before, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, and 24 h after administration. After kept at 4° C. for 30 min, the blood samples were centrifugated at 2000 rpm for 10 min under low temperature, then the serum was separated immediately and stored at −20° C. for further analysis.
The quantitative double sandwich immunoassay was used. A monoclonal antibody specific to the recombinant human IFN-α, was pre-coated on microtiter plate. The standard and the samples were pipetted into the microtiter wells, wherein the rhIFN-α2a or YPEG-IFN-α2a SP2 would bind to the immobilized antibody. The plate was washed to remove unbound substances, and then anti-human IFN-α IgG (secondary antibody) was added into the wells. After the reaction was complete, the plate was washed and the horseradish peroxidase (HRP) was added into the wells. After washing away the unbound enzyme and reagents, the color generated by adding HRP substrate solution into each well was proportional to the amount of the bound IFN-α2a or YPEG-IFN-α2a SP2 in the first step. The reaction was stopped and the color intensity was measured. The higher the OD value of absorbance, the higher the concentration of IFN-α2a or YPEG-IFN-α2a SP2 in the sample. The standard curves were plotted for IFN-α2a and YPEG-IFN-α2a SP2 respectively so as to measure the serum drug concentration in the blood samples.
According to the protocol in the description of the kit (American Biomedical Co., lot number 3271), 100 μl standard or blood sample was added into each well, and mixed with plate mixer gently. According to the anticipated concentration of an unknown sample, the sample was diluted with the dilute solution to the concentration ranges of the standard curve. The rhIFN-α2a or YPEG-IFN-α2a SP2 standard curve for each plate was plotted so as to calculate the concentration of the unknown sample in that plate. The plate was incubated at room temperature for 1 h, and washed once with plate washing solution. 100 μl secondary antibody was added to each well, and kept under room temperature for 1 h. The plate was washed 3 times, and 100 μl HRP conjugate was added to each well. The plate was incubated under room temperature for 1 h and washed 4 times. 100 μl TMB substrate was added into each well, and kept under room temperature in the dark for 15 min. 100 μl stop solution was added to each well, and mixed gently to stop the reaction. The absorbance OD value at 450 nm was measured with a microplate reader within 5 min to determine the concentration of each sample.
After a single s.c. injection of 7.5, 30 or 120 μg·kg −1 YPEG-rhIFN-α2a into Crab-eating Macaque, the half-lives were 35.81±2.50, 31.38±11.84 and 36.77±2.24 h, respectively. After a single s.c. injection of 7.5 μg·kg −1 rhIFN-α2a into Crab-eating Macaque, the half-life was 3.02±0.55 h. The half-life of rhIFN-α2a was significantly prolonged after PEGylation.
(7) In Vitro Specific Activity
The in vitro biological activity of each YPEG-IFN-α2a modification isomers was estimated using cytopathic effect inhibition assay. According to the method described in Determination Method of Interferon Activity ( Pharmacopoeia of the People's Republic of China, 2005, Volume 3, Appendix X C), interferon protects human amniotic cells (WISH) from the damage caused by vesicular stomatitis virus (VSV). Crystal violet was used to stain survived WISH cells, and the absorbance OD value was measured at 570 nm. The interferon protection effect curve was plotted for WISH cells, so as to determine the in vitro biological activity of interferons. The results of in vitro biological activity of each samples are shown in Table 2, and 3 parallel tests were carried out for each sample. After YPEG modification, in all the modification isomers of the products modified by PEG at a single amino acid residue, the SP2 sample showed the highest in vitro specific activity, which was 1-2 times higher than SP1 and SP3, and also 1-2 times higher than the unresolved sample and PEGASYS (manufactured by Hoffmann-La Roche, Basel, Switzerland; packaged separately by Shanghai Roche Pharmaceuticals Ltd., product lot number B1016, package lot number SH0020).
TABLE 2 In vitro biological activity results for each modification isomer of YPEG-IFN-α2a (3 parallel tests) Average PEG No. of Specific M.W. Modification Activity Sample PEG Type (KD) Positions (×10 6 IU/mg) YPEG-IFN-α2a SP1 Y-branched 40 1 1.04 ± 0.110 YPEG-IFN-α2a SP2 Y-branched 40 1 2.26 ± 0.129 YPEG-IFN-α2a SP3 Y-branched 40 1 1.11 ± 0.091 YPEG-IFN-α2a Y-branched 40 1 1.01 ± 0.173 unresolved sample PEGASYS U-branched 40 1 0.903 ± 0.056
(8) The Resolution of the Modification Position in YPEG-IFN-α2a SP2
The solvent system of YPEG-IFN-α2a SP2 was changed to 50 mM NH 4 HCO 3 (pH8.0) by ultrafiltration with 5K ultrafilter (Millipore, polyethersulfone material), and the protein concentration was determined to be 4.02 mg/ml using UV spectroscopy. TPCK Trypsin (Promega) was dissolved (0.5 μg/μl) in the solution provided by the manufacturer. Samples were added according to Table 3:
TABLE 3
Reaction composition of YPEG-IFN-α2a SP2 trypsin digestion
Reaction Components
Volume
50 mM NH 4 HCO3, pH8.0
7.15 ml
PEG-IFN-α2a SP2 (4.02 mg/ml)
1.25 ml
Trypsin (0.5 μg/μl)
0.2 ml
Total reaction volume
8.6 ml
The reaction system was kept in a water bath at 37° C. for 48 h, then 1.52 ml of 20% acetic acid was added to stop the reaction. A small amount of sample was taken for HPLC-RP C18 peptide mapping. The instrument for analysis was Waters HPLC system, with a controller of type 600, 2487 double wavelength detector, and the software for data processing was Empower 2. The HPLC analytical column was Jupiter C18 (particle diameter 5 μm, pore diameter 300 Å, (Φ4.6×150 mm, produced by Phenomenex, USA). Mobile phase A was 0.1% TFA/H 2 O, Mobile phase B was 0.1% TFA/90% ACN/H 2 O, the flow rate was 1 mL/min, and the detection wavelength was set at 214 nm. Please refer to Table 4 for the elution gradients, and the results were shown in FIG. 8-9 .
TABLE 4
The elution gradients for HPLC-RP C18 peptide mapping
of the trypsin digested YPEG-IFN-α2a SP 2
Time (min)
A %
B %
ACN %
1
0
100
0
0
2
8
100
0
0
3
68
40
60
54
4
72
40
60
54
5
75
100
0
0
6
80
100
0
0
Based on the detection results, it can be determined that the sample was almost completely digested. The products were treated with DTT reduction after the reaction was stopped. The Sephacryl S-100HR column (Φ18×255 mm, 1 CV-64 ml; GE Healthcare) was pre-equilibrated with 3 CV of 20 mM PBNa-400 mM NaCl (pH7.0), and 3% CV of the YPEG-IFN-α2a SP2 sample by TPCK trypsin digested completely was loaded by hydrostatic pressure. 20 mM PBNa-400 mM NaCl (pH7.0) was used for elution, and the detection wavelength was set at 280 nm. The sample from the first elution peak was collected (sample number: YPEG-IFN-α2a S100-1, FIG. 10 ), and the solvent system was changed to 5 mM PBNa (pH 7) with 5K ultrafilter. Vacuum freeze-drying was done. The N-terminal amino acids of the freeze-dried sample were determined using Edman degradation, and the sequence of the 7 amino acids at the N-terminus of the sample was XYSPXAW (Table 5), wherein X denotes α-amino acid cysteine (Cys), a non-α-amino acid or another modified amino acid that cannot be detected using Edman degradation. According to the sequence shown in SEQ ID NO: 1, it can be determined that the YPEG-IFN-α2a SP2 was primarily the product modified by YPEG at Lys134.
TABLE 5
Sequencing result for the N-terminal
amino acids of YPEG-IFN-α2a S100-1
Detected
The corresponding
N-terminal
PEG modification
Sample
Sequence
position.
YPEG-IFN-α2a S100-1
XYSPXAW
Lys134
Note:
X denotes α-amino acid cysteine, a non-α-amino acid or another modified amino acid that cannot be detected using Edman degradation.
|
The present invention relates to interferon (IFN)-α2a modified at a specific Lys residue with Y-shaped branched polyethylene glycol (PEG) derivative and the preparation thereof, as well as the use of the prepared IFN-α2a modified by PEG at a single amino acid residue in medicines.
| 0 |
CROSS REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of the following provisional application; Ser. No. 60/421,950, filed Oct. 29, 2002, under 35 U.S.C. 119(e)(1).
FIELD OF THE INVENTION
[0002] The invention relates generally to the process of target validation in the pharmaceutical industry.
BACKGROUND
[0003] The pharmaceutical industry abandons many compounds in the early stages of clinical development due to the discovery of toxic effects in humans. Because of the years of animal testing that precedes testing in humans, this is an expensive loss. To reduce expenses, it is desirable to identify compounds with adverse effects early and eliminate them from further development. Additionally, if adverse effects could be identified earlier, it may be possible to design safer compounds at an earlier stage, thus significantly accelerating the time required to develop drugs that are both safe and efficacious. One early stage for identifying potential problems is during the selection of molecular targets that will be inhibited or stimulated by new drugs. This process is termed “target validation.”
[0004] One problem with the present path of drug development is that the test animals are kept in uniform, carefully controlled environments. While this allows reproducible and scientifically accurate data collection, it does not accurately mimic the human situation, in which people are exposed to concurrent illnesses, psychological stresses, traumatic injury, nutritional problems, and other common physiologic perturbations.
[0005] Here, we propose a process in which target validation can be efficiently tested in animals using defined perturbations and a clearly defined, measurable, and rapid method to analyze the results.
Literature Cited
[0006]
1. Brayton, C., M. Justice, and C. A. Montgomery. 2001. Evaluating mutant mice: Anatomic pathology. Veterinary Pathology 38:1-19.
2. Campbell, K. H. S., J. McWhir, W. A. Ritchie, & I. Wilmut, 1996. Sheep Cloned by Nuclear Transfer from a Cultured Cell Line, Nature 380: 64-66.
3. Gavaghan, C. L., E. Holmes, E. Lenz, I. D. Wilson, and J. K. Nicholson. 2000. An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk: ApfCD mouse. FEBS Letters 484: 169-174.
4. Griebel, G., J. Simiand, R. Steinberg, M. Jung, D. Gully, P. Roger, M. Geslin, B. Scatton, J. P. Maffrand, and P. Soubrie. 2002. 4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factor(1) receptor antagonist. II. Characterization in rodent models of stress-related disorders. Journal of Pharmacology and Experimental Therapeutics 301:333-345.
5. Houdebine, L. M.; Transgenic Animal Generation and Use, Harwood Academic Press, 1997.
6. Robertson, D. G., M. D. Reily, J. C. Lindon, E. Holmes, and J. K. Nicholson. 2002. Metabonomic technology as a tool for rapid throughput in vivo toxicity screening, p. 583-626. In J. P. Vanden Heuvel, G. H. Perdew, W. B. Mattes, and W. F. Greenlee (ed.), Comprehensive Toxicology, vol. 14. Elsevier, Amsterdam.
7. Robertson, D. G., E. M. Urda, M. A. Breider, and R. M. Gauthier. 1998. Evaluation of hepatic toxicity of seven-day repeated-dose glutathione-depleting regimens in rats. Toxicology Methods 8:233-244.
8. Warren, T. K., K. A. Mitchell, and B. P. Lawrence. 2000. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses the humoral and cell-mediated immune responses to influenza A virus without affecting cytolytic activity in the lung. Toxicological Sciences 56: 114-123.
9. Wilmut, I., A. E. Schnieke, J. McWhir, A. J. Kind, & K. H. S. Campbell, 1997. Viable Offspring Derived From Fetal and Adult Mammalian Cells. Nature, 385: 810-813.
Books
[0015]
10. Sundberg, J. P., and D. Boggess. 2000. Systematic approach to evaluation of mouse mutations, 1 ed. CRC Press, Boca Raton, Fla.
11. Tymms, M. J., and I. Kola. 2001. Gene knockout protocols. Humana Press, Totawa, N.J.
12. Ward, J. M., J. F. Mahler, R. R. Maronpot, and J. P. Sundberg. 2000. Pathology of genetically engineered mice, 1 ed. Iowa State University Press, Ames, Iowa.
Patents
[0018]
13. U.S. Pat. No. 5,523,222
SUMMARY OF THE INVENTION
[0019] The invention comprises in one aspect a process for predicting adverse responses to drugs against a target gene by assessing the responses of animal models, comprising:
(a) providing a genetically engineered non-human mammal. wherein said mammal exhibits either over-expression or under-expression of a target gene; (b) subjecting said mammal to a pre-selected perturbance causing a desired physiologic stress in the mammal, and (c) thereafter evaluating the responses of said genetically engineered mammal by determining the metabonomic profile of the mammal wherein said metabonomic profile is indicative of an adverse response to a drug effecting a target in conjunction with the pre-selected perturbance.
[0023] The invention also comprises a process for determining adverse responses to drugs against a target gene comprising:
a.) comparing the responses of at least two groups, each being of substantially identical non-human mammals, one of which is composed of genetically engineered mammals which exhibit either over-expression or under-expression of said target gene and the other of which exhibit substantially normal expression, that is, neither substantial over-expression nor under-expression, of said target gene; b.) subjecting said mammals to substantively identical, pre-selected perturbances which cause a desired physiological stress in said mammals; c.) determining the metabonomic profiles of said mammals and d.) thereafter comparing said profiles to evaluate the adverse responses related to expression of the target gene and the preselected pertubances.
[0028] In addition to the foregoing, the invention includes as an additional aspect, all embodiments of the invention narrower in scope in any way than the variations specifically mentioned above.
DETAILED DESCRIPTION OF THE INVENTION
[0029] The foregoing is provided to further facilitate understanding of the applicant's invention but is not intended to limit the scope of applicant's invention.
[heading-0030] Definitions
[0031] The term “genetically engineered non-human mammal” (sometimes referred to below as an “engineered animal” for convenience sake) refers to all members of the class Mammalia except humans whose genome has been altered by human intervention so as to alter the expression level or pattern of a specific predetermined gene product. The genetically engineered non-human mammal utilized in this invention include, but are not limited to farm animals (pigs, goats, sheep, cows, horses, rabbits and the like), rodents (such as rats and mice), and domestic pets (for example, cats and dogs). Rodents are sometimes preferred because of their small size.
[0032] The term “genetically engineered non-human mammal” encompasses both knockout and transgenic animals which alter the level of expression of a particular gene product. Methods of genetic manipulation of mammals to alter gene expression are well known in the art. It also includes non-human mammals in which the temporal or spatial control of a specific predetermined gene product has been altered as described further below.
[0033] Nucleic molecules can be introduced into embryos by a variety of means to produce engineered animals. For instance, totipotent or pluripotent stem cells can be transformed by microinjection, calcium phosphate mediated precipitation, liposome fusion, retroviral infection or by other means. The transformed cells can then be introduced into embryos and incorporated therein to form engineered animals. In one method, developing embryos can be infected with retroviral vectors and engineered animals can be formed from the infected embryos. In another method, however, the DNA molecules of the invention are injected into embryos, preferably at the single-cell stage, which are allowed to develop into mature engineered animals. However, the invention is not limited to any of these methods but other methods of making engineered animals can be used as described, for example, in Transgenic Animal Generation and Use by L. M. Houdebine, Harwood Academic Press, 1997. Engineered animals also can be generated using methods of nuclear transfer or cloning using embryonic or adult cell lines as described for example in Campbell et al., Nature 380: 64-66 (1996) and Wilmut et al., Nature 385: 810-813 (1997). Further a technique utilizing cytoplasmic injection of DNA can be used as described in U.S. Pat. No. 5,523,222.
[0034] The term “determining the metabonomic profile” of an engineered animal refers to a procedure of determining the pattern of trace molecules in a biofluid obtained from the animal typically using high-resolution 1 H nuclear magnetic resonance (NMR) or mass spectroscopy, coupled with pattern recognition technology. The technique has been described by Robertson et. al. Biofluids upon which the technique is employed include but are not limited to urine, milk, plasma and serum We describe here a process in which engineered animals are exposed to a panel of perturbations and their response to the perturbations is quantitatively assessed by metabonomic profiling analysis of urine, serum, or plasma.
[0035] During target validation, an early stage of drug development, engineered animals (often rodents) are used to mimic the effects of drugs and evaluate drug safety.(Brayton, et. al.; Sundberg, et. al.; Ward, et. al.) For example, knockout mammals, i.e. mammals in which a specific gene is deleted, can be used to predict the effects of an inhibitory drug that prevents the function of a specific gene product (the target). That is, a knockout mammal in which the target gene of interest is deleted is a model to predict the effects, including adverse side effects, of an animal given a drug to inhibit the target molecule. Similarly, transgenic non-human mammals that overexpress a specific gene can be used to predict the effects of an agonist drug that causes increased function of a specific gene product. Additionally, engineered animals can be made that either under- or over-express the gene of interest only at certain times (temporal control) or in certain organs or tissues (spatial control) (Tymms, et al.). The advantage of using engineered animals for this purpose is that they can be examined and tested even before efficacious compounds or drugs have been synthesized.
[0036] Importantly, however, this conventional method of analyzing or “phenotyping” engineered animal is done in otherwise healthy, unstressed animals. Results from these tests may not predict safety in humans, whom often suffer from multiple diseases and a variety of stresses, nutritional problems, and adverse life style choices.
[0037] We propose two approaches to obtain better information about drug effects from engineered animals.
1. By perturbing or challenging the engineered animal with various agents or conditions instead of examining the non-human mammals only in an unperturbed state. For example, low doses of lipopolysaccharide (LPS), a component of the outer membrane of Gram-negative bacteria, simulate many of the effects of bacterial infection including fever and inflammation. Many of the physiologic responses to psychological stress can be evoked by animal behavior challenges, including exposure to flashing strobe lights, reversal of light:dark cycles by turning on the lights during the night and turning off the lights during the day, restraint for 20 minutes in a plastic tube, exposure to the odor of a cat or a rat, and foot shock for 10 seconds (Griebel, et. al.). Oxidative stress, a common effect of concurrent drug therapy, certain nutritional inadequacies, or illness, can be induced by feeding of buthionine sulfoximine, a compound that inhibits glutathione (Robertson, et. al.). Viral infections can be tested using experimental infection with a highly attenuated strain of influenza that is not pathogenic to humans and normally induces only minimal lesions in the mouse (Warren, et. al.). 2. Some alterations only have adverse effects in individuals with genetic predispositions to disease. For example, individuals vary in susceptibility to oxidative stress, epileptic seizures, and bacterial or viral disease. Effects of a drug on individuals with disease predisposition can be tested by breeding the engineered animals to strains with increased sensitivity to develop particular disorders. The progeny, then, will have both the original genetic modification (for example, deletion of the specific gene of interest) plus increased sensitivity to a particular disorder. Uncovering phenotypic abnormalities in these cross-bred non-human mammals may indicate potential adverse effects.
[0040] When expanding the battery of tests to be performed on engineered animals, it is highly desirable to accelerate the way the testing is evaluated. A rapid yet comprehensive way to evaluate responses is by metabonomics analysis. The advantage of metabonomics is that it simultaneously measures in a non-specific way all endogenous chemicals of a range of molecular sizes in biological fluids. Results are quantitative, can be compared among animals, and can be examined as a comprehensive pattern (by a process called “pattern recognition analysis”) rather than by individual chemical. Urine is collected by placing non-human mammals in metabolic cages, in which the urine is separated from feces and spilled food and diverted into a cooled collection vessel. Alternatively, serum or plasma could be used for metabonomics analyses. The body fluids are tested using 1 H-nuclear magnetic resonance (NMR) spectroscopy or mass spectroscopy. The spectra are analyzed by pattern recognition analysis and principal component analyses(Robertson, et. al.). An advantage of metabonomic analysis is that it is unbiased and broad. That is, it can measure changes in a wide variety of the body's endogenous chemicals in urine, serum, or plasma, even if those chemicals were not previously believed to be of interest.
[0041] It is expected that the metabonomic pattern of most strains of engineered animals will differ from wild-type (Gavaghan, et. al.). In the perturbation analysis, the difference between the metabonomic pattern after perturbation from the basal pattern will be assessed. Strains of engineered animals can be identified that have a metabonomic response to perturbation that is either (a) markedly increased or decreased from the metabonomic response of corresponding wild-type non-human mammals or (b) goes in a different direction from the metabonomic response of wild-type non-human mammals will be considered abnormal (see FIG. 1). The purpose of this screening test is to identify engineered animals with specific gene alterations that have abnormal responses to perturbations. This enables early prediction that drugs designed to inhibit or stimulate target proteins produced by a specific gene (i.e., the gene that is altered) may be unsafe in some humans under commonly encountered situations of physiologic perturbation. That is, the engineered animals will be used to model effects in individuals who are taking a drug at the same time that they are undergoing stress or perturbation.
[0042] Results of the screening test can then be followed by more detailed tests of particular analytes or mechanisms to better confirm or understand the results.
[0043] It will be clear that the invention may be practiced otherwise than as particularly described in the foregoing description and examples.
[0044] Numerous modifications and variations of the present invention are possible in light of the above teachings and, therefore, are within the scope of the invention.
[0045] The entire disclosure of all publications cited herein are hereby incorporated by reference.
|
The invention relates generally to the process of target validation in the pharmaceutical industry. A process for validating molecular targets is disclosed.
| 0 |
This application is a continuation of U.S. application Ser. No. 07/713,052 filed Jun. 10, 1991, now abandoned.
FIELD OF THE INVENTION
This invention relates to a tablet prepared from a dried product obtained by pulverization under cooling and subsequent vacuum freeze-drying of a fresh entire aloe leaf, a method for preparing the tablet, and use thereof.
The tablet according to the present invention is useful as a medicine or so-called health food, such as laxative, stomachics, anti-gastrointestinal ulcer drug, anti-inflammatory drug, anti-fungal drug, anti-hyperglycemia drug, anti-burn edema drug for oral administration, or immunomodulator.
BACKGROUND
Aloe has been extensively used as folk medicine. Reference to aloe powders is also made in the Japanese Pharmacopeia.
The present inventors and laboratories both in Japan and abroad have succeeded in separating low-, medium- and high molecular weight ingredients contained in aloe.
For example, it is known that Aloe arborescens var. natalensis (referred to as “Kidachi aloe” hereinafter) contains polysaccharides such as aloetin, aloenin, aloeursin or D-mannose, aloemannan or aloe albonacite: aloe vera contains polysaccharides; and that Cape aloe contains anthraquinonic ingredients, such as aloin or aloe-emodin.
with this in mind, attempts have intensively been made to process the aloe into medicines. Presently, as the officially allowed health food, food products prepared from Kidachi aloe have been commercialized in Japan extensively.
Most of these products, however, are prepared by drying aloe leaves under sun shine or by hot air and, at the time of tableting, 7-10% of an additive, such as Avicel (Trade name of micro crystalline cellurose) or corn starch, is added as a binder to facilitate tableting.
DISCUSSION OF THE RELATED ART
It is noted that most ingredients that are isolated and purified from the aloe and found to be efficaceous to animals by animal experiments, are polysaccharides, glycoproteins or enzymes, all of which may exhibit activity in a stable state only when treated for purification at lower temperatures. For this reason, it is generally thought to be desirable to apply as small a quantity of heat as possible for the preparation of the health food or medicine from aloe.
However, since the products now presented to the market are prepared by drying aloe leaves under sun shine or by circulation of hot air, the above mentioned components, namely the polysaccharides, glycoproteins or enzymes, have been thermally degraded or oxidized in the course of drying.
Furthermore, the additives for facilitating tableting, such as Avicel or corn starch, are added in an amount of 7-10% in the conventional aloe tablet products. Since a small amount of water is added under heating to knead the additives with the dried aloe mass, the resulting product undergoes further thermal degradation by such heating.
SUMMARY OF THE DISCLOSURE
It is therefore an object of the present invention to provide a dried mass or powder, granule, tablet or a medicine of a plant belonging to the genus Aloe of the family Liliaceae, which is free from the above described inconveniences in the conventional preparation of Aloe product.
It is another object of the present invention to provide a method for producing the dried mass or powder, granule, tablet or medicine.
According to the present invention, the above object is accomplished by the following dried mass, granule, tablet, and medicine and a method for producing the dried mass, granule, tablet and medicine.
i) A vacuum freeze-dried mass of a plant belonging to the genus Aloe of the family Liliaceae.
ii) A method for producing a dried mass of a plant belonging to the genus Aloe of the family Liliaceae comprising crushing the plant and freeze-drying the crushed mass in vacuum.
iii) A vacuum freeze-dried granule of a plant belonging to the genus Aloe of the family Liliaceae.
iv) A method for producing a granule of a plant belonging to the genus Aloe of the family Liliaceae comprising molding the dried mass according to item i) under pressure for granulating.
v) A tablet comprising a vacuum freeze-dried mass of a plant belonging to the genus Aloe of the family Liliaceae.
vi) A method for producing a tablet comprising tableting the granule according to item iii).
vii) A tablet according to item v) further comprising nutrient and/or medicinal ingredients.
viii) A method for producing a tablet comprising tableting the granule according to item iii) with nutrient or medically effective ingredients.
ix) A medicine comprising the tablet according to item v) or vii).
The dried mass, granule or tablet according to the present invention exhibits the following properties:
i) It has a pale green color;
ii) It has a grassy smell;
iii) It has a strongly bitter taste;
iv) It is soluble in water, while being partially insoluble in methanol, ethanol or acetone;
v) In protein determination reactions, it is positive both in bicinchoninic acid (BCA) reaction and in Lowry-Folin reaction;
vi) With regard to saccharides determination reactions, it is positive in anthrone sulfuric acid reaction and in phenol sulfuric acid reaction;
vii) With regard to proteolytic enzyme activities, it has activities of carboxypeptidase and trypsin, and it has also protease-inhibitory activity;
viii) It exhibits positive cell agglutination activity with erythrocytes and weakly positive cell agglutination activity with cancer cells; and
ix) It exhibits weakly positive blastogenetic activity with lymphocytes.
The dried mass, granule and tablet of the plant belonging to the genus Aloe of the family Liliaceae according to the present invention contains efficaceous ingredients endogenously contained in the genus Aloe of the family Liliaceae, such as polysaccharides, glycoproteins and enzymes, in a state substantially free from degradation otherwise caused by heating, such as thermal degradation or oxidation. A variety of physiologically active substances, found to be contained in the plant by animal experiments, such as aloin or aloe carboxypeptidase, are also present without undergoing thermal degradation. Hence, the dried mass, granule and tablet according to the present invention may be used as medicines, such as laxative, stomachics, anti-gastrointestinal ulcer drug, anti-inflammatory drug, anti-fungal drug, anti-hyperglycemia drug, anti-burn edema drug, or immunomodulator, or in a variety of health foods.
The tablet of the present invention may consist of 100% of the above mentioned dried mass, without needing an additive for tableting as an essential constituent, so that a high quality tablet is provided which contains the efficaceous or medicinal ingredients of the plant belonging to the genus Aloe of the family Liliaceae with a high purity.
The tablet of the present invention is easy to swallow, even though it has a strong bitter taste and a flavor displayed by the plant when chewed.
In the present method for producing the dried mass of the present invention, the liquid obtained by crushing the plant belonging to the genus Aloe of the family Liliaceae is freeze-dried in vacuum, without resorting to the step of drying the liquid by heating it at a temperature higher than the ambient temperature, therefore, the dried mass containing the above mentioned efficaceous ingredients in the plant is prepared without degrading those ingredients.
According to the method for preparing the granule of the present invention, the dried mass is press molded into the granule. The granule contains the efficaceous ingredients without thermally degrading these efficaceous ingredients.
In the method for producing the tablet of the present invention, the dried mass is press molded into the granule, and then tableted. Thus, the tablet containing the above mentioned efficaceous ingredients is produced without degrading the efficaceous ingredients in the plant. Since no additive for facilitating tableting is required, the tablet containing the above efficaceous ingredients in higher percentages are produced. Thus the tablet contains up to 100 percent of effective ingredients.
In this method for preparing the tablet in the present invention, the granule can be tableted with the fortified nutrient or medicinal ingredients, not originally contained in the plant. Thus the nutrients or medicinal ingredients originally contained in the plant can be supplemented to be found in increased concentrations in the produced tablet.
DESCRIPTION OF THE PREFERRED EMBODIMENT
Dried Mass
The vacuum freeze-dried mass of a plant belonging to the genus Aloe of the family Liliaceae, such as Kidachi aloe, Aloe vela or Cape aloe, is obtained by freeze-drying a liquid obtained by crushing the plant. The dried mass obtained in this manner is usually in the flocculated state and is easily pulverized, for example, by charging the mass into a bag. The specific gravity of the dried mass is usually from 0.085 to 0.090.
Method for Preparing the Dried Mass
The liquid obtained by crushing the plant is obtained by crushing the plant with the use of, for example, a homogenizer. Since the heat is generated during homogenization, the outer side of the homogenizer is cooled by ice water.
The entire time for freeze-drying the crushed liquid in vacuum is about 30 hours. The vacuum degree, expressed in terms of the pressure of the remaining gas, is less than 0.4 mbar, not more than 0.2 mbar, and not more than 0.1 mbar during the initial ten hours, during intermediate ten hours, and during the final ten hours, respectively. The temperature of the crushed and freezed liquid during drying is not higher than −20° C., and preferably not higher than −40° C. during the above mentioned initial and intermediate periods, and gradually raised from minus −40° C. to ambient temperature, e.g., plus +25° C., during the period of ten hours from the start until the end of the final drying period. This enables the moisture to be vaporized off to provide a completely dried mass. According to the method of the present invention, the temperature at the end of the final drying period is are ambient temperature, e.g., from plus +20° C. to plus 25° C.
Granule
The particle size of the granule for producing the tablet preferably range from 18 to 20 mesh, and the specific gravity of the granule preferably ranges from 0.65 to 0.75.
Method for Producing the Granule
The granule is produced by press molding (or compacting) the dried mass under a pressure of, for example, 150 kgf/cm 2 . The granules having a specific gravity of 0.74, produced by press molding under the above pressure. Granulation may be carried out by using a commercially available granulator.
Tablet
The tablet may be in the form of, for example, a cylindrical column with a length of 5 mm and a diameter of 5 mm.
Preferably, the tablet weighs 130 to 150 mg, and has a specific gravity of 1.3 to 1.5.
The tablet may contain nutrient or medicinal ingredients not originally contained in or contained only in a limited quantity in the genus Aloe of the family Liliaceae. For example, the tablet may contain garlic powders or vitamin C.
Method for Producing the Tablets
The tablets may be produced by tableting granules which contain endogenous nutrient and/or medicinal ingredients in the plant of the genus Aloe of family Liliaceae, or a mixture of the granules and the powders or granules of the other nutrient or medicinal ingredients. The tableting may be carried out, for example, at a pressure of 600 kgf/cm 2 , resulting in a specific gravity of about 1.3 when the granules alone.
About 11 kg of fully grown leaves of Kidachi aloe, cultivated for about three to four years, with each leaf weighing about 100 to 120 g, are collected.
These leaves are washed thoroughly with a scrubbing brush and, after the thorns and white hard fibers at the leaf roots are removed by a cutter, and the remaining portions of the leaves are washed with distilled water.
The leaves weigh about 9 kg at this time, so that, with 9 kg, corresponding to a volume of 9 liters, of the aloe leaves as one unit, the leaves are cut into small pieces and charged into a homogenizer to produce a crushed aloe liquid, referred to hereinafter as aloe juice.
Since the capacity of a vacuum freeze-drying tray for KYOWA vacuum freeze-drier RLE 203 is 3 liters, the homogenate weighing 9 kg is divided into three fractions.
The three aliauotes of homogenates are frozen at minus 30° C. to minus 40° C. and charged into a freeze-drier. The 9 liters of the aloe juice were dried in about 30 hours by the KYOWA vacuum freeze-drier RLE 203 to produce 360 g of dried powders.
These powders are charged into a dry granulator, such as a roll compactor, for granulation. The volume of the powders at this stage is reduced to about one tenth.
If the granules are not of the uniform size, the tableted product tends to fluctuate in quality. In order to prevent this, granulation by the roll compactor may be repeated two or three times.
The granules are tableted immediately on a tablet machine. If tableting is to be achieved without additives, each tablet preferably weighs about 130 to 150 mg.
In this manner, about 350 g of the vacuum freeze-dried powders are produced from the batch of 9 kg of the aloe juice, so that about 2,600 tablet products are produced.
A about 3-10% of an additive, such as Avisel or corn starch, is added in the conventional aloe tablet to facilitate tableting. Also, a humidifier such as water or alcohol is added to the powders and kneaded with the additive and the resulting mixture is formed into a tablet through drying with hot air.
On the contrary, according to the present invention, the dry granulator, such as the roll compactor, is used to eliminate the kneading step for granulation as well as to raise the density of the mass to facilitate the subsequent tableting.
According to the above described method of the present invention, the aloe powders are formed into tablets without using an additive as a binder.
The tablets prepared from the vacuum freeze-dried aloe powders are in the form of a cylindrical column with a length of 5 mm and a diameter of 5 mm.
The tablets have a fresh pale green color and a bitter taste similar to that of the fresh aloe leaf. On the other hand, conventional aloe tablets, produced by drying at a higher temperature, are excessively oxidized, have a pale yellow to brownish color, and have a bitter taste somewhat different from the taste of the fresh aloe. This is due to increased oxidized derivatives of aloin, calcium succinate salt, which is yellowish and is mainly composed of barbaloin, i.e., anthrone C glycoside.
Comparative Test Between Inventive and Conventional Products
The inventive product and the conventional product (control) were compared with respect to test items (a) to (h), as shown in Table 1.
As the inventive product, the tablets produced in the preceding example were employed. As the control product, commercially available conventional aloe tablets were used. These tablets were prepared by drying under hot air circulation and subsequently tableting a dried mass obtained by admixing an additive for facilitating tableting, such as Avicel or corn starch, and a humidifier, such as water or alcohol, to dried aloe leaves.
TABLE 1
Test items
Inventive
Control
(a) Color
Pale green color
Yellowish
green color
(b) Smell
Strong grassy smell
Grassy smell
(c) Taste
Strong bitter taste
Bitter taste
similar to that of
green raw leaf
(d) Solubility
Soluble in water,
Same as
partially insoluble
inventive
in organic solvent
product
(e) Protein determination
reaction
1) BCA reaction
15.7 mg/ml*
4.1 mg/ml*
2) Lowry-Folin reaction
20.2 mg/ml*
6.5 mg/ml*
(f) Saccharide determination
reaction
1) Anthrone-Sulfulic Acid
13.6 mg/ml*
8.0 mg/ml*
reaction
2) Phenol-Sulfulic Acid
48.0 mg/ml*
30.5 mg/ml*
reaction
(g) Proteolytic enzyme
1) Carboxypeptidase
5.4 U/ml*
0.69 U/ml*
2) Trypsin
18.1 μg/ml*
0.5 μg/ml*
3) Protease inhibitory
42%
5%
(pepsin inhibitory)
activity
(h) Erythrocyte agglutination
16 titer
2 titer
activity, human O-type
1.0 g of tablet was dissolved into 10.0 ml of distilled water and was measured by each reaction, ml represents 1.0 ml of this solution.
The methods for the tests on the items (e) to (h), the results and their significances are summarized as follows:
(e) Protein Determination Reaction
The inventive tablet product and the control tablet product obtained under drying in hot air were crushed into powders. 1.0 g each of the tablets were dissolved in 10 ml of distilled water, stirred and centrifuged at 12,000 rpm for 30 minutes at 4° C. The total protein in the produced supernatant was determined by the bicinchoninic acid method (BCA method), using a protein assay reagent kit. manufactured by PIERCE, U.S.A. as described by Smith, P. K. et al (Measurement of Protein Using Bicinchoninic Acid. Anal. Biochem. (1985) 150. 76-85), and also by the Lowry-Folin method, as described by Lowry et al. (Protein Measurement with the Folin Phenol Reagent, J. Biol. Chem. (1951) 193. 265-275).
The results of the analyses have revealed that the inventive product contained 15.7 mg of the protein per each 1 ml of a liquid extract, as measured with the BCA method, whereas the protein content of the control product was 4.1 mg.
The protein content of the inventive product, as measured by the Lowry-Folin's method, was 20.2 mg, whereas that of the control product was 6.5 mg.
The results show that the inventive product contains natural proteins more abundantly and that the amount of the aloe material per unit weight is higher in the inventive product because of the absence of the additive(s).
(f) Saccharide Determination Reaction
The inventive tablet product and the control tablet product obtained under drying in hot air were crushed into powders. 1.0 g of each of the powdered tablets was dissolved in 10 ml of distilled water, stirred and centrifuged at 12,000 rpm for 30 minutes at 4° C. Saccharide determination tests were conducted on the produced supernatents by the anthrone-sulfuric acid reaction with respect to the monosaccharide, as described by R. Drywood (Ind. Eng. Chem., Anal. Ed., 18. 499 (1946)), and also by the phenol-sulfuric acid reaction for oligosaccharides, polysaccharides or glycoprotein, as described by M. Dudols et al. (Anal. Chem., 28. 350 (1956)).
A large amount of hexose, such as glucose, is contained in both the inventive and control products, as indicated by strong anthrone-sulfuric acid reaction with green to blue green color.
The hexose concentration, calculated as glucose, was 13.6 mg/ml and 8.0 mg/ml for the inventive and control products, respectively.
Both the inventive and control products present a yellow-brown color in the phenol-sulfuric acid reaction, and the concentration, measured as glucose, was 48.0 mg/ml and 30.5 mg/ml for the inventive and control products, respectively.
It is shown that the succharides originating from the glycoprotein and polysaccharides remain in the inventive product.
(g) Proteolytic Enzyme Activity
Three proteolytic enzymes have been isolated from Kidachi aloe by the present inventors. Since these enzymes are the heat-labile proteins or glycoproteins, it is crucial from the viewpoint of the product quality whether these enzymes remain in fact in the inventive product.
The inventive tablet product and the tablet product of the control obtained by drying under hot air circulation were crushed into powders. Then, 1 g each of the powders was dissolved in 10 ml of distilled water, stirred and centrifuged at 12,000 rpm for 30 minutes at 4° C. The supernatents were subjected to the following activities tests.
i) Test on Carboxypeptidase Activity
Bradykinin or Z-Phe-Tyr, Z-Gly-Pro-Leu-Gly was incubated with 50 μl of the supernatants of the inventive and control products at 37° C. for one hour at pH 5.0, and the products, amino acids, were subjected to a ninhydrin reaction to measure the enzyme activity.
The reaction with Z-Gly-Pro-Leu-Gly as substrate revealed that the inventive product and the control product exhibit the carboxypeptidase activity 5.4 units and 0.69 unit per 1 ml of the supernatant, respectively.
The inventive product thus exhibits enzyme activity of carboxypeptidase even after tableting. Carboxypeptidase enzyme exhibits anti-inflammatory effects and anti-edematous effects on burn and is capable of effectively decomposing bradykinin, the chemical mediator of inflammation.
2) Trypsin Activity
A proteolytic enzyme similar to trypsin was separated by the present inventors from Kidachi aloe.
N-Benzoil alginine p-nitroanilide or acetyl alginine p-nitroanilide was incubated with 200 μl of the inventive and control products at 37° C. at pH 8.0 for three hours.
The results of the measurement of isolated p-nitroaniline revealed that the inventive and control products contained p-nitroaniline in amounts of 18.1 μg/ml and 0.5 μg/ml, respectively, thus indicating that trypsin remains in the inventive product without loss of its activity.
Trypsin exhibits similar reactivity as enterokinase, thrombin, plasmin or kallikrein. It has been known that trypsin separated from actinomyces exhibits anti-inflammatory effects when administered orally.
3) Protease Inhibitor
200 μl of the supernatants of the inventive and control products, or distilled water, were added to 1 ml of casein as a substrate, respectively, and the reaction was continued under pH 2.0 at 37° C. for three minutes. Then 0.1 ml of the pepsin solution was added to the reaction system arid the reaction was further carried out for 30 minutes.
For termination of the reaction, 2 ml of 1.7M perchloric acid solution was added, and the resulting mixture was centrifuged. Absorbance of the supernatants was measured at a wavelength of 280 nm.
With the absorbance of the reaction system, added to by the distilled water, equal to 100%, the absorbance of the inventive product was 142%, while that of the control product was 105%. The inventive and the control products inhibited the reaction of pepsin with casein as substrate by 42 percents and 5 percents, respectively. Thus, the pepsin inhibitor activity was found to persist in the inventive product.
The presence of the pepsin inhibitor in the inventive product indicates that pepsin in gastric ulcer may be inhibited by oral administration of the inventive product.
(h) Erythrocyte Agglutination
The inventive tablet and the control tablet obtained by drying under hot air circulation, were crushed into powders. 1.0 g each of the powders was dissolved in 10 ml of distilled water. After stirring, each of the resulting solutions was centrifuged at 4° C. for 30 minutes at 12,000 rpm.
The erythrocyte agglutination activity of each of the produced supernatants was examined in accordance with the microtiter method.
A buffer solution obtained by mixing phosphoric acid with physiological saline to pH 7.4 was added to 100 μl each of the supernatants for two-stage dilution until 128-fold dilution was reached. To each diluted solution, 100 μl of the 1% human O-type erythrocytes were added, and reaction was carried out at 37° C. for one hour to observe the progress of agglutination.
It was found that the agglutination titer of the inventive product was 16 titer, while that of the control product was 2 titer. The agglutination titer of Concanavalin A, used as control, was 32 titer, at a concentration of 1 mg/ml.
Therefore, the substance termed lectin which produces erythrocyte agglutination as Concanavalin A is contained at a higher concentration in the inventive tablet.
Lectin has been demonstrated to specifically agglutinate tumor cells and to exhibit cytotoxity, or as to modulate immune-related cells, such as promotion of blastogenesis or differentiation of lymphocytes.
These results prove that the inventive product contains a larger quantity of lectin than in the control product.
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A vacuum freeze-dried mass of a plant belonging to the genus Aloe of the family Liliaceae, a vacuum freeze-dried granule of the plant, a tablet formed by a vacuum freeze-dried mass of the plant, a medicine formed by the tablet, and the method for producing the vacuum freeze-dried mass, the vacuum freeze-dried granule, the tablet and the medicine. The vacuum freeze-dried product maintains the inherent properties of living aloe useful for medicine or health food.
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This application is a divisional of U.S. application Ser. No. 13/103,420, filed on May 9, 2011, and claims priority from and the benefit of U.S. Provisional Application No. 61/333,938, filed on May 12, 2010, both of which are hereby incorporated by reference for all purposes as if fully set forth herein.
FIELD
[0002] This disclosure generally relates to measuring extruded ceramic logs, and in particular to laser scanning systems and methods for making three-dimensional measurements of extruded ceramic logs.
BACKGROUND
[0003] Ceramic honeycomb structures are used in a variety of applications, and in particular plugged ceramic honeycomb structures can be used as filters in vehicular exhaust systems to reduce pollutants. The honeycomb structures can be formed by extruding a plasticized ceramic-forming precursor in the form of a log. The log has a network of interconnected web walls that form a matrix of elongated cells which may be, for example, square, octagonal or hexagonal in shape. The network of web walls is surrounded by a cylindrical outer wall or “skin” that is integrally connected to the outer edges of the web walls of the matrix to form a cylindrical structure having opposing inlet and outlet endfaces for receiving and expelling exhaust gases through the matrix of cells.
[0004] The extruded log needs to be measured to ensure it meets specifications with respect to its size and shape, and in particular with respect to the amount of bow in an axial direction, in the direction of extrusion.
SUMMARY
[0005] The systems and methods disclosed herein can provide quick and efficient measurement of extruded logs, particularly related to log shape, during manufacture. The systems and methods disclosed herein preferably provide a non-contact measurement of the extruded log, thereby also helping to reduce the risk of physically damaging the log. As used herein, a ceramic log refers to an extruded, generally cylindrical body comprised of a ceramic composition and/or a ceramic-forming composition, that can be sintered and/or reaction sintered, to form a ceramic article upon heating of the log. The ceramic log may vary from its generally cylindrical shape due to imperfections in the manufacturing process.
[0006] It is to be understood that both the foregoing general description and the following detailed description present embodiments of the disclosure, and are intended to provide an overview or framework for understanding the nature and character of the disclosure as it is claimed. The accompanying drawings are included to provide a further understanding of the disclosure, and are incorporated into and constitute a part of this specification. The drawings illustrate various embodiments of the disclosure and, together with the description, serve to explain the principles and operations of the disclosure. In some of the Figures, Cartesian coordinates are shown for reference.
DESCRIPTION OF THE DRAWINGS
[0007] FIG. 1 is a schematic diagram of an example extrusion system used to create fired ceramic articles from ceramic logs formed by extrusion, where the system includes two laser scanning systems for measuring the ceramic logs at different stages during the manufacturing process;
[0008] FIG. 2 is a more detailed schematic diagram of the example extrusion system of FIG. 1 ;
[0009] FIG. 3 is a close-up, top-down view of the conveyor in the process of transporting ceramic logs supported by trays from the extruder unit to the drying unit;
[0010] FIG. 4 is an isometric view of an example cylindrical extrudate formed by extrusion using the extrusion system of FIG. 1 and FIG. 2 , and also showing how the extrudate is cut into logs and then into smaller pieces (wares) prior to firing;
[0011] FIG. 5 is a close-up, isometric view of an example ceramic log;
[0012] FIG. 6 is a view the −Y-direction and FIG. 7 is a view in the -X-direction of an example laser scanning system arranged relative to a ceramic log supported by a tray on a conveyor, where the tray needs to be lifted from the conveyor to place the ceramic log in the measurement position;
[0013] FIG. 8 is a bottom-up view of an example support arm with the laser scanners attached at opposite ends, with the support arm attached to the central beam of the support structure;
[0014] FIG. 9 and FIG. 10 are similar to FIG. 6 and FIG. 7 , except that the lifting mechanism has been activated to place the ceramic log in the measurement position above the conveyor;
[0015] FIG. 11 shows an embodiment of the laser scanning system similar to that shown in FIG. 6 , except that the system is configured so that laser scanning measurements can be taken with the ceramic log and tray resting on an unmoving conveyor;
[0016] FIG. 12 illustrates an example two-dimensional measured surface shape profile as determined by the controller from the two-dimensional scan data and displayed on the controller display;
[0017] FIG. 13 illustrates an example three-dimensional image of the measured surface shape of a ceramic log as determined by the controller from the three-dimensional scan data and displayed on the controller display; and
[0018] FIG. 14 plots an example of the “profile of the line” (POL) in inches versus the log position in inches based on hypothetical two-dimensional scan data.
DETAILED DESCRIPTION
[0019] Reference is now made in detail to embodiments of the disclosure, examples of which are illustrated in the accompanying drawings. Whenever possible, the same or like reference numbers are used throughout the drawings to refer to the same or like parts.
[0020] FIG. 1 is a generalized schematic diagram and FIG. 2 is a more detailed schematic diagram of an example embodiment of an extrusion system 10 used to create ceramic articles from ceramic logs formed by extruding a ceramic-forming extrusion material. Extrusion system 10 includes an extruder portion 12 that has a mixing stage or “wet tower” 20 having an input end 22 and an output end 24 . Wet tower 20 initially receives at input end 22 the various batch material constituents 30 in dry form from respective constituent sources 31 , and mixes them along with water (and optionally oil) to form an initial ceramic-forming batch material 34 . The aqueous-based ceramic precursor mixture formed in wet tower 20 preferably comprises a batch material mixture of ceramic (such as cordierite) forming inorganic precursor materials, an optional pore former such as graphite or starch, a binder, a lubricant, and a vehicle. The inorganic batch material components can be any combination of inorganic components (including one or more ceramics) which can, upon firing, provide a porous ceramic having primary sintered phase composition (such as a primary sintered phase composition of cordierite or aluminum titanate).
[0021] Wet tower 20 includes, for example, a mixer 40 followed by a rotary cone 44 . Wet tower 20 also includes a water unit 50 configured to provide water to mixer 40 in select amounts, e.g., by weighing the amount of water added to the mixer. In an example embodiment, water unit 50 is controlled manually and/or automatically, as discussed below. Examples of batch material 34 are discussed below.
[0022] Extruder portion 12 further includes a conveyer unit 60 arranged adjacent output end 24 of wet tower 20 . Conveyor unit 60 includes a conveyor belt 64 with an input end 66 and an output end 68 . Conveyor belt 64 rotates clockwise as shown. Conveyor unit 60 includes a protective cover 70 .
[0023] Conveyor belt input end 66 is arranged at the output end 24 of wet tower 20 to receive batch material 34 therefrom. In an example embodiment, rotary cone 44 serves to deliver batch material 34 to conveyor belt input end 66 in a relatively uniform layer. Wet tower 20 is configured to adjust the thickness of the layer of batch material 34 carried by conveyor belt 64 .
[0024] The extruder portion 12 of extrusion system 10 further includes a chute 80 and an extrusion unit 90 . Chute 80 is arranged between conveyor unit 60 and extrusion unit 90 . Chute 80 is configured to receive batch material 34 from the output end 68 of conveyor belt 64 and deliver it to extrusion unit 90 . Extrusion unit 90 is configured to receive batch material 34 and form billets therefrom, which are then pressed through an extrusion die 92 (e.g., by a twin-screw extruder) to form an extrudate 100 . In an example embodiment, extrusion unit 90 includes multiple extrusion dies that operate at once to simultaneously form multiple extrudates 100 .
[0025] In an example embodiment, extrusion system 10 includes a pressure sensor 94 in extrusion unit 90 electrically connected to a master controller MC and configured to measure the pressure during extrusion. Pressure sensor generates an electrical signal S P that is sent to and received by master controller MC, which processes and preferably displays the pressure measurements on a display (not shown). This feedback allows the master controller MC to control the extrusion process.
[0026] Extrudate 100 is deposited onto a conveyor 110 arranged adjacent extrusion die 92 . In an example embodiment, extrudate 100 is cut into sections called “logs” 101 , as shown in FIG. 4 and in FIG. 5 The cross-sectional shape can be round or non-round, e.g., oval. Logs 101 are supported in trays 114 . FIG. 3 is a top-down close-up view of conveyor 110 showing logs 101 supported in trays 114 being conveyed in the +X direction away from extrusion unit 90 .
[0027] At this point, logs 101 are “green” and “wet”. The green and wet logs 101 are conveyed by conveyor 110 to a drying station (e.g., an oven or “applicator”) 120 . Drying station 120 has an interior 122 where logs 101 reside while drying. Drying station 110 may use, for example, radio-frequency (RF) radiation or microwave frequency (MF) radiation, to effectuate drying.
[0028] Extrusion system 10 also includes a cutting station 130 for cutting dried logs 101 into smaller pieces or wares 102 (see FIG. 4 ) and a firing station 134 downstream of drying station 120 for firing the smaller, dried wares.
[0029] Extrusion system 10 further includes at least one laser scanning measurement system 200 disposed adjacent and above conveyor 110 . The example extrusion system 10 of FIG. 1 and FIG. 2 includes a first laser scanning system 200 disposed between extrusion unit 90 and drying station 120 and a second laser scanning system disposed between the drying station and firing station 134 .
[0030] FIG. 5 is a close-up view of an example ceramic log 101 . Ceramic log 101 has a central axis A 1 , opposite endfaces 148 and a matrix of intersecting, thin, porous walls 150 that extend across and between the endfaces and that define longitudinally extending cells 152 that collectively form a honeycomb structure 154 . Honeycomb structure 154 is surrounded by an outer skin 156 that defines an outer surface 160 . Both endfaces 148 have the same general contour shape, such as circular or oval.
[0031] The contours of outer skin 156 and endfaces 148 define an overall shape of outer surface 160 , and this shape is referred to as the “surface shape.” This shape can vary from being perfectly cylindrical due to imperfections in the extrusion process. The surface shape taken at a given cross-section perpendicular to axis Al is referred to as the “two-dimensional surface shape,” while the surface shape of an extended portion of outer surface 160 is referred to as the “three-dimensional surface shape.”
[0032] In an example embodiment, master controller MC is operably connected to wet tower 20 , to conveyor units 60 and 110 , to extruder 90 , to drying station 120 and to the at least one laser scanning system 200 , and is configured to control the operation of these system components to control the overall operation of the extrusion system.
[0033] When logs 101 are sufficiently dry (meaning that most or all of the liquid initially present in the logs has been removed so that the moisture content has been reduced to a level acceptable for cutting and firing), they are cut into smaller greenware pieces 102 (see FIG. 4 ) at cutting station 130 . Greenware pieces 102 are then fired at firing station 134 , which includes for example a hot-air oven or kiln. The resultant heat transforms the relatively soft and fragile dried greenware pieces 102 into hardened, fired wares 102 ′ having a rigid honeycomb structure 154 and outer surface 160 with a fixed surface shape. In an example embodiment, fired wares 102 ′ are used to form ceramic filters wherein the ceramic is porous enough to allow fluid (gas and/or liquid) to flow therethrough.
[0034] Exemplary AT-based ceramic materials are discussed in U.S. Pat. No. 7,001,861, U.S. Pat. No. 6,942,713, U.S. Pat. No. 6,620,751, and U.S. Pat. No. 7,259,120, which patents are incorporated by reference herein. Such AT-based bodies may be used as an alternative to cordierite and silicon carbide (SiC) bodies for high-temperature applications, such as automotive emissions control applications. The systems and methods disclosed herein apply to any type of extruded greenware.
[0035] During the manufacturing process, the wet and dried green ceramic logs 101 preferably have a surface shape that conforms to a particular specification, for example as defined by a desired end product shape. For example, where the end product is a filter, ceramic logs 101 preferably have a surface shape consistent with that of the filter holder prior to firing the logs and fixing the surface shape. In some applications, a resultant filter might not sit properly in the filter holder if it has a surface shape that does not meet the filter specification. Thus, the measurement of the surface shape allows for out-of-spec ceramic logs to be rejected before they are processed into end products. Further, measurement of the surface shape provides feedback for the manufacturing process and allows the manufacturing process to be adjusted so that the surface shape deviations can be corrected.
Laser Scanning Measurement System
[0036] FIG. 6 is a front-on view (i.e., in the −Y-direction) and FIG. 7 is a side view (i.e., in the −X-direction) of an example embodiment of laser scanning system 200 , along with log 101 supported by tray 114 . Laser scanning system 200 includes a support frame 210 having vertical support columns 214 oriented in the Z-direction and mechanically connected to horizontal crossbeams 220 oriented in the X and Y directions. Support frame 210 is fixed to or solidly rests upon a floor FL. A central cross-beam 220 C runs in the Y direction in the center of the support frame. Central cross-beam 220 C supports a mounting fixture 230 in a manner that allows the mounting fixture to move in the Y-direction. In an example, central cross-beam 220 C includes a flanged section that runs in the Y-direction, and mounting fixture 230 includes a central channel configured to slidingly engage the central cross-beam at the flanged section so that the mounting fixture can move in the Y-direction. Other known movable mount configurations can also be used.
[0037] Laser scanning system 200 also includes a drive unit 240 operably connected to mounting fixture 230 to move the mounting fixture. Drive unit 240 is operably connected to a controller 250 that controls the movement of mounting fixture 230 along central cross-beam 220 C via drive unit 240 , including stepping the mounting fixture in the Y-direction in select increments (e.g., 1 mm). In an example embodiment, drive unit 240 includes a motor, such as a stepping motor or servomotor. In one example, drive unit 240 is incorporated into movable mount 230 . In another example, drive unit 240 , mounting fixture 230 and central cross-beam 220 C may comprise a servo motor and a servo slide mechanism.
[0038] In an example embodiment, controller 250 is part of main controller MC. Also in an example embodiment, controller 250 is or includes a computer 252 (e.g., a personal computer (PC), workstation, etc.) with processor 254 and a memory unit (“memory”) 256 , and includes an operating system such as Microsoft WINDOWS® or LINUX. In an example embodiment, processor 254 is or includes any processor or device capable of executing a series of software instructions and includes, without limitation, a general- or special-purpose microprocessor, finite state machine, controller, computer, central-processing unit (CPU), field-programmable gate array (FPGA), or digital signal processor. Also, memory 256 includes refers to any processor-readable medium, including but not limited to RAM, ROM, EPROM, PROM, EEPROM, disk, floppy disk, hard disk, CD-ROM, DVD, or the like, on which may be stored a series of instructions executable by processor 254 .
[0039] The surface shape measurement methods described herein may be implemented in various embodiments via a set of machine readable instructions (e.g., computer programs and/or software modules) stored in memory 256 and operable in processor 254 for causing controller 250 to operate laser scanning system 200 to perform the measurement methods described herein. In an example embodiment, the computer programs run on image processor 254 out of memory 256 , and may be transferred to main memory from permanent storage via a disk drive or port 257 when stored on removable media 116 , or via a network connection or modem connection when stored outside of controller 250 , or via other types of computer or machine-readable media from which it can be read and utilized.
[0040] The computer programs and/or software modules may comprise multiple modules or objects to perform the various methods described herein, and control the operation and function of the various components in laser scanning system 200 . The type of computer programming languages used for the code may vary between procedural code-type languages to object-oriented languages. The files or objects need not have a one-to-one correspondence to the modules or method steps described. Further, the method and apparatus may comprise combinations of software, hardware and firmware. Firmware can be downloaded into processor 254 for implementing the various example embodiments described herein.
[0041] Controller 250 optionally includes a data-entry device 258 , such as a keyboard, that allows a user of laser scanning system 200 to input information into controller 250 (e.g., the part number), and to manually control the operation of the laser scanning system. Controller 250 further optionally includes a display 259 that can be used to display information using a wide variety of alphanumeric and graphical representations. For example, display 259 is useful for displaying the measured three-dimensional surface shape, as well as any of individual two-dimensional surface shapes, as discussed below.
[0042] Laser scanning system 200 also includes a support arm 260 attached to mounting fixture 230 . FIG. 8 is a bottom-up view of an example support arm 260 and mounting fixture 230 as attached to central beam 220 C. An electrical cable 262 that connects controller 250 (not shown in FIG. 8 ) to laser scanners 270 L and 270 R is shown in FIG. 8 . Support arm 260 includes opposite ends 264 L and 264 R to which are attached respective laser scanners 270 L and 270 R.
[0043] With reference again to FIG. 6 , laser scanners 270 L and 270 have, when activated, respective two-dimensional laser scan paths 272 L and 272 R that include respective central axes A L and A R and that subtend respective scanning angles θ L and θ R . Central axes A L and A R intersect at a location 280 and define a central angle φ between laser scan paths 272 L and 272 R. Location 280 serves as a reference for defining a measurement position MP, which is the position where ceramic log 101 can be scanned by laser scanners 270 L and 270 R. An exemplary measurement position is when ceramic log central axis A 1 coincides with location 280 . In an example embodiment, scan paths 272 L and 272 R overlap on ceramic log outer surface 160 when ceramic log 101 is in the measurement position. Laser scanners 270 suitable for use in laser scanning system 200 are available, for example, from Sick AG, Waldkirch, Germany, model no. IVC-3D 100 .
[0044] Support frame 210 is arranged relative to conveyor 110 so that the conveyor can move trays 114 into place below laser scanners 270 L and 270 R, thereby allowing for an in situ measurement of ceramic log 101 . In the example embodiment illustrated in FIGS. 6 , 7 , 9 and 10 (and also shown in one of the laser scanning systems 200 in FIG. 1 and FIG. 2 ), laser scanning system 200 includes a lifting mechanism 300 configured to lift tray 114 and the ceramic log 101 supported thereby so that ceramic log 101 is placed at the measurement position. This allows for scan paths 272 L and 272 R to be incident upon ceramic log outer surface 160 at a particular axial location, i.e., at a given Y-position, as discussed in greater detail below.
[0045] Lifting mechanism 300 allows for ceramic log 101 and tray 114 to be physically isolated from conveyor 110 when the ceramic log is being measured so that vibrations caused by the movement of the conveyor do not adversely affect the laser scanning measurements.
[0046] In an alternative embodiment illustrated in FIG. 10 and FIG. 11 , ceramic log 101 and tray 114 remain on conveyor 110 and the conveyor is stopped while laser scanning measurements are taken. In this case, support structure 210 is configured so that laser scanning measurements can be taken when ceramic log 101 is conveyed by conveyor 110 to the measurement position while tray 114 resides on the conveyor.
[0047] In the operation of laser scanning system 200 , once ceramic log 101 is disposed in the measurement position, controller 250 sends a control signal S 1 to drive unit 240 to move mount 230 and thus laser scanners 270 L and 270 R into an initial Y position PI ( FIG. 10 ) for scanning the ceramic log. In one example, initial position PI is such that the laser scan paths 272 L and 272 R are adjacent endface 148 so that they are not incident upon outer surface 160 but are incident upon tray 114 . Controller 250 then sends control signals S 1 to driver unit 240 to move mount 230 and thus laser scanners 270 L and 270 R in the −Y-direction in small increments, e.g., about 1 mm. For each Y-position, controller 250 activates laser scanners 270 L and 270 R with an activation signal SA so that they perform a two-dimensional scan of outer surface 160 of ceramic log 101 . For a tray 114 having a length of 1000 mm, performing two-dimensional scans in 1 mm increments results in 1000 two-dimensional surface-shape measurements.
[0048] FIG. 10 also shows an intermediate or middle Y-position PM at about the middle of ceramic log 101 , and an end position PE just adjacent the opposite endface 148 from initial position PI. The raw scan data from each Y-position is sent to controller 250 via respective scan signals S 2 L and S 2 R, thereby forming two sets of raw two-dimensional scans (“two-dimensional scan data”) that are stored in memory 256 . The two sets of two-dimensional scan data are then combined by processor 254 to form a single set of raw three-dimensional scan data for ceramic log 101 . Note that since scan paths 272 L and 272 R can include portions of tray 114 , the two-dimensional scan data and the three-dimensional scan data can also include tray information (tray scan data).
[0049] The raw scan data are stored in memory 256 and can be analyzed by processor 254 in a variety of ways to establish measurement information about ceramic log 101 . A preliminary data processing step includes finding the ceramic log ends (i.e., the axial locations of endfaces 148 ) by comparing adjacent scan data and finding where the tray measurements end and the outer surface measurements begin. This also provides a measurement of the log length. Once the ceramic logs ends are established, the raw scan data can be separated into log scan data and tray scan data.
[0050] Another preliminary data processing step includes combining the two sets of two-dimensional scan data from laser scanners 270 L and 270 R to obtain a composite two-dimensional scan for each Y-position. This combining step can be carried out in processor 254 based on instructions stored in memory 256 . In an example embodiment, the information from the overlap of scan paths 272 L and 272 R is used to stitch the two two-dimensional scans together to establish a single two-dimensional surface shape for each Y-position. FIG. 12 illustrates an example two-dimensional measured surface shape 160 ′ as determined by controller 250 from the two-dimensional scan data and displayed on controller display 259 . Major and minor axes MA and MI are shown for reference. Note that an image 101 ′ of ceramic log 101 is displayed as well, showing the Y-position YP at which the scan was taken.
[0051] Once the log scan data is obtained, then the two-dimensional log data can be combined (e.g., in processor 254 ) to form the three-dimensional surface shape. FIG. 13 illustrates an example three-dimensional image 101 ′ of the measured surface shape of ceramic log 101 as displayed on controller display 259 . Parameters relating to the surface shape can also be calculated and displayed with image 101 ′, such as the measured log length, the amount of bow along the major and minor axes, the maximum amount of bow, bow limit, etc. An example of the measurement values that can be displayed in a window 261 on controller display 259 , along with the three-dimensional image 101 ′, is shown in Table 1 below:
[0000]
TABLE 1
EXAMPLE LOG MEASUREMENT VALUES
PARAMETER
VALUE (INCHES)
TOTAL LOG LENGTH
33.51
BOW - MAJOR AXIS
0.034
BOW - MINOR AXIS
0.038
BOW - MAXIMUM
0.041
[0052] In an example, the amount of bow is established by deducing from the two-dimensional scan data relative height measurements of outer surface 160 at three spaced-apart locations (e.g., at the middle and the respective ends) of ceramic log 101 in analogous fashion to a contact measurement.
[0053] FIG. 14 plots an example of the “profile of the line” (POL) in inches versus the log position (i.e., the Y position along the log) in inches based on hypothetical laser scan data. The plot shows substantial variation in the POL at the ceramic log ends with smaller variations in between. The POL plots can also be displayed on controller display 259 .
[0054] In an example, the results of processing the log scan data and/or the tray scan data in controller 250 to obtain a ceramic log measurement is used to adjust the extrusion process for forming ceramic logs 101 . Because the surface shape of ceramic log outer surface 160 is determined by the extrusion process, and the extrusion process includes many variables such as die shape, flow rate, pressure, moisture content of the batch material, etc., one or more of the extrusion process parameters can be adjusted based on the ceramic log measurements obtained by laser scanning system 200 .
[0055] In one case, if the measured log length is out of specification, then this information can be used to adjust the cutting of extrudate 100 into green ceramic logs at the exit of extrusion unit 90 . In another example, impedance plate 95 in extrusion unit 90 is adjusted to adjust the flow of batch material 34 through die 92 when forming extrudate 100 . For example, when a ceramic log 101 has a “banana” type bow, it is indicative of different flow rates of batch material 34 through die 92 . Thus, when an upward banana-type of bow is measured, impedance plate 95 in extrusion unit 90 is adjusted to reduce the rate of flow through the bottom of the die to reduce or remove the bow. Also, as discussed above, in an example, one or more ceramic log measurements, such as bow and log length, are compared to corresponding limits, such as a bow limit and a log-length limit, to reject ceramic logs 101 that are out of specification.
[0056] In an example, the tray scan data is processed to determine if the tray 114 carrying ceramic log 101 has any shape variations that are being imparted to the ceramic log. The processing of tray scan data by controller 250 can also be used to compare to at least one tray standard to determine which if any trays are non-conforming and, removing the non-conforming trays from the manufacturing process.
[0057] While the disclosure has been described with respect to several preferred embodiments, various modifications and additions will become evident to persons of skill in the art. All such additions, variations and modifications are encompassed within the scope of the disclosure, which is limited only by the appended claims, and equivalents thereto.
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Laser scanning systems and methods are disclosed herein that can provide quick and efficient measurement of extruded ceramic logs, particularly related to log shape, during manufacture. Two two-dimensional laser scans from respective laser scanners are performed and the resulting laser scan data is combined to form a three-dimensional surface shape measurement of the ceramic log. The systems and methods disclosed herein enable a non-contact measurement of the extruded ceramic log, which reduces the risk of physically damaging the log. The measurement results can be used to adjust the extrusion process of the extruder that forms the extruded ceramic logs.
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FIELD OF THE INVENTION
[0001] The present invention relates to elevator group control methods and control devices, and aims, in particular, to provide a group control method and a group control device capable of efficiently control the operation of the elevators in diversified traffic situations and under a variety of specific conditions required for a group management system.
BACKGROUND OF THE INVENTION
[0002] In general, the objective of operation control of conventional group management systems is to reduce the average waiting time of passengers in elevators by efficiently controlling the operation of a plurality of elevators within a building.
[0003] Therefore, what the group management system must truly evaluate in its control operation is that the waiting time of passengers, including prospective passengers, and the significance of waiting time of individual passengers should be basically considered to be equivalent. However, a group management system has difficulty in directly figuring out the waiting time of individual passengers. Accordingly, the control operation is conventionally performed by evaluating the waiting time of a hall call as an alternative, that is, evaluating a time period as waiting time from a hall call is registered until an elevator arrives in response to the call.
[0004] Further, when evaluating, a focus of the evaluation is placed on the waiting time of a newly registered hall call as a target of assignment, and the waiting time of individual hall calls is not treated equivalently. In addition, as an assignment of a hall call affects, not only a call that has already been made but also a hall call that is possibly made in the near future, it is essential that the evaluation includes any hall call that may be made in the future. However, even if a hall call that is possibly made in the future is evaluated, an evaluation value for the call is usually treated only as a correction term (e.g., Patent Publication 1).
[0005] On the other hand, the conventional group management system is typically based on an “immediate assignment method” which determines a car to respond instantly upon registration of a hall call, and an “immediate prediction method” of which announces an assigned car instantly at an elevator hall. In a group management system employing the “immediate prediction method”, as any change in an assignment of a hall call that has been made may cause confusion among passengers waiting for an elevator, it is desirable not to change the assignment if circumstances allow. Accordingly, the assignment change is limited to a case satisfying specific conditions, such as changing an assignment of a potentially long waiting hall call to a different car (e.g., Patent Publication 2).
[0006] Further, the conventional group management system is provided with controlling means for moving a car to a random floor by assigning a pseudo call (virtual call) to the car. However, such means are used only under limited traffic situations such as distributed waiting during down peak and reference floor recalling when people arrive before working hours (e.g., Patent Publication 3).
[0007] Moreover, development of the conventional group management systems has been promoted in the policy of reducing waiting time of the hall call as much as possible with the application of artificial intelligence technologies such as “fuzzy” and “neuro” (e.g., Patent Publication 4).
CITATION LIST
Patent Publication
[0000]
Patent Publication 1: Japanese Examined Patent Publication No. H06-62259
Patent Publication 2: Japanese Unexamined Patent Publication No. 2006-124075
Patent Publication 3: Japanese Examined Patent Publication No. H06-2553
Patent Publication 4: Japanese Unexamined Patent Publication No. H08-225256
SUMMARY OF THE INVENTION
Problems to be Solved by the Invention
[0012] As described above, what a group management system must truly evaluate in its control operation is the waiting time of passengers including prospective passengers. However, when the control operation is performed by evaluating the waiting time of a hall call as an alternative as described in Patent Publication 1, only the waiting time of a person who first registers a hall call is evaluated when a plurality of waiting passengers are present on one floor, and it is not possible to appropriately evaluate the waiting time of a plurality of passengers waiting after this hall call. In addition, unless considering all, not just a part, of the hall calls (waiting passengers) that are possibly made in the future, the waiting time of passengers as a result of control operation of a group management system cannot be appropriately evaluated. Consequently, in a traffic situation in which waiting passengers are concentrated on a plurality of unspecified floors, it is a difficult challenge to reduce long waiting periods by adequately evaluating the waiting time and controlling the operation of elevators. For example, if it is presumed that passengers are concentrated only on a specific floor such as in the case when people arrive before working hours in an office building, it is relatively easy to prepare a control method suitable for such a traffic situation. However, it is difficult to flexibly control the operation of elevators by appropriately evaluating waiting time in complicated and diversified traffic situations such as a case where the traffic is concentrated on a plurality of unspecified floors.
[0013] Further, according to Patent Publication 2, an assignment is changed only when a specific event such as a long waiting occurs. However, the “immediate prediction method” on which a typical group management system is based may not be necessary in the first place depending on the country or region the system is employed or on the clients' view. In addition, immediate prediction is often not applicable in the case in which a number of elevators in a group management system is small. In such a case, while an assignment of a hall call can normally be changed freely as long as the waiting time of passengers can be reduced if only a little, as different evaluative criteria are used in an assignment of a hall call and an assignment change of a hall call, an assignment change of a hall call is not exactly used to the best effect in the reduction of waiting time of passengers.
[0014] Similarly, while Patent Publication 3 is provided with the controlling means for assigning a pseudo call (virtual call) to an empty car (car stopping without a traveling direction) and moving the car to any floor, such means are still used only under limited traffic situations such as distributed waiting during down peak and reference floor recalling when people arrive before working hours. Accordingly, although there is the possibility that waiting time can be reduced by assigning a pseudo call in any traffic situation, as different evaluative criteria are used in an assignment of a hall call and an assignment of a pseudo call, an assignment of pseudo call is not exactly used to the full extent in the reduction of waiting time at an elevator hall.
[0015] Moreover, an acceptable degree of repetition of an assignment change and an assignment of a pseudo call varies depending on the group management specification, the elevator specification, the user interface of an elevator hall, the use of the building, clients' needs, or traffic situation, and it is difficult to perform group control to reduce waiting time of passengers while conducting an assignment change or an assignment of a pseudo call at an adequate degree of repetition according to various requirements and specific conditions.
[0016] Furthermore, when it is intended to reduce the waiting time of a hall call as much as possible with applying artificial intelligence technologies as described in Patent Publication 4, while a highly advanced control can provide some effects, this also increases complexity and size of the system, making the system a black box. Therefore, it is difficult to respond to tasks such as adding a new control function within a limited development period, in addition to the problems as described above, and it is extremely difficult to analyze, explain, and adjust a problem in the control even if it is pointed out.
Means of Solving the Problems
[0017] The present invention has been made in order to address the various problems described above, and to provide an elevator group control method, including: placing a plurality of elevators in service for a plurality of floors; calculating an evaluation index for a newly made hall call; and selecting and assigning the best suited car to the hall call based on the evaluation index, wherein a waiting time expectation value of all passengers on all floors for each direction either that have already occurred or that is expected to occur within a predetermined time period is taken as the evaluation index, the waiting time expectation value being the expected value the sum or the average of the waiting time.
[0018] Further, according to the present invention, other than the assignment of the new hall call is performed using the waiting time expectation value as the evaluation index, an assignment change of a hall call or a pseudo call assignment to an empty car is performed based on the same evaluation index every predetermined time period or at the same time with the assignment of the new hall call.
[0019] Moreover, according to the present invention, the waiting time expectation value is calculated by using an estimated value of the passenger arrival rate on each floor and for each direction, an estimated value of hall call occurrence rate for an entire group, and an estimated time of arrival for each car, for each floor and in each direction.
Effects of Invention
[0020] According to the present invention, employing a method of stochastically evaluating the waiting time of passengers, instead of the waiting time of a hall call as in a conventional example, allows appropriate evaluation of a bias of the passenger arrival rate on each floor and the waiting time of prospective passengers, and it is possible to reduce the waiting time of passengers as originally desired in complicated and diversified traffic situations.
[0021] Further, according to the present invention, as the evaluation of the waiting time of a hall call is not necessary, it is possible to evaluate a situation as needed even when there is no new hall call. Therefore, the same evaluation index (waiting time expectation value of the all passengers) can be applied in a versatile manner for controlling means other than means for assigning a hall call, that is, an assignment change of a hall call or an assignment of a pseudo call to an empty car that is stopping without a traveling direction, and thus it is possible to facilitate optimization of the control as a whole.
[0022] Moreover, according to the present invention, when the group management system does not employ the immediate prediction, by constantly and effectively utilizing an assignment change of a hall call without restricting to a limited traffic situation, it is possible to reduce the waiting time of passengers.
[0023] Furthermore, according to the present invention, by constantly and effectively utilizing a pseudo call assignment without restricting to a limited traffic situation, that is, by moving an empty car that is stopping without any traveling direction to an appropriate position as needed, it is possible to reduce the waiting time of passengers.
[0024] Further, according to the present invention, a degree of repetition of an assignment change or a pseudo call assignment can be adjusted according to diverse needs and specific conditions that vary depending on individual buildings, and it is possible to reduce the waiting time of passengers under adjusted conditions.
[0025] Moreover, according to the present invention, a group control method based on a unified evaluation index of the waiting time of passengers can be realized, and consequently it is possible to simplify the control structure as compared to the group control to which conventional artificial intelligence is applied. Therefore, it is possible to facilitate addition of a new control function, and to easily analyze, explain, and adjust a problem in the control when it is pointed out.
BRIEF DESCRIPTION OF DRAWINGS
[0026] FIG. 1 is a diagram showing an entire configuration of a group management system of elevators according to a first embodiment of the present invention.
[0027] FIG. 2 is a diagram showing a relation between the position of a car and a call for explaining the estimated arrival time of the car.
[0028] FIG. 3 is a table illustrating one example of a table for estimated time of arrival according to the present invention.
[0029] FIG. 4 is a main flowchart showing an entire procedure according to the first embodiment of the present invention.
[0030] FIG. 5 is a chart showing a variation in the estimated time of arrival of each car at one station position.
[0031] FIG. 6 is a chart showing a part of FIG. 5 by dividing the shaded region.
[0032] FIG. 7 is a flowchart explaining a specific procedure of the new hall call assignment process in Step S 2 in FIG. 4 .
[0033] FIG. 8 is a flowchart explaining specific steps of the waiting time expectation value calculation process for all passengers at all station positions in Step S 24 in FIG. 7 .
[0034] FIG. 9 is apart of a flowchart explaining specific steps of the waiting time expectation value calculation process for all passengers at a station position “s” in Step S 204 in FIG. 8 .
[0035] FIG. 10 is a part of the flowchart explaining specific steps of the waiting time expectation value calculation process for all passengers at a station positions in Step S 204 in FIG. 8 .
[0036] FIG. 11 is a part of a flowchart explaining specific steps of the hall call assignment change process in Step S 4 in FIG. 4 .
[0037] FIG. 12 is a part of the flowchart explaining specific steps of the hall call assignment change process in Step S 4 in FIG. 4 .
[0038] FIG. 13 is a part of the flowchart explaining specific steps of the hall call assignment change process in Step S 4 in FIG. 4 .
[0039] FIG. 14 is a part of a flowchart explaining specific steps of the pseudo call assignment process in Step S 5 in FIG. 4 .
[0040] FIG. 15 is a part of the flowchart explaining specific steps of the pseudo call assignment process in Step S 5 in FIG. 4 .
[0041] FIG. 16 is a part of the flowchart explaining specific steps of the pseudo call assignment process in Step S 5 in FIG. 4 .
[0042] FIG. 17 is a part of a flowchart showing steps of a process of assigning a new hall call and changing the assignment according to a second embodiment of the present invention.
[0043] FIG. 18 is a part of the flowchart showing steps of the process of assigning a new hall call and changing the assignment according to the second embodiment of the present invention.
[0044] FIG. 19 is a part of the flowchart showing steps of the process of assigning a new hall call and changing the assignment according to the second embodiment of the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
First Embodiment
[0045] In general, the car position in a group control cannot be judged only by a floor level, the traveling direction of the car should be included in the judgment. Therefore, in the description hereinafter, the term “station position” is used as a concept for expressing the stop position of a car including both floor and direction to simplify explanation.
[0046] Now, one embodiment of the present invention will be described with reference to FIG. 1 through FIG. 16 .
[0047] FIG. 1 is a diagram showing an entire configuration of a group management system of elevators according to a first embodiment of the present invention. Here, the description is given taking an example in which three elevator cars including a first car to a third car are controlled as a group. However, it should be appreciated that the number of the elevators is not limited to three.
[0048] Referring to FIG. 1 , reference number 11 represents an elevator control device configured to perform elevator control operation of the first car, reference numbers 12 and 13 similarly represent elevator control devices configured to perform elevator control operation respectively of the second car and the third car, a reference number 20 represents a hall call registration device that is common to all elevators and configured to register a hall call, and a reference number 30 represents a group control device configured to control the operation of the elevators as a group while communicating with the elevator control devices 11 - 13 .
[0049] Reference number 31 represents passenger arrival rate estimating means configured to estimate a passenger arrival rate at a station position. The passenger arrival rate estimating means estimates the passenger arrival rate using a conventional method such as, for example, stochastic estimation of the passenger arrival rate based on learned data relating to a time period during which no hall call is made by presuming the arrival of a passenger who uses an elevator to be Poisson arrival. It is also possible to correct the passenger arrival rate according to variations in a number of car calls and a live load of a car.
[0050] Reference number 32 represents hall call occurrence rate estimating means configured to estimate the rate of occurrence of hall calls in an entire group. This also can be easily obtained using a conventional method such as division of the number of hall calls occurring per a predetermined time, this time period is based on a short-term learning or a long-term learning by the predetermined time.
[0051] Reference number 33 represents car arrival time estimating means configured to estimate time at which each car can arrive at each station position, and it is possible to use various methods of conventional hall call waiting time estimation as the method to estimate the time of arrival. However, while estimation of waiting time for a single entire loop of car is sufficient in the conventional hall call waiting time estimation, as the present invention is also required to estimate waiting time of prospective passengers, it is necessary to estimate waiting time for a single entire loop and a half considering a farthest car call that is set off from an assigned hall call on a back side as shown in FIG. 2 , and to estimate for two entire loops and a half at maximum, considering the necessity of estimating waiting time of passengers that may occur after responding to all the calls that can be assumed.
[0052] One example of a table for estimated time of arrival produced by the car arrival time estimating means is shown in FIG. 3 . Here, while calculation is made by assuming that time required for a car to travel a single floor is 2 seconds and that the time required for a car to make a single stop is 10 seconds to simplify an explanation, traveling time and such are calculated based on learned data of group management in practice.
[0053] Referring back to FIG. 1 , a reference number 34 represents waiting time expectation value calculating means configured to stochastically calculate, as a general evaluation index, an expectation value of a sum or an average of the waiting time of all the passengers (including passengers that have already appeared) estimated to appear at all of the station positions within predetermined time (hereinafter, the expectation value of the sum or the average of waiting time is simply referred to as a waiting time expectation value). A concept and a method of calculation of the waiting time expectation value of all passengers will be described later.
[0054] A reference number 35 represents hall call assigning means configured to evaluate a newly registered hall call taking the waiting time expectation value as an evaluation index, or holistically in conjunction with other evaluation indices, and to assign the call to the best suited car. The hall call assigning means performs an assignment process every time a new hall call is made.
[0055] A reference number 36 represents hall call assignment changing means configured to change an assignment of a hall call that has been assigned based on the waiting time expectation value. The hall call assignment changing means calculates, every predetermined time, the waiting time expectation value assuming that the assignment is changed, compares the calculated waiting time expectation value with the waiting time expectation value before the assignment change is made, and performs the assignment change of the hall call if a difference between the two values satisfies a predetermined condition.
[0056] A reference number 37 represents pseudo call assigning means configured to assign a pseudo call to an empty car based on the waiting time expectation value. The pseudo call assigning means calculates, every predetermined time, the waiting time expectation value assuming that a pseudo call is assigned, compares the calculated waiting time expectation value with the waiting time expectation value before the assignment of a pseudo call is made, and assigns a pseudo call to the empty car if a difference between the two values satisfies a predetermined condition.
[0057] A reference number 38 represents learning means configured to perform statistical processing of data received from the elevator control devices 11 - 13 and the hall call registration device 20 and accumulates the data. The learning means is configured by, similarly to those used in conventional group control, such as short-term learning means for learning about current traffic situation, and long-term learning means for learning about traffic situation in each time period on weekday, weekend, or the same day.
[0058] A reference number 39 represents communicating means configured to communicate with each of the elevator control devices 11 - 13 .
[0059] Next, a procedure of an elevator group control method according to the present invention of the above configuration is described with reference to flowcharts in FIG. 4 through FIG. 16 .
[0060] FIG. 4 is the main flowchart of the entire procedure, showing that the assignment process is performed every time when a new hall call is made, and a hall call assignment change process and a pseudo call process are performed every predetermined time. This procedure is constantly and repeatedly performed.
[0061] First, in Step S 1 , it is determined whether or not a new hall call is present, and if present, awaiting time expectation value of all passengers at all station positions is calculated in Step S 2 , and the hall call is assigned to the best suited car based on a result of the calculation. Further, separately from the assignment of the new hall call, every time a predetermined time passes (Step S 3 ), the current waiting time expectation value of all the passengers and the waiting time expectation value assuming that an assignment change is performed, are compared in Step S 4 , and the assignment change is performed if a difference between the two values satisfies a predetermined condition. Similarly, the current waiting time expectation value and the waiting time expectation value assuming that a pseudo call is assigned to an empty car are compared in Step S 5 , and the assignment process of a pseudo call is performed if a difference between the two values satisfies a predetermined condition. Details of these processes will be described later. As described above, according to the first embodiment, the waiting time expectation value of all the passengers is calculated when a new hall call is made and every predetermined time, the assignment change of a hall call and the assignment of a pseudo call to an empty car, in addition to the assignment of a new hall call are performed based on the same evaluation index every predetermined time so that the value is as small as possible, that is, so that the waiting time of all the passengers is reduced.
[0062] Here, before describing the details of the processes, an idea of the waiting time expectation value of all the passengers at all of the station positions as a general evaluation index and how to calculate this value according to the present invention are described.
[0063] First, when evaluating the waiting time of all the passengers, how to evaluate arrival time of an empty car (car stopping without a traveling direction) must be considered. Unless the arrival time of an empty car can be appropriately evaluated, it is not possible to obtain a general evaluation index that can be applied to every traffic situation. In particular, as the pseudo call assignment control is in principle performed for an empty car, it is important to appropriately evaluate the arrival time of an empty car.
[0064] However, there are many uncertain elements regarding a time point and a direction at and in which an empty car starts traveling, and it is not possible to estimate the arrival time of an empty car to each station position in the same manner as a traveling car. For example, when a hall call is made at one station position in the future, the empty car may have responded to a different hall call and may not be present at an original position. Therefore, based on a hall call occurrence rate and the number of cars in an entire group, a probability P(t) that an empty car is present at an original position in a standby state is expressed as an exponential function of time t in equation 1 listed below, and it is assumed that the empty car can arrive at any station position in response to a call from this station position if the car is in the standby state, and that the empty car is removed from evaluation targets when the car is not in standby state.
[0000] P ( t )=exp(−α t ) [Equation 1]
α: A hall call occurrence rate per car
[0066] In this manner, by expressing the standby probability of an empty car in an exponential function, and using this in the calculation of the waiting time expectation value, as will be described later, it is possible to stochastically evaluate an influence of the presence of an empty car to the waiting time of prospective passengers although in a simplified manner.
[0067] Next, the calculation of “the waiting time expectation value of all the passengers expected to occur within predetermined time T” at one station position is described by schematizing as shown in FIG. 5 .
[0068] FIG. 5 is a graphic chart showing variation in estimated time of arrival of each car at one station position, in which a horizontal axis represents time and a vertical axis represents the estimated time of arrival. Here, the chart shows that the first car is always traveling within the time T, and passes once by a station position as a target. The chart also shows that the second car currently stops as an empty car, and that the third car is currently traveling but stops at time t 4 and becomes an empty car.
[0069] In FIG. 5 , the waiting time expectation value of all the passengers is obtained by the integration of the shaded area and multiplication of a passenger arrival rate λ. However, when there is an empty car present closer than a traveling car, the expectation value of the waiting time is calculated assuming that this empty car responds at the probability P(t) expressed by the equation 1.
[0070] Regions in the shaded area are divided by time that satisfies conditions as listed below.
[0000] (a) Time at which estimated time of arrival of the traveling car becomes equal to estimated time of arrival of the empty car.
(b) Time at which the traveling car becomes an empty car in a stopped state.
(c) Time at which the traveling car arrives at the target station position.
[0071] As the region divided in this manner shows a simple shape as shown in FIG. 6 , it is possible to perform integral calculation easily, and to obtain the waiting time expectation value of all the passengers that occur in a time period represented by the divided region.
[0072] For example, the waiting time expectation value of all the passengers in a region E 5 shown in FIG. 5 can be obtained by equation 2 listed below.
[0000] E =∫ λ ( w 1 P ( t )+ w 2 P ( t )(1 −P ( t ))+( w 0 −( t−t 4 ))(1 −P ( t )) 2 ) dt [Equation 2]
[0073] λ s : A passenger arrival rate at the station position s
[0074] Similarly, where a number of empty cars that can influence the waiting time of passengers at a station position as a general target is m, a waiting time expectation value E Z of all the passengers in time periods t a −t b can be obtained by equation 3 listed below.
[0000]
E
z
=
∫
t
a
t
b
λ
(
∑
k
=
1
m
(
w
k
P
(
t
)
(
1
-
P
(
t
)
)
k
-
1
)
+
(
w
0
-
(
t
-
t
a
)
)
(
1
-
P
(
t
)
)
m
)
t
[
Equation
3
]
[0075] w 0 : Estimated time of arrival at time t a of a car that arrives at a target station position in the shortest time out of all traveling cars
[0076] w 1 , w 2 , . . . : Estimated time of arrival of cars whose estimated time of arrival at target station position is shorter than w 0 out of empty cars, where w 1 , w 2 , . . . are in ascending order of estimated time of arrival.
[0077] In this manner, by summing up the waiting time expectation values of the passengers obtained for the respective regions, a waiting time expectation value Es of all the passengers that appear at a station position s within a predetermined time T is obtained by equation 4 listed below.
[0000]
E
s
=
∑
k
=
1
n
E
z
[
Equation
4
]
[0078] n: A number of divided regions
[0079] It should be noted that there must be a single passenger at hall call registration if a hall call has already been made at this station position, and it is possible to ignore the presence of an empty car until a car assigned to this hall call arrives. Therefore, the waiting time expectation value of the passengers in this case can be obtained by equation 5 listed below.
[0000]
E
z
=
h
c
w
t
+
λ
·
h
c
w
t
2
2
[
Equation
5
]
[0080] Then, the waiting time expectation value ET of all the passengers that have appeared or may appear within the predetermined time T at all the station positions can be finally obtained by equation 6 listed below.
[0000]
E
T
=
∑
s
∈
S
E
s
[
Equation
6
]
[0081] S: A class representing all station positions
[0082] E T is “the waiting time expectation value of all the passengers at all the station positions” used as a general evaluation index in the group control method according to the present invention.
[0083] Based on what has been described above, the steps for calculating the waiting time expectation value of all the passengers at all the station positions, and the procedure for assigning a new hall call based on the result of the calculation are described with reference to flowcharts in FIG. 7 through FIG. 10 .
[0084] FIG. 7 is a flowchart explaining a specific procedure in Step S 2 in FIG. 4 , showing the steps for calculating the waiting time expectation value of all the passengers at all the station positions assuming that a new hall call is tentatively assigned to each car, and assigning the new hall call to a car whose waiting time expectation value is the smallest.
[0085] First, in Step S 21 , the initial value of a variable eval representing the waiting time expectation value is set to be the maximum value, and based on Step S 22 and Step S 27 , the process between these steps is repeated for all of the cars.
[0086] In Step S 23 , a table for estimated time of arrival for a case in which a new hall call HC is tentatively assigned to an “i” car is generated for each car as shown in FIG. 3 . Then, in Step S 24 , the waiting time expectation value of all the passengers at all the station positions, assuming that the hall call is tentatively assigned to the “i” car, is calculated based on the generated table for estimated time of arrival (detailed steps will be described later), and stored as variable e.
[0087] In Step S 25 , the variable e is compared with the variable eval. If e<eval, a waiting time expectation value e at this time is substituted for the variable eval, and a car number “i” is substituted for “car” in Step S 26 . Similarly, Step S 23 through Step S 26 are repeated for all of the cars, and the smallest value out of the waiting time expectation values of all the passengers at all the station positions assuming that the new hall call is tentatively assigned to the respective cars is stored as eval, and the car that is tentatively assigned at this time is stored as “car”. Then, in Step S 28 , the new hall call HC is actually assigned to the “car” car whose waiting time expectation value is the smallest.
[0088] Next, a specific procedure in Step S 24 for calculating the waiting time expectation value of all the passengers at all the station positions, assuming that the new hall call is tentatively assigned to one car, is shown in the flowchart in FIG. 8 .
[0089] First, in Step S 201 , the initial value of the variable E T representing the waiting time expectation value of all the passengers at all of the station positions is set to be 0. In Step S 202 , the hall call occurrence rate shown by equation 1 is obtained as α, and based on Step S 203 and Step S 206 , the process between these steps is repeated for all station positions. Specifically, in Step S 204 , the waiting time expectation value of all the passengers at the station position is calculated as E S , and in Step S 206 , the value obtained by adding E S to E T is newly stored as E T by updating. In this manner, Step S 204 and Step S 205 are repeated for all of the station positions, and the waiting time expectation value of all the passengers at all the station positions, assuming that the new hall call is tentatively assigned to one car, is obtained as E T . Then, in Step S 207 , the value of E T is returned to Step S 24 in FIG. 7 and substituted for e.
[0090] Next, a specific procedure in Step S 204 for calculating the waiting time expectation value of all the passengers at one station position s is shown in flowcharts in FIG. 9 and FIG. 10 . The procedure is divided into two flows at a connecting sign G for convenience sake.
[0091] First, in Step S 251 , a passenger arrival rate at the station position s is obtained as λ, and in Step S 252 , the predetermined time T (e.g., about 60 seconds) is divided into a plurality of time periods that can be subjected to the integral calculation of the waiting time expectation value, as described with reference to FIG. 5 . In Step S 253 , a number of the divided time periods is taken as n, and in Step S 254 , the initial value of E S is set to be 0 and the initial value of t a is set to be the current time.
[0092] Then, based on Step S 255 and Step S 269 , the process between these steps is repeated for all of the time periods. Specifically, in Step S 256 , the end time of a time period z is set to be t b , and in Step S 257 , it is determined whether or not the time period z is a leading time period. If the time period z is the leading time period, then, in Step S 258 , it is determined whether or not there is a hall call at station position s. If there is no hall call at station position s, only the passengers that possibly appear within the predetermined time are considered, and the waiting time expectation value is calculated based on equation 3. Then, the process proceeds to Step S 259 .
[0093] In Step S 259 , the estimated time of arrival of a car that can arrive at the station position s in the shortest time out of all cars with a traveling direction during the time period z is substituted for w 0 . In Step S 260 , arrival time of all cars whose estimated time of arrival at the station position s is shorter than w 0 out of cars without any traveling direction during the time period z is substituted for w 1 -w m in ascending order, and the number of the cars is substituted for m. Then, in Step S 261 , based on equation 3, the waiting time expectation value E Z during time period z is calculated.
[0094] On the other hand, if the time period z is the leading time period in Step S 257 , and if there is a hall call at the station position s in Step S 258 , the passengers that have already appeared are considered, and the waiting time expectation value is calculated based on equation 5. Then, the process proceeds to Step S 262 .
[0095] In Step S 262 , a car to which the hall call at the station position s is assigned is taken as “acar”. Then, hall call occurrence time at the station position s is taken as t a in Step S 263 , estimated time of arrival of the “acar” carat the station position s is taken as t b in Step S 264 , estimated time of arrival hcwt is obtained based on the difference between t a and t b in Step S 265 , and the waiting time expectation value E Z is calculated during time period z based on equation 5 in Step S 266 .
[0096] Then, in Step S 267 , the value obtained by adding E Z obtained in Step S 261 or Step S 266 to the original value of E S is newly taken as E S , and in Step S 268 , t b is newly stored as t a by updating. In this manner, the steps from Step S 256 to Step S 268 are repeated for all of the time periods, and the waiting time expectation value E S of all the passengers at the station position s is obtained. Then, in Step S 270 , the value of E S is returned to Step S 204 in FIG. 8 , and newly stored as E S by updating.
[0097] The above described is the new hall call assignment process taking the waiting time expectation value of all the passengers at all the station positions as the evaluation index.
[0098] Next, the hall call assignment change process that is performed every predetermined time is described similarly by taking the waiting time expectation value of all the passengers at all the station positions as the evaluation index.
[0099] FIG. 11 through FIG. 13 are flowcharts explaining specific steps of the hall call assignment change process in Step S 4 in FIG. 4 . The process shown is divided into three flows at connecting signs C and D for convenience sake. In this process, the waiting time expectation value of all the passengers at all of the station positions, assuming that an assignment of a hall call that has been performed to one car, is changed to a different car is calculated, the calculated waiting time expectation value is compared with the waiting time expectation value before the assignment change, and the assignment change is performed if a difference between the two values satisfies a predetermined condition.
[0100] First, in Step S 401 , the current table for estimated time of arrival is generated for each car, and the generated tables are stored as Tab. In Step S 402 , the current waiting time expectation value of all the passengers at all the station positions is calculated based on the tables for estimated time of arrival, and stored as eval 0 . The calculation steps of the waiting time expectation value of all the passengers in Step S 402 is the same as the process in Step S 24 in FIG. 7 as described above, and therefore an explanation is omitted. In Step S 403 , the initial value of the variable eval representing the waiting time expectation value when the assignment change is performed is set to be the maximum value.
[0101] Then, based on Step S 404 and Step S 415 , the process between these steps is repeated for all of the station positions. Specifically, in Step S 405 , it is determined whether or not there is an assigned hall call at the station position s. If there is an assigned hall call, the assigned car is taken as “acar” in Step S 406 .
[0102] Further, based on Step S 407 and Step S 414 , the process between these steps is repeated for all of the cars from the first car. In Step S 408 , it is determined whether or not the “i” car is the “acar” car. If the “i” car is not the “acar” car, that is, not the car assigned for the station position s, it is determined whether or not the “i” car can service the station position s in Step S 409 . Then, if the “i” car can service, in Step S 410 , a table for the estimated time of arrival, assuming that the assigned car for the station position s is tentatively changed to the “i” car, is generated as shown in FIG. 3 , and in Step S 411 , the waiting time expectation value of all the passengers is calculated based on the generated table for estimated time of arrival, and stored as variable e. The calculation steps of the waiting time expectation value of all the passengers in Step S 411 is performed in the same manner as the process in Step S 24 in FIG. 7 as described above, and therefore an explanation is omitted.
[0103] Then, in Step S 412 , the value of e and the value of eval are compared, and if e is smaller, e is newly stored as eval by updating, and the car number “i” of the assigned car at this time is stored as “car”. Subsequently, the same process is repeated for all of the cars in Step S 414 , and then for all the station positions in Step S 415 , and the minimum value out of the waiting time expectation values, assuming that the assignment change is performed, is stored as eval, and the car to which the assignment is changed to this time is stored as “car”.
[0104] Then, in Step S 416 , it is determined whether or not a difference between the current waiting time expectation value eval 0 (before the tentative assignment change) and the minimum value eval after the tentative assignment change is greater than the set value ReasParam 1 . Further, in Step S 417 , it is determined whether or not the reduction rate of the waiting time expectation value (a value obtained by dividing the difference between the current waiting time expectation value eval 0 and the minimum value eval after the tentative assignment change by eval 0 and then multiplying by 100%) is no smaller than the set value ReasParam 2 . If the reduction rate is no smaller than the set value, in Step S 418 , the assignment of the hall call at the station position s is changed to the “car” car, and the hall call assignment change process is terminated. Specifically, in this example, in order to prevent unnecessary confusion due to the assignment change, the assignment change is performed only when the waiting time expectation value of all the passengers at all the station positions decreases by an amount of the set value or more and when the reduction rate is no smaller than the set value.
[0105] Next, a pseudo call assignment process that is performed every predetermined time is described similarly by taking the waiting time expectation value of all the passengers at all the station positions as the evaluation index.
[0106] FIG. 14 through FIG. 16 are flowcharts explaining specific steps of the pseudo call assignment process in Step S 5 in FIG. 4 . The process shown is divided into three flows at connecting signs E and F for convenience sake. In this process, the waiting time expectation value of all the passengers at all of the station positions assuming that a pseudo call at one station position is tentatively assigned to an empty car is calculated, the calculated waiting time expectation value is compared with the waiting time expectation value before the tentative assignment, and the pseudo call assignment is performed if a difference between the two values satisfies a predetermined condition.
[0107] First, in Step S 501 , the current table for estimated time of arrival is generated for each car, and the generated tables are stored as Tab. In Step S 502 , the current waiting time expectation value of all the passengers at all of the station positions is calculated based on the tables for estimated time of arrival, and stored as eval 0 . The calculation steps of the waiting time expectation value of all the passengers at all of the station positions in Step S 502 are performed in the same manner as the process in Step S 24 in FIG. 7 as described above, and therefore an explanation is omitted. In Step S 503 , the initial value of the variable eval is set to be the maximum value.
[0108] Then, based on Step S 504 and Step S 513 , the process between these steps is repeated for all of the cars from the first car. Specifically, in Step S 505 , it is determined whether or not the “i” car is an empty car. If the “i” car is an empty car, based on Step S 506 and Step S 512 , the process between these steps is repeated for all of the station positions s.
[0109] In Step S 507 , it is determined whether or not the “i” car can service the station positions. If the “i” car can service, in Step S 508 , a table for estimated time of arrival assuming that a pseudo call at the station position s is tentatively assigned to the “i” car is generated as shown in FIG. 3 , and in Step S 509 , the waiting time expectation value of all the passengers is calculated based on the generated table for estimated time of arrival, and stored as the variable e. The calculation steps of the waiting time expectation value of all the passengers in Step S 509 are performed in the same manner as the process in Step S 24 in FIG. 7 as described above, and therefore an explanation is omitted.
[0110] Then, in Step S 510 , the value of e and the value of eval are compared, and if e is smaller, in Step S 511 , e is newly stored as eval by updating, and the car number “i” of the assigned car at this time is stored as “car” by updating. Subsequently, the same process is repeated for all of the station positions, and then for all of the cars, and the minimum value out of the waiting time expectation values assuming that the pseudo call assignment is performed is stored as eval, and the car to which the pseudo call is tentatively assigned is stored as “car”.
[0111] Then, in Step S 514 , it is determined whether or not the difference between the current waiting time expectation value eval 0 (before the tentative pseudo call assignment) and the minimum value eval after the tentative pseudo call assignment is greater than the set value PseudoParam 1 . Further, in Step S 515 , it is determined whether or not the reduction rate of the waiting time expectation value (a value obtained by dividing the difference between the current waiting time expectation value eval 0 and the minimum value eval after the tentative pseudo call assignment by eval 0 and then multiplying by 100%) is no smaller than the set value PseudoParam 2 . If the reduction rate is no smaller than the set value, in Step S 516 , the pseudo call at station position s is assigned to the “car” car, and the pseudo call assignment process to an empty car is terminated. Specifically, in this example, similarly to the case of the assignment change, in order to prevent unnecessary movement due to the pseudo call assignment, the pseudo call is assigned only when the waiting time expectation value of all the passengers decreases by the set value or more and the reduction rate is no smaller than the set value.
Second Embodiment
[0112] According to the first embodiment, the assignment of a new hall call is performed at a different timing from the assignment change of the hall call or the assignment of a pseudo call. However, the two processes can be performed at the same time.
[0113] FIG. 17 through FIG. 19 are flowcharts showing a specific procedure for assigning a new hall call and changing an assignment of a hall call at the same time. The process shown is divided into three flows at connecting signs A and B for convenience sake.
[0114] This process is an example in which the waiting time expectation value of all the passengers at all of the station positions assuming that a new hall call is assigned to each car is compared with the waiting time expectation value of all the passengers at all of the station positions assuming that the assignment of an assigned hall call is changed to a different car at the same time, and the new hall call assignment and the assigned hall call assignment change are performed at the same time if a difference between the two values satisfies a predetermined condition. The process is performed when a new hall call is made.
[0115] First, in Step S 601 , a variable evalA representing the waiting time expectation value, assuming that a new hall call is tentatively assigned and a variable evalB representing the waiting time expectation value, assuming that the assignment change is performed at the same time with the tentative assignment of the new hall call, are respectively set to be maximum values, and based on Step S 602 and Step S 617 , the process between these steps is repeated for all of the cars. Specifically, in Step S 603 , a table for estimated time of arrival assuming that a new hall call HC is tentatively assigned to an “i” car is generated, and then, in Step S 604 , the waiting time expectation value of all passengers at all station positions is calculated based on the generated table for estimated time of arrival, and set as a variable e. The calculation steps of the waiting time expectation value of all the passengers in Step S 604 are performed in the same manner as the process in Step S 24 in FIG. 7 as described above, and therefore an explanation is omitted.
[0116] Then, in Step S 605 , the value of e and the value of evalA are compared, and if e is smaller, in Step S 606 , e is newly stored as evalA by updating, and the car number “i” of the tentatively assigned car at this time is stored as “acarA” by updating.
[0117] Subsequently, based on Step S 607 and Step S 616 , the process between these steps is repeated for all hall calls AHC that are assigned to the tentatively assigned car “i”. Specifically, in Step S 608 , it is determined whether or not HC and AHC are calls made on the same floor, and if not med on the same floor, based on Step S 609 and Step S 615 , the process between these steps is repeated for all cars “j”. The reason why it is determined whether or not HC and AHC are calls for the same floor here is not to consider a hall call that is made on the same floor as a new hall call, but as a target of the assignment change when assigning the new hall call, because performing the assignment of a hall call and the assignment change on the same floor at the same time may confuse waiting passengers when a hall call in an opposite direction has already been registered on the floor on which the new hall call is made.
[0118] Then, in Step S 610 , it is determined whether or not i=j. If i≠j, in Step S 611 , a table for the estimated time of arrival assuming that HC is tentatively assigned to the “i” car and the assignment of AHC is tentatively changed to the “j” car is generated. In Step S 612 , the waiting time expectation value of all the passengers at all station positions is calculated based on the table for estimated time of arrival, and the obtained value is set as the variable e. The calculation steps of the waiting time expectation value of all the passengers in Step S 612 are performed in the same manner as the process in Step S 24 in FIG. 7 as described above, and therefore an explanation is omitted.
[0119] In Step S 613 , the value of e and the value of evalB are compared, and if e is smaller, in Step S 614 , e is newly stored as evalB by updating, the tentatively assigned car “i” assigned to HC is stored as “acarB” by updating, and the car whose assignment is tentatively changed to AHC is stored as “rcarB” by updating. The tentatively assignment change is repeated for all the cars in Step S 615 , and for all of the hall calls AHC in Step S 616 , and the minimum value out of the waiting time expectation values assuming that the tentative assignment of the new hall call is performed at the same time as the tentative assignment change of the assigned hall call is stored as evalB, the tentatively assigned car at this time is stored as “acarB”, and the car whose assignment is tentatively changed is stored as “rcarB”.
[0120] Furthermore, this process is repeated for all the cars in Step S 617 , and the minimum value out of the waiting time expectation values assuming that the tentative assignment of the new hall call is performed is stored as evalA, and the tentatively assigned car at this time is stored as “acarA”.
[0121] In Step S 618 , it is determined whether or not the difference between evalA and evalB is greater than the set value ReasParam 1 . Further, in Step S 619 , it is determined whether or not the reduction rate of the waiting time expectation value (a value obtained by dividing the difference between evalA and evalB by evalA, and then multiplying by 100%) is no smaller than the set value ReasParam 2 . If the reduction rate is no smaller than the set value, HC is assigned to the “acarB” car in Step S 620 , and the assignment of AHC is changed to the “rcarB” car in Step S 621 . Moreover, when even one of Step S 618 and Step S 619 is not satisfied, HC is assigned to the “acarA” car in Step S 622 , and the assignment of the assigned hall call is not changed. Specifically, in this example, in order to prevent unnecessary confusion due to the assignment change, the assignment of a new hall call and the assignment change are performed at the same time only when the waiting time expectation value of all passengers at all of the station positions decreases by the amount of the set value or more and when the reduction rate is no smaller than the set value, and only the assignment of a new hall call is performed when not.
[0122] While, in this example, the case in which the assignment change is performed at the same time with the assignment of a new hall call is described, it is also possible to perform the assignment of a pseudo call to an empty car at the same time with the assignment of a new hall call, instead of or along with the hall call assignment change.
Other Embodiments
[0123] It should be appreciated that, while in the above embodiments, the difference and the reduction rate from the current waiting time expectation value is compared with a set value as criteria for performing the hall call assignment change and the assignment of a pseudo call, such set value is not required to be a fixed value. The value can be set to be any value according to the group management specifications and conditions of the building; for example, the set value regarding the assignment change can be set to be closer to 0 when the immediate prediction is not performed, and the hall call assignment change is performed if there is possibility of improvement in the waiting time expectation value if only a little, or the set value regarding the pseudo call assignment can be set to be a greater value when energy saving is considered to be important, and standby operation using a pseudo call is performed only in a situation in which it is expected to reduce the waiting time to a large extent.
[0124] Further, in the above embodiments, as the waiting time expectation value of all passengers at all the station positions is taken as the general evaluation index, it is not necessarily possible to assign a car that can arrive in the shortest time to individual hall calls, and there is a case in which the car can pass without responding to a hall call. In such a case, if the group management system is provided with only a hall lantern as a guiding device in the elevator hall, then there is no problem as waiting passengers cannot see whether or not a car passes by without responding to the hall call. However, in the case that the group management system is provided with a hall indicator indicating the floor at which the car is currently in as the guiding device in an elevator hall, the waiting passengers at the elevator hall can see the car passing without responding to the hall call. Further, a car passing without responding to the hall call can also be recognized in the case in which doors at the hall has a window. Therefore, in a group management system of such specifications, there is a problem where the waiting passengers seeing the car passing without responding to the hall call may feel that their requests are unduly ignored or that the passengers are given a low priority, and thus dissatisfy with the group management system.
[0125] In order to address such a problem, it is possible to provide means for converting the car passing without responding to the hall call (including changing the direction of an approaching car) contrary to the expectation of the waiting passenger as a penalty value into waiting time.
[0126] For example, where the time of passage of the car is t p and the time at which the hall call is serviced by the car is t s , the penalty value can be calculated by equation 7 listed below.
[0000] Penalty Value= A+B ( t s −t p ) [Equation 7]
[0127] Here, A is an invariable for converting customers' dissatisfaction with passage of the car into time, and B is a coefficient representing dissatisfaction of the customers that increases in proportion to the time elapsed after the passage. Further, t s and t p can be obtained in the table for estimated time of arrival described above.
[0128] In the case in which the waiting passengers can recognize the passage of the car due to installation of the hall indicator or such, the evaluation can be made by adding the penalty value to the waiting time expectation value of all the passengers as the general evaluation index according to the present invention, or comprehensive evaluation can be performed by further adding other evaluation indices.
[0129] In addition, the present invention is not limited to the above embodiments, and various modifications can be made without departing the spirit of the present invention.
REFERENCE MARKS IN THE DRAWINGS
[0000]
11 - 13 Elevator Control Device
20 Hall Call Registration Device
30 Group Control Device
31 Passenger Arrival Rate Estimating Means
32 Hall Call Occurrence Rate Estimating Means
33 Car Arrival Time Estimating Means
34 Waiting Time Expectation Value Calculating Means
35 Hall Call Assigning Means
36 Hall Call Assignment Changing Means
37 Pseudo Call Assigning Means
38 Learning Means
39 Communicating Means
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Provided are a group control method and a group control device capable of efficiently controlling the operation of elevators in diversified traffic situations and under a variety of specification conditions required for a group management system. A plurality of elevators are placed in service for a plurality of floors, an evaluation index for a newly made hall call is calculated, and the best suited car is selected and assigned to the hall call based on the evaluation index in the group control method of elevators. A waiting time expectation value of all passengers on all floors for each direction, either that have already occurred or that are expected to occur within a predetermined time period, is taken as the evaluation index, the waiting time expectation value being the expectation value for the sum or the average of waiting time.
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FIELD OF THE INVENTION
The present invention relates to an apparatus and methods for recovering magnetically attractable articles from fluid, and more particularly to an apparatus and methods for recovering magnetically attractable fragments from fluid that has passed through oil and gas well casings to determine the metal loss from the well casings.
BACKGROUND OF THE INVENTION
Casings used to line wells in oil- and gas-producing formations typically suffer damage from erosion, perforation (such as for the purpose of running additional lines into such a formation), and ordinary wear and tear from the operation of the wells. Since the integrity of well casing is important to the integrity of the well, monitoring the condition of well casing is an important part of well maintenance. Drilling fluid is circulated in well casing for purposes including removing drill cuttings from the casing and from the face of the bit, so one way to monitor the condition of the casing is to collect and analyze the casing fragments released into the drilling fluid. The quantity of casing fragments collected from the drilling fluid is indicative of the quantity of fragments being generated down hole.
Solids and cuttings are generally removed from drilling fluids at the surface by solids control equipment such as shale shakers and hydrocyclones, which dump solids into collection bins. It is known to place a “ditch magnet” into the drilling fluid system to collect casing fragments from the drilling fluids. The shale shaker is a device in an oil well drilling process used to collect oversize drill cuttings, etc. from drilling fluid. The shale shaker is monitored for metal filings to assess metal wear such as for example, casing wear. For monitoring the metal wear, a shale shaker magnet is often used to magnetically attract and collect thereon at least a portion of metal filings that enter the shale shaker. The magnets are periodically removed from the shale shaker and the metal filings collected therefrom and weighed in order to quantify the filings that have been collected in the time period. The quantity of filings that are collected are indicative of the amount of metal filings passing into the shale shaker and, therefore, also indicative of the amount of metal filings being generated down hole.
The typical ditch magnet is heavy, and requires at least two persons to lower it into the drilling fluid stream. As metal fragments adhere to the ditch magnet, the device becomes even heavier and difficult for personnel to remove. Removal of the metal particles from the ditch magnet is difficult because of the strong magnetic field, which can also result in the magnetization of handles or other features of the device. Drilling personnel usually run their hands over the surface of the ditch magnet in an effort to strip the magnetic materials from the magnet. In prior art devices, the handle often complicates the collection of the magnetic materials attracted about it. The collection process becomes slow and laborious, and the completeness of the collection process can vary from person to person and from time to time because of the added complexity of removing the collected materials about the handle. Thus, the amount of metal fragments retrieved and therefore the accuracy of the calculation of total metal loss in the casing depends on the skill and thoroughness of the personnel removing the fragments from the ditch magnets.
Another known method of fragment removal employs shrouded or sheathed magnets in a non-magnetic housing which includes a lid connectable to the housing so that the magnets are removable from the housing. By removing the magnets from the housing, the housing can be demagnetized to facilitate collection of the metal filings from the exterior surface of the housing. However, the connection between the lid and the housing can become fouled by drilling mud and metal filings so that the reconnection of the lid to the housing becomes difficult. There is a need for an apparatus and method for inexpensive removal of casing fragments from drilling fluids without the disadvantages of the known devices and methods.
SUMMARY OF THE INVENTION
The present invention is directed to methods and apparatus for removing casing fragments from fluids circulated in hydrocarbon-producing wells.
In one aspect, the invention is directed to a method for monitoring the condition of well casing by recovering magnetically attractable casing fragments from fluid in a vessel having an upper end, including placing a reusable magnetic separator in the fluid in the vessel, wherein the separator includes a magnetic body, at least one nonmagnetic end contiguous to the body, an exterior surface spanning the body and nonmagnetic end, and a hanger; retaining the separator in the fluid for a selected period of time; removing the separator from the vessel; and urging the casing fragments along the exterior surface of the separator to the nonmagnetic end and collecting them. In another aspect, the invention is directed to a magnetic separator, having a bare magnet body, at least one nonmagnetic end contiguous to the body, and an exterior surface spanning the body and nonmagnetic end.
It is to be understood that other aspects of the present invention will become readily apparent to those skilled in the art from the following detailed description, wherein various embodiments of the invention are shown and described by way of illustration. As will be realized, the invention is capable for other and different embodiments and its several details are capable of modification in various other respects, all without departing from the spirit and scope of the present invention. Accordingly the drawings and detailed description are to be regarded as illustrative in nature and not as restrictive.
BRIEF DESCRIPTION OF THE DRAWINGS
Referring to the drawings wherein like reference numerals indicate similar parts throughout the several views, several aspects of the present invention are illustrated by way of example, and not by way of limitation, in detail in the figures, wherein:
FIG. 1A is a side elevation of an embodiment of an apparatus according to the present invention.
FIG. 1B is a perspective view of another embodiment of an apparatus according to the disclosed invention.
FIG. 2 is a schematic view of a device and a method according to the disclosed invention.
FIG. 3 shows an exploded isometric view of an embodiment the disclosed invention.
DETAILED DESCRIPTION OF THE EMBODIMENTS
The detailed description set forth below in connection with the appended drawings is intended as a description of various embodiments of the present invention and is not intended to represent the only embodiments contemplated by the inventor. The detailed description includes specific details for the purpose of providing a comprehensive understanding of the present invention. However, it will be apparent to those skilled in the art that the present invention may be practiced without these specific details.
Referring to FIG. 1A , one apparatus according to the invention is a reusable magnetic separator 10 for retrieving metal fragments from hydrocarbon well fluids including a magnet body 12 contiguous to at least one nonmagnetic end 14 , and an exterior surface 16 .
In some embodiments of the invention, the separator may include more than one nonmagnetic end. In other embodiment, the separator may be connectable to one or more hangers, for suspension thereof in use. The hanger may include a cable, a rope, a chain, or other conventional materials. Where more than one hanger is used, the points of connection of the hanger may be spaced apart and furthermore the points of connection of the hangers may each be disposed at a nonmagnetic end.
Referring to FIG. 1B , another reusable magnetic separator 10 a is shown. Reusable magnetic separator 10 a is formed as an elongate member including a magnetically attractant body 12 a , a first nonmagnetic end 14 a ′ and an opposite nonmagnetic end 14 a ″. A first connector 15 a ′ is positioned at first nonmagnetic end 14 a ″ for accepting connection of a hanger (not shown) and a second connector 15 a ′ is positioned at the opposite nonmagnetic end for connection of a second hanger (not shown). The first and the second connectors may be in the form of eyebolts, as shown. Body 12 a and ends 14 a ′ and 14 a ″ are contiguous and formed by a housing 17 a that extends about the separator. Housing 17 a contains therein one or more magnetic sources, illustrated herein as bar magnets 22 a , forming the magnetic body 12 a . The magnets 22 a do not extend into the housing at its ends forming nonmagnetic ends 14 a ′, 14 a ″. Housing 17 a may have a surface that is substantially smooth and substantially free of protrusions along its sides.
Referring to FIG. 2 , a method of the invention includes placing a reusable magnetic separator 10 b into fluid 28 in a vessel 20 , such as a shale shaker, and retaining the separator 10 b in the fluid 28 for a selected period of time; the magnetic field separates and magnetically collects the casing fragments 30 and other magnetically attractable materials from the fluid 28 . After a suitable selected period of time, the separator 10 b is removed from the vessel 20 and the collected materials are collected from the separator. To release the casing fragments 30 from the separator 10 b , the casing fragments 30 are urged along the exterior surface 16 b to the nonmagnetic end 14 b , when they are no longer attracted to, and will fall away from, the separator. If the separator includes more than one nonmagnetic end, the magnetically attractable casing fragments may be collected by urging them to either or both nonmagnetic ends. The recovered casing fragments 30 may be analyzed (qualitatively and/or quantitatively) to assess the condition of the well casing.
As shown in FIG. 2 , in some embodiments, the separator 10 b may be suspended in the fluid 28 with one or more hangers 18 a . In various embodiments of the invention, the length of the hanger or hangers may be selected to maintain the separator above the bottom of the vessel. Since a shale shaker may accumulate settled materials, suspending the separator may facilitate collection of materials thereon as the separator is held up out of the accumulated materials and open in the flow of the fluid moving therepast. The selected length of the hanger may be fixed in some embodiments of the inventive methods so that when the separator is removed and repositioned within the vessel, it is suspended at the same position within the vessel each time.
Another aspect of the invention is a method for monitoring the condition of well casing by recovering magnetically attractable casing fragments from drilling fluid returning from the well, wherein the casing fragments may be generated by use or modification of the well casing. In this method, a reusable magnetic separator having a magnetic body and a nonmagnetic end contiguous to the body is placed in drilling fluid contained in a vessel, such as a shale shaker, whereby magnetically attractable casing fragments are separated from the fluid by the magnetic field created by the magnetic body. After a suitable selected period of time, the separator is removed from the fluid, and the casing fragments are urged along the exterior surface of the separator to the nonmagnetic end where they can be removed easily. The magnetic separator used in some embodiments may include a housing substantially free of protrusions along its sides and containing bar magnets, at least one nonmagnetic end, an eye bolt on the at least one nonmagnetic end attaching such nonmagnetic end to a hanger (such as a chain or other hanger type). In some embodiments, the collected casing fragments may be weighed after each of a number of similar time periods such that the amounts collected per time period may be compared over time. In another embodiment, weight of the recovered casing fragments may calculated and compared to a total weight of the casing originally installed in the well, which may be known or calculated, so that the percent of metal lost from the casing is obtainable for example by dividing the weight of the casing fragments recovered from the well by the total weight of the casing originally installed in the well. The casing fragments may also be subjected to qualitative assessment, such as by visual inspection.
Yet another aspect of the invention is a method for collecting magnetically attractable particles from fluid including placing a reusable magnetic separator in fluid, wherein the separator includes a magnetic body which in turn may have bare magnet, at least one nonmagnetic end contiguous to the body, and an exterior surface spanning the body and the nonmagnetic end; retaining the separator in the fluid for a selected period of time; removing the separator from the fluid; and, urging the particles along the exterior surface of the separator to the nonmagnetic end and collecting them.
Referring to FIG. 3 , in some embodiments of the invention the body 12 c may include at least one magnet 22 , and each magnet 22 may have a bore 26 such that the bores 26 of adjacent magnets 22 are aligned along an axis and a retainer 24 can be inserted through the bore 26 of each magnet 22 . At least one end of the retainer 24 may be attached to a nonmagnetic end 14 c , which nonmagnetic end is further attached by a connector to a hanger 18 .
The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to those embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein, but is to be accorded the full scope as defined in the claims, wherein reference to an element in the singular, such as by use of the article “a” or “an” is not intended to mean “one and only one” unless specifically so stated, but rather “one or more”. All structural and functional equivalents to the elements of the various embodiments described throughout the disclosure that are know or later come to be known to those of ordinary skill in the art are intended to be encompassed by the elements of the claims. Moreover, nothing disclosed herein is intended to be dedicated to the public regardless of whether such disclosure is explicitly recited in the claims. No claim element is to be construed under the provisions of 35 USC 112, sixth paragraph, unless the element is expressly recited using the phrase “means for” or “step for”.
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Methods and apparatus are disclosed for recovering magnetically attractable wellbore casing fragments from drilling fluid used in hydrocarbon-producing formations.
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FIELD OF THE INVENTION
The present invention relates to the field of infusion pumps, and in particular, to an infusion pump system having one or more individually controlled pumps, simplified controls, and respective multi-line displays.
BACKGROUND OF THE INVENTION
Syringe pumps conventionally consist of a pole or table mounted unit in which a syringe from which fluid material is to be pumped is cradled in a vertical or horizontal position within a syringe pump designed to fit a specific size or range of sizes.
However, the user interface on such pumps is typically complex, cluttered, and incompatible with syringe pump internal function upgrades. Exemplary interfaces provide large footprint keyboards, dedicated function keys, or manually adjusted knobs having plural, hard-wired detents for each variable. Such interfaces typically allow limited automatic mode transition, relying upon spring loaded knobs or dials; manual intervention is most often required to change pump mode. Displayed information is typically less than comprehensive and is incompatible with efforts at customizing complex infusion regimens. Such pumps further fail to provide sequential or simultaneous infusions from plural syringes, fail to allow simple customized entry of drug information along with default administration conditions for a wide range of drug types and chemistries, and fail to provide ease of insertion or installation of the syringe in the vertical orientation.
SUMMARY OF THE INVENTION
These and other deficiencies of prior art syringe pumps are corrected in accordance with the teaching of the present invention.
The processor driven syringe pump for one or more, typically two syringes, which are held vertically in corresponding pumping stations of a housing unit which itself is typically suspended from an IV pole. The pump features, in the case of two syringe holding stations, a central display, typically a color or monochrome back lit liquid crystal or plasma display having first and second portions, one corresponding to each of the syringes operated by the pump. The syringe holding station includes a pusher assembly having a plunger clamp assembly in which a top plate over a load cell is provided to measure force exerted on the plunger flange, and front and back clamps which are positioned beneath the plunger flange and notched to fit around the plunger itself, securely cradling the plunger between the top plate and the clamps. An actuation pad and linkage separates the two clamps in a manner to facilitate plunger flange installation. The two clamps close by spring force, thus capturing the plunger securely from two sides as the actuation pad is released.
Below the display screen, for each syringe station, a data entry knob cooperative with a display processor is provided which, upon turning, causes a selection highlighter issue on the display to step through the menu selections. Knob pushing causes selection of the highlighted menu item, which may cause a numerical field to open, a pull-down menu of selectable parameters to be displayed, or a new screen and/or pumping state to be reached. The menu typically includes several layers to permit a large array of selections and commands to be accessible through a small window area. Each syringe station corresponds to the right or left portion of the split screen display and each operates independently, although a single display screen is provided. Below the data entry knob is a function select knob which is operative to select five operating states including Purge, Setup, Stop, Run and Bolus in a virtual or software driven selection manner such that transition from one state to another is controlled by software, thus preventing transition despite rotation if conditions under processor control are improper for that transition, and allowing the pump state to change without the user having to adjust the knob.
The syringe pump operates in a rate, volume or amount per time, or pharmacokinetic mode by accepting input selections for a regimen and displaying operating conditions, in that format, a format which is more intuitive for operating medical personnel. The software provides a number of feedback warnings and alarms including battery status, remaining infusion time, indications that, where a regimen provides for bolus infusion, that the bolus is insufficient, and empty syringe, among others. The software further provides a continuous indication of remaining battery life on the display. The pump may be provided with a drug library in its internal memory or may be user-entered via an interface from a personal or other computer which can simplify the selection and identification of drugs and default regimens for the drugs as well. In one embodiment, a PC program enables creation and modification of the drug library prior to its downloading to the pump.
The plunger is driven downward into the syringe barrel by a motor system referred to as a pusher assembly. The pump motor is operated by multiple processor controls including a hardware charge pump which provides a failsafe feature against a short circuit in a drive circuit element feeding continuous current into the pump motor.
The pusher assembly includes a split nut which is forced around a drive screw driven by the motor. The split nut is positioned within a tapered aperture frame or lock plate which is linked to an actuation pad or lever that opens the plunger clamps, such that upon lever activation the tapered aperture in the lock plate moves downward allowing the split nut to open due to the force provided by the torsion spring. When the lever returns to its resting position the lock plate moves upwards providing a substantial leverage advantage to close the split nut against a spring providing positioning of the lock plate so that a plunger flange can be securely nested between the plunger clamps and a top plate.
Also disclosed are further embodiments of the present invention in which: the pump is responsive to commands from a patient for increased dosage (patient controlled analgesia or PCA); two pumps are jointly programmable and operable to allow the automatic stopping of a first pump and starting of a second pump for extended sequential infusion; and a multiple station, modular infusion system for user customized combinations of syringe pumps and/or volumetric pumps.
BRIEF DESCRIPTION OF THE DRAWINGS
These and other features of the present invention are more fully set forth below in the fully exemplary detailed description and accompanying drawings of which:
FIG. 1 is a schematic view of a preferred implementation of a plural syringe pumping station according to the invention;
FIG. 2 is a perspective view of an alternative embodiment of the syringe pumping station according to the invention;
FIG. 3 is a perspective view of a further alternative embodiment of the syringe pumping station according to the invention;
FIG. 4 is a block diagram of the system level electronics for the pumping system of FIG. 1;
FIG. 5 is a component level diagram for the main processor apparatus of the block diagram of FIG. 1;
FIG. 6 is a component level diagram of the display electronics for the system block diagram of FIG. 1;
FIG. 7 is a mechanical diagram of a syringe pusher assembly for controlled plunger driving;
FIG. 8 is a view of a portion of the components of the FIG. 7 mechanics;
FIG. 9 is an exploded component diagram of the components of FIGS. 7 and 8;
FIG. 10 is a detailed view of components of the pusher assembly of FIG. 7;
FIG. 11 is a top view of the pusher assembly of FIG. 7;
FIG. 12 is a cutaway view of the pump of FIG. 1 showing sensor displacement;
FIG. 13 is a perspective view of syringe barrel clamp components of the pump of FIG. 1;
FIG. 14 is a flow chart depicting state relationships in a pump according to the present invention;
FIG. 15 is a flow chart depicting further state relationships in the pump of FIG. 14;
FIG. 16 provides exemplary Initialization state display screens in the pump of FIG. 14;
FIG. 17 provides exemplary Setup state Pre-Purge display screens for the pump of FIG. 14;
FIG. 18 provides exemplary Purge state Purge display screens for the pump of FIG. 14;
FIG. 19 provides exemplary display screens in a flow chart depicting installation of a syringe in the pump of FIG. 14;
FIGS. 20-31 provide exemplary display screens in flow charts depicting definition of infusion parameters in the pump of FIG. 14;
FIGS. 32-34 provide exemplary Stop state display screens for the pump of FIG. 14;
FIGS. 35-38 provide exemplary Run state display screens for the pump of FIG. 14;
FIGS. 39 and 40 provide exemplary sequential mode screens for the pump of FIG. 14;
FIG. 41 provides exemplary Bolus state display screens for the pump of FIG. 14;
FIG. 42 provides exemplary display screens in flow charts depicting pump environment definition in the pump of FIG. 14;
FIG. 43 is a flow chart depicting further state relationships in the pump of FIG. 14;
FIGS. 44-49 provide exemplary display screens in flow charts depicting pump environment definition in the pump of FIG. 14;
FIG. 50 provides exemplary display screens in a flow chart depicting diagnostic options in the pump of FIG. 14;
FIG. 51 illustrates various types of warnings provided by the pump of FIG. 14;
FIGS. 52 through 61 provide exemplary warning screens for the pump of FIG. 14;
FIG. 62 illustrates various types of alarms and associated display screens provided by the pump of FIG. 14;
FIG. 63 provides exemplary Drug Library updating display screens provided for the pump of FIG. 14; and
FIGS. 64 through 66 provide exemplary History Log displays for the pump of FIG. 14.
DETAILED DESCRIPTION OF THE INVENTION
The present invention as illustrated in FIG. 1 contemplates a pole mount control unit 12 attached to an IV pole 14 by conventional clamping means at the rear, not shown, and having arrayed about it one or more syringe docking or holding stations 16. The syringe holding station includes a syringe barrel clamp 18, activated by a paddle 19, in which the barrel 20 of a syringe is secured. A pusher assembly 22 securely holds a plunger flange against a load cell to sense plunger pressure as a plunger 17 is driven downward into the syringe body 20 held within the clamp 18 to force fluid into a line 21. A handle 15 is provided atop the control unit.
The control unit 12 has a display 24, typically a back lit LCD, which is typically divided into first and second portions 26, 28 for respective first and second syringes controlled by the control unit 12. In an alternative embodiment, the present control unit 12 has a plasma display. The display 24 is preferably a color display, though a monochrome embodiment is also envisioned. Below the display 12 are command identification and select controls including left and right hand data entry knobs 30, 32, also referred to as menu roam dials, each corresponding to the display portion above it and to the controlled syringe associated therewith. The data entry knobs 30, 32 are software driven such that rotation thereof moves a highlighter, such as a video inversion segment, past each data entry line in the display 24. The knobs 30, 32 have a push to select function such that pushing of a knob 30, 32 with the highlighter at a corresponding selection causes that selection to be entered by the control unit 12. The selection may invoke a pull-down menu through which the user can select another item by again turning then pushing the knob 30, 32 to select the new item. The selection may also open up a numerical field, allowing its value to be changed by turning and depressing the knob 30, 32 to enter the new value. Further, the selection may include selection of a specific portion of an infusion regimen or the selection of a further menu in one or more layers to permit access to a large range of menu selectable commands or information or the selection of a new state.
Below each knob 30 and 32 are corresponding plunger drive state selectors having function selection knobs 36, 38 which, upon manual rotation, select among five functions: purge, setup, stop, run, and bolus, that are available to the system. A series of five lights 40, such as LED lights, are disposed about each of the function knobs 36, 38 and indicate which of the five functions (purge, setup, stop, run and Bolus) are operative at any one moment. Alternatively, the LED's associated with the function knobs 36, 38 are located elsewhere on the front panel of the control unit 12, for instance proximate the display 24. These function knobs 36, 38 also software operated to select among functions without user intervention. Because the switch between functions is software controlled, the control unit 12, as described below, prevents switching between functions if conditions under software monitoring are not correct. Additionally, this software control allows the software itself to switch functions based upon operation of a state being finished or acceptance of a data entry knob 30, 32 selection. For example, upon the successful completion of a Bolus (Bolus LED lit), the software causes the function to electronically switch to the Run state (Run LED lit) without the switch mechanically moving. The software also analyzes sensor indications such as alarms, as described below, in determining whether a function transition is allowable.
An alternative embodiment of the present invention is illustrated in FIG. 2, wherein only one syringe docking or holding station 16 is associated with a respective control unit 12. As a result, there is only one data entry knob 30, 32 and only one function selection knob 36, 38. Further, rather than having a split display for two or more docking stations 16, the display 24 of FIG. 2 is undivided. For the sake of clarity, a syringe 20 has been omitted from the syringe barrel clamp 18 in FIG. 2. In all other respects, the embodiment of FIG. 2 is the same in form and function as the embodiment of FIG. 1.
In a further alternative embodiment of the present invention illustrated in FIG. 3, the control unit 612, which encircles and is attached to a pole 14 for easy access and space conservation, provides an infusion module interface 616 in place of the syringe docking or holding stations 16 shown in FIG. 1. These module interfaces enable the interconnection of up to eight pump modules adapted for either syringe contents infusion or for continuous infusion of a large volume. Other configurations interface more or less than eight modules 616.
Thus, one type of pump module in this alternative embodiment is a syringe pump module 616A similar in function to the syringe docking stations 16 illustrated in FIG. 1, with the exception that the syringe pump module 616A is removable from the control unit 612 and receives power from, and communicates over a serial communications link such as an RS-232 with, the control unit 612 via a module interface. Another type of pump module to be used with this alternative embodiment is a volumetric pump module like a peristaltic pump module 616B or a volumetric cassette pumping module (not shown) which enables continuous infusion of large volumes. Once again, this module 616B has an interface for removable connection to a suitably adapted control unit 612. Regardless of configuration, each pump module 616A, 616B contains a pumping mechanism also referred to as a pusher assembly 22 (as described below with reference to FIGS. 7, 8 and 9), motor drive circuitry, an LCD 624 for displaying a drug name or drug concentration, a confirmation button 626 for enabling a user to verify the displayed contents of the attached container, and an LED 628, typically red, to indicate a failure condition.
Control over these detachable pump modules 616A, 616B is provided by a control unit 612 having an undivided display, similar in appearance to the display 24 in FIG. 1. However, in contrast to the control unit 12 of FIG. 1, the presently described alternative embodiment has one data entry knob 630 and one function selection knob 636 for all pump modules. An upper level display screen provides information such as drug name or concentration, infusion, bolus, or dose data, and operational information such as current function for all attached pump modules 616A, 616B. A touch sensitive overlay can be provided on the display 624 in this embodiment to enable invocation of lower level screens which provide more detailed information for only one of the pump modules 616A, 616B. The data entry knob 630 can also be used to invoke such lower level screens by highlighting a drug name or concentration and depressing the knob 630. Once one pump module 616A, 616B is selected, the data entry knob 630 and the function knob 636 affect only the displayed parameters and mode of that one pump module 616A, 616B. The appropriate mode LED 640 about the function selection knob 636 will light. The control unit 612 further provides battery power to the individual modules 616A, 616B.
Note that while pertinent information is displayed at all times for all modules, more detailed information including infusion parameters and statistics are displayed for only one module 616A, 616B at a time. The control unit 612 keeps track of the infusion parameters and statistics for all attached modules 616A, 616B. Just as with the first embodiment described herein, if one module 616B has been designated as providing a "carrier" such as saline and another pump 616A or pumps are providing drugs, the control unit 612 can automatically adjust the rate of flow of the carrier depending upon the flow rate of the associated drugs, thus to provide a constant total flow.
In order to provide a safeguard against the infusion of an incorrect material into a patient, the following procedure must be followed when introducing a new module 616A, 616B to the control unit 612. Once this new module has been attached, the red LED 628 found thereon is lit, and the user is prompted to enter the drug name or concentration for the drug being infused by the newly introduced module 616A, 616B. Once the user has done so, the entered drug name or concentration is also displayed on the LCD 624 found on the module 616A, 616B. The user must then read the drug name or concentration displayed on that module 616A, 616B, verify that it indeed reflects the drug to be infused by that module as entered on the main display 624, and then must depress the module button 626 to enable the infusion regimen.
This embodiment therefore provides an expandable, adaptable system of pumps which can be customized according to the need of the application. Further, replacement of a defective pump is facilitated.
With reference now to FIG. 4, there is shown a general block diagram of the control unit 12 of the present invention which is divided into two main boards, a display board 44 having a processor for each display, and a main CPU board 46, respectively shown in FIGS. 6 and 5. The main CPU board 46 communicates with a force sensor 48 via a load cell board 47 which has a load cell position to sense the pressure applied to the plunger flange as described below. A position sensor 50 is associated with each syringe holding station 16 in order to sense the position of the plunger and therefore the amount of fluid left in the syringe to be pumped. At certain intervals, a warning is provided which indicates how much longer the present syringe can be pumped. This warning is based on a known current volume of the syringe and the rate of infusion, not based solely upon the plunger position. Thus, a more detailed, useful and accurate indication of infusion time remaining is provided.
A syringe plunger sensor 49 is also in communication with the main CPU 46 via the load cell board 47. This sensor 49, as will be discussed in detail below, provides an indication of whether a syringe plunger flange has been positively engaged by the pusher assembly 22. If not, the infusion is inhibited until an indication of engagement is returned from the plunger sensor 49.
A syringe barrel sensor 52 associated with each syringe barrel clamp 18 senses the presence of a syringe and its size. A detailed description of the placement of the position sensor 50, the syringe plunger sensor 49, and the syringe barrel sensor 52 will be given subsequently.
An RS-232, or other, data interface 54 is provided for bidirectional communication to a variety of input or output devices including a PC computer 56 or patient monitor or workstation which can provide remote control or monitoring of the pump, or library information for download into memory associated with the CPU board 46 as shown in FIG. 4. The CPU board is also in communication with the left and right syringe plunger drive motors 82, 84, as discussed further with respect to FIG. 5.
There are three power sources capable of powering the pump. A battery 58 and an international line AC power supply are housed within the pump chassis. The device is also equipped to handle a DC source at the RS-232 connector. The battery 58 provides operating power to the entire system through the main CPU board 46 and alternatively a battery replacing power supply 60 operates from the AC household current or a DC source.
The main CPU board 46 is illustrated in FIG. 5 and includes a data bus 62 for data and address information communicated by a central processor 64, typically of a model 80C562 derivative, having a clock controlled by a crystal oscillator 66 on the data and address bus 62 is a program PROM 68 which typically contains system programming, such as illustrated in FIGS. 14 et. seq. A SRAM 70 (static random access memory) is also provided for holding specific additional data. A battery backed random access memory 72 is provided on the data bus 62 to hold operating information such as regimen setup data for individual syringe infusions. A data PROM 74 is provided to access such information as any language or country specific data including syringe information. Drop-in upgrades and customization are enabled by use of this data PROM 74. A communications FIFO (first-in-first-out device) queue 76 is provided to communicate with a display board 44 shown in FIG. 6.
The battery 58 applies DC current through a voltage regulator 78 for system power to a battery management circuit 80 which, for example, provides remaining battery life, and charge determinations that are provided to the CPU 64 over the bus 62. When on battery power, a battery icon is displayed with battery life in hours and minutes.
First and second motors, for the embodiment of a two syringe pump as illustrated in FIG. 1, are provided as DC motors 82 and 84. These are driven by common and respective right and left motor drive specific circuits 86, 88. Safe operation is achieved by drive circuits 86, 88 including a charge pump driver, an integrated processor PWM (pulse width modulator) and MOSFET controlling run/brake and strobe controls from the processor port 62 set up by the processor 64 and the software control described below. The charge pump driver circuits 86 and 88 provide quantum power to each DC motor 82 and 84. Because motor rotation requires continuous charge pumping, the potential for a failure mode in which the motors 82 or 84 could free run, such as by short circuiting of a transistor in the drive circuitry, is minimized or eliminated.
As illustrated in FIG. 6, a display board provides driving signals and power to the backlit and active matrix TFT LCD display 24. This includes an AC voltage excitation from an electrical inverter 90 driven by 12 volts DC from the system power source through the voltage regulator 78. The display 24 can provide as an input the composite of the two video processors: red, green, blue and synchronization signals. Colors used to indicate normal running conditions are green. Red type on yellow background is used for warnings, and yellow type on a red background is used for alarms. Other colors may be used as appropriate. In an alternative embodiment, the display can be a monochrome LCD display, with emphasized messages or data being provided in reverse video or via flashing characters or segments.
A display driver 92 in the form of a video and timing control PAL is provided and receives separate inputs, corresponding to the separate display portions 26, 28, from respective separate processors 94, 96 for each display portion, thereby providing through a single display essentially multi-syringe user interfacing. It is again noted that the present disclosure describes a two-syringe embodiment only for illustrative purposes. More than two syringes can be controlled and pumped using the present concept.
A crystal 98 and a pixel clock 99 time and synchronize the operations of the processors 94, 96. The data entry knobs 30, 32 as well as the function knobs 36, 38 drive the processors 94, 96 respectively to control the display information and to generate selection data for use by the CPU 64. Under software control, CPU 64 in turn controls the lights 40. The CPU 64 also controls a set of lights 41 which provide an indication of pump status independent of the display 24.
With respect now to FIGS. 7, 8 and 9, the mechanics of each of the syringe docking and holding stations 16 is illustrated in mechanical details. As shown in each docking station in FIG. 7, the pusher assembly 22 is driven by a threaded lead screw 104 which passes through (shown in phantom) a split nut 106 held in a lock plate 108. Portions of the split nut 106 held against the lead screw 104 are cooperatively threaded. The lock plate 108 has on a side portion a bevel cut aperture 110 in which the two halves of the split nut 106 are forced together by the lock plate aperture 110 when the lock plate is in an upward position relative to the split nut 106. The two halves of the split nut 106 tend to spread apart under the urging of a torsion spring 107 attached to each of the two halves. Thus, the bevel aperture 110 with the lock plate 108 in the upward position forces threaded halves of the split nut 106 securely around the lead screw 104.
The lead screw 104 is driven by a motor 82, 84, as shown in both FIGS. 7 and 8. In the latter, the lead screw 104 is shown in phantom, and the motor 82, 84 is shown schematically. When driven in an infusion mode, the lead screw forces a pusher assembly 22 via the lead screw 104 down thereby depressing the syringe plunger 17 and forcing the infusion of fluid from the syringe. The split nut 106 is opened by forcing the lock plate 108 down under a control link 114 by a mechanism, to be described below, including a rotatable actuation lever or pad 130 associated with the pusher assembly 22 thereby forcing the lock plate 108 downward and allowing the split nut 106 to slide open by the torsion spring 107 with relatively little force. Upon release of the actuation lever 130 and retraction of linkage 114, allowing the split nut 106 to return to the clamp position by a spring 112 pushing the lock plate 108 upward, the syringe plunger flange is securely held within the pusher assembly 22 as described below.
As illustrated more fully in FIGS. 8 and 9, the plunger is held in position by front and rear plunger clamps 120, 122 having respective notches 124 for holding the syringe plunger 17 with the plunger flange positioned thereabove on bevelled surfaces 126 associated with each plunger clamp 120, 122. The separation of the plunger clamps 120 and 122 is provided by the actuation lever 130 which rotates a shaft 132 which in turn rotates a set of lever arms 134 having a central rod therethrough (not shown for clarity) which bears upon an upper end of the control link 114 at the end of a rotation. The lock plate 108 is forced down as a result.
Another set of lever arms 136 (and a shaft extending therebetween, not shown) moves a drive plate 138 forward. Teeth 139 formed in the drive plate 138 cause a first compound pulley 140 to rotate about first pulley shaft 141. The first compound pulley 140 has a smaller, lower gear (not shown) which is rotated by the motion of the drive plate 138. This rotation similarly rotates the upper gear of the first compound pulley 140, visible in FIGS. 8 and 9. Clockwise rotation of the first pulley 140 winds a band 142 about the first pulley 140. This band 142 is pulled past a second pulley 144 pinned by a second pulley pin 145, thus pulling forward an upper surface 148 of the front plunger clamp 120 connected by a pin 146 to the end of the band 142.
A load cell 160 is held beneath load cell plate 162. The load cell 160 receives force from the plunger flange through a ball bearing 164 which rides between the load cell 160 and a force receiving plate 166. The plunger flange fits in between the plunger clamps 120, 122 and the force receiving plate 166 in such manner as to provide a balanced force on the load cell 160 independent of syringe size. A spring (not shown) extends between the front plunger clamp 120 and the drive plate 138 so that upon release of the actuation pad 130, the front and rear plunger clamps 120, 122 are drawn toward each other, securing the plunger flange therebetween.
Upon complete rotation of the actuation lever 130, the lever arms 136 and shaft extending therebetween bear against the linkage 114 pushing the lock plate 108 down and forcing the bevel cut aperture 110 to push downward against spring 112 and allowing the split nut 106 to move open at the lead screw into the larger aperture region where it separates under the spring resilience of the torsion spring 107. This allows the lead screw 104 to slide, permitting positioning of the plunger clamps 120, 122 about the plunger flange with the syringe barrel in the barrel clamp 100. The syringe barrel 20 is secured therein when the barrel clamp is released by paddle 19, as described below.
Because of the manner in which the clamps 120, 122 open to accommodate plunger positions for a wide variety of syringe sizes, the system can accommodate syringes typically in the range of 1-60 cc, automatically.
As noted above, a syringe plunger sensor 49, shown in FIG. 10 as detail A from FIG. 7 and as shown in FIG. 11, provides an indication of proper syringe installation within the pusher assembly 22. A spring 170 acts against an LED block 172, driving the block 172 downward toward the underlying rear plunger clamp 122. An LED source 174 and optical sensor 176 are positioned such that a light blocking portion 178 is capable of passing therebetween. In the view illustrated in FIG. 10, the light blocking portion 178 and the LED source and sensor 174, 176 are in front of the spring 170. Once a plunger flange is in place between the front and rear plunger clamps 120, 122 and against the force receiving plate 166, the LED block 172 is driven upward and the light blocking portion 178 interrupts the receipt of light at the LED sensor 176 from the LED source 174.
The placement of the position sensor 50 with respect to the pusher assembly 22 is discussed with respect to FIG. 12 in which a cut-away side view of a syringe docking or holding station 16 of the pump of FIG. 1 is illustrated. Each pusher assembly 22 has on a back side a row of teeth 31 extending the height of the pusher assembly 22. These teeth 31 cooperate with an idler gear 33, which in turn cooperates with a position sensor gear 35. This position sensor gear 35 is axially attached to the position sensor 50. Thus, as the pusher assembly 22 travels, the position sensor 50 enables the control unit 12 to determine how much material remains to be infused based on the known size of the installed syringe.
Also shown in FIG. 12 and in FIG. 13 is the syringe barrel sensor 52. As previously noted, a user presses down on the paddle 19 to install a syringe into the syringe barrel clamp 18. This is achieved in the illustrated embodiment by rotation of a paddle gear 23 cooperating with teeth 27 disposed on a paddle extension 19A. A spring (not shown) connects an upper end of the paddle extension 19A to the pump frame, thus urging the paddle upward. The paddle gear 23 further cooperates with teeth 29 disposed in a barrel clamp extension 18A. Thus, as the paddle is pulled downward, the paddle extension teeth 27 rotate the paddle gear 23, which is mounted on a barrel sensor shaft 25. Rotation of the paddle gear 23 causes the barrel clamp extension 18A and the barrel clamp 18 to extend out away from the pump and simultaneously causes the barrel sensor 52 to register the movement. Release of the paddle 19 allows the spring to contract, and draws the barrel clamp 18 to draw inward against the installed syringe. If this sensor 52 is properly calibrated, the distance from the pump the barrel clamp 18 must be to hold a syringe provides an indication of syringe size.
As noted, each of the two pumps within a pump system has five operating states: Purge, Setup, Stop, Run and Bolus. Entry into and exit from each of these states is controlled by manipulation of the respective function knob 36, 38 on the front panel of the pump below the data entry knob 30, 32, and/or pushing a data entry knob to stop one function or start another or by software control upon completion of a certain function. LED's associated with each function knob 36, 38 indicate the current state of the respective pump. Illumination of each of these LED's is controlled by software; transition between operating states is software controlled and thus allows automatic transition between states as well as prevents inadvertent or inappropriate operating state transition.
Each pump has two additional operating states: Power-up and Alarm. Entry into and exit from these states is similarly controlled by software, as recited above. Thus, user manipulation of the function knob has no impact on these states.
The following is a discussion of the various states, the options presented to the user therein, and the possible state transitions available in an illustrative embodiment of the present invention. For the sake of clarity, the names of the various states have been capitalized. The relationships between the pump states are illustrated in the finite state diagrams of FIG. 14 et seq., which should be referred to as one progresses through the following descriptions of each state.
Power-up
With reference to FIG. 14 and FIG. 16, when the pump is first turned on 200, initialization software is executed which places the pump in an Initialization State 202, in which tasks such as clearing internal RAM, setting up registers and executing the power-on self-test are performed. A high quality, non-destructive memory test is performed on the entire non-volatile RAM utilizing internal RAM as a scratch pad and without the requirement of a large shadow RAM for temporary data storage. Upon successful completion of this self-test, the initial Setup state screen, also referred to as the First Setup screen, is displayed 204.
Purge
The Purge state can only be accessed from the Setup state, thus avoiding excitation of purge functions while the pump is connected to a patient. If the pump is in the Setup state with the first Setup screen 204 displayed, the Purge state is accessed by turning the function knob (counterclockwise in the illustrated embodiment) toward the word "Purge". A Setup state Pre-Purge screen is then displayed 208, as illustrated in FIG. 17. In an illustrative embodiment, a message such as "READY TO PURGE THE LINE" is displayed, and "START" and "CANCEL" options are each displayed with "START" highlighted and the warning message "DO NOT PURGE WHEN CONNECTED TO PATIENT" displayed. The "Setup" LED remains lighted.
With further regard to FIG. 17, if a purge of the associated syringe is not desired or if the function knob was inadvertently turned to the Purge function, the user can push the data entry knob when "CANCEL" is highlighted to return to the first Setup screen 204; This allows the user to avoid initiation of an unwanted purge. The user can also turn the function knob clockwise (CW) to return to the first Setup screen 204. As a further safeguard, if the user does not select "START" or "CANCEL" from the Pre-Purge screen 208 after a short period of time, the pump will automatically revert to the first Setup screen 204, and the Setup LED will remain lighted.
If the Purge state is indeed desired, the user must push the data entry knob to select "START", thus verifying selection of the Purge state and enabling the display of the Purge state screen 210, shown in an illustrative embodiment in FIG. 18. Once the Purge function has been initiated, the Purge screen 210 will indicate the quantity being purged (typically in milliliters (ml)), this number incrementing.
During a purge, the pump will run at a rate dependent on the syringe size (e.g. 360 ml/hr with a 60 cc syringe) until a certain volume is delivered or until the pump is stopped by the user, at which point the pump will return to the first Setup screen 204. A user can also halt the purge prematurely by depressing the data entry knob, thus selecting the word "STOP", which is highlighted. Alternately, the user can turn the function knob CW. In each case, the Setup state is reentered and the first Setup screen is displayed 204.
Setup
The Setup state is used to enter all of the information necessary to run the pump, such as: syringe manufacturer and size; infusion units or type; mode or drug name; concentration; patient weight; infusion rate; bolus amount and duration; and dose amount, dose duration, number of doses and dose interval. Entry of this information is enabled through the use of plural variations on the first and second Setup screens 204, 206. In general, the variations are prompted in conformity with the sequential entry of such information.
In a further embodiment of the pump of the present invention, a Drug Library can be installed in the pump. This Library contains for each entry the following information: type; drug name; default concentration and other selectable concentrations; default infusion rate; minimum and maximum infusion rate limits; default bolus amount and duration; minimum and maximum bolus amount and rate limits; default dose amount, dose duration, number of doses, dose interval; and minimum and maximum dose amount and rate limits. A further discussion of the Drug Library is found below. Such stored information is displayed on the first and second Setup screens to simplify the data entry process.
Access to the Setup state 204 is provided via the Initialization state 202 by turning on the pump 200, by selecting the "STOP" option from the Purge screen 210, or by turning the function knob to light the setup LED. First initiation of the Setup state causes the display of the first Setup screen 204. The setup for the last two infusions, if any, is displayed.
With reference now to FIG. 19, if a syringe has not yet been installed in the pump, the user is prompted by the first setup screen 204, 212 (see FIG. 52) to so install a syringe. After the user has installed the syringe, the pump can signal that the syringe has been recognized 216 via automatic detection of the syringe diameter by a potentiometer associated with the syringe barrel clamp, or that the pump has not recognized the syringe 218. In the latter case, either the syringe is installed improperly, or the wrong manufacturer is identified for the detected syringe. The user is given an opportunity to correct the situation 220 (see FIG. 52), after which the pump recognizes the syringe 216.
Typically, if the pump recognizes the syringe diameter, the screen will display the manufacturer associated with that syringe diameter and syringe size as previously entered and stored in non-volatile memory. Default values for the remaining settings found in the first Setup screen, such as Units/Type, Mode, and Concentration, are provided from memory based on most recent entries. Each of these elements may be altered by user selection via the data entry knob and pop-up menus, such as the selection of syringe manufacturer 222 as illustrated in FIG. 20.
In one embodiment of the present pump, the units/type, mode or drug name, and concentration that were last used in the pump are stored in non-volatile memory and are displayed in the first Setup screen 216 upon power-up. The user then has the option of either accepting the displayed information by selecting " OK/NEXT!" or " OK/RUN!" and transitioning to the second Setup screen 260 or Pre-Run screen 470 (see FIG. 32), or changing the infusion information.
As illustrated in FIG. 20, pop-up menus also provide the ability to select the appropriate units/type 232, 234, 236, 238 in all cases, and drug name 240 if a Drug Library is installed in the pump.
If the Units/Type has been chosen as "ml/hr", the user is presented with three mode options 244, as illustrated in FIG. 21: "CONTINUOUS" 246, "CONTINUOUS W/BOLUS" 248, or "DOSE/TIME" 250. In the "ml/hr" type "CONTINUOUS" mode case 246, once the user has selected the appropriate Mode, the user can accept the currently displayed Rate by selecting " OK/RUN!", or can adjust it using the data entry knob prior to selecting " OK/RUN!". The pump then transitions to the Stop state Pre-Run Screen 470, since all information required has been accepted.
With reference to FIG. 14, if the user selects " HELP!" from the first Setup screen, the pump will display one or more of the help screens illustrated in FIGS. 24 and 25. These Help screens, referred to generally as 600, provide instructions and prompt the user to enter all of the required information on the first Setup screen and load the syringe.
In the "CONTINUOUS W/BOLUS" 248 and "DOSE/TIME" 250 modes, more information is required to be supplied in the second Setup screen 206. Thus, selection of " OK/NEXT!" from these screen variations 248, 250 causes the pump to display second Setup screens 300, 302, shown in FIG. 26.
At this point, i.e. from the first Setup screen, the user may also wish to alter other pump system information, which is accomplished by selection of the " MORE!" option from any of the "CONTINUOUS" 246, "CONTINUOUS W/BOLUS" 248, or "DOSE/TIME" 250 variations. The More screens and the options available therein are discussed below.
Another value to be confirmed or altered by the user in the first Setup screen "ml/hr" Units/Type is the Rate information associated with the continuous mode 252. To enter a new value into the Rate field, the user may either dial in a new value using the Data Entry Knob 254, or by selecting a value from a menu of values 256. Again, acceptance of the data displayed in the first Setup screen with the mode set to "CONTINUOUS" causes the pump to transition to the Stop state and display the Pre-Run screen 470.
FIG. 22 illustrates that the variations on the first Setup screen associated with the "DRUG CALC" Units/Type 238 are quite analogous to those displayed when the Units/Type has been set to "ml/hr" 236, shown in FIG. 21. Specifically, Mode options 264 include "CONTINUOUS" 266, "CONTINUOUS W/BOLUS" 268, and "DOSE/TIME" 270. However, with the Units/Type set to "DRUG CALC" (FIG. 22), the user has the ability to select the desired concentration 272 and units 274 from the first Setup screen 238. Note that when the Units/Type is set to "DRUG CALC", acceptance of the information provided by the first Setup screen causes the display of a unique second Setup screen 304, 306, 308 for all variations (i.e. for all Modes 266, 268, 270, respectively), as illustrated in FIG. 26.
For the Units/Type to be set to any option other than "ml/hr" 236 or "DRUG CALC" 238, a Drug Library must be installed in the pump. The first Setup screen in this case 240, FIG. 23, will have a Units/Type name taken from a menu 280 of names provided on the display. As noted below in further detail, drug names can be categorized into various Types by the user in the Drug Library.
The next field to be addressed in the drug Setup screen 240 is the Drug, which is selected from a menu 282 similar to the Units/Type menu 280. Note that with the "ml/hr" and "DRUG CALC" Types 236, 238, the next entry was Mode. In the case of any other Units/Type, this next entry is Drug. The drug chosen from the subsequent menu 282 will initiate the display of one of three further variations 284, 286, 288 on the first Setup screen 240 for this Units/Type, each displaying a default value for drug concentration stored in association with the selected drug in the library. In each case, acceptance of the default concentration values invokes second Setup screens similar to those for "DRUG CALC" Units/Type shown in FIG. 26 but with the drug name displayed and defaults from the Drug Library displayed for all of the selectable parameters. Selection of the " MORE!" option enables the user to manipulate the options discussed herein with respect to the More screens.
As with the "DRUG CALC" Units/Type 238, the user has the option of dialing in another concentration 290, 292, and/or changing the default units 290, 292, 294 in the first Setup screen for the drug Units/Type. In addition, other default concentrations may be selected from the menu.
In FIGS. 27, 28, 29, 30 and 31, exemplary second Setup screens are displayed for "ml/hr" Units/Type and "DRUG CALC" Units/Type with concentrations of ug/ml, mg/ml, g/ml and U/ml indicating the units that can be selected for the infusion rate, bolus amount and dose amount.
As noted, the second Setup screens 206 are illustrated in FIGS. 26 through 31. In each case 300, 302, 304, 306, 308, further options are provided for defining the desired drug infusion, including infusion value and units or dose value and units, dose time in hours and minutes, number of doses and dose interval in hours and minutes, bolus quantity and units, bolus time in minutes and seconds, and patient weight. These options are selected as above, in that the user can dial in a desired number, or can select desired units from a menu.
Once all of the information required in the Setup screens has been entered by the user, the function knob is turned by the user to light the Stop LED and display the Pre-Run screen 470. If the Setup information to be supplied is incomplete, one or more of the Information Setup 492, Pump Limit 494 or Library Range Warning 502 screens will be displayed and the Setup LED will remain lighted.
Stop
The Stop state is entered by turning the function knob clockwise from the Setup state first or second Setup screen to display the Pre-Run screen 470. The Run state is then accessed by pressing the data entry knob when "START" is highlighted.
The Bolus state 482 can be accessed to infuse a displayed bolus amount over a specified period of time by turning the function knob further clockwise from the Stop state Pre-Run screen 470 to display the Stop state Pre-Bolus screen 480 and then pressing the Data Entry knob when "START" is highlighted.
Once the function knob is turned counterclockwise from the Pre-Run screen, "CANCEL" is selected from the Pre-Run screen or the user does nothing for a brief period of time, the Stop state Stop screen 260 is displayed. As indicated in FIG. 34, displayed information in the Stop state 260 includes: concentration or drug name; infusion rate; bolus amount and duration; dose amount; dose duration; number of doses; dose interval; and the total amount of drug infused. The entered Setup information, with the exception of the infusion rate value, Bolus Amount and Duration, and Dose Amount and Duration, Number of Doses and Dose Interval may not be changed.
From the Stop state Stop screen, the following states and functions can be accessed. The Setup state first screen 204 can be entered to change a syringe or to enter new information for a new drug by user selection of the new syringe option displayed on the Stop screen 260. The second Setup screen 206 is displayed if the user turns the function knob to illuminate the Setup LED from the Stop state. The Pre-Run screen is displayed if the user turns the function knob clockwise. Finally, the user has access to the options available in the More screens by selecting the MORE! option 400 from the Stop screen.
Run
Each pump has two run states as indicated in FIG. 35: Continuous; and Dose/Time. In Continuous Run state, the pump delivers a drug at the displayed rate until the function knob is turned from the Run state to Stop or a Bolus is confirmed if the Mode is "CONTINUOUS W/BOLUS". In the Dose/Time mode, one or more fixed dose amounts of drug are infused over a specified period of time. The doses may be repeated automatically at set intervals.
The Run state is determined by the Mode associated with the Units/Type defined in the first Setup screen 204. If the Units/Type is "ml/hr" or "DRUG CALC", the Mode must be chosen from among "CONTINUOUS", "CONTINUOUS W/BOLUS", or "DOSE/TIME". If a Drug Library is installed in the pump and the Units/Type in the first Setup screen was chosen from this Library, the Mode is determined by the drug selected from a Drug Library.
Upon turning the function knob clockwise from the Setup state or Stop state, a Pre-Run screen 470 is displayed, as in FIG. 32, and the Stop LED will be lighted. The Pre-Run screen 470 provides a summary of the infusion information entered in the Setup screens 204, 206. In FIG. 32, an exemplary Pre-Run screen is illustrated for each of the Units/Type, Mode combinations. Note that for each of these screens, pushing the data entry knob causes a Run screen 472 to be displayed (FIG. 36) and the pump to begin infusing. If the mode is "CONTINUOUS W/ BOLUS" and the user turns the function knob further clockwise, the pump will transition to the Pre-Bolus screen 480, to be discussed. Otherwise, the user can turn the function knob counterclockwise to display the Stop screen, or the user can do nothing for a fixed period of time. In either case, the pump will display the Stop screen.
Once the Run state has been activated and the Run screen 472 is displayed as in FIG. 36, the pump begins running according to the specified parameters, and total amounts infused are updated and displayed. Also in FIG. 36 are examples of Run state screens for each of the Units/Type, Mode combinations.
The various pathways out of these various Run state screens 472 are also illustrated in FIG. 36. By turning the function knob to light the Stop LED, or if an alarm is triggered, the pump enters the Stop state 260. If the mode is "CONTINUOUS W/ BOLUS", by turning the function knob clockwise toward the Bolus LED, the pump continues running, but displays the Run state Pre-Bolus screen 602. Once the data entry knob is pressed to select START, the Bolus state is entered and the Bolus screen 482 is displayed. Finally, if the user selects " MORE!" from the Run state screen, the pump continues to infuse while the user is presented with the first More screen 400, described above.
As indicated in FIG. 38, if the Run state is Dose/Time and the number of doses is greater than one, after each does is given, the Dose Interval screen 604 will be displayed and the time will decrement until it is time for the next dose and the Dose/Time Run screen is again displayed. If the delivery of the dose or doses is incomplete, the pump will prompt the user to continue the infusion of the incomplete dose 606, 608 begin the infusion of the next dose 608 (if the number of doses is greater than one), or stop 606, 608.
Infusion of a drug while the pump is in the Run state can also be accomplished by patient demand. In order to enable patient controlled analgesia (PCA), and/or patient controlled sedation, a patient actuator such as a thumb switch is provided, one for each pump module. To avoid confusion between thumb switches, one such switch can have a square cross-section while another can have a round cross-section. Further, identifying letters or numbers such as "L", "R", "1", or "2" are disposed on the thumb switches to identify the associated pump module. A connector such as an RJ-11 connector can be employed as the interface between the thumb switch and the pump. The pump may further have circuitry which senses the presence of a thumb switch and may condition the enablement of PCA on its presence.
From the any mode, a user can enable PCA by selecting the appropriate icon on the display and entering information relevant to PCA including the ability to define the quantity of drug to be infused upon each patient activation of the thumb switch and the maximum amount of drug the patient can infuse over a specific period of time. A software lockout and mechanical means are provided for preventing the patient from changing the infusion information and from manually pushing the syringe plunger into the syringe barrel. Note that the continuous infusion rate can be set to zero, so that the pump can solely provide PCA.
With reference now to FIGS. 39 and 40, in a further alternative embodiment of the present invention, a user can also select a "SEQUENTIAL" mode from a screen 476 displayed only if information on a first Setup screen 204 for both pumps is identical (excluding syringe manufacturer and size), and if the user selects " OK/NEXT!" or " OK/RUN!" on both first Setup screens 204. The user is given the option of entering the "SEQUENTIAL" mode at this point. If the user selects "NO" using either data entry knob 30, 32, individual second Setup screens 206 are displayed. Note that the data entry knobs 30, 32 are not illustrated in FIG. 40 for the sake of clarity.
However, if the user selects "YES" with either data entry knob 30, 32, a combined second Setup screen 477, that is, a second Setup screen which fills the entire display 24, is displayed. Next, if the user turns the left function knob 36 clockwise, a combined Pre-Run screen similar to that previously discussed but filling the entire screen will be displayed with "START" on the left half of the display. Alternatively, if the user turns the right function knob 38 clockwise, the combined Pre-Run screen will again be displayed, but with "START" displayed on the right half of the display 24. Depressing the data entry knob 30, 32 of the respective pump (not illustrated in FIG. 40) causes a combined Run screen 486 to be displayed, and to begin infusion with that pump. FIG. 40 illustrates exemplary combined Run state screens for both left and right pumps. Note the state of the associated function selection knob state LED's 40 and the placement of "INFUSE" 42.
Therefore, the "SEQUENTIAL" mode enables a user to program both pumps for a sequential infusion of the same drug from one of the pumps, then the other, resulting in a continuous infusion from multiple syringes not limited by the capacity of any one syringe. Once a first syringe is emptied or nearly emptied of its contents, the first syringe pumping is ceased and a second syringe is pumped. A warning can be provided to the user that the transition between syringes has taken place, and that the first syringe can now be replaced. Once the second syringe is emptied or nearly emptied, the pump once again switches syringes. Alternatively, the pump can be programmed to empty the contents of the two syringes and stop. Any other number of syringes can be employed in order to infuse a required quantity.
A Y-junction or other connection known in the art is employed to enable the continuous pumping from multiple syringes. It is preferred that the junction have check-valves to prevent flow back into the unused channel during replacement of an empty syringe.
During the execution of the "SEQUENTIAL" mode, the display can provide one undivided screen of information relating to the infusion under progress as an alternative to the split screen of the previously described modes. Such information can include a summary of the history of the current infusion, as well as information regarding the active pump such as the quantity remaining in the installed syringe, and the status of the currently inactive pump.
Bolus
In the Bolus state, a fixed amount of drug is delivered over an indicated time. If a Drug Library is installed in the pump and if the recommended Bolus Amount and Bolus Duration are specified in the Drug Library for the desired drug, the pump will display those default values to simplify data entry. The user may change both the Bolus Amount and the Bolus Duration to other values as desired. Minimum/maximum recommended Bolus Amounts and/or minimum/maximum recommended Bolus Rates are used by the pump to provide a library range warning 502 if the user enters values outside these windows.
The Bolus state is accessed from either the Stop state (FIG. 33) or the Run state (FIG. 37). With reference to both, a Pre-Bolus screen 480, 602 is displayed with an option such as "START" highlighted once the function knob has been turned toward the Bolus LED. The Bolus state can only be entered from the Run or Stop states; the user can cancel entry into the Bolus state by selecting the "CANCEL" option from the Pre-Bolus screen, by turning the function knob toward the Run or Stop LED's or by waiting for a timeout to occur, thus returning the pump to the Run screen 472 or Pre-Run screen 470.
Exemplary Pre-Bolus screens are illustrated in FIGS. 33 and 37. In each case, the preselected Bolus parameters are displayed. At this juncture, the user only has the option of exiting the Bolus state as described above, or of starting the Bolus; Bolus parameters cannot be altered from the Pre-Bolus screen.
Pushing the data entry knob when "START" is highlighted begins the Bolus and invokes a Bolus screen 482, illustrated in FIG. 41. The information provided in the Pre-Bolus screen 480 is displayed, in addition to running totals for the bolus delivered and the infusion information. In contrast to the Pre-Bolus screen 480, Bolus amount and duration can be changed from the Bolus screen 482 using the data entry knob by highlighting the desired item, dialing up the desired quantity, and selecting the change.
The Bolus delivery can also be interrupted prematurely, completely stopping the infusion or continuing with the programmed continuous infusion. To transition to the Run or Stop states, the function knob is turned counterclockwise until the appropriate LED is lighted, thus stopping the Bolus. Further, the user can alter other information in the More screens by selecting the " MORE!" option from the Bolus screen 482.
The pump automatically returns to the Run state 472 and automatically lights the Run LED after the Bolus Amount is delivered, thus infusing the drug at the specified rate. If it is desired that the pump stop after infusing a Bolus Amount, the rate for the pump should be set to zero. If an alarm is encountered during the Bolus infusion, the pump automatically transitions to the Stop state and the alarm condition is indicated.
More
In FIG. 42, an exemplary first More screen 400 is displayed, along with the options available therein. First, if the user has inadvertently selected the first More screen 400, the " EXIT!" option can be selected to return to the previous state or the user can do nothing and wait for a timeout 402 to cause the pump to return to the previous state. The user can also turn the function knob, which will cause the pump to transition to the new state and/or screen as illustrated in FIG. 43.
One feature which can be displayed from the first More screen is the Pressure alarm limit. The purpose of this alarm is to provide an indication to the user that an event such as an occlusion has occurred and that the infusion may not be executing as intended. By turning the data entry knob until "PRESSURE" is highlighted, then pressing the same knob to select the option, the Pressure screen 406 will be displayed, as further illustrated in FIG. 44.
Two alarm limits are available to the user, Sensitive and High-Fixed, each selectable from a menu 409. Once selected, the corresponding letter (S, H) on the pressure indicator 408 is highlighted. In this indicator 408, pressure in the infusion system is represented by a bar graph. As pressure builds from zero, the bar graph will illuminate from the left in the illustrated indicator 408. The Sensitive alarm setting increases the sensitivity of the pump in detecting an occlusion and decreases the time it takes the pump to alarm at rates less than 50 ml/hr. Other limits are employable in alternative embodiments. If a Sensitive pressure alarm has been selected, the pump will automatically adjust the pressure alarm limit to be just above the measured pressure and will display a highlighted `S`. If a High-Fixed pressure alarm has been selected, the `H` is highlighted, and when the pressure is at or above the High-Fixed limit, the alarm will become active. The user further has the option of having the pressure indicator illustrated on the last line at the bottom of the display continuously. The Pressure screen is exited by selecting the " EXIT!" option. Alternatively, the user can turn the function knob to transition to the new state and/or new screen, as in FIG. 43.
The user has the ability to zero the running infusion totals by selecting the "TOTALS" option from the first More screen 400, bringing up the Totals screen 410 as further illustrated in FIG. 45. The user can either zero the infusion totals by selecting the "ZERO TOTALS" option, display the totals in all available units on the Stop or Run screens by entering "YES" or can return to the first More screen by selecting " EXIT!".
A "CALL BACK" option can be set to on or off by selecting "CALL BACK" from the first More screen to display the Call Back screen 610 as illustrated in FIG. 46. When "CALL BACK" is on, a Second Degree Warning as shown in FIG. 61 will occur when the user doesn't enter all of the setup information and the pump is inactive for 1 minute; the user enters all of the setup information but does not start the infusion or bolus after 1 minute has elapsed or the mode is "DOSE/TIME" and the pump has finished the delivery of a Dose.
The audible alarms for the "Syringe 15 minutes", "Syringe 5 minutes" and "Syringe Empty" warnings and alarms as in FIGS. 60 through 62 can be enabled or disabled from the first More screen 400 by turning the data entry knob to highlight "SYRINGE ALARM" and depressing the knob to display the Syringe Alarm screen 612, as further illustrated in FIG. 47. Then, turning the data entry knob toggles between a syringe and alarm bell symbol 412 and a syringe and alarm bell symbol having a diagonal line there through 414, indicating no audible alarm. The data entry knob is depressed again to make the selection.
A "LOCKOUT" option can be set to ON or OFF by selecting "LOCKOUT" from the First More screen to display the Lockout screen 614 illustrated in FIG. 48.
When the "LOCKOUT" option is ON, the data entry and function knobs can not be used without the pump prompting the user to enter the lockout code 616, thus preventing non-medical personnel from tampering with the pump.
When the user selects ON 618, the 3-digit lockout code that was last entered will be displayed. If this code is fixed on the Lockout Diagnostics screen 620 illustrated in FIG. 50, the code cannot be changed. If this code is not fixed, it can be changed by the user. When the user selects " OK/EXIT!" the pump is "locked-out" and displays the top-level screen 622.
If the correct code is not entered the Second Degree Warning (Wrong Code) 626 illustrated in FIG. 61 will be displayed and the pump will still be locked out and will return to the top level screen 624. Each pump can be separately locked out.
As in FIG. 42, each pump maintains a history log indicating how the pump was programmed, what states were transitioned between, and what warnings or alarms were encountered. This log 422 is accessed through the first More screen 400, and is discussed in further detail below. The history log is printed (and a screen 420 is displayed indicating this) via the RS-232 interface by selection of the "PRINT LOG" option from the first More screen 400.
A second More screen 424, illustrated in FIG. 49, is invoked by user selection of the MORE! option on the first More screen 400. As indicated in this figure, the user turns the data entry knob to adjust the entries for the date 426 and time 428. The desired baud rate is selected 430 from a menu of rates.
The Drug Library, discussed below, can be printed 432 from the second More screen via the RS-232 port. During the printing process, the user is provided with the opportunity to stop the print by selection of the "STOP" option.
The second More screen enables user manipulation of the screen brightness level 434. Once the "BRIGHTNESS" option has been selected, the data entry knob is turned until the desired brightness is achieved, then this knob is depressed.
The user can choose between a soft or loud audible alarm 416.
Diagnostic information and tests are available by selection of the "DIAGNOSTICS" option 251 on the second More screen 424, as shown in FIG. 50. Once selected, an initial authorization screen 253 is provided, giving someone other than service personnel an opportunity to return to the second More screen 424 by selecting the EXIT! option. By selecting "OK", service personnel are provided with a first diagnostics screen 255 indicating current conditions measured by associated sensors, such as current force applied to a syringe plunger, and plunger position and width.
From the first diagnostics screen 255, service personnel can further access more detailed pump information, such as shown in a battery status screen 257 and a software version screen 259, and additional pump related information 630. Further, from the first diagnostics screen 255, the pump can test the data entry and function knobs 30, 32, 36, 38 as described in the mode test 255. Further, from the first diagnostics screen, authorized service personnel can select BIOMED! and enter a biomed code 632 to perform additional options 634 such as calibrating the syringes 636, entering the maximum Continuous and Dose/Time rate 638 and entering a fixed lockout code 620. The pump is returned to the first More screen 400 by selecting EXIT! from the first diagnostics screen 255.
Warnings and Alarms
In the pump of the present invention, warnings are all recoverable, whereas alarms are classified as either recoverable or non-recoverable. FIGS. 51 through 62 illustrate how information accumulated at various points results in warnings, what prompts are provided by the pump, and to what state the pump returns. Typically, warnings, which can be further classified according to severity, are either status messages (added to current screen or new screens) and may require only that the user acknowledge the warning by depression of the data entry knob, and can be displayed in yellow. With reference to FIGS. 51 through 61 examples of warnings 490 are: wrong syringe manufacturer or syringe not loaded properly (syringe setup warnings 496); user uses data entry or function knob incorrectly (user interface warnings 640); incomplete information being supplied (information setup warnings 492); requested rate exceeds pump rate (pump limit warning 494); entered data beyond stored library window (library range warning 502); battery capacity needs to be recalibrated (battery service warning 642); pump needs to be calibrated for syringes (syringe calibration warning 644); first degree warnings 646; and second degree warnings 648. In all second degree warnings, the audio alarm will sound continuously, though the alarm can be permanently silenced by pressing the data entry knob, except for "ENT INTRVAL".
With reference to FIG. 62, examples of alarms 491 are: syringe barrel not captured, syringe plunger not captured, pusher moved, occlusion and, syringe empty (syringe alarms 500); five minutes of battery remaining (battery alarm 504); and non-recoverable alarms 510. Exemplary alarm screens are found in FIG. 62, and can be displayed in red for visibility.
Non-recoverable alarms 510, such as battery depleted, are referred to a system faults. Recovery from these alarm conditions requires recycling the pump power and re-entry of information into the Setup mode screens 204, 206.
Serial Communications
Bidirectional Serial Communications via at least one RS-232 port enables the pump of the present invention to either be controlled by a computer or other external device, or to transfer information to such computer or other device for electronic record keeping upon prompt by the external device. In addition, the pump can print the history logs and drug library through an RS-232 port. The RS-232 port (or ports) in the control unit enables remote control from a computer initiated by a remote host device, with the pump acting only as a slave machine and the host providing all Setup information with the exception of the syringe, concentration and drug information. All communications are initiated by the external computer or host device, with the exception of pump to printer data.
Once the pump has received a message and is in communication with the computer or remote host device, the Remote LED is lit and will remain lit until the communication is interrupted. Once a user controls the pump locally by turning the data entry knob or function knob, remote pump control is interrupted. Syringe information such as concentration and drug information must be entered locally, or must be entered remotely and confirmed locally, despite the pump being remotely controlled.
If the pump is being monitored by a remote device, the word "MONITOR" will appear on the display. Similarly, if the pump is being controlled remotely by an external device, the word "REMOTE" will appear on the display.
Drug Library
A Drug Library for use with the pump of the present invention can contain up to 300 Drug Names and default information particular to each drug. Each Drug Name can be listed under one or more user-defined Types. The drug's default infusion information and recommended safety limits can be different under each Type. Exemplary types include: Analgesics, Antibiotics, Cardiovasc., Hypnotics, ICU Meds, MUSC Relax. Alternatively, the types may be user-defined by hospital area, e.g. NICU, OR, clinician name, or any other desired grouping. Typical default information for infused drugs can include: up to three default concentrations; default infusion rate and units; minimum and/or maximum recommended infusion rates; default Bolus Amount, Duration and units; minimum and/or maximum recommended Bolus rates; minimum and/or maximum recommended Bolus Amounts; and default and minimum and/or maximum recommended Dose Amounts, Dose Rate, Number of Doses, and Dose Interval.
In addition to the option of providing the pump with a Drug Library already loaded in pump memory, a program running on a personal computer can be used to create a custom Drug Library. Once complete, this customized library can be downloaded to the pump via the at least one RS-232 port found on the control unit. When the Drug Library is downloaded or updated when both pumps display the first Setup screen, the update drug library screen 650 will be displayed, as illustrated in FIG. 63.
Infusion Loa
An Infusion Log stored within the device of the present invention provides the operational history of a respective pump contained therein with respect to the current and previous drugs infused. As illustrated in FIG. 64, information recorded within the Current Log Setup screen 422 includes setup information for the current log, including the start date and time, Units/Type, Mode or drug name, concentration, and patient weight. From this screen 422, the user can select PREV LOG! to access the previous Log Setup screen 652, select EXIT! to return to the first More screen 400, or select BCK! to display the settings for the current log 654.
By selecting BCK! from the Settings screen 654, a series of Log Record screens 423 will be displayed, each having the date, a time tag and a description of the event or occurrence. Alternatively, the date may only be displayed if it has changed from the previous entry. Such events or occurrences are divided into pages of screen displays. Each record consists of date, time and event information.
Each Log Record screen 423 display can include information regarding a transition from one functional state (Purge, Setup, Stop, Run or Bolus) to another. Any change made by the user to an Infusion Rate, Bolus Amount or Bolus Duration, and Dose Amount, Dose Duration, Number of Doses and Dose Interval is included in the Log Record screen 423 along with the value and units of the change. The installation of a new syringe is also included in the Log Record screen 423, as are date and time stamped alarms. Exemplary Log Record screens 423 are presented in FIGS. 65 and 66. Events or occurrences are recorded sequentially, enabling the user to scroll through the history of the pump in question using the " BCK!" and " FWD!" options. The Log is exited by selecting the " EXIT!" option, returning the user to the first More screen 400. The entire Infusion Log may also be uploaded to a computer or host device via the RS-232 interface as described above.
These and other examples of the concept of the invention illustrated above are intended by way of example and the actual scope of the invention is to be determined from the following claims.
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A processor driven syringe pump for one or more, typically two syringes, which are held vertically in corresponding pumping stations of a housing unit which itself is typically suspended from an IV pole. The pump features a central display having portions corresponding to each of the syringes operated by the pump. A data entry knob cooperative with a display processor, causes a cursor issue on the display to step through and choose the menu selections. A function knob is operative to select five operating states including: Purge, Setup, Stop, Run and Bolus in a virtual or software driven manner. The syringe holding station includes a pusher assembly having plunger clamp assembly and a load cell to measure force exerted on the plunger flange. An actuation pad and associated linkage provides for easy syringe flange capturing, while a syringe barrel clamp provides for easy syringe loading and secure syringe barrel positioning for many sizes of syringe. The pump operates in a rate, volume per time, or pharmacokinetic mode. The software provides a number of feedback warnings and alarms. The pump may be provided with a drug library. The syringe plunger is driven into the syringe barrel by a motor operated by a charge pump which provides a failsafe feature. The pusher assembly for the syringe includes a split nut that on actuation pad rotation releases to allow proper positioning of the syringe.
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application is filed under the provisions of 35 U.S.C. §371 and claims the priority of International Patent Application No. PCT/EP2008/010012 filed on 26 Nov. 2008 entitled “Stable Crystalline Salt of (R)-3-Fluorophenyl-3,4,5-Trifluorobenzylcarbamic Acid 1-Azabicyclo[2.2.2]Oct-3-yl Ester” in the name of Juan Lorenzo Catena Ruiz, et al., which claims priority of European Patent Application No. 07384038.1 filed on 28 Nov. 2007, both of which are hereby incorporated by reference herein in their entirety.
FIELD OF THE INVENTION
The present invention relates to a stable crystalline salt of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester and to pharmaceutical formulations of this salt, in particular for medical use including treatment of urinary incontinence urge or other diseases involving genitourinary disorders.
BACKGROUND OF THE INVENTION
WO0200652 discloses compound I ((R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester) which has the following formula (I)
Compound I is also disclosed in WO2004000840. On the other hand, compound I is exemplified as hydrochloride salt in WO2003053966 as an intermediate in the synthesis of other compounds. However, this acid addition salt known from the prior art had the disadvantage that its physicochemical stability was poor. Upon storage or formulation of said known salt, progressive decomposition and concomitantly an increase in the amount and number of impurities was observed. Obviously, this problem is further aggravated under demanding environmental conditions such as light, heat, humidity or acidity.
SUMMARY OF THE INVENTION
It has been particularly difficult to find stable, crystalline forms of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester. The hydrochloride salt of compound I has the disadvantage of being highly hygroscopic, and when purified, the initial white foam quickly becomes a sticky gum due to its humidity uptake. Thus, there remains a need for a salt of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester that forms a crystalline solid that has a desirable morphology, be stable in the presence of water and under conditions of a high relative humidity (above 85%) and can readily be prepared on a large scale.
It has now been found that the above mentioned problem can be solved with the D-tartrate salt of compound I. The D-tartrate salt is more stable than the hydrochloride salt at room, enhanced temperature and at relative high humidity and in aqueous media. In addition, this D-tartrate salt in crystalline form has also been found to be stable, highly soluble in water and easy to handle or process.
Thus, a first aspect of the invention relates to a D-tartrate salt of compound I, ((R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester) of structural formula (II):
possessing a stoichiometry of substantially 1:1 of compound I to D-tartaric acid, and in the form of crystalline polymorph I, which is characterized by an X-Ray powder diffractogram pattern with peaks at °2θ as shown in FIG. 1 .
A second aspect of the invention relates to a pharmaceutical composition comprising a D-tartrate salt of compound I as described above, with at least one pharmaceutically acceptable carrier or excipient.
A third aspect of the invention relates to a D-tartrate salt of compound I as described above for use as a medicament.
A further aspect of the invention relates to the use of a D-tartrate salt of compound I as described above in the preparation of a medicament for the treatment of a disease or condition involving genitourinary disorders, in particular for the treatment of urinary incontinence, and more particularly for the treatment of overactive bladder.
A further aspect of the invention relates to a method for the treatment of a disease or condition involving genitourinary disorders, in particular for the treatment of urinary incontinence, and more particularly for the treatment of overactive bladder, comprising administering to a subject in need thereof a therapeutically effective amount of a D-tartrate salt of compound I as described above.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 : Shows an X-ray powder diffractogram (XRPD) of a crystalline D-tartrate salt of compound I, polymorph I (obtained using copper Kα radiation) prepared in Example 2.
FIG. 2 : Shows an X-ray powder diffractogram (XRPD) of a crystalline D-tartrate salt of compound I, polymorph II (obtained using copper Kα radiation) prepared in Example 3.
FIG. 3 : Shows a DSC of a crystalline D-tartrate salt of compound I, prepared in Example 2.
FIG. 4 : Shows a DSC of a crystalline D-tartrate salt of compound I, prepared in Example 3.
FIG. 5 : Shows a DSC of a crystalline D-tartrate salt of compound I, prepared in Example 4.
FIG. 6 : Shows a DSC of a crystalline D-tartrate salt of compound I, prepared in Example 5.
FIG. 7A shows the isotherms derived from the data shown in FIG. 7B by representing the equilibrium mass change values at each relative humidity step. Isotherms are divided into two components: sorption for increasing humidity steps and desorption for decreasing humidity steps.
FIG. 7B shows the vapor sorption kinetic obtained by exposing the product to a series of step changes in relative humidity and monitoring the mass change as a function of time. The darker line represents the mass change of the product as a function of time and the lighter line with squares represents the relative humidity as a function of time.
FIG. 8 : Shows a FT-Raman of a crystalline D-tartrate salt of compound I, prepared in Example 1.
FIG. 9 : Shows a FT-Raman of a crystalline D-tartrate salt of compound I, prepared in Example 3.
FIG. 10 : Shows a FT-Raman of a crystalline D-tartrate salt of compound I, prepared in Example 4.
FIG. 11A : Shows FT-Raman differences between the different polymorphs ( FIGS. 8 , 9 and 10 ) for 1-3500 cm −1 .
FIG. 11B : Shows FT-Raman differences between the different polymorphs ( FIGS. 8 , 9 and 10 ) for 2850-3150 cm −1 .
FIG. 11C : Shows FT-Raman differences between the different polymorphs ( FIGS. 8 , 9 and 10 ) for 760-810 cm −1 .
Further details for the figures are revealed in the Examples below.
DETAILED DESCRIPTION OF THE INVENTION
The present invention relates to a D-tartrate salt of compound I. D-tartrate provides optimal properties for formulation due to its stability, and it has the structural formula (II):
In order to be considered as a candidate for further development as a pharmaceutical, a compound must not only possess desirable biological properties, but also physical properties that permit its use in the manufacture of a pharmaceutical composition. In particular, the compound should form a stable, preferably crystalline, solid that can be readily manufactured and formulated.
Salt formation studies provide a means of altering the physicochemical and resultant biological characteristics of a drug without modifying its chemical structure. A salt form can have a dramatic influence on the properties of the drug. The selection of a suitable salt is partially dictated by yield, rate and quantity of the crystalline structure. In addition, hygroscopicity, stability, solubility and the process profile of the salt form are important considerations. Solubility of a salt form can affect its suitability for use as a drug. Where aqueous solubility is low, i.e. less than 10 mg/ml, the dissolution rate at in vivo administration can be rate limiting in the absorption process leading to poor bioavailability. Hygroscopicity is also an important characteristic. Compounds having low hygroscopicity tend to have better stability and easier processing. Stability at low and high relative humidity is desirable in a product to be used or sold in a wide diversity of environments.
The inventors have found that it is difficult to obtain a suitable salt of compound I for pharmaceutical formulation. The present invention has overcome these problems with the D-tartrate salt disclosed herein, which is crystalline, is relatively non-hygroscopic, and generally has better physical properties than other salts of the compound. Also, it has been found that the final content of impurities may be significantly reduced by precipitation of the D-tartrate salt of compound I as described herein.
To select the most suitable salt of compound I and minimize the undesirable hygroscopic properties of the hydrochloride, several acids were tested. The free base of compound I was dissolved in hot ethanol, and then acid solution in hot ethanol was added. The mixture was then stirred and heated for 30 min. After cooling to room temperature, the solvent was removed by evaporation. Acids tested included acetic, L-ascorbic, benzenesulphonic, (RS)-10-camphorsulfonic, (S)-10-camphorsulfonic, citric, embonic, fumaric, DL-lactic, L-lactic, maleic, D-malic L-malic, DL-malic, malonic, mandelic, D-mandelic, L-mandelic, methanesulphonic, orotic, oxalic, propionic, sorbic, succinic, DL-tartaric, L-tartaric and D-tartaric. The results concerning the salts obtained were as indicated in Table 1.
TABLE 1
Acid
Aspect of the salt
Acetic
Hygroscopic white foam
L(+)-Ascorbic
White foam
Benzenesulphonic
Oil
(RS)-10-Camphorsulfonic
Hygroscopic pink foam
(S)-10-Camphorsulfonic
Oil
Citric
Oil
Embonic
Yellow solid
Fumaric (0.5 eq)
White foam
Fumaric
White foam
Hydrochloric
Hygroscopic white foam
DL-Lactic
Oil
L-Lactic
Oil
Maleic
Oil
D-Malic (0.5 eq)
Hygroscopic red foam
DL-Malic (0.5 eq)
Hygroscopic red foam
D-Malic
Hygroscopic red foam
L-Malic (0.5 eq)
Oil
L-Malic
Oil
DL-Malic
Hygroscopic red foam
Malonic
Oil
Mandelic
White foam
(S)-Mandelic
Oil
(R)-Mandelic
Oil
Methanesulphonic
Oil
Orotic
Acid too insoluble in ethanol
Oxalic
Hygroscopic white foam
Propionic
Hygroscopic white foam
Sorbic
Oil
Succinic
Hygroscopic white foam
DL-Tartaric
Adding MTBE precipitated a white solid
L-Tartaric (0.5 eq)
White foam
D-Tartaric (0.5 eq)
White solid crystal precipitated in EtOH.
L-Tartaric
White foam
D-Tartaric
White solid crystal precipitated in EtOH.
As indicated in Table 1, most of the acids tested yielded oils or hygroscopic foams, whereas salt obtained with D-tartaric acid was the only one to yield a non-hygroscopic solid crystal under these conditions.
D-tartaric acid is a dicarboxylic acid and thus it may form both hydrogentartarate and tartrate salts. The invention refers to both a salt in which the molar ratio of compound I to tartaric acid is about 1:1 (i.e., a hydrogentartarate) and a salt in which the molar ratio of compound I to tartaric acid is about 2:1 (i.e., a tartrate), as well as mixed salts, with for example an alkali metal or ammonium cation. The crystalline polymorphs (i.e. Forms I, II, III, and IV) of D-tartrate of compound I discussed below are hydrogentartarate salts, i.e., the molar ratio of compound I to tartaric acid is about 1:1.
Salts of the present invention can be crystalline and may exist as more than one polymorph. Hydrates as well as anhydrous forms of the salt are also encompassed by the invention. In particular the anhydrous form of the D-tartrate salt of compound I is preferred. In an embodiment of the invention, the salt is a substantially anhydrous crystalline salt.
D-tartaric acid salts may be formed by contacting stoichiometric amounts of the acid with compound I free base. Alternatively, the acid may be used in excess, usually no more than 1.25 equivalents. Preferably the base and/or the acid are in solution, more preferably both are in solution.
Broadly speaking, the crystalline salts of the invention may be prepared by mixing a solution of either reactant in solvent, i.e. a suitable single solvent or a suitable mixture of solvents, preferably at room temperature or at elevated temperature, or by adding a solution of either reactant to a solid form of the other reactant and with subsequent precipitation of the crystalline compound I salt. The term “a solvent” as used herein include both a single solvent or a mixture of different solvents. It is understood that the solvent may comprise water as the case may be, e.g. about 0-20% water. The term suitable solvent as used herein in relation to the preparation of the D-tartrate salt and the recrystallization defines any lower alkanol, water or ketone solvent in which the compound I is soluble and includes primary, secondary and tertiary alcohols and the corresponding ketones of from 1 to 6 carbon atoms. Suitable lower alkanol solvents include, but are not limited to, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 2-methyl-1-propanol, 1,1-dimethyl-ethanol and cyclohexanol.
Improved yield may be obtained by evaporation of some or all of the solvent or by crystallization at elevated temperatures followed by controlled cooling, preferably in stages. Careful control of precipitation temperature and seeding may be used to improve the reproducibility of the production process and the particle size distribution and form of the product. Particularly good yields have been obtained using EtOH as solvent. Conveniently (R)-3-Fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester and one equivalent of D-tartaric acid are dissolved in hot EtOH. Seeding with a small quantity of previously prepared crystals may help initiate crystallization.
The present invention also provides four crystalline polymorphic forms of D-tartrate of compound I (hereinafter referred to as Forms I, II, III, and IV, respectively).
The pharmaceutical composition of the present invention may comprise about 20, 30, 40, 50, 60, 70, 80, 90, 95, 96, 97, 98, 99, 99.1, 99.2, 99.3, 99.4, 99.5, 99.6, 99.7, 99.8, 99.9 or 100% by weight of Form I, II, III, or IV of D-tartrate of compound I, based upon 100% total weight of D-tartrate of compound I in the pharmaceutical composition (or the total weight of crystalline D-tartrate of compound I in the pharmaceutical composition).
Crystalline polymorph Form I of D-tartrate of compound I is stable at room temperature. Form I is physically stable at room temperature but it is enantiotropically related with Form II, this means that at room temperature Form I (lower melting polymorph) is the more stable one and at higher temperatures the higher melting polymorph (Form II) is the more stable one. According to Differential Scanning calorimetry (DSC), Form I has a double endotherm at about 139° C. and at about 145° C. (see FIG. 3 ).
Form I may be prepared from the free base of compound I as follows. The free base of compound I and D-tartaric acid are dissolved in hot ethanol. The solution is then slowly cooled (e.g., for 3 hours or longer) to yield Form I of D-tartrate of compound I. The crystals of Form I may be recovered by any method known in the art.
Form I can also be prepared by preparing a slurry containing Form II, Form III or Form IV, or a mixture thereof, with EtOH at room temperature.
Any crystal prepared by the aforementioned methods may be recovered by techniques known to those skilled in the art, such as, for example, filtration.
Crystalline polymorph Form II of D-tartrate of compound I was obtained under controlled temperature conditions and according to DSC has an endotherm at about 149° C. (see FIG. 4 ).
Crystalline polymorph Form III of D-tartrate of compound I was obtained by equilibration in Water and according to DSC has an broad endotherm at about 110° C. (see FIG. 5 ).
Crystalline polymorph Form IV of D-tartrate of compound I was obtained by equilibration in hot Ethanol (60° C.) and according to DSC has an endotherm at about 162° C. (see FIG. 6 ).
As used herein, by expressions like “crystalline form of a specific salt of compound I characterized by the X-Ray powder diffractogram shown in FIG. ( 1 )” is meant the crystalline form of salt of compound I in question having an X-ray powder diffractogram substantially similar to FIG. ( 1 ), i.e. exhibiting an X-ray powder diffraction pattern substantially as exemplified in that Figure and measured under comparable conditions as described herein or by any comparable method. Generally, all data herein are understood to be approximate and subject to normal measurement error depending e.g. on the apparatus used and other parameters influencing peak positions and peak intensities.
The reaction of (R)-3-Quinuclidinol with carbonyldiimidazole (CDI) in dichloromethane, at 0° C. during 4 h, afford the corresponding imidazolide carbamate (intermediate 2).
Intermediate 1 was obtained by imine formation between 3,4,5-trifluorobenzaldehyde and 3-fluoroaniline (in a Dean-Stark system) and later reduction with sodium borohydride in ethanol.
The key coupling reaction was carried out by deprotonation of the amine (intermediate 1) with hexyl lithium at −10° C. and subsequent addition of imidazolide (intermediate 2), in THF, at −10° C., stirring it during 2 h.
Finally, D-tartrate of compound I was obtained by crystallization in hot ethanol adding 1 equivalent of D-tartaric acid to the compound I.
An object of the invention is a pharmaceutical composition comprising the active pharmaceutical ingredient (D-tartrate of compound I) or mixture of the active pharmaceutical ingredient with other active pharmaceutical ingredients and/or pharmaceutically acceptable carriers or excipients.
Such pharmaceutical composition can be administered orally, in the form of powders, granulates, tablets, capsules, lozenges, multiparticulates, lyophilised forms, solutions or suspensions, transdermal or buccal patches, emulsions or microemulsions, for immediate-, or modified-release applications (sustained-, delayed- or pulsed-release applications). Such pharmaceutical composition, as described above, may be administered by direct intake or as soluble, dispersible, orodispersible, chewable, effervescent or bioadhesive dosage forms, or through the skin.
Powders and granulates may be obtained by direct mix o successive mix of their components or by dry or wet granulation, aqueous or organic. Powders and granulates may contain excipients such as diluents, binders, disintegrants, wetting agents, glidants, lubricants, plastificants, absorbent or adsorbent agents, immediate- or modified-release polymers, sweetening or flavouring agents, colouring matter or dyes agents, or preservatives and may be dosified as monodose or multidose pharmaceutical forms.
Tablets cited above may be obtained from powders, granulates, other tablets or lozenges or any combination thereof. These tablets may be any conventional, multilayer, effervescent, dispersible, soluble, orodispersible, gastro-resistant, modified release, bioadhesive, chewable, buccal or matricial dosage forms. These tablets may also be coated with one or more functional layers in order to protect the active pharmaceutical ingredient or modify its release. Any layer may contain the active pharmaceutical ingredient, alone or with one or more modified-release polymers. Tablets described above may contain excipients such as diluents, binders, disintegrants, wetting agents, glidants, lubricants, plastificants, absorbent or adsorbent agents, immediate- or modified-release polymers, sweetening or flavouring agents, colouring matter or dyes agents, or preservatives.
Capsules cited above may be manufactured from gelatin, HPMC, cellulosic or polysaccharide derivates, flour cereals or a combination thereof, and may be soft or hard capsules. Capsules may contain powders, granulates, multiparticulate pharmaceutical forms, tablets, lozenges, liquids or semisolids, or a combination thereof. These capsules may also be coated with one or more functional layers in order to protect the active pharmaceutical ingredient or modify its release. Any layer may contain the active pharmaceutical ingredient, alone or with one or more modified-release polymers. Capsules described above may contain excipients such as diluents, binders, disintegrants, wetting agents, glidants, lubricants, plastificants, absorbent or adsorbent agents, immediate- or modified-release polymers, sweetening or flavouring agents, colouring matter or dyes agents, or preservatives.
Multiparticulate pharmaceutical forms may be administered under a monodose or multidose way. These pharmaceutical forms may be administered as capsules, tablets, sachets or strips, suspensions, solutions, vials, flasks or bottles or any other device. Such multiparticulate pharmaceutical forms may be used for immediate or modified-release applications and obtained from an inert or active core containing the active pharmaceutical ingredient. Cores may be coated by one or more functional layers in order to protect or modify the release of the active pharmaceutical ingredient. This ingredient may be included in one or more layers, alone or with one or more modified-release polymers. Additional layers, including protecting agents or modified-release polymers may be included in other external layer next to the layer containing the active pharmaceutical ingredient. Such multiparticulate pharmaceutical forms may contain excipients such diluents, binders, disintegrants, wetting agents, glidants, lubricants, plastificants, absorbent or adsorbent agents, immediate- or modified-release polymers, sweetening or flavouring agents, colouring matter or dyes agents, or preservatives.
The liquid and semi-solid pharmaceutical forms, as solutions, suspensions, gels, emulsions, micro-emulsions and others, incorporate the active ingredient, in a soluble form, disperse or in a multiparticular form, and adequate excipients. They can be dosed in monodose or multidose form, being able to be of extemporaneous preparation. It can contain excipients such as emulsifiers, solubility enhancers, dispersants, humectants, co-emulsifiers, emollients, viscosity increasing agents, vehicles, preservatives, pH adjustment agents, flavouring agents or sweeteners. These components can be liquids of aqueous, lipidic or organic nature.
The active pharmaceutical ingredient may be released via the skin, or any suitable external surface, including mucosal membranes, such as those found inside the mouth. Transdermal or buccal patches may incorporate the drug into the device and be included in a matrix, in an adhesive or in a reservoir. Formulates may incorporate wetting agents, immediate- or modified-release polymers, enhancers, emulsifiers, dispersants, co-emulsifiers, solubility enhancers, adhesives, humectants, emollients, viscosity increasing agents, vehicles, preservatives or pH adjustment agents. These components can be semisolids or liquids, of aqueous, lipidic or organic nature. Matrix may be solid or semisolid in one or more layers. Patches include a permeable membrane on one side and also some form of adhesive to maintain the patch in place on the patient's skin, with the membrane in contact with the skin so that the medication can diffuse out of the patch reservoir and into and through the skin. The outer side of the patch is formed of an impermeable layer of material, and the membrane side and the outer side are joined around the perimeter of the patch, forming a reservoir for the medication and carrier between the two layers.
EXAMPLES
Analytical Methods
1 H-NMR and 13 C-NMR spectra was recorded at 400 MHz and 100.61 MHz respectively on a Bruker ARX 400 instrument. Dimethyl sulfoxide (99.8% D) was used as solvent, and tetramethylsilane (TMS) was used as internal reference standard.
The purity of D-tartrate of compound I was determined by HPLC/MS using a Gemini 5 u C18 110A, 50×4.6 mm column at 25° C. The mobile phase was 70% of solution A (0.025 M orthophosphoric acid at pH 3.0-3.1 with triethylamine) and 30% of solution B (Acetonitrile/methanol (9:1)) at a flow rate of 1.4 ml/minute. Run time 20 min. Detection was performed using a UV detector at 200 nm. D-tartrate of compound I showed a retention time of approximately 6.5 min.
The enantiomeric excess of compound I was determined by using a Quirabiotic V-2 column, 25×0.46 cm L, at 25° C. The mobile phase 0.1% (w/v) trifluoroacetic acid in methanol adjusted to pH about 6.5 with ammonium hydroxide at a flow rate of 0.5 ml/min, run time 25 min. Detection was performed using a UV detector at 230 nm. D-tartrate of compound I had a retention time of approximately 16 min, and its enantiomer had a retention time of approximately 17 min.
The Melting points were measured using Differential Scanning calorimetry (DSC). The equipment was a Perkin Elmer DSC 7 or a Perkin Elmer Pyris 1 with various crucibles (gold, alumina, open, closed, microhole), heating rate variable and range variable.
X-Ray powder diffractograms were measured on a Philips X'Pert PW 3040 or Philips PW 1710 using Cu kα radiation. The samples were measured in reflection mode in the 2θ-range 2-50°
FT-Raman Spectroscopy was registered on a Bruker RFS100 equipment. Nd:YAG 1064 nm excitation, 100 mW laser power, Ge-detector, 64 scans, range 25-3500 cm −1 , 2 cm −1 resolution.
TG-FTIR: Netzsch Thermo-Microbalance TG 209 with Bruker FT-IR Spectrometer Vector 22. Al-crucible (open or with Microhole); N 2 atmosphere, heating rate 10° C. min −1 , range 25-250° C.
Dynamic Vapour Sorption (DVS). The equipment was a Surface Measurement Systems Ltd. DVS-1 Water vapour sorption analyser. The sample was placed on a quartz or platinum holder on top of a microbalance, and the sample was allowed to equilibrate at 50% r.h. before starting a pre-defined humidity program.
Specific rotation measurements were performed using a polarimeter from Schmidt+Haensch, model Polartronic-E (series number 27586), equipped with a thermostatic bath from Techne, model TE-8J.
Synthesis
Example 1
Synthesis of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester (compound I)
Intermediate 2
(R)-imidazole-1-Carboxylic acid 1-azabicyclo[2.2.2]oct-3-yl ester
To a suspension of 1.86 Kg of (R)-3-quinuclidinol in 30 L of dichloromethane, 2.92 Kg of DCI were added at 0° C. The solution was stirred during 3 h under inert atmosphere. Then, 23 L of water were added and extracted. The organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The obtained white solid was crystallized with isopropyl acetate (IPAC)-heptane to give 24.1 Kg of the title compound.
IR (KBr, cm −1 ): 1746;
1 H-NMR: 1.33-1.43 (m, 1H); 1.47-1.57 (m, 1H); 1.58-1.70 (m, 1H); 1.75-1.87 (m, 1H); 2.07-2.12 (m, 1H); 2.56-2.90 (m, 5H); 3.18 (ddd, J=14.5, J=8, J=2, 1H); 4.95-5.00 (m, 1H); 7.07 (s, 1H); 7.61 (s, 1H); 8.29 (s, 1H).
13 C-NMR: 18.9; 23.7; 24.9; 45.7; 46.6; 54.1; 75.7; 117.3; 130.1; 137.1; 147.9.
Intermediate 1
(3-Fluorophenyl)-(3,4,5-trifluorobenzyl)amine
In a 300 L reactor fitted with a Dean-Stark funnel and refluxing condenser, toluene (63 L), 3,4,5-trifluorobenzaldehyde (2.1 Kg) and 3-fluoroaniline (1.33 Kg) were refluxed (112° C.) during 10 h.
After cooling, the resulting solution was concentrated to give the imine as an oil in a quantitative yield (3.2 Kg). Then ethanol (35 L) and sodium borohydride (0.5 Kg) was added. The resulting suspension was stirred 3 h, Then, 42 L of water were added, the ethanol was distilled off and the aqueous layer extracted with dichloromethane (2×40 L). The organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure giving 2.72 kg of the title compound as an yellow oil.
1H-NMR: 4.29 (s, 2H); 4.33 (br., 1H), 6.28 (dtd, J=11, J=2.5; J=1, 1H), 6.40 (ddd, J=8.5; J=2, J=1, 1H), 6.46 (tdt, J=8.5; J=2.5, J=1); 7.24 (dd, J=8; J=7, 2H); 7.14 (tdd, J=8; J=6.5, J=1).
13 C-NMR: 47.1; 99.9 (d, J=25.5); 104.8 (d, J=21); 109.1 (d, J=2); 111.0 (d, J=10.5); 111.0 (d, J=21.5); 149.4 (dd, J=11, J=1); 136.0 (tdd, J=6, J=4, J=2); 139.0 (dt, J=248, J=5); 151.6 (ddd, J=248, J=10, J=4); 164.3 (d, J=241).
Compound I
(R)-3-Fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester
To a solution of 2.72 Kg of intermediate (1) in 17 L of THF, cooled at −10° C., were added slowly (2 h), under inert atmosphere, 3 Kg of hexyl Lithium (33% in hexanes) and the resulting mixture was stirred for 1 h at −10° C. Then at −10° C. 2.41 Kg of intermediate 2 in 23 L of THF were slowly added (75 min). The resulting mixture was stirred for 2 h and allowed to rise room temperature, then water was added and the solution was extracted with methyl tertbuthylether. The organic phase was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure giving 3.6 kg of the title compound as an orange oil.
Example 2
Synthesis of (R)-3-Fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester (compound I) D-tartrate salt
To a solution of 3 Kg of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester (compound I) in ethanol (3 L) at 60° C., 1.1 Kg D-tartaric acid in 30 L of ethanol, warmed at 60° C. were added and the resulting mixture stirred 1 h and then cooled to below room temperature and kept at this temperature for 1 hour. The precipitate is filtered off and the filter cake is washed with ethanol (8 L). The filter cake is sucked free of most of the solvent, and the product is dried at 45° during 16 h. Yielding 3.5 kg of the title compound as a white crystalline solid.
1 H-NMR: 1.45-1.49 (m, 2H) 1.65-1.75 (m, 2H), 2.05 (m, 1H); 2.87-3.01 (m, 3H); 3.07-3.11 (m, 1H); 3.08-3.11 (d, J=14, 1H); 3.39-3.45 (ddd, J=12, J=8, J=2, 1H); 4.00 (s, 2H); 4.83-4.89 (m, 1H); 4.84-4.89 (d, J=16.5, 1H); 4.93-4.97 (d, J=16.5, 1H); 7.05 (td, J=8.5; J=2, 1H); 7.21 (dd, J=8; J=1.5, 1H); 7.24 (dd, J=8.5; J=7, 2H), 7.33-7.38 (m, 2H).
13 C-NMR: 17.1; 20.4; 24.0; 44.5; 45.1; 51.6; 52.7; 69.5; 72.1; 111.8 (d, J=19.5); 113.4 (d, J=20.5); 114.1 (d, J=22); 122.6; 130.3 (d, J=9); 135.1; 137.8 (dt, J=246, J=16); 142.6 (d, J=9); 150.2 (ddd, J=246, J=9.5, J=3.5); 154.0; 161.9 (d, J=242); 174.7
Elemental Analysis. Calculated for C 25 H 26 F 4 N 2 O 8 : C, 53.77; H, 4.69; N, 5.02. Found: C, 53.63; H, 4.73; N, 5.01
An XRPD pattern for the crystals prepared is shown in FIG. 1 .
Specific rotation was determined. 1.00 g of substance was diluted with methanol in a 100 mL volumetric flask. α (c=1, MeOH) c=g/100 mL. The measured specific rotation was −35.2°.
On the other hand, the equilibrium solubility of the D-tartrate salt with several solvents was measured at 25° C. and was found to be (measured as the free base) as indicated in Table 2.
TABLE 2
Solvent
Solubility (mg/ml)
Methanol
258.5
Ethanol
10
Isopropyl alcohol
1.5
Dichloromethane
2.2
Hexane
0.3
n-Octanol
0.5
Water
250.8
0.1 Hydrochloric acid
366.6
0.1N sodium hydroxide
0.09
Evaluation of Hygroscopicity: No significant mass gain or mass loss was observed at 93% RH or below conditions. A significant water addition issue was observed at 97% RH, but no hygroscopicity issues related to standard atmospheric conditions are expected as shown in Table 3.
TABLE 3
HYGROSCOPICITY STUDY (KF initial = 0.9692%)
Time (h)
12% RH
22% RH
33% RH
43% RH
53% RH
64% RH
75% RH
85% RH
93% RH
97% RH
4
−0.26
−0.16
−0.25
−0.38
−0.19
−0.08
−0.08
0.16
0.16
1.51
8
−0.20
−0.26
−0.24
−0.32
−0.21
−0.07
0.02
0.13
0.03
1.06
14
−0.30
−0.25
−0.21
−0.21
−0.16
−0.07
0.01
0.22
0.24
4.36
48
−0.04
−0.21
−0.19
−0.25
−0.17
0.02
0.06
0.26
0.44
7.86
72
−0.28
−0.24
−0.23
−0.31
−0.16
−0.07
0.01
0.14
0.41
10.88
96
−0.30
−0.26
−0.17
−0.30
−0.19
−0.07
−0.06
0.07
0.40
13.77
144
−0.33
−0.18
−0.30
−0.40
−0.17
0.15
−0.08
0.24
0.43
23.58
168
−0.32
−0.28
−0.39
−0.34
−0.16
0.15
−0.05
0.18
0.39
23.62
192
−0.27
−0.21
−0.11
−0.19
−0.20
0.20
0.00
0.15
0.38
23.06
216
−0.29
−0.19
−0.15
−0.25
−0.14
0.25
0.01
0.23
0.43
22.13
240
−0.08
−0.11
−0.18
−0.18
0.00
0.59
0.29
0.59
0.81
19.88
Example 3
Preparation of Form II of D-Tartrate of Compound I
Form I (Example I) was treated as follows in DSC: Closed pan (STGF), 0.0295 g, 25 to 143.5° C., 2° C. min −1 , scan down to 130° C., hold isotherm for 15 minutes, cool to 25° C.
Example 4
Preparation of Form III of Compound I D-Tartrate
0.49 g of form I were suspended in 1 mL of water and then shaken at 20° C. during 10 minutes (until dissolution), after 2 h the sample was thickened.
Example 5
Preparation of Form IV of Compound I D-Tartrate
0.522 g of form I were suspended in 1 mL of EtOH abs. and then shaken at 60° C., After 1 day the suspension disappeared and a new white crystalline crust was formed above the solvent sticking on the container wall.
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The present invention refers to a stable crystalline salt of (R)-3-fluorophenyl-3,4,5-trifluorobenzylcarbamic acid 1-azabicyclo[2.2.2]oct-3-yl ester and its use as medicament, in particular for the treatment of urinary incontinence or other diseases involving genitourinary disorders.
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BACKGROUND OF THE INVENTION
This invention relates to improvements to waterproofing materials which are in the form of pre-formed, sheet-like laminates of (a) a waterproof and waterproofing bituminous membrane adhered to (b) a support sheet material covering at least one major surface of the bituminous membrane.
It is known that structural surfaces and the like such as concrete decks, foundations, roofs, etc., can be sealed in a waterproof manner by forming thereon a continuous membrane of a bituminous composition which is substantially impermeable to moisture. The term "bituminous composition" as used in the present disclosure refers to compositions based on tar, asphalt or pitch with or without added components. In the past such waterproofing membranes have been formed by "in situ" application of a hot bituminous composition or of a cold solution or emulsion of bitumen, tar or pitch, typically in combination with one or more "plys" of bitumen-saturated felts. These known methods of "in situ" application of adhesive and felts suffer serious disadvantages. The procedures require the formation of a layer of waterproofing sealant at the job site which does not permit the assurance of a uniform application or of a resultant uniform layer. In addition, such application causes additional expenses of labor at the job site. Finally, application of such waterproofing to vertical substructural membranes is both tedious and in certain instances unmanageable.
More recently, waterproofing of structural surfaces has been accomplished by the application of pre-formed, flexible membranes of bituminous compositions which are pressure sensitive-adhesive such as those disclosed in U.S. Pat. Nos. 3,741,856; 3,853,682 and 3,900,102 to John Hurst. These waterproofing materials have a laminate structure comprising a sheet-like support member such as a polymer film adhered to a membrane of a flexible bituminous composition superimposed thereon. The bituminous composition may be single or multilayered and has self-adhesive properties which render it adherent to the support sheet and also to the substrate surface to which it is applied.
Generally, the known pre-formed self-adhered waterproofing structures of the foregoing type have a support sheet such as polymer film and a membrane of bituminous composition which are essentially co-extensive and, in addition, have a removable protective or release sheet positioned on the free surface of the adhesive membrane which must be removed before application of the waterproofing laminate to the structural surface. Pre-formed waterproofing laminates of each type have also been formed with the membrane of bituminous composition extending a short distance beyond the support sheet to yield a partially exposed surface. These partially exposed surfaces aid in forming watertight joints at overlaps of successively-applied laminates.
Pre-formed waterproofing laminates comprised of polymer film layers and bituminous waterproofing membranes and which are not self-adhesive to the substrate are also known. For example, a pre-manufactured membrane laminate product "KMM" described in a product brochure entitled "KMM Koppers Roofing and Waterproofing Membrane", published by Koppers Company, Inc., 1976, is a non-self adhesive, multi-layer laminate comprised of several layers of plastic film and bitumen composition which is laid upon a substrate and thereafter abutting edges of like laminates are heated to "weld" the laminates into a continuous waterproofing layer non-adherent to the substrate. Also, in U.S. Pat. No. 4,039,706 to Tajima Roofing Co. Ltd., self-adhesive strip-laminates comprised of a sheet support and self-adhesive bituminous layers are said in one embodiment to be applicable to roofs, etc., adhesive-side up. Another like laminate is then applied adhesive-side down to the upper exposed layer of adhesive of the first applied laminate resulting in a continuous waterproofing membrane layer composed over its entirety of "multi-layers" of bituminous adhesive and sheet support.
A drawback inherent in all of the aforementioned types of pre-formed waterproofing laminates is that the support sheets for the bituminous membranes often used therein can sometimes be adversely affected by oils present in the bituminous composition. For example, the dimensional stability of polyethylene film, a popular support sheet often used in such pre-manufactured waterproofing membranes, can be adversely affected when the film is contacted by oils such as aromatic oils present in the bituminous composition. A decrease in the dimensional stability of the polymer film by prolonged contact with such oils can lead to undesirable curling of the applied laminate upon exposure to elevated temperature.
SUMMARY OF THE INVENTION
The present invention is directed to a novel, flexible pre-formed waterproofing laminate of improved dimensional stability. The improved waterproofing structure comprises a pre-formed laminate structure of a waterproofing flexible bituminous membrane preferably pressure-sensitive adhesive, having substantially co-extensively superimposed on at least one major face of the membrane a flexible polymeric support sheet material. An oil-impermeable coating is positioned between the membrane and the support sheet to substantially prevent contact of the support by oils in the bituminous composition.
DESCRIPTION OF THE DRAWING
The FIGURE is a perspective view of a preferred waterproofing laminate construction according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
In the attached FIGURE, a flexible pre-formed waterproofing laminate strip is shown as comprised of a comparatively thick layer of normally self-adhesive oil-containing bituminous water-proofing composition 1, non-removably adhered to a comparatively thinner support sheet 3, for example a sheet of polyethylene film. To protect the polyethylene film 3 from being substantially contacted by oils present in the bituminous composition 1, a polymer coating barrier layer 2 hereinafter described is positioned between the layers 1 and 3. The polymer coating could be pre-applied to either or both of the layers 1 and 3. To protect the self-adhesive surface of the bituminous adhesive layer remote from layer 3, a removable protective sheet 4, for example a sheet of siliconized paper, is applied thereto. The sheet 4 adheres sufficiently to the bituminous adhesive to keep it in place during rolling up and handling of the laminate, but is easily removable therefrom without physical damage to the layer 1. The flexible laminate strip shown in FIG. 1 preferably has a width ("w") say of thirty six inches and a length ("l") of say sixty feet and is conveniently produced in the form of a roll for delivery to the job-site.
The self-adhesive or pressure-sensitive bituminous waterproofing layer 1 preferred for use herein is preferably of the type described in U.S. Pat. Nos. 3,741,856; 3,853,682 and 3,400,102 to John Hurst. The adhesive composition comprises a mixture of (a) a bituminous material and (b) natural or synthetic polymer preferably a rubber or other elastomer polymer. The amount of polymer employed in such compositions is typically from about 1 to 100, preferably about 20 to 50, percent by weight of the bituminous material. The term "bituminous material" as used herein includes compositions containing asphalt, tar such as coal tar, or pitch. The bituminous adhesive may be reinforced with fibers and/or particulate fillers. In addition to any oils normally present in the bitumen, the adhesive composition may also contain a conventional extender component such as mineral oil. Suitable polymer components for use in the adhesive composition include thermoplastic polymers such as polyethylene and the like. As aforementioned, the preferred polymer component is rubber which may be virgin rubber or a synthetic rubber which is blended into the bitumen and preferably extender oil at elevated temperature, to form a smooth mix. Generally, suitable adhesive compositions have softening points (measured by the Ring and Ball method) of 70° to 120° C., preferably 75° to 100° C., and penetration values of 50 to 400, preferably 50 to 100 dmm. at 25° C. (150 g/5-ASTM D217), and are thermoplastic in nature.
As mentioned in the aforementioned Hurst patents,in order to give optimum sealing and waterproofing performance the adhesive layer should be at least 0.010 inch thick and preferably in the range of about 0.025 to about 0.200 inch thick. The adhesive layer can be comprised of one or more layers of the aforementioned bituminous adhesive, not necessarily of the same composition, to give an adhesive layer within the overall aforementioned thickness range. Further, the adhesive layer can have a reinforcement such as an open weave fabric, gauze, scrim or the like located therein to strengthen it. The adhesive layer 1, at least at its surface remote from support sheet 3 is as aforementioned preferably pressure-sensitive and tacky at normal ambient temperature in order that it be self-adhesive to the substrate. The bituminous adhesive layer serves to form a continuous waterproofing layer which is elastic and self-sealing against punctures at high and low temperature.
The support film layer 3 serves as a strength imparting and supporting member in the laminate and also as a barrier to prevent moisture vapor transmission through the laminate. Thus while of less thickness than that of the bituminous waterproofing layer 1, the support layer 3 should be of sufficient thickness to impart e.g. tear and puncture resistance to the laminate. The support layer 3 suitably has a thickness in the range of from about 0.002 to about 0.025 inches, preferably from about 0.004 to about 0.010 inches.
The polymeric sheet materials used in the layer 3 are films of synthetic organic polymers, the dimensional stability of which is adversely affected by oils present in the bituminous membrane 1. Thus the layer 3 may be comprised of a polyolefin film such as polyethylene, and the film may be uniaxially oriented, biaxially-oriented or cross laminated, as is known in the art. Moreover, the support layer 3 may be rendered opaque, for example by inclusion of a pigment such as carbon black, to increase its weatherability as is also well known in the art.
The oil impermeable polymeric barrier 2 can be any known polymeric material which is capable of acting as an oil passage barrier with respect to the support sheet member 3. Polymeric materials which are suitable for this purpose include polyvinyl acetate, polyvinylidene chloride, polyacrylonitrile (cured), casein, alpha protein, zein, cellulose polymers such as hydroxypropyl methyl cellulose, as well as neoprene rubber, etc. The polymeric material may contain additives, e.g. plasticizers, to improve one or more of its properties.
The barrier 2 can be formed by depositing a coating of the polymer to the support sheet 3 or to the surface of adhesive by any known method such as spray application or by solution application. The polymer coating member should have substantially compatible tensile and adhesive properties to allow the coating to form a flexible barrier layer having the desired physical properties disclosed and described hereinabove. The thickness of the barrier coating can be of any dimension which is suitable to form an oil impermeable membrane. It is preferred that the thickness be less than half of the thickness of the support sheet 3.
As aforementioned, a sheet of paper, e.g. Kraft paper, having a coating thereon of silicon "release" composition as is well know in the art, may be used as the protective layer 4. Other sheet materials, for example plastic films having the requisite "release" properties per se or coated with "release" coatings could be used.
The following example is for illustrative purposes only and is not intended to limit the invention except as defined by the claims set forth hereinbelow. All parts and percentages are by weight except when otherwise indicated.
EXAMPLE
In an experiment, an 8 mil thick opaque cross-laminated, high density polyethylene film was coated with a solution of hydroxy methyl cellulose as a barrier coating and the coating thereafter dried. To improve the flexibility of the resulting cellulose film and its adhesion to the polyethylene film, to the coating composition was previously added a small amount of an oil-resistant plasticizer, RESOFLEX.sup.(R) 296, a proprietary product of Cambridge Industries Co., described in the literature as a resinous, non-volatile, non-migrating plasticizer having excellent resistance to oil, fats, etc., and excellent flexibility and toughness. The barrier coated surface of the polyethylene film was in turn coated with a 60 mil thick bituminous water-proofing composition having self-adhesive or pressure-sensitive adhesive properties. The adhesive composition was a blend containing approximately 46 parts asphalt, 16 parts styrene-butadiene rubber, 9 parts filler, 27 parts aromatic petroleum oil as well as minor additional additives. The resulting laminate sample was tested in a manner described below.
For comparison purposes, a "control" laminate sample was prepared as above, except that no barrier coating was applied to the polyethylene film previous to the application of the bituminous adhesive. The two laminates were than tested for dimensional stability after exposure to elevated temperature by placing the samples in an oven heated to 160° F. Within two weeks, the laminate containing no barrier coating was 95 percent curled, while the barrier coated sample essentially retained its dimensional stability for the duration of the test (approximately 26 days). The test established that an oil-barrier coating would have a significant effect upon the dimensional stability of the film.
While the invention has been described in connection with one of the preferred embodiments, it is not intended to limit the invention to a particular set form, but, on the contrary, it is intended to cover such alternatives, modifications and equivalents as may be included within the spirit and scope of the invention as defined by the appended claims.
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An improved pre-formed, sheet-like flexible laminate suitable for waterproofing of structural surfaces, the sheet-like material having a laminate structure of (a) a flexible waterproof and waterproofing bituminous membrane and (b) a support sheet material covering at least one major surface of the bituminous membrane; an oil-impermeable polymeric coating being provided between said support sheet material and the adjacent surface of the bituminous membrane to protect the support sheet from adverse effects of oil present in the bituminous membrane.
| 1 |
BACKGROUND
[0001] The invention relates to a bottle opener for opening a bottle closed with a screw cap, particularly a wine bottle.
[0002] In recent years, more and more wine bottles have entered the market, which are no longer closed with the traditional cork but rather with a screw cap. On the one hand, this is more hygienic, on the other hand, the screw cap guarantees a safe and also long lasting air-tight seal of the wine bottles, which is not always ensured in the traditional cork.
[0003] In particularly in restaurants, there is the need for bottle openers, which allow opening wine bottles with a screw cap, or other bottles provided with a screw cap, in an elegant and reliable fashion, requiring as little force as possible.
SUMMARY
[0004] This objective is attained according to the invention in the bottle opener comprising an annular contact element with an inside surface to contact the screw cap, with the inside surface delimiting a receiving cavity to accept the screw cap and the inside surface being delimited by two preferably annular edges of the contact element, and the diameter of the receiving cavity delimited by the inside surface tapering sectionally beginning at least at one of the edges in the direction towards the other edge and the inside surface being embodied as a counter-clockwise internal thread.
[0005] A contact element embodied in this fashion allows a reliable and also low-force removal of a screw cap from the bottle, particularly a wine bottle. Here, the bottle opener can be placed onto the screw cap at different angles, without risking that the attempt to open the bottle might fail. The bottle opener according to the invention therefore requires no particularly precise placement of the screw cap. By the combination of the features of a diameter of the inside surface and/or the receiving cavity delimited thereby reducing in one direction with the counter-clockwise thread inserted into the inside surface a high operating comfort is yielded and a secure opening of the bottle.
[0006] Upon placement of the bottle opener onto the screw cap, first the internal thread of the bottle opener cuts into the screw cap when the operator begins to turn the bottle opener in the normal opening direction of a screw cap. This way, after a relatively small rotational angle a good lasting connection is produced between the bottle opener and the screw cap. When the bottle opener is then simply turned further in the same direction, the screw cap is screwed off the bottle. The fastening of the bottle opener to the screw cap as well as the unscrewing of the screw cap therefore occur both in the same direction of rotation, allowing a reliable and quick opening of the bottle. Even when such bottle openers, particularly in restaurants, are primarily intended for opening wine bottle, of course any other bottle comprising a screw cap can also be opened therewith in a simple and quick fashion.
[0007] Beneficial embodiments of the invention provide that the top of the internal threads of the inside surface are located on a rotation-symmetrical surface and/or that the roots of the internal threads of the inside surface are located on a rotation-symmetrical surface. In particular, it may be provided here that the top of the internal threads of the inside surface are located on a frustum surface and/or that the roots of the internal threads of the inside surface are located on a frustum surface. Extensive experiments have shown that it is beneficial for the internal thread to have a thread pitch and/or a so-called lead ranging from 0.1 mm/rotation to 0.4 mm/rotation, preferably from 0.2 mm/rotation to 0.27 mm/rotation. The thread depth, i.e. the depth of a convolution of the internal thread should beneficially range from 0.01 mm to 0.5 mm, preferably from 0.15 mm to 0.25 mm. During the tests performed it has shown that in case of deviations from the above-mentioned values either no reliable connection developed between the screw top and the bottle opener or the screw top was deformed by the internal thread to such an extent that an unscrewing of the screw top was hindered.
[0008] In order for the internal thread to reliably cut into the screw top it is beneficial for the threads tops to be embodied with an acutely angled cross-section. The roots of the threads however may have a rounded cross-section.
[0009] Beneficially the annular contact element is formed from metal, at least in the area of the inside surface and the internal thread, but preferably in its entirety. For the production of the contact element the use of steel is particularly beneficial and here especially stainless steel.
[0010] In order to prevent the contact element and/or the bottle opener from being accidentally placed in the wrong manner onto the screw cap to be opened, preferred embodiments of the invention provide that the diameter of the receiving cavity, delimited by the inside surface, at least partially tapers beginning at each of the edges in the direction to the respectively other edge. Such variants may be embodied essentially symmetrical in reference to a central level, at least concerning the progression of the diameter of the inside surface and/or the receiving cavity. In such embodiments it is beneficially provided that a minimal diameter of the receiving cavity, limited by the inside surface, is located in the middle between the edges. Particularly for screw caps common for wine bottles it is beneficial for the diameter of the receiving cavity, delimited by the inside surfaces, to amount to a value ranging from 30 mm to 30.5 mm at one edge, preferably at both edges of the contact element. The minimal diameter of the receiving cavity delimited by the inside surface ranges in preferred embodiments of the invention from 28 mm to 29 mm.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] Additional features and details of preferred embodiments of the invention are explained using the description of the figures. Shown here are:
[0012] FIG. 1 an exemplary embodiment of a bottle opener according to the invention,
[0013] FIG. 2 a top view from the direction of the longitudinal central axis of the annular contact element of said bottle opener,
[0014] FIG. 3 the detail A of FIG. 2 ,
[0015] FIG. 4 a longitudinal cross-section through the annular contact element of the bottle opener according to FIG. 1 ,
[0016] FIG. 5 an alternative embodiment of an annular contact element, and
[0017] FIG. 6 the detailed views B of FIGS. 4 and 5 .
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0018] FIG. 1 shows a perspective view of a bottle opener embodied according to the invention. The contact element 1 is here made from stainless steel, in the present case arranged centrally in a handle part 20 . In the exemplary embodiment shown the handle part 20 is embodied disk-shaped, at least sectionally, and may e.g. be made from wood. Of course, this is only an example. The essential technical effect of the handle part 20 is the increase of the torque by enlarging the distance of the part of the bottle opener, at which it is grasped, from the longitudinal axis 17 . For reasons of completeness it shall be pointed out that the handle part 20 may also have any other suitable shape. In the exemplary embodiment shown, a recess 21 is provided at the exterior edge of the handle part 20 . This allows placing the bottle opener standing on its edge in the area of said recess 21 .
[0019] The annular contact element 1 embodied according to the invention is arranged in a central recess of the handle part 20 of the bottle opener shown. It encompasses with its inside surface 2 the receiving cavity 3 , into which the screw cap to be removed, particularly from a wine bottle, can be inserted. According to the invention the inside surface 2 comprises, as shown according to the following figures, a diameter 5 sectionally tapering from one edge 4 of the contact element 1 in the direction towards the other edge 4 ′. Additionally, at the inside surface a counter-clockwise internal thread 6 is formed, i.e. an internal thread 6 threaded counter-clockwise. The depth of the thread 10 and the pitch 9 are embodied so small, however, that the internal thread 6 is only discernible in a detailed view.
[0020] Optionally, as in the exemplary embodiment shown according to FIG. 1 , notches 18 may be arranged in the inside surface 2 . They beneficially extend essentially parallel to the longitudinal central axis 17 and thus at an angle 19 ranging from 80° to 100°, preferably from 87° to 93°, in reference to the thread tops 7 and/or thread roots 8 of the internal thread 6 , as particularly indicated in FIG. 4 . The edges in the inside surface 2 caused by the notches further facilitate the cutting of the internal thread 6 into the screw cap. As already stated, the notches 18 may be omitted, though.
[0021] FIG. 2 shows a top view of the annular contact element 1 from the direction of the longitudinal central axis 17 . Here, the notches 18 are shown particularly well. In the exemplary embodiment shown they are arranged in a regular hexagon. However, this is not mandatory, of course. In the exemplary embodiment shown, the width 22 is 25.82 mm. FIG. 3 shows the detail A from FIG. 2 . The opening angle 23 of the notch 18 shown in detail, is similar to the other notches 18 shown in FIG. 2 , and is 120°. Of course, this is only exemplary.
[0022] FIG. 4 shows a longitudinal cross-section through the contact element 1 of the first exemplary embodiment. This longitudinal cross-section extends on the one side along and/or parallel to the longitudinal central axis 17 of the contact element 1 , on the other side this longitudinal cross-section extends in the exemplary embodiment shown also parallel and/or along a direction 13 , which extends normally to a plane 14 stretched between the edges 4 and 4 ′ of the contact element 1 .
[0023] In FIG. 4 it is shown particularly well how the diameter 5 of the receiving cavity 3 , starting at the edge 4 , tapers in the direction 11 towards the other edge 4 ′ within a first section. This first section ends at the minimal diameter 12 , which in the exemplary embodiment shown here, seen along the longitudinal central axis 17 , is located in the center between the edges 4 and 4 ′. Coming from the other side, i.e. starting at the edge 4 ′, the diameter 5 of the receiving cavity 3 tapers equally, but in the opposite direction, namely towards the other edge 4 . This section, beginning at the edge 4 ′, also ends at the centrally arranged minimal diameter 12 . In the exemplary embodiment shown the minimal diameter 12 is 28.5 mm, the diameter 5 in the area of the edges is 30.3 mm. The contact element 1 of this exemplary embodiment further comprises an exterior diameter 24 of 33 mm. The overall width 27 of the exemplary embodiment is 20 mm, measured parallel in reference to the longitudinal central axis 18 and/or the normal 13 . Half of the maximum difference of the diameter 26 amounts to 0.6 mm. The width 28 of the notches 18 , again in the direction parallel in reference to the longitudinal central axis 17 and/or the normal 13 , amounts to 13.33 mm. Shown particularly in FIG. 6 , the angle 16 between a straight line 15 through the thread tops 7 of the internal thread 6 and the longitudinal central axis 17 and/or the normal 13 is 14° in the illustrated exemplary embodiment 5. Tests have shown that this angle 16 should range at least from 1° to 10°, preferably from 3° to 7°. The internal thread 6 arranged and/or formed at the inside surfaces 2 is not discernible in the illustration according to FIG. 4 . Here, reference is made to the detail B, as shown enlarged in FIG. 6 . FIG. 6 shows the internal thread 6 of the exemplary embodiment shown, arranged at the inside surface 2 encircling the longitudinal central axis 17 , at a scale of 50:1. This illustrates that it represents a thread with a very low pitch 9 and also very low thread depth 10 . In the exemplary embodiment shown the pitch 9 and/or the height of the thread only amounts to 0.24 mm/rotation, with the pitch 9 , as generally known, being calculated from the distance of two adjacent thread tops 7 . The depth of the thread 10 , which states the difference in height in the direction towards a normal on the straight line 15 between the top of the thread 7 and an adjacent base of the thread 8 , amounts to only 0.2 mm in the exemplary embodiment shown. The pitch 9 and depth of the thread 10 may however be varied within the value range stated at the outset. Additionally, in FIG. 6 it is shown particularly well that the thread tops 7 are embodied with an acute angle in the cross-section shown, while the roots of the threads may also be embodied rounded. In any case, by the acutely angled thread tops 7 the cutting of the internal thread 6 into the screw cap to be removed from a bottle is facilitated. Of course, the thread roots 8 and the thread tops 7 may also have different forms. The cutting of the respective internal thread 6 into the inside surface 2 can be performed by cutting methods known from prior art.
[0024] The exemplary embodiment of an annular contact element 1 according to FIG. 4 is advantageous, as explained at the outset, in that the screw cap to be removed from the bottle can be inserted into the receiving cavity 3 from both the direction 11 as well as the direction 11 ′. The operator is therefore not required to pay attention to place the bottle opener correctly onto the screw cap. Although it is surely beneficial in the sense of a practical handling, such a symmetrical design of the annular contact element is not mandatory. Accordingly, FIG. 5 shows an exemplary embodiment, otherwise embodied like in FIG. 4 , in which the diameter of the receiving cavity 3 tapers exclusively from the edge 4 in the direction 11 towards the other edge 4 ′. This allows a flatter design of the contact element and thus the bottle opener, however it is disadvantageous here in that the screw cap to be removed must always be inserted from the direction 11 into the receiving cavity 3 . The overall width 27 of this exemplary embodiment amounts to only 1 cm. The width 28 of the notches 18 amounts to approx. 6.6 mm. The other dimensions are consistent with those of the exemplary embodiment according to FIG. 4 , and here it is pointed out once more that this is only one of many potential examples, of course.
[0025] For reasons of completeness, finally it is also pointed out that in the exemplary embodiments shown the thread tops 7 of the respective internal thread are each located on a frustum surface, as are the thread roots 8 . In the exemplary embodiments shown the rotational axis of these frustum surfaces coincides with the longitudinal central axis 17 . Deviating from this conical embodiment there are other potential embodiments, in which the thread tops 7 and/or the thread roots 8 are located on a rotationally symmetrical surface, which not mandatorily represents a frustum surface.
LEGEND OF THE REFERENCE CHARACTERS
[0000]
1 Contact element
2 Inside surface
3 Receiving cavity
4 , 4 ′ Edge
5 Diameter
6 Internal thread
7 Thread Top
8 Thread Root
9 Pitch
10 Depth of the tread
11 , 11 ′ Direction
12 Minimum diameter
13 Direction
14 Level
15 Straight line
16 Angle
17 Longitudinal central axis
18 Notch
19 Angle
20 Handle part
21 Recess
22 Width
23 Opening angle
24 Exterior diameter
25 Rounded exterior edge
26 Half of maximum diameter difference
27 Overall width
28 Width
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Bottle opener for opening a bottle closed with a screw cap, in particular a wine bottle, wherein the bottle opener includes an annular contact element ( 1 ) having an inside surface ( 2 ) for resting against the screw cap, wthe inside surface ( 2 ) delimits a receiving cavity ( 3 ) for receiving the screw cap, and the inside surface ( 2 ) is delimited by two, preferably circular, edges ( 4, 4 ′) of the contact element ( 1 ) and the diameter ( 5 ) of the receiving cavity ( 3 ) delimited by the inside surface ( 2 ) decreases at least sectionally, starting from at least one of the edges ( 4 ) in the direction toward the other edge ( 4 ″), and a counter-clockwise internal thread ( 6 ) is formed on the inside surface.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is a continuation-in-part of U.S. patent application Ser. No. 09/942,239, filed on Aug. 29, 2001.
FIELD OF THE INVENTION
[0002] The present invention relates to systems and methods for generating hydrogen, and more particularly to systems and methods for generating hydrogen gas at pressures high enough to fill gas storage cylinders.
BACKGROUND OF THE INVENTION
[0003] Hydrogen gas must be generated at high pressures to fill hydrogen storage cylinders for stationary and transportation applications, including on board a vehicle and at refueling stations. To produce hydrogen for use or storage at high pressure, water electrolysis may be performed at the required high pressure, generating both hydrogen and oxygen at high pressure. Alternatively, differential-pressure electrolysis may be employed to generate hydrogen at high pressure and oxygen at substantially atmospheric pressure. To date, high pressure water electrolyzers have been fabricated that either generate both hydrogen and oxygen at 3000 psia, where psia is the pressure in pounds per square inch, absolute, or generate hydrogen at 2500 psia and oxygen at atmospheric pressure. For example, Giner Electrochemical Systems, LLC has fabricated a water electrolyzer that operates at a differential pressure (H 2 >O 2 ) of 2500 psia using plastic materials as frames and proton-exchange membranes (PEMs) as solid-polymer electrolytes. A low-pressure pump provides liquid water at near-ambient pressure to the anode side of the electrolyzer. When DC current is applied, the water is decomposed at the anode to oxygen, protons and electrons. The oxygen is separated from the excess circulating water, which acts as a reactant and coolant, with a low-pressure gas/water separator. All functions on the anode side are conducted at near-ambient pressure. The protons, along with some water, are electrochemically transported across the membrane to the cathode, where they react with the externally transported electrons to produce hydrogen at the required higher operating pressure. The hydrogen is separated from the transported water in a high-pressure gas/water separator.
[0004] Electrolyzers operating totally or partially at high pressure may be expensive, involve complex construction, and present safety hazards. Therefore, a need exists in the art for simple, safe, and inexpensive systems and methods for generating hydrogen gas at high pressures.
SUMMARY OF THE INVENTION
[0005] The systems of the present invention can generate hydrogen gas at pressures high enough to fill a gas storage cylinder for stationary and transportation applications, including on board a vehicle and at refueling stations. The electrochemical process for generating hydrogen at pressures that may be greater than 3000 psia features feeding the hydrogen output of a water electrolyzer or other hydrogen gas generating device operated at atmospheric or moderate pressure to an electrochemical hydrogen compressor operating in a high-differential-pressure mode. “Atmospheric or moderate pressure,” as used herein, means from about 0 psia to about 3000 psia. The electrochemical hydrogen compressor has an anode operating at the same pressure as the cathode of the electrochemical hydrogen generator or other hydrogen gas generating device, and a cathode operating at the higher pressure required to fill the gas storage cylinder. The compressor, which may be operated at a 3000 psia or greater pressure differential, elevates hydrogen produced by the electrochemical hydrogen generator or other hydrogen gas generating device to the desired high pressure, for example, 6000 psia.
[0006] The electrochemical hydrogen generator and compressor of the invention are stacks comprising one or more cells connected electrically in series or in parallel. In some preferred embodiments, each cell contains a membrane and electrode assembly (MEA) comprising an anode and a cathode in intimate contact with and separated by an ionic conductive membrane such as a proton-exchange membrane (PEM) or solid alkaline membrane. When power is applied to each cell in the electrochemical hydrogen generator stack, protons and electrons are generated at the anode. The protons are electrochemically transported across the membrane to the cathode, where they combine with the externally transported electrons to form hydrogen gas. This hydrogen gas is fed to the hydrogen compressor, where it is oxidized at the anode of each cell to form protons and electrons. The protons are transported across the membrane to the cathode, where they are reduced by the externally transported electrons to form hydrogen at the desired higher pressure.
[0007] The anticipated benefits of the invention include safety of operation and relative simplicity of constructing a differential-pressure hydrogen compressor cell compared to an electrolyzer with the same pressure difference, which translates into cost savings. The two-cell system of the invention is safer to operate than a high-pressure electrolyzer. Membrane failure in the compressor cell presents little hazard as long as there is a pressure shut off valve, and membrane failure in the low-pressure electrolyzer is less dangerous than it would be in a high-pressure electrolyzer. Thus, the two-cell system allows for the use of thinner membranes, resulting in lower voltage. This compensates for the somewhat higher overall voltage and power inefficiency anticipated when using two cells instead of one. In addition, less risk of explosion exists in recirculating water accumulated at the anode or cathode side of the compressor to the low-pressure electrolyzer of the two-cell system than in feeding a pressurized reactor with cathode water, even if the water contains some hydrogen.
[0008] A water electrolyzer alone could be used to generate hydrogen at high pressure; however, above 2500 psia differential pressure, difficulties arise in supporting the MEA as mechanical properties of the membrane, metallic support structures and compression pads rapidly deteriorate. A high-pressure PEM electrolyzer is also more expensive than an integrated low-pressure electrolyzer and electrochemical hydrogen compressor. Low-cost materials that may be used in the compressor, but not in the high-pressure electrolyzer, include carbon-supported electrode structures, stainless steels, inconels, hastelloys, low-cost hydrocarbon PEMs, and anion exchange (hydroxide transport) solid alkaline membranes. In the compressor, carbon, graphite, hastelloys, stainless, and inconels may replace the costly valve metals (Ti, Zr, Nb) used in electrolyzers. In addition, small noble metal loadings are required due to the high reversibility of the hydrogen electrode in the absence of carbon monoxide and other inhibiting gas traces.
[0009] Further, there are sizable voltage efficiency losses associated with operating a high-pressure (or high-pressure-differential) water electrolyzer, because the oxygen electrode in the water electrolyzer is quite irreversible. Operating the electrolyzer at near atmospheric pressure also allows for the use of lower current densities at the electrolyzer stack without a substantial decrease in faradaic efficiency (efficiency losses due to gas crossover), which is close to 100%. Decreased current density may be achieved by distributing approximately the same amount of electro-catalyst over a larger membrane surface, resulting in higher voltage efficiency of the electrolyzer. These advantages more than compensate for the additional voltage required by the hydrogen compressor cell (which may contribute 5 to 10% to the overall system voltage compared to single cell voltage) and the existence of two stacks versus one.
[0010] These and other benefits and features of the present invention will be more fully understood from the following detailed description, which should be read in light of the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] [0011]FIG. 1 is a schematic diagram of an integrated electrolyzer stack and electrochemical hydrogen compressor stack.
[0012] [0012]FIG. 2 is a perspective view of an electrolyzer stack.
[0013] [0013]FIG. 3 is a cross-sectional view of a single water electrolysis cell or electrochemical compressor cell.
[0014] [0014]FIG. 4 is a cross-sectional view of a water electrolysis cell.
[0015] [0015]FIG. 5 is a schematic diagram of an integrated and unitized electrolyzer stack and hydrogen compressor stack.
[0016] [0016]FIG. 6 is a graph showing the performance of the electrochemical compressor described in Example 1 at various temperatures.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0017] Referring to FIG. 1, a system 10 of the present invention is shown, comprising an integrated electrochemical hydrogen generating stack 12 and electrochemical hydrogen compressor stack 14 . In the embodiment of FIG. 1, the electrochemical hydrogen generating stack 12 is a water electrolysis stack comprising an anode 16 , a membrane and electrode assembly (MEA) 18 , and a cathode 20 . At the anode 16 , water is used as a reactant and oxygen is generated at a near-ambient pressure P 0 . The operable range for P 0 is from about 0 psia to about 2,500 psia, with a preferred range of from about 0 psia to about 200 psia, where a low pressure pump could be used. Protons formed at the anode 16 are electrochemically driven across the MEA 18 to the cathode 20 where they combine with externally driven electrons to form hydrogen at an elevated pressure P 1 , which is greater than P 0 . The operable range for P 1 is from about 30 psia to about 3,000 psia, with a preferred range of from about 300 psia to about 2,500 psia. The generated moist hydrogen from the electrolyzer is fed to an anode 22 of the electrochemical hydrogen compressor stack 14 , where it is oxidized to form protons. The protons are electrochemically driven across an MEA 24 to a cathode 26 , where they combine with externally driven electrons to form hydrogen at a high pressure P 2 , which is greater than P 1 . The operable range for P 2 is from about 500 psia to about 10,000 psia, with a preferred range of from about 2,500 psia to about 5,000 psia. The electrode reactions are as follows, where P 0 <P 1 <P 2 :
H 2 O → ½O 2 (P 0 ) + 2H + + 2e − @ electrolyzer anode [1] 2H + + 2e − → H 2 (P 1 ) @ electrolyzer cathode [2] H 2 O → ½O 2 (P 0 ) + H 2 (P 1 ) Electrolyzer net reaction [3] H 2 (P 1 ) → 2H + + 2e − @ compressor anode [4] 2H + + 2e − → H 2 (P 2 ) @ compressor cathode [5] H 2 (P 1 ) → H 2 (P 2 ) Compressor net reaction [6]
[0018] A power conditioner (DC power generator) 28 provides the power required for electrochemical hydrogen generation and compression. The power supplied to the compressor 14 is equal to the difference between the total power of the power conditioner 28 and the power supplied to the electrolyzer 12 .
[0019] The electrochemical hydrogen generating stack 12 and hydrogen compressor stack 14 comprise one or more cells 30 connected electrically in series, as shown in FIG. 5. In some alternative embodiments, the cells 30 may be connected in parallel. FIG. 2 shows a perspective view of a typical water electrolyzer stack 12 . The cells 30 are held between a set of end plates 32 . Water enters the stack 12 through an opening 35 . Product humidified hydrogen leaves the stack 12 through an opening 37 . Product oxygen and water leave the stack 12 through an opening 39 . A water purge opening 41 may be used to remove hydrogen from the cells 30 and manifolds during extended periods (days) of shutdown. A typical hydrogen compressor stack 14 has a similar configuration to the electrolyzer stack 12 .
[0020] [0020]FIG. 3 shows a cross-sectional view of a typical single cell 30 , with substantially the same configuration for the electrolyzer cell 30 as for the compressor cell 30 . The cell 30 may have an active cell area of from about 5 cm 2 to about 1 M 2 per cell, with a preferred active cell area of from about 50 cm 2 to about 1000 cm 2 . The cell 30 includes an MEA 100 comprising an ionic conductive membrane such as a thin proton-exchange membrane (PEM) 102 to which an anode 104 and a cathode 106 are attached. The ionic conductive membrane of the MEA 100 may be, for example, perfluorocarbon sulfonic acid sold under the trade name Nafion (DuPont, Wilmington, Del.) for PEM electrolyzers or compressors; sulfonated grafted polystyrene-TFE based materials such as R-4010 sold by RAI (Hauppauge, N.Y.) for PEM hydrogen compressors; and grafted, quaternary ammonium hydroxide polystyrene-TFE based materials such as R-4030 sold by RAI (Hauppauge, N.Y.) for alkaline hydrogen compressors. The ionic conductive membrane of the MEA 100 may have a thickness of from about 18 micrometers to about 200 micrometers, with a preferred thickness of from about 25 micrometers to about 100 micrometers. The electrodes of the MEA 100 may be, for example, of the types disclosed in U.S. Pat. Nos. 3,992,271; 4,039,409; and 4,311,569, the teachings of which are incorporated herein by reference. The electrodes of the MEA 100 may have noble metal (N.M.) catalyst loadings of from about 0.05 mg N.M./cm 2 to about 8 mg N.M./cm 2 , with preferred N.M. catalyst loadings ranging from about 0.1 mg N.M./cm 2 to about 0.8 mg N.M./cm 2 . Suitable noble metal catalysts include, for example, Pt, Ir, Ru, Pd, Rh, Re, Os, and their oxides. Such catalysts are especially preferred for PEM embodiments. In some alternative embodiments, the electrodes of the MEA 100 may include non-noble metal catalysts and their oxides, for example, Ti, Nb, Ta, Zr, W, Mo, Ni, Ag, Co, Fe, and La, used in combination with one another and also supported on high surface area catalyst supports such as carbons, graphites, carbides, nitrides, valve metal oxides and transition metal oxides. Such catalysts are especially preferred for alkaline embodiments of the invention.
[0021] Expanded metal distributor screens 108 on each side of the MEA 100 conduct current and improve the flow distribution of gas and liquid products and reactants through the cell 30 . Suitable materials for current collectors and fluid, electric current distributors of the invention include, for example, valve metals, transition metals, carbons, graphites, carbides, and composites thereof with polymers such as Kynar (Elf Atochem, Philadelphia, Pa.) and polysulfone. Preferred materials include Ti for PEM electrolyzer anodes; graphite, Zr, and carbon for PEM electrolyzer cathodes; and graphite, carbon, stainless, hastalloys, and inconels for PEM hydrogen compressors and alkaline systems applications. The metal screens 108 mechanically support the MEA 100 , which can easily withstand differential pressures (H 2 >O 2 ) in excess of 2500 psia. Separators 114 , 116 contain fluids on the face of the screens 108 or active area of the cell assembly.
[0022] The reactants, water in a water electrolyzer cell 30 and hydrogen in a hydrogen compressor cell 30 , enter the applicable cell 30 through an opening 107 on the anode side. The reactants flowing along the screen 108 on the anode side contact the anode 104 , where protons and electrons are produced. In a water electrolyzer cell 30 , oxygen is also produced at the anode 104 . The oxygen flows along the screen 108 and leaves the cell 30 , along with excess water, through an opening 109 on the anode side, at the opposite end of the cell 30 from the opening 107 through which water enters the cell 30 . Protons produced at the anode 104 are electrochemically transported across the PEM 102 to the cathode 106 , where they combine with the externally transported electrons, which flow from anode 104 (loss of electrons) to cathode 106 (gain of electrons), to form hydrogen gas at an elevated pressure relative to the anode-side gas. Hydrogen gas produced at the cathode 106 flows along the screen 108 and leaves the cell 30 through an opening 111 on the cathode side.
[0023] [0023]FIG. 4 depicts a typical single water electrolysis cell 30 (see also FIG. 2). The MEA 100 is contacted on each side by metal screen 108 comprising a multi-layer screen package. The screen package is preferably about 0.03 inches thick and may be, for example, of the type disclosed in U.S. Pat. No. 6,179,986, the teachings of which are incorporated herein by reference. For example, the screen package may be an integral lightly platinized (0.2 mg/cm 2 ) Ti current collector/water distribution mesh package fabricated by spot welding two or more expanded meshes, sold by Exmet Corp. of Naugatuck, Conn. under the trade name Exmet, until the total mesh thickness is equivalent to the thickness of cell frame 112 . Alternatively, the screen package may be a grooved carbon current collector/water distribution structure made of materials such as porous C, solid C, or molded C or TiC composites with polymers such as Kynar (Elf Atochem, Philadelphia, Pa.), polysulfone, polyesters, terephthalates, or liquid crystal polymers (e.g., Kevlar (DuPont, Wilmington, Del.), Vectra (Ticona, Summit, N.J.), and polybenzimidazole).
[0024] The screens 108 form fluid cavities for the water, hydrogen, and oxygen. Behind each screen 108 on the cathode side is an insert 110 , which, along with oxygen separator 114 and hydrogen separator 116 , contains the fluids on the face of the screens 108 or active area of the cell assembly. The insert 110 may be a solid foil, a porous foil, a mesh, or a combination thereof, with a total thickness ranging from about 0.01 cm to about 0.15 cm, preferably from about 0.025 cm to about 0.075 cm. Suitable materials for the insert 110 include, for example, metals such as Ti and Nb, stainless, and carbon. The separators 114 , 116 may, for example, comprise thin composite, conductive plates made of materials such as Nb or Ti foil on the anode side and Zr foil or molded carbon on the cathode side. In some embodiments, the separators 114 , 116 may be of the types described in U.S. Pat. Nos. 6,179,986, 4,214,969 and 4,339,322, the teachings of which are incorporated herein by reference.
[0025] Each screen 108 is surrounded by a cell frame 112 , made of polysulfone or another material with similar properties, that externally contains the fluids and manifold or ports that direct fluids in and out of the screen cavities. Suitable materials for the cell frame 112 include, for example, organic and inorganic polymers or plastics, carbons, graphites, composites of carbons or graphites with polymers, ceramics and electrically inerted or coated metals. The cell frame may have a total thickness of from about 0.05 cm to about 0.5 cm, with a preferred thickness of from about 0.15 cm to about 0.3 cm. Liquid water, preferably distilled or deionized, enters the cell 30 through an opening 107 in the frame 112 on the anode side and flows along the screen 108 . The water is uniformly distributed along the screen 108 and is oxidized along the anode 104 of the MEA 100 to form oxygen, protons, and electrons. The oxygen and some water are released from the cell 30 through an opening 109 in the frame 112 on the anode side, at the opposite end of the cell 30 from the opening 107 through which water enters the cell 30 . The protons and some water are transported across the PEM 102 to the cathode side of the cell 30 . The protons are reduced along the cathode 106 by externally transported electrons to form humidified hydrogen, which is released from the cell 30 through an opening 111 in the cathode side of the frame 112 . This process is repeated for any additional cells 30 in the electrolyzer stack 12 , and the humidified product hydrogen is fed to the hydrogen compressor stack 14 . A water purge opening 113 in the cathode side of the frame 112 may be used to remove hydrogen from the cells 30 and manifolds during extended periods (days) of shutdown.
[0026] The screens 108 also serve as current collectors, conducting electrons from the cell anode 104 to the oxygen separator sheet 114 , from which they pass through the adjacent hydrogen separator 116 and screen package 108 to the cathode 106 of the next cell in a bipolar configuration. Gaskets 118 , preferably 0.005-inch-thick plastic, seal the cell frame 112 to the metal separators 114 , 116 , while the membrane 102 seals the frame 112 on the opposite side. A pressure pad assembly 120 , for example made of silicone and woven metal strips, and breather screen 122 between two adjacent hydrogen and oxygen metal separators 114 , 116 provide the contact pressure against the cell active area through the separators 114 , 116 . A plastic manifold gasket 124 surrounds the pressure pad assembly 120 between the separators 114 , 116 to seal the fluid manifold parts between cells 30 in the stack 12 .
[0027] The mechanical design configuration for a typical hydrogen compressor cell 30 of the invention is similar to that of the water electrolysis cell 30 shown in FIG. 4, except that humidified hydrogen gas is introduced to the anode side of the cell 30 instead of liquid water, so hydrogen is oxidized to protons and electrons but no oxygen is produced. The hydrogen-generating reaction at the cathode side is the same for the compressor as for the electrolyzer, the reduction of protons with electrons to form hydrogen, and hydrogen may be generated at 2500 psia above the anode side. The concept of a PEM hydrogen concentrator/compressor is described by Sedlak et al., Int. J. Hydrogen Energy 6:45-51 (1981), the teachings of which are incorporated herein by reference.
[0028] [0028]FIG. 5 shows an example of a preferred system 10 of the invention, comprising an integrated electrochemical hydrogen generating stack 12 and electrochemical hydrogen compressor stack 14 , and a power conditioner 28 . The electrochemical hydrogen generating stack 12 is a 2-inch high water electrolyzer stack composed of 14 cells 30 in electrical series, each with 0.05 ft 2 (3-inch diameter) of active area. The stack 12 generates oxygen at between about 40 psia and about 200 psia and hydrogen at about 1000 psia. The stack 12 runs at 15.5 amps (310 mA/cm 2 ) at 1.58 volts per cell. The cell voltage and diffusional losses of 0.5 amps result in a stack efficiency of slightly above 90% on the basis of the higher heating value of hydrogen (1.48 volts), with 37 Watts of waste heat. The electrochemical hydrogen compressor stack 14 comprises cells 30 of similar number and size to those of the electrolyzer stack 12 , in electrical series with one another, and in parallel with the electrolyzer stack 12 . The compressor elevates hydrogen from about 1,000 psia to about 5,000 psia. The electrolyzer and electrochemical compressor stacks 12 , 14 are unitized and held between a single set of 6-inch diameter end plates 32 to minimize weight, volume and cost. Polysulfone cell frames 112 of 4.5-inch diameter with ridges and containment rings surround the cells 30 in each stack 12 , 14 . An electrical bus 34 separates the stacks 12 , 14 and allows them to be operated at different currents as required by their different production rates. A control circuit 36 controls the voltage across the electrochemical hydrogen compressor 14 at the required 0.05 to 0.1 volt/cell. If the hydrogen feed stream to the electrochemical hydrogen compressor 14 is interrupted, causing the voltage to rise, the current of 15.5 amps is shunted around the compressor 14 to prevent the voltage from rising to the point where oxygen would be generated on the anode side of the compressor 14 .
[0029] The equation for the thermodynamic voltage of the electrochemical hydrogen compressor cell of the invention is as follows, if the anode is fed at 30 psia (˜2 Atm, a, where Atm, a is the pressure in atmospheres, absolute):
E = 29.5 T 298 log P P a tm , m V [ 7 ]
[0030] At 100° C. (373° K) and 3000 psia (˜200 Atm, a) pressure differential, E=74 mV. The thermodynamic voltage required by the hydrogen compressor cell is equal to the additional thermodynamic voltage of a differential-pressure electrolyzer with a cathode operating at the same high pressure over the potential of an all-atmospheric-pressure electrolyzer, i.e., there is no difference in thermodynamic voltage attributable to the high-pressure cathode in the two approaches. However, the hydrogen compressor cell contributes to overall voltage through an additional polarization due to current multiplied by ionic resistance and very slight activation overvoltages. Operable voltages for electrolyzers of the invention range from about 1.4 V to about 3.0 V, with a preferred range of from about 1.5 V to about 2.0 V. Operable voltages for hydrogen compressors of the invention range from about 0 V to about 0.5 V, with a preferred range of from about 0.05 V to about 0.30 V. Operable current densities for electrolyzers and electrochemical compressors of the invention range from about 0 mA/cm 2 to about 10,000 mA/cm 2 , with a preferred range of from about 300 mA/cm 2 to about 3,000 mA/cm 2 .
[0031] A consequence of high-pressure hydrogen cathode operation is permeation of hydrogen through the PEM, which significantly reduces faradaic efficiency. This applies for both a high-pressure electrolyzer and a high-differential-pressure hydrogen compressor, but an electrolyzer with pressurized anode and cathode has significant additional inefficiency due to oxygen permeation. A much smaller oxygen permeation inefficiency exists when the anode operates at low pressure. The faradaic inefficiency effects a power efficiency loss, which is about 10 times higher for a high-pressure electrolyzer than for a high-differential-pressure hydrogen compressor because the cell voltage of the electrolyzer is about ten times higher.
[0032] In a system with electrolyzer and compressor stacks connected electrically in series and having the same number of cells, the hydrogen migration from high-pressure cathode to low-pressure anode in the compressor stack would create a continuous pressure buildup in the low-pressure hydrogen space, the gas space of the compressor anode, the electrolyzer cathode, and the associated plumbing. If the number of cells in each stack is sufficiently large, pressure balance in the low-pressure hydrogen space may be achieved by using one or more additional cells in the electrochemical compressor stack than in the electrolyzer stack. The number of additional cells in the compressor stack will depend on total cell number, cell characteristics, and operating pressures. As demonstrated in Example 3 below, a typical system of the invention may comprise 15 cells per stack, requiring one additional cell in the electrochemical compressor stack. This solution does not lend it self to a perfect match due to the stepwise introduction of additional cells.
[0033] Alternatively, or to fine-tune a design with a slightly larger electrochemical compressor stack than electrolyzer stack, an additional power source may be connected between the terminals of the electrochemical compressor (low voltage) stack. Other alternative or additional measures include shunting the electrolyzer (high voltage) stack by a resistor or periodically venting hydrogen pressure. The latter two approaches are recommended only if the unbalance is small, such that the lost power or hydrogen represents a small fraction of the supplied power or pressurized hydrogen. Low pressure in the hydrogen space, for example due to over-correction in selecting the number of cells by which the electrochemical compressor stack exceeds the electrolyzer stack, may be remedied by shunting the hydrogen compressor (low voltage) stack by a resistor or by connecting an additional power source between the terminals of the electrolyzer (high voltage) stack.
[0034] Those of skill in the art will appreciate that adding water to a low-pressure electrolyzer is relatively straightforward and routinely practiced. Net water addition is not required in the hydrogen compressor cells, but humidification of anode hydrogen is usually necessary in PEM cells since the transported proton is hydrated. Hydrogen produced by the electrolyzer is humidified, and the humidity can be regulated by controlling the temperature of the electrolyzer or the hydrogen gas. The moderate pressure and the temperature of the electrolyzer is selected to produce optimal electrochemical PEM hydrogen compressor anode operation, especially with respect to humidity. In addition to requiring two stacks, the systems of the present invention require a gas-diffusion electrode, which is the anode of the hydrogen compressor cells. However, this electrode is straightforward to operate, especially since the hydrogen gas from the electrolyzer is humidified at saturation and the electrolyzer temperature may be controlled to create ideal humidification for the hydrogen compressor cell. The operational temperature ranges for the system are from about 25 ° C. to about 130° C., with a preferred temperature range of from about 25 ° C. to about 80° C. The operating pressure of the system ranges from about 0 psia to about 10,000 psia, with a preferred pressure range of from about 30 psia to about 5,000 psia. Net removal of water from the cells at the high- or low-pressure end is reasonably straightforward.
[0035] As shown in the figures and demonstrated in the examples below, the electrochemical hydrogen generating stack of the invention may be a PEM water electrolyzer stack. However, the electrochemical hydrogen generating stack may be any ionic conductive membrane electrochemical stack operating at atmospheric or moderate pressure to produce protons and electrons at the anode by oxidation and generate hydrogen gas at an elevated pressure at the cathode by electrochemical reduction of the protons with the electrons. Alternative electrochemical hydrogen generating stacks of the invention include cells that generate hydrogen gas at the cathode and also produce protons at the anode and/or hydroxide ions at the cathode. For example, an alkaline liquid electrolyzer that generates hydroxide ions as well as hydrogen at the cathode may be used, as long as precautions are taken to eliminate any NaOH entrapped in the low-pressure hydrogen stream from the integral electrochemical compressor. In some embodiments, sodium sulfate electrolyzers may be used, wherein sulfuric acid (from protons) and oxygen gas are generated at the anode, and sodium hydroxide (from hydroxide ions) and hydrogen are produced at the cathode. In other alternative embodiments, electrolyzers of the invention include brine, chloralkali electrolyzers, which generate chlorine at the anode and hydrogen gas and hydroxide ions at the cathode, and HCI or HBr electrolyzers, which generate chlorine or bromine, respectively, and protons at the anode and hydrogen gas at the cathode. In still other alternative embodiments of the invention, a methanol/hydrogen stack may be used, in which methanol is oxidized at the anode to produce protons, electrons and carbon dioxide, and hydrogen gas is evolved at an elevated pressure at the cathode by reduction of the protons with the electrons. In still other embodiments, the electrochemical hydrogen generating stack is a reformate/hydrogen stack, in which the reformate gas contains hydrogen gas diluted with carbon dioxide, nitrogen, and water vapor. The diluted hydrogen gas is oxidized at the anode to form protons and electrons, and pure hydrogen gas at an elevated pressure is produced at the cathode from the reduction of the protons and electrons.
[0036] As shown in the figures and examples herein, the electrochemical hydrogen compressor stack of the invention may be a PEM hydrogen compressor. In some alternative embodiments of the invention, the electrochemical hydrogen compressor may be a solid alkaline membrane electrochemical hydrogen compressor. An example of a solid alkaline membrane is RAI 4030, supplied by RAI, Hauppauge, N.Y., a fluorocarbon-grafted quaternary ammonium hydroxide anion exchange membrane. A solid alkaline membrane generally is not sufficiently stable for use in electrolyzers or fuel cells where hydrogen and oxygen are present, but stability is significantly enhanced in an electrochemical hydrogen compressor where only a hydrogen atmosphere is present.
[0037] In an alternative embodiment to an electrochemical H 2 generator, a reactor that converts a hydrogen-containing compound to a hydrogen-containing gas is used as a hydrogen source for the electrochemical hydrogen compressor. Non-limiting examples of such reactors include hydrocarbon processors, such as, e.g., hydrocarbon gas reformers, and ammonia crackers. For example, certain embodiments employ a gas reformer such as described by Rostrop-Nielson et al., “Steam Reforming, ATR, Partial Oxidation: Catalysts and Reaction Engineering” in Handbook of Fuel Cells, Vol. 3, Fuel Cell Technology and Applications, p. 159 (Vielstich et al. eds., John Wiley & Sons, 2003) or an ammonia cracker such as described by Hacker et al., “Ammonia Crackers” in Handbook of Fuel Cells, Vol. 3, Fuel Cell Technology and Applications, p. 121 (Vielstich et al. eds., John Wiley & Sons, 2003), the teachings of the foregoing references being incorporated herein by reference. In yet another alternative embodiment to an electrochemical H 2 generator, a PEM fuel cell that exhausts an effluent of a not completely reacted, dilute hydrogen stream is used as the H 2 source. In some of these alternative embodiments, the hydrogen-containing gas produced by the reactor is treated using a gas conditioner (e.g., a humidifier) before it enters the hydrogen compressor.
[0038] Thus, in a first system, a reactor (e.g., an electrolyzer, hydrocarbon processor, or ammonia processor) converts a hydrogen-containing compound to a hydrogen-containing gas at a first pressure P 1 . Alternatively, the first system is a PEM fuel cell that supplies a diluted H 2 stream at pressure P 1 . Integrated with the first system is a second system, an electrochemical hydrogen compressor that produces hydrogen at a second pressure P 2 . The electrochemical hydrogen compressor includes at least one cell containing an anode, which is, in at least some instances, a gas diffusion electrode, a cathode, and an ionic conductive membrane in intimate contact with and separating the anode and the cathode. The electrochemical hydrogen compressor anode oxidizes hydrogen at pressure P 1 supplied by the first system, and the cathode evolves hydrogen at pressure P 2 , which is greater than P 1 .
[0039] As an alternative to a conventional hydrogen-evolving cathode (e.g., Pt black particles with binder alone, or Pt dispersed on carbon with binder), in some embodiments, the electrochemical hydrogen compressor cathode includes a solid metallic film such as, for example, palladium (Pd) or a Pd alloy. Hydrogen atoms are formed at the inner surface of the metallic film, which is in contact with the ionic conductive membrane, and transported to the outer surface of the metallic film, where they combine to form hydrogen gas at pressure P 2 , which is greater than the pressure P 1 at the anode.
[0040] In particular embodiments, to accelerate atomic hydrogen transport, one or both surfaces of the metallic film, e.g., a palladium (Pd) or a Pd alloy film, are treated. The treatment includes, for example, roughening the metallic surface and/or depositing noble metals or particulate materials containing noble metals (e.g., Ir or Rh) or transition metals (e.g., Co) on one or both sides of the Pd foil.
[0041] In some embodiments, the ionic conductive membrane in the electrochemical hydrogen compressor is a solid alkaline membrane. In this case, the following electrochemical reactions take place:
Anode: H 2 (P 1 )+2OH − →2H 2 O+2 e − [8]
[0042] Cathode: Pd foil surface facing the solid alkaline membrane
2H 2 O+2 e − →2OH − +2H. [9]
[0043] Outer surface of Pd foil
2H.→H 2 (P 2 ) [10]
[0044] Atomic hydrogen (2H.) is transported through the Pd foil and combines at the outer surface to form hydrogen at pressure P 2 .
[0045] In some alternative embodiments, the ionic conductive membrane in the electrochemical hydrogen compressor is a proton exchange membrane. In this case the following electrochemical reactions take place:
Anode: H 2 (P 1 )→2H + +2 e − [11]
[0046] Cathode: Pd foil surface facing the PEM
2H + +2 e − →2H. [12]
[0047] Outer surface of Pd foil
2H.→H 2 (P 2 ) [13]
[0048] Atomic hydrogen (2H.) is transported through the Pd foil and combines at the outer surface to form hydrogen at pressure P 2 .
[0049] The following nonlimiting examples further illustrate certain preferred embodiments of the present invention:
EXAMPLE 1
[0050] A hydrogen compressor cell 30 with active cell area of 0.05 ft 2 was assembled with a 5-mil (dry) membrane 102 (Dow Chemical, Midland, Mich., Dow XUS 13204), having an equivalent weight of approximately 800 and an ion-exchange capacity (meq of H + ion/g of dry polymer) of 1.25. Pt black electrode structures 104 , 106 were integrally bonded to each surface of the membrane 102 . Ambient-pressure hydrogen was fed to the anode 104 of the PEM compressor cell 30 , where it was continually oxidized, by the application of a direct electric current from a DC power generator, to form protons, which were electrochemically transported across the membrane 102 to the cathode 106 . At the cathode 106 , the protons were reduced back to hydrogen, which was allowed to rise to a higher pressure. Because the hydrogen oxidation and reduction reactions are highly reversible, essentially all of the voltage losses were due to current multiplied by ionic resistance. The hydrogen gas was compressed from approximately 15 psia to approximately 30 psia. The performance of the electrochemical compressor 14 at 30° C., 60° C., and 80° C. is shown in FIG. 6.
EXAMPLE 2
[0051] A hydrogen compressor cell 30 with an active cell area of 0.23 ft 2 was assembled with 10-mil (dry) Nafion 120 membrane 102 (E. I. DuPont, Wilmington, Del.) and successfully operated by the application of a direct electric current from a DC power generator at 1000 mA/cm 2 , compressing hydrogen gas from approximately 15 psia to approximately 1000 psia. Cell voltage was approximately 0.32 V at 40° C.
EXAMPLE 3
[0052] A compressor stack 14 with a 15-mil Nafion membrane 102 (E. I. DuPont, Wilmington, Del.), having a water content of 0.37 g of water per 1 g of dry membrane operates at a differential pressure of 3000 psia (˜200 Atm, a). The compressor stack 14 is integrated with an electrolyzer stack 12 with the same number of cells 30 operating at 80° C. and near-atmospheric pressure, with a current density of 1000 mA/cm 2 by the application of a direct electric current from a DC power generator. The hydrogen lost from the high-pressure to the low-pressure side of the compressor stack 14 is 6.7% of the total hydrogen generated; the electrolyzer 12 has a negligible effect on the amount of hydrogen transferred to the low-pressure hydrogen space. The 6.7% hydrogen loss is offset by adding 1 cell per every 15 cells of a theoretical (no hydrogen permeability) compressor stack 14 while leaving the electrolyzer stack 12 untouched.
[0053] While the foregoing invention has been described with reference to its preferred embodiments, various alterations and modifications will occur to those skilled in the art. All such alterations and modifications are intended to fall within the scope of the invention and the appended claims.
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Disclosed are methods and systems for generating hydrogen gas at pressures high enough to fill a hydrogen storage cylinder for stationary and transportation applications. The hydrogen output of an electrochemical hydrogen gas generating device, a hydrogen-producing reactor, or a diluted hydrogen stream is integrated with an electrochemical hydrogen compressor operating in a high-differential-pressure mode. The compressor brings the hydrogen produced by the hydrogen generating device to the high pressure required to fill the storage cylinder.
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BACKGROUND OF THE INVENTION
[0001] This invention relates to the packaging and delivery of flowable bulk materials intended to be consumed, and in particular, but not exclusively, to a sleeve arranged to receive a pouch in which the flowable bulk material is contained. The invention has application to a wide range of flowable bulk materials including beverages and other flowable food products such as soups, sauces, syrups, ice cream, sorbet and the like. For convenience the invention is described hereinafter with reference to the packaging and delivery of beverages but it will be understood that we do not intend to be limited thereto and that the invention extends to and includes any flowable bulk materials that can be consumed either directly or when added to another food product.
[0002] Both alcoholic and non-alcoholic beverages are traditionally sold pre-packaged in plastic or glass bottles, cans or pre-filled cartons. They are sold through different retail outlets such as shops, bars, cafes and restaurants or through vending machines. There are a number of problems associated with the packaging traditionally used, primarily the amount of space required by a retailer to store the packaged beverages. The majority of retailers store beverages in refrigerated cabinets with a limited capacity. The shape of pre-packaged beverages, such as a bottle, is inefficient for storage thereby limiting the amount of stock, and therefore the range, that can be offered by the retailer. Furthermore, the inefficient storage shape of the packaging increases the space required for transport of the beverages. Pre-packaging a beverage before supplying to a retailer also means that the brand owner protects the profit in the branded beverage.
[0003] An additional problem is the large amount of energy consumed in keeping the cabinets refrigerated and there can also be problems with stock rotation. For example, most bars use refrigerators that are both stocked from the front and emptied from the front, often leaving beverages at the back of the cabinet for long periods of time, which can lead to waste. The packaging itself also generates a large amount of waste and this can result in problems associated with waste management and the disposal of waste containing a number of different materials.
SUMMARY OF INVENTION
[0004] It is known to provide a plastic pouch arranged to contain a beverage. A beverage can be dispensed into the pouch at the point of sale or, alternatively, the pouches can be provided pre-filled. However, the pouches can be unstable and difficult to handle, especially if containing a particularly hot or cold beverage. It may also prove difficult to sufficiently distinguish different brands of beverages.
[0005] In one aspect, the present invention provides a method of packaging a bulk flowable material at the point of sale comprising providing a flexible pouch, filling the pouch with bulk flowable material and providing the pouch with an indication of the contents before, during or after filling the pouch. The invention also provides apparatus for carrying out the method.
[0006] In one arrangement, the indication of the contents may be applied to the pouch, for example by printing on the material of the pouch or by attaching a label to the pouch. For example, apparatus for filling the pouch may include a printing station before or after the filling head for printing details of the contents onto the pouch itself or onto a label that is attached to the pouch by adhesive or other suitable means prior to dispensing the filled pouch.
[0007] In this way, blank pouches or pouches carrying information common to all products to be dispensed can be provided for filling and labelling with specific details of the type of product being applied to the pouch at the point of dispense. As a result, non-product specific pouches can be supplied and the product specific information applied in response to selection of a particular product to be dispensed. This simplifies packaging of different products at the point of sale with resulting advantages for the retailer. Also the consumer benefits from the packaging of product dispensed at the point of sale thereby ensuring product freshness.
[0008] The pouch may be made of transparent or translucent material and arranged so that the customer can see the contents as the pouch is being filled. This may add to the “theatre” of dispense, especially where dispense is accompanied by a change in the characteristics of the product in the pouch, for example where ice or other special effects are created in the product. In one preferred arrangement, the contents of the pouch can be illuminated with light from the side remote from the customer and this may further enhance the “theatre” of dispense. Alternatively or additionally, the pouch may be provided with a reflective or other suitable surface onto which an image or other special effect can be displayed to the customer while dispensing a product to enhance the “theatre” of dispense. Alternatively or additionally, the pouch may incorporate temperature responsive materials that change colour (thermochromic materials) or some other change to the appearance of the pouch when a cold or hot product is added to the pouch thereby creating a visual effect to enhance the “theatre” of dispense.
[0009] In another arrangement, the indication of the contents of the pouch may be provided on packaging for the pouch itself. The packaging may be in the form of a sleeve in which the pouch is received. The indication of the contents may be applied to the sleeve, for example by printing on the sleeve or by attaching a label to the sleeve. For example, apparatus for filling the pouch may include a printing station for printing details of the contents onto the sleeve or onto a label that is attached to the sleeve by adhesive or other suitable means. The filled pouch and printed sleeve may be dispensed separately and the pouch placed in the sleeve by hand. Alternatively, the filled pouch may be dispensed already within the printed sleeve. With this arrangement, the apparatus for filling the pouch and printing the sleeve may be combined or separate filling and printing apparatus may be provided.
[0010] In this way, blank sleeves or sleeves carrying information common to all products to be dispensed can be provided for labelling with specific details of the type of product to be dispensed into the pouch at the point of dispense. As a result, non-product specific sleeves can be supplied and the product specific information applied in response to selection of a particular product to be dispensed. This simplifies packaging of different products at the point of sale with resulting advantages for the retailer. Also the consumer benefits from the packaging of product dispensed at the point of sale thereby ensuring product freshness.
[0011] The pouch is preferably made of transparent or translucent material and the sleeve arranged so that, when the pouch is filled in the sleeve, the customer can see the contents of the pouch through a window as the pouch is being filled. This may add to the “theatre” of dispense, especially where dispense is accompanied by a change in the characteristics of the product in the pouch, for example where ice or other special effects are created in the product. In a preferred arrangement, the sleeve is provided with windows in front and rear panels. With this arrangement, the contents of the pouch can be illuminated with light from the side remote from the customer and this may further enhance the “theatre” of dispense. Alternatively or additionally, the sleeve may be provided with a reflective or other suitable surface onto which an image or other special effect can be displayed to the customer while dispensing a product to enhance the “theatre” of dispense. Alternatively or additionally, the sleeve may incorporate temperature responsive materials that change colour (thermochromic materials) or some other change to the appearance of the sleeve when a cold or hot product is added to the pouch thereby creating a visual effect to enhance the “theatre” of dispense.
[0012] Accordingly, the present invention also provides a sleeve for a pouch for a flowable bulk material, the sleeve being configured to define a cavity arranged to receive the pouch.
[0013] In one embodiment, the sleeve comprises a flexible member made of materials such as paperboard materials, for example cardboard, especially corrugated cardboard. However, this is not essential and any one of a number of other suitable materials may be used including plastic and/or metallic film materials. The sleeve may comprise a single sheet of the material. The sheet of material may be divided into a plurality of panels and at least one panel may be fastened to another panel to define the cavity. Alternatively, the sheet of material may comprise a single panel, one part of which may be fastened to another to define the cavity. The material may be fastened to secure the sleeve in the erected condition using interlocking formations such as tabs, tongues and the like, or adhesive such as one or more adhesive stripes. Where provided, the adhesive stripe(s) may be protected by a removable cover strip until it is required to assemble the sleeve. It will be understood that any suitable fastening means or combination of fastening means may be employed. The erected sleeve may be self-supporting allowing the sleeve to stand on a surface while retaining a degree of flexibility such that the sides of the sleeve can be easily compressed thereby compressing the pouch to assist discharge of the product contained in the pouch. This may be particularly beneficial for products having a relatively high viscosity such as milkshakes or ice cream that can be squeezed out of the pouch by compressing the sleeve.
[0014] In another embodiment, the sleeve comprises a rigid or semi-rigid member made of materials such as plastics, metals or elastomers, for example neoprene. The rigid or semi-rigid member may be formed by any suitable means such as injection moulding plastics or elastomers. The formed sleeve may be self-supporting capable of standing on a surface with the pouch supported therein and may provide a container such as a cup into which the contents of the pouch may be poured for consumption. Thus, the sleeve may serve as packaging for carrying the pouch with the product therein until it is desired to consume the product when the pouch can be removed from the sleeve and the contents emptied into the sleeve.
[0015] The sleeve may have an opening at one end such that the pouch can be inserted into the cavity in the sleeve. In one arrangement, the base of the sleeve is open allowing the sleeve to slide over the pouch. In another arrangement, the top of the sleeve is open allowing the pouch to be dropped into the sleeve. In a further arrangement, the sleeve may be assembled around the pouch, or the pouch may be inserted into a partially assembled sleeve. The pouch may be pre-filled before locating in the sleeve, or alternatively the pouch may be filled when in the sleeve.
[0016] The sleeve may further comprise means to retain the pouch in the sleeve. For example, where the base of the sleeve is open, the sleeve may include a panel, flap or projections arranged to extend across and at least partially close the base to support and retain the pouch in the sleeve. Alternatively or additionally, the sleeve may define an opening for a neck or spout of the pouch and the opening may be configured to engage the neck or spout to retain the pouch in the sleeve, for example the neck or spout may be a snap fit in the aperture. Alternatively or additionally, the sleeve may be provided with one or more adhesive regions that secure the pouch to the sleeve within the cavity. The adhesive regions may be provided with a removable cover strip until it is required to attach the pouch to the sleeve.
[0017] Preferably, the sides of the sleeve are tapered and may be tapered out towards the bottom of the sleeve. This arrangement results in a sleeve that opens out at the bottom to provide a stable base for standing the sleeve on a surface such as a table with the pouch located in the cavity.
[0018] Alternatively, or additionally, at least two of the panels may have a curved shape. For example, in one plane the sleeve may be narrower at a centre portion than at either the top or bottom to provide a more comfortable shape to hold.
[0019] Preferably, the material of the sleeve is thermally insulating to reduce heat transfer to or from the pouch. In this way chilled contents of the pouch remain cold and heated contents remain hot. In addition, the thermal insulation properties of the sleeve allow the pouch to be held comfortably when the contents of the pouch are chilled or heated.
[0020] The sleeve may be pre-printed before assembly. For example, the sleeve may be printed with a brand name or logo to correspond with a beverage on offer at a retail outlet. The sleeve may further comprise a window in at least one panel, arranged to enable the contents of the beverage pouch to be seen.
[0021] The pouch is preferably made of transparent or translucent material and the sleeve arranged so that, when the pouch is filled in the sleeve, the customer can see the contents of the pouch through the window as the pouch is being filled. This may add to the “theatre” of dispense, especially where dispense is accompanied by a change in the characteristics of the product in the pouch, for example where ice or other special effects are created in the product. In a preferred arrangement, the sleeve is provided with windows in front and rear panels. With this arrangement, the contents of the pouch can be illuminated with light from the side remote from the customer and this may further enhance the “theatre” of dispense. Alternatively or additionally, the sleeve may be provided with a reflective or other suitable surface onto which an image or other special effect can be displayed to the customer while dispensing a product to enhance the “theatre” of dispense. Alternatively or additionally, the sleeve may incorporate temperature responsive materials that change colour (thermochromic materials) or some other change to the appearance of the sleeve when a cold or hot product is added to the pouch thereby creating a visual effect to enhance the “theatre” of dispense.
[0022] The sleeve may be configured to fit in a carrier and the carrier may be capable of supporting a plurality of sleeves having pouches located therein. For example, the carrier may comprise a tray having recesses in which the base end of the sleeve is received to support the sleeve. In this way, several pouches may be carried in a safe and convenient manner that reduces the risk of the contents of the pouches being spilled.
[0023] According to a yet another aspect of the invention, there is provided a system for packaging and delivery of a bulk flowable material, the system comprising a pouch for the bulk flowable material and a sleeve configured to define a cavity in which the pouch is received
[0024] Preferably, the sleeve is as described above in connection with the preceding aspect of the invention. The pouch may comprise a flexible bag of a food-grade material provided with a neck or spout through which the flowable bulk material can be introduced to fill the pouch and withdrawn to consume the flowable bulk material. The neck or spout may be provided with a closure to retain the flowable bulk material in the pouch until it is desired to consume the flowable bulk material. The closure may comprise a screw cap, flip-top cap, sports cap, push-fit cap or any other suitable closure device. The closure may be re-closable to allow the neck or spout to be closed when the contents of the pouch have been partially consumed. The closure may be configured to allow the pouch to be employed with automatic pouch filling equipment.
[0025] The bulk flowable material may be a beverage, for example an alcoholic beverage such as beer, lager, cider, wine, spirits (with or without a mixer), alcopop, cocktail or a non-alcoholic beverage such as still or carbonated water with or without additional flavouring, or fruit juice. The beverage may be chilled for dispense into the pouch. The beverage may be a semi-frozen beverage sometimes referred to as a slush beverage. The semi-frozen beverage may be formed by partially freezing the beverage to produce an ice content prior to filling the pouch. Alternatively or additionally, the semi-frozen beverage may be formed in the pouch. For example we may dispense a supercooled beverage and subject the beverage to a shock such as by ultrasonics, injection of carbon dioxide gas or other additive that will cause ice crystals to nucleate in the supercooled fluid when the beverage is dispensed and/or when the beverage is in the pouch to cause formation of an ice content. Alternatively or additionally, we may add an ice slurry to the beverage when the beverage is dispensed and/or when the beverage is in the pouch. The beverage may be a hot beverage such as tea, coffee, chocolate. Other consumable flowable hot or cold products that may be contained in the pouch include soups, milkshakes, ice cream, sorbet etc.
[0026] According to a still further aspect of the invention, there is provided a method of serving a flowable bulk material comprising the steps of selecting a flowable bulk material, dispensing the flowable bulk material into a pouch, selecting a sleeve corresponding to the selected flowable bulk material and inserting the pouch into the sleeve.
[0027] The flowable bulk material may be a chilled beverage or a partially or semi frozen beverage—often referred to as slush beverage—or alternatively may be a hot beverage. Where the flowable bulk material is a beverage, it may be a still beverage or a carbonated beverage and it may be an alcoholic beverage or a non-alcoholic beverage.
[0028] According to another aspect of the invention, there is provided a method of dispensing a flowable bulk material into a pouch at the point of sale or delivery of the beverage for consumption.
[0029] The flowable bulk material may be a chilled beverage or a partially or semi frozen beverage—often referred to as slush beverage—or alternatively may be a hot beverage. Partially or semi-frozen beverages may have an ice content formed from the beverage itself or by the addition of an ice slurry to the beverage. The ice content may be formed before, during or after filling the pouch with the beverage. The beverage may be a still beverage or a carbonated beverage and it may be an alcoholic beverage or a non-alcoholic beverage. The flowable bulk material may be a food product such as soup, ice cream, sorbet.
[0030] The invention also includes a pouch filled with a flowable bulk material suitable for consumption at the point of sale or delivery.
[0031] The invention further includes apparatus for filling a pouch with a flowable bulk material. The apparatus may also provide the pouch with a sleeve identifying the contents of the pouch. The apparatus may be provided for packaging products at the point of sale in a shop or other retail outlet for supply to customer order. Alternatively, the apparatus may be embodied in a vending machine or the like with suitable controls for customer selection of the product to be packaged and dispensed.
[0032] Preferred embodiments of the invention will now be described, with reference to the accompanying drawings, in which;
BRIEF DESCRIPTION OF THE DRAWINGS
[0033] FIG. 1 is a front view of an assembled sleeve and beverage pouch;
[0034] FIG. 2 shows a blank for constructing the sleeve of FIG. 1 ;
[0035] FIG. 3 is a front view of an assembled sleeve with a viewing window;
[0036] FIG. 4 is a front view of an alternative assembled sleeve; and
[0037] FIG. 5 shows a blank for constructing the sleeve of FIG. 4 .
DESCRIPTION OF THE PREFERRED EMBODIMENT
[0038] Referring to FIGS. 1 and 2 , according to a first embodiment of the invention, a beverage pouch sleeve 2 comprises a single sheet of folded cardboard. The sleeve comprises a front panel 6 , a back panel 4 and two shaped panels 8 , 10 . The front and back panels, 4 , 6 are joined at a top edge and folded about a score line 12 until the bottom edge 18 of the back panel 4 is substantially level with the bottom edge 20 of the front panel 6 . One shaped panel 10 extends from a side edge of the back panel 4 and is folded about a score line 14 until it overlaps the front panel 6 . Similarly, a shaped panel 8 extends from a side edge of the front panel 6 and is folded about a score line 16 until it overlaps the back panel 4 .
[0039] The shaped panels 8 , 10 are secured to the outer faces of the front and back panels 6 , 4 and the bottom edges of the front and back panels 6 , 4 are left open. The assembled sleeve defines a cavity into which a beverage pouch 22 can be inserted. The outer faces of the sleeve 2 are printed with a design or brand name corresponding to a beverage on sale in a particular retail outlet. The cardboard is die-cut and pre-printed before assembly into the sleeve.
[0040] In this embodiment, the panels 8 , 10 are provided with one or more stripes of adhesive (not shown) such as a contact adhesive by means of which the panels 8 , 10 are adhered to the outer faces of the panels 6 , 4 . The adhesive stripes may be provided with a protective cover strip that is removed when the sleeve is to be assembled. Any other suitable means may be employed to secure the panels 8 , 10 to the panels 6 , 4 . For example, the panels 8 , 10 may be secured to the panels 6 , 4 by engagement of interlocking formation such as tongues or tabs in slots.
[0041] The sides of the front and back panels 6 , 4 are tapered outwards towards the bottom so that, in use, the open base is a substantially oval shape. This provides a stable base enabling the sleeve to be stood on a surface.
[0042] A slit 24 is cut along the score line 12 at a mid-way point and is arranged to allow the neck or spout 25 of the beverage pouch 22 to pass through the top edge of the sleeve. The neck or spout 25 is provided with a cap 26 , for example a screw cap, that can be removed when the pouch is to be filled and attached to seal and retain the contents within the pouch 22 . The cap 26 can be removed when the contents of the pouch are to be consumed and may be re-attached to re-seal the pouch if the contents are only partially consumed. The slit 24 may be configured to co-operate with the neck or spout 25 to retain the pouch 22 in the sleeve 2 . For example the neck or spout 25 may be a snap fit in the slit 24 .
[0043] Referring to FIG. 3 , in an alternative embodiment of the invention, the sleeve 2 includes a window 27 in at least one face, for example the front face 6 of the sleeve. The front panel 6 is shaped to mirror the shape of the shaped panel 10 such that, when assembled, the shaped edges of the two panels 6 , 10 define a window allowing the contents of the pouch to be seen.
[0044] In use, the beverage pouch 22 is filled with a selected beverage from a dispensing machine in a retail outlet. The pouch may be filled by hand or automatically. For example the pouch may be fed to a filler head part of an automated pouch filling system where the cap 26 is removed, the beverage dispensed into the pouch and the cap 26 re-attached. The retailer then selects the sleeve 2 corresponding to the selected beverage and slides the sleeve 2 over the filled pouch before handing to the customer. Alternatively, the filled pouch and sleeve may be dispensed in a vending machine.
[0045] The sleeves 2 and pouches 22 may be delivered flat-packed to the retail outlet, which considerably reduces the amount of storage space required. A sleeve 2 can then be erected on site as and when required. Sleeves with a number of different designs, brands or logos printed can be stored, to correspond with the range of beverages offered by the retailer. This system allows the beverages to be stored in chilled dispensers and dispensed as required, which is much more economical in the amount of storage space required than pre-filled bottles in refrigerated cabinets. This therefore reduces the amount of energy required to chill the beverages and allows a greater range of beverages to be stocked.
[0046] Referring to FIGS. 4 and 5 , in an alternative embodiment of the invention, the sleeve 102 comprises a front panel 106 attached along its bottom edge defined by a score line 114 to a rectangular base panel 112 , which in turn is joined along a score line 116 to a back panel 104 . The front and back panels are shaped to have curved sides, curved inwardly from the base to substantially halfway along the length of the panel and then outwardly towards the top. This shaping makes the assembled sleeve more comfortable to hold. The front and back panels are folded about the score lines to extend upwards from the base 112 .
[0047] Two side panels 108 , 110 extend from either side of the front panel 106 and are arranged to fold about score lines 117 . The side panels are shaped to correspond with the shaping of the front and back panels and come to a point at the top. The base edges of the side panels 108 , 110 correspond to the side edges of the base panel 112 and, when assembled, tabs 118 extending from the base of the side panels are secured to the base panel 122 by adhesive or other suitable means. The solid base 112 provides a stable sleeve that can be stood on a surface.
[0048] Tab portions 120 also extend from each of the side panels 108 , 110 and are arranged to fold about score lines 123 . Tabs 122 are arranged to interlock to form a back portion. The back panel 104 is then folded up behind the interlocking tabs, concealing them.
[0049] A flap 124 extends from the top of the back panel 104 , is folded over the top of the sleeve about score line 126 , and is secured to the front panel 106 by adhesive or other suitable means. This secures each of the panels in their place, forming a box-like sleeve 102 . A hole 128 is cut along score line 126 between the back panel 104 and the flap 124 to allow the neck or spout of a beverage pouch to project outside of the sleeve 102 for attaching the cap.
[0050] In use, a beverage pouch is filled with a selected beverage as described above and inserted into the appropriate sleeve 102 . In this embodiment, the sleeve may be supplied assembled with an unfilled pouch within the sleeve and a beverage may be dispensed into the pouch through the neck or spout extending through the hole 128 in the sleeve with the cap removed and the cap attached to seal and retain the product in the pouch. Alternatively, the sleeve may be supplied unassembled and is assembled around a filled or unfilled pouch or may be supplied partially assembled, the pouch filled and placed into the partially assembled sleeve, and the remainder of the sleeve assembled around the pouch. For example, the flap 124 may be left open to allow the pouch to be inserted into the sleeve 102 before securing the flap 124 to the front panel 106 by adhesive or other suitable means.
[0051] In addition to reducing storage space, the sleeve acts as a thermal insulator trapping a layer of air between the beverage pouch and the sleeve. This allows both hot and cold drinks to be dispensed into the pouch and handled safely. The cardboard may be corrugated to further improve the insulation provided by the sleeve.
[0052] Cardboard is easily compressed and this allows more viscous products such as ice cream or milkshake to be dispensed into the pouch and squeezed out. The use of the pouch, which is enabled by the sleeve, is also more hygienic since there is limited handling and no oxidisation and also minimises the risk of carbonated drinks going flat. Furthermore, the production of waste is minimised and the cost of packaging production is competitive.
[0053] Dispensing beverages on site also provides the retailer with a higher profit. It will be appreciated that the sleeves can be produced in a range of sizes, to accommodate pouches of varying portion sizes. For example, pouches may be 150 ml, 200 ml, 330 ml, 400 ml, 1 litre, 3 litres or any other suitable size. The sleeves may also be produced in a variety of shapes. The shape may be distinctive of the type of beverage contained within the pouch or of the brand of the beverage.
[0054] It will also be appreciated that the sleeve may be used in combination with pouches of a variety of different shapes, sizes and materials. Furthermore, the pouches may comprise one of a number of different closing means, for example a screw cap, a sports cap or a seal. Alternatively, the pouch may comprise an opening means that is independent of an opening used for filling the pouch, such as a punch hole for use with a straw.
[0055] The invention has application for packaging and serving alcoholic and non-alcoholic drinks. Alcoholic drinks may include beer, lager, cider, wine, alcopops such as Bacardi Breezer®, Smirnoff Ice®, spirits and combinations of a spirit and mixer, for example gin and tonic. Non-alcoholic drinks may include still or carbonated water with or without additional flavourings, fruit juices, fruit drinks such as J20®, and other hot or cold drinks. Beverages may have a range of viscosities from low viscosity products such as liquids to high viscosity semi-solid or paste-like products such as milkshakes. Both alcoholic and non-alcoholic drinks may be provided with an ice content either formed from the drink itself or by mixing ice or an ice slurry with the beverage. An ice content may be formed from the drink itself by freezing the drink in a freeze cylinder or similar apparatus or by dispensing the drink in a super-cooled condition and subjecting it to a shock by ultrasonics or other suitable means such as injection of carbon dioxide gas or other additive that will cause a phase change creating ice in the drink.
[0056] It will be understood that the invention is not limited to the embodiment above-described. For example, the sleeve may be pre-printed with product specific information for selection and use of the appropriate sleeve when dispensing a beverage. Alternatively, the sleeve may be blank or pre-printed with non-product specific information and the product specific information applied to the sleeve when the beverage is dispensed. For example the product specific information may be printed on the sleeve or on a label to be attached to the sleeve. In some applications of the invention, the sleeve may be omitted and the product specific information applied to the pouch, for example by printing on the pouch or printing a label to be attached to the pouch.
[0057] Although the invention has particular application to beverages, it may also be used to package and serve other flowable bulk materials, including food products such as soups, ice cream, sorbet which may vary from a low viscosity to a high viscosity.
[0058] Other applications of the invention will be apparent to those skilled in the art.
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A packaging sleeve for a beverage pouch having a spout through which the pouch can be filled and a removable cap for closing the spout until it is desired to consume the beverage. The sleeve is configured to define a cavity arranged to receive the pouch so that the spout projects from the sleeve at one end and the sleeve is capable of standing unsupported on a surface at the other end while the pouch is supported in the sleeve. The sleeve is flexible to allow the pouch to be squeezed while consuming the beverage.
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FIELD OF THE INVENTION
The present invention relates generally to the field of spray dispensers, and specifically to electric-powered automatic dispensers.
BACKGROUND OF THE INVENTION
Certain products such as insecticides and air fresheners are commonly supplied in pressurized containers. The contents of the container are usually dispensed to the atmosphere by pressing down on a valve at the top of the container. The contents of the container are consequently emitted through a channel in the valve.
In many cases it is desired that the contents of the container be automatically dispensed periodically. Many automatic dispensers are known in the art.
A first type of automatic dispenser includes dispensers with mechanical means, such as an arm, which periodically presses the valve of the container. Such dispensers are described, for example, in U.S. Pat. Nos. 4,184,612, 3,739,944, 3,543,122, 3,768,732, 5,038,972 and 3,018,056. However, these dispensers cannot accurately control the output of the container, since the valve and the contact of the dispenser with the valve are not accurately controlled by the dispenser. Also these dispensers are generally not portable and are fit for use only with containers of a specific size. The valves are also susceptible to failure because of valve sticking, resulting in complete discharge of the contents of the container within a short period.
Another type of automatic dispenser employs a solenoid, which is periodically energized in order to emit a burst of the contents of the container. Such dispensers are described, for example, in U.S. Pat. Nos. 4,415,797, 3,351,240 and 3,187,949. These dispensers require substantial electrical power, and are dependent on gravity and/or the fluid pressure in the container for successful operation.
A third type of automatic dispenser is described, for example, in U.S. Pat. No. 5,447,273. In this automatic dispenser the pneumatic pressure of the container is used to operate a timing device causing the contents of the container to be periodically dispensed. However, the ability to control the dispensation intervals is complicated and limited due to the pneumatic characteristic of the timing device.
Automatic dispensation from non-pressurized containers is described, for example, in U.S. Pat. No. 5,449,117.
SUMMARY OF THE INVENTION
It is an object of some aspects of the present invention to provide an automatic spray dispenser, which allows accurate control of the amount of discharged material. Therefore, it is possible to use the dispenser with materials which require dispensing in accurate quantities.
It is a further object of some aspects of the present invention to provide an automatic spray dispenser which allows flexibility in setting the frequency of dispensation.
It is yet another object of some aspects of the present invention to provide an automatic spray dispenser which is compatible with a large variety of containers.
It is yet another object of some aspects of the present invention to provide an automatic spray dispenser which is compact and portable.
It is yet another object of some aspects of the present invention to provide an automatic spray dispenser which is operationally reliable.
It is yet another object of some aspects of the present invention to provide an automatic spray dispenser which is of a simple construction.
It is yet another object of some aspects of the present invention to provide an automatic spray dispenser which has low energy consumption.
In accordance with preferred embodiments of the present invention, there is provided a spray dispenser which can be mounted on a large variety of pressurized containers, for dispensing aerosol materials and other fluids. Such containers typically have a built-in valve, which is actuated by being pressed down. The spray dispenser is firmly attached to the container, whereupon the valve of the container is kept constantly open by an actuator.
Preferably, the valve is continuously depressed by a corresponding plunger in the dispenser. Preferably, the plunger is an integral part of the dispenser. Alternatively or additionally, the plunger is a separate unit which accommodates the dispenser to the container. Thus, the valve is held constantly open, but the dispenser prevents the contents of the container from being released. This feature enables the dispenser to operate substantially independently of any particular characteristics of the container, and it is possible to employ the dispenser of the present invention with a large variety of standard and non-standard containers. The dispenser includes an outlet which controllably releases portions of the contents of the container according to predefined or user actuated instructions.
Preferably, the dispenser allows automatic periodic dispensing of the spray. The amount of spray emitted at each period is preferably controlled by setting the time in which the outlet is open.
In some preferred embodiments of the present invention, the dispenser comprises an electric circuit, preferably including a microprocessor, which controls the release of material from the container, according to predetermined settings, preferably set by a user. Preferably, the settings include the interval between dispensations and the duration of each dispensation. Alternatively or additionally, the dispenser includes an operation switch for selecting among constant/periodic/off modes of operation. Further preferably, the dispenser can be programmed to have different frequencies of operation at different times. For example, an insecticide may be dispensed in an office during nights before work days at a first rate, while during nights before holidays the insecticide is dispensed at a second rate.
In some preferred embodiments of the present invention, a photoelectric cell is coupled to the microprocessor, to change the operation mode of the dispenser between day and night modes of operation. The microprocessor may be further coupled to a thermostat, wind sensor or any other required sensors, such as sensors of “MEMS” (Micro-Electro-Mechanical-Systems) technology, so as to operate the dispenser in response thereto. In one such preferred embodiment, the dispenser has a plug for connecting to external sensors and/or remote controls.
In some preferred embodiments of the present invention, the dispenser actively opens and closes the controlled outlet, so that its operation is not dependent on gravity or on the pressure within the container. Thus the dispenser may be positioned in any orientation without causing problems in its operation.
In some preferred embodiments of the present invention, the dispenser has an open state in which a fluid is emitted from the dispenser, and a closed state in which the fluid is prevented from leaving the dispenser. The dispenser substantially does not consume energy during the open and closed states, and consumes energy only during transition between the open and closed states.
In preferred embodiments of the present invention, the dispenser comprises a motor, which applies rotational movement in order to dispense material from the dispenser. The use of rotational, rather than linear, movement generally requires less energy and allows better control of the dispenser. The use of a motor requires energy only when opening and closing the outlet, whereas a solenoid continuously requires energy in order to dispense the material in the container.
Preferably, the dispenser is assembled in a simple manner without use of screws, in order to reduce the cost and skill required for assembly. Further preferably, the dispenser does not include gears or cams, so that accurate sizing and placement is not required in the manufacturing process.
Preferably, the spray dispenser is battery-operated and contains within it batteries which supply operation power. Preferably, the batteries are packed in an easily replaceable battery power pack. Most preferably, the batteries are rechargeable, and may be recharged within the dispenser, while the dispenser is in use, for example, using a car battery, an AC electric supply, a solar power cell or any other suitable power source. Alternatively or additionally, the dispenser may operate directly on power received from a car battery or from an AC electric supply and, preferably, contains a transformer suitable for connecting to a local electric line. In addition to the battery or AC power, or as an alternative thereto, the dispenser may receive power from a solar cell, so that it may be placed in remote areas, without any wired connection and without the necessity of replacing its power supply. In some preferred embodiments of the present invention, the microprocessor has a separate power supply from the power supply of the motor, so that short failures in the main power supply do not erase the time settings of the microprocessor. The power supply of the microprocessor is preferably a miniature battery, such as used for example in electric watches.
In some preferred embodiments of the present invention, the outlet of the dispenser comprises an orifice which allows attachment of a large variety of different orifice heads thereto. Such orifice heads may include nozzles of various dispersion properties, for example, wide-range heads for covering large angles at a close range, long-range orifice heads, and curved orifice heads which preferably turn in response to emission of the spray, to cover a wider area. Other orifice heads may also be used, including moisture heads, illumination heads, whistle heads and flame heads. The orifice heads may have various orifice sizes, including small diameters which may achieve a directional force sufficient to mechanically move an object, such as a switch.
Dispensers in accordance with the present invention may be used in conjunction with containers of a wide variety of materials, including, but not limited to, sterilizers, insecticides, deodorants, smoke absorbents, colored smoke, oil, glue (for example, for use on factory production lines), fuels (which are periodically sprayed into a furnace or engine, for example), gases (including air), paints, fire extinguishers, cleaning materials and water. Whereas prior art dispensers are unsuitable or unsafe to use with certain materials that are considered harmful at large concentrations, such as insecticides, the dispenser of the present invention allows very small quantities of such materials to be dispensed at a high accuracy. This accuracy is achieved partially due to the feature that as the dispenser holds the valve of the container constantly open, the emission of the contents of the container is controlled solely by the dispenser. In addition, the rotational movements of the motor cause the speed at which the dispenser is opened and closed to be fast and precisely defined. Therefore, dispensers in accordance with preferred embodiments of the present invention can be used to dispense insecticides and other materials in rooms occupied by humans, animals or delicate plants, with fewer restrictions than may be required by prior art dispensers.
In preferred embodiments of the present invention, adapters are provided for connecting the dispenser to containers of various sizes, shapes, structures and positions and to containers having valves of various sizes. Preferably, such adapters fit between the valve and the dispenser, forming an airtight connection therebetween. Furthermore, adapters may also be provided for connecting the dispenser to containers which do not have valves of their own.
In some preferred embodiments of the present invention, a hose adapter is used to connect between the container and the dispenser. At one end the hose adapter has a connector which fits the container. The connector may either include a plunger, as described above, which fits on standard valves or any other suitable fitting. On its other end, the adapter has a valve or other fitting for connecting to the dispenser. Use of such a hose adapter allows placement of the dispenser at a high or otherwise inaccessible location, while dispensing material from a large container positioned on a lower surface. Furthermore, the hose adapter may be connected to a multiplicity of containers and/or to a multiplicity of dispensers.
It is noted that the fluid in the containers of preferred embodiments of the present invention may be pre-pressurized or may be pressurized each time it is desired to extract the fluid. For example, the motor of the dispenser may be used to pressurize the contents of the container each time it extracts fluid from the dispenser.
Dispensers in accordance with other preferred embodiments of the present invention may also be utilized to periodically emit accurate amounts of material from non-pressurized containers. For example, such a dispenser may be used to water plants with a water container placed with its orifice facing down. A fertilizer or other nutrient may be mixed with the water, as is known in the art. Alternatively, an air pressure supply or a container of pressurized air or other gas may be used along with a Venturi jet to emit the contents of one or more non-pressurized containers.
Although in the above embodiments the dispenser is described as forming a unit separate from the container, it will be appreciated by those skilled in the art that the dispenser may be designed to fit a specific container or may be formed as part of a container.
There is therefore provided in accordance with a preferred embodiment of the present invention, a dispenser for attachment to a container containing a fluid material, including:
an actuator which keeps the container in a substantially constantly open configuration so as to allow the fluid to pass into the dispenser; and
a controllable outlet, through which a portion of the fluid is emitted from the dispenser, substantially independent of the fluid pressure in the container.
Preferably, the fluid material in the container is pressurized or non-pressurized.
Preferably, the size of the emitted portion is controlled by varying an amount of time in which the controllable outlet is in an open state.
Preferably, the dispenser has an open state in which the fluid is emitted from the dispenser, and a closed state in which the fluid is prevented from leaving the dispenser, and the dispenser consumes energy substantially only during transition between the open and closed states.
Preferably, the dispenser includes an electric motor which controls passage of the portion of the fluid through the outlet.
There is further provided in accordance with a preferred embodiment of the present invention, a dispenser for attachment to a container containing a fluid material, including:
an actuator, which keeps the container substantially constantly in an open configuration so as to allow the fluid to pass into the dispenser; and
an electric motor, which opens the dispenser so that fluid is emitted therefrom and closes the dispenser to prevent the fluid emission.
Preferably, the motor is battery operated and/or is connected to an electric line.
Further preferably, the motor opens and closes the dispenser by a rotational movement.
Preferably, the container has a valve, and the dispenser has a bore therethrough, which receives the fluid from the valve; the bore including a first part having a first inner diameter and a second part having a second inner diameter, larger than the first inner diameter, wherein the dispenser includes:
a hollow shaft, axially movable within the bore, the shaft having a hole disposed along the length thereof such that when the hole is positioned in the first part of the bore, the fluid does not pass through the shaft, and when the hole is in the second part of the bore, the fluid passes through the shaft and is emitted from the dispenser.
Preferably, the dispenser includes a lever connected to the shaft, such that the shaft is axially moved by the lever.
Further preferably, the dispenser includes a screw which drives the lever, and the lever includes an internal thread for receiving the screw.
Preferably, the outlet includes an orifice through which the material is emitted, and the size of the orifice is not substantially smaller than the size of the hole, so that a gas leaving the container does not expand within the dispenser.
Preferably, the dispenser operates substantially without dependence on gears or cams.
Preferably, the container has a valve and the actuator includes a plunger which depresses the valve. Alternatively or additionally, the actuator includes a hose.
Preferably, the dispenser includes a processor which periodically actuates emission of the fluid.
Further preferably, the dispenser includes a user interface for controlling the operation of the dispenser.
Preferably, the processor is programmed to actuate different emission durations at different times.
Preferably, the dispenser includes an adapter for attaching the dispenser to different types of containers.
There is further provided in accordance with a preferred embodiment of the present invention, a dispensing container including:
a can containing a fluid;
a dispenser head which has an open state in which the fluid is emitted from the can and a closed state in which the fluid is not emitted; and
a motor which changes the state of the dispenser head between the open and closed states.
Preferably, the dispenser head has a bore therethrough, which receives the fluid from the can, the bore comprising a first part having a first inner diameter and a second part having a second inner diameter, larger than the first inner diameter, wherein the dispenser head includes:
a hollow shaft, axially movable within the bore, the shaft having a hole disposed along the length thereof such that when the hole is positioned in the first part of the bore, the fluid does not pass through the shaft, and when the hole is in the second part of the bore, the fluid passes through the shaft and is emitted from the dispenser head.
Preferably, the dispenser is portable.
In a preferred embodiment, the fluid is dispensed to water a plant.
In other preferred embodiments, the fluid includes a deodorant, an insecticide, and/or a smoke-producing material.
In a preferred embodiment, the dispenser includes a horn mounted on the dispenser so as to make a sound when the fluid is emitted.
Preferably, the fluid is emitted as an aerosol.
Preferably, the dispenser includes a hanger for hanging the dispenser such that the dispenser is free to turn. There is further provided in accordance with a preferred embodiment of the present invention, a cooling device including:
an insulating case;
a pressurized gas container; and
a dispenser, arranged to periodically emit the gas from the container into the case in order to cool the interior of the case.
Preferably, the device includes a one-way valve for emitting excess gas from the case.
Preferably, the excess gas emitted from the case includes gas that is generally warmer than an average temperature of the gas in the case.
Preferably, the excess gas emitted from the case includes gas that has been in the case for a generally longer period than most of the gas in the case.
Preferably, the insulating case includes passages and the gas emitted from the container leaves the case substantially only through the passages.
Preferably, the dispenser is fixed to the container such that the container is in a substantially constantly open position, allowing the gas to pass into the dispenser, and the dispenser emits the gas substantially independently of the gas pressure in the container.
Preferably, the dispenser includes an electric motor which drives the dispenser to emit the gas by rotational movements of the motor.
Preferably, the device includes a thermostat which actuates emission of the gas.
There is further provided in accordance with a preferred embodiment of the present invention, a method for dispensing a material from a container having a valve, including:
fixing a dispenser to the container, such that the dispenser holds the valve in a substantially constantly open position, so as to allow the material to pass into the dispenser; and
emitting the material from the dispenser substantially independently of the pressure of the material in the container.
Preferably, fixing the dispenser to the container includes fixing the dispenser to a container containing a pressurized material.
Preferably, the dispenser includes an electric motor, and emitting the material includes actuating the motor so as to cause the material to be emitted.
Further preferably, actuating the motor includes driving a rotational movement using the electric motor.
Preferably, emitting the material includes emitting the material periodically.
Further preferably, emitting the material includes emitting the material at a first rate during a first period and emitting the material at a second rate during a second period.
Alternatively or additionally, emitting the material includes emitting the material in response to an external signal.
Preferably, emitting the material includes emitting the material in response to a signal received from a sensor. Preferably, emitting the material includes emitting an aerosol.
Alternatively or additionally, emitting the material includes emitting a deodorant.
Alternatively, emitting the material includes emitting an insecticide.
Alternatively or additionally, emitting the material includes emitting smoke.
Further alternatively, emitting the material includes watering a plant.
Preferably, the method includes hanging the dispenser such that it is free to turn.
Preferably, emitting the material includes bringing the dispenser from a closed state to an open state in which the material is emitted from the dispenser, and wherein the dispenser consumes energy substantially only during transition between the open and closed states.
There is further provided in accordance with a preferred embodiment of the present invention, a method of maintaining a concentration level of a material within an area including:
receiving a signal from a sensing device, in response to the level of the material in the area; and
setting an automatic dispenser mounted on a container of the material to operate responsive to the sensor.
Preferably, setting the dispenser includes setting the dispenser to operate when the level is beneath a predetermined level.
Preferably, the material includes oxygen.
There is further provided in accordance with a preferred embodiment of the present invention, apparatus for maintaining a concentration level of a material within an area, including:
a container containing the material;
a sensor which senses the concentration of the material within the area and generates signals responsive to the concentration; and
an automatic dispenser mounted an the container which dispenses the material in response to the signals from the sensor, wherein the apparatus operates substantially independently of any wired or fluid communication with elements other than the sensor, container and dispenser. Preferably, the sensor generates signals responsive to a concentration below a predetermined level.
There is further provided in accordance with a preferred embodiment of the present invention, a method of maintaining a low temperature in a volume including controlling an automatic dispenser to automatically emit a gas from a pressurized gas container into the volume.
Preferably, directing the dispenser includes setting the dispenser to periodically emit the gas.
Alternatively or additionally, directing the dispenser includes directing the dispenser to emit the gas responsive to a temperature sensor.
Preferably, the gas includes air.
Preferably, the method includes emitting excess gas from the volume which is generally warmer than an average temperature of the gas in the volume.
Preferably, the method includes emitting excess gas from the volume which gas has been in the volume generally for a longer period than most of the gas therein.
There is further provided in accordance with a preferred embodiment of the present invention, a method of pest control including:
mounting an automatic dispenser having a horn head on a pressurized gas container; and
operating the dispenser automatically to periodically emit a portion of the gas in the container so as to operate the horn.
Preferably, periodically emitting the gas includes emitting gas in response to detection of a pest
Preferably, periodically emitting the gas includes emitting gas so as to cause movement disturbing to the pest.
The present invention will be more fully understood from the following detailed description of the preferred embodiments thereof, taken together with the drawings, in which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic perspective view of an automatic dispenser in operation, attached to a container, in accordance with a preferred embodiment of the present invention;
FIGS. 2-4 are schematic perspective views of the dispenser of FIG. 1 with various mounting devices, in accordance with preferred embodiments of the present invention;
FIG. 5 is an exploded perspective view of the dispenser of FIG. 4;
FIG. 6 is a schematic cross-sectional view of the dispenser of FIG. 4 in a closed position;
FIG. 7 is a perspective, partly sectional view of the dispenser of FIG. 4, in the closed position;
FIG. 8 is a schematic cross-sectional view of the dispenser of FIG. 4 in an open position;
FIG. 9 is a perspective, partly sectional view of the dispenser of FIG. 4 in the open position;
FIG. 10 is a schematic view of a dispenser which operates on a remote container, in accordance with a preferred embodiment of the present invention;
FIG. 11 is a perspective view of a scarecrow utilizing an automatic dispenser, in accordance with a preferred embodiment of the present invention;
FIG. 12 is a schematic view of a dispenser with a Venturi jet, in accordance with a preferred embodiment of the present invention;
FIG. 13 is a perspective view of a cooler utilizing an automatic dispenser, in accordance with a preferred embodiment of the present invention;
FIG. 14 is a perspective view of a cooler utilizing an automatic dispenser, in accordance with another preferred embodiment of the present invention; and
FIG. 15 is a schematic diagram illustrating air flow in the cooler of FIG. 14, in accordance with a preferred embodiment of the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
FIG. 1 shows an automatic dispenser 20 mounted on a pressurized aerosol container 22 , in accordance with a preferred embodiment of the present invention. Dispenser 20 dispenses a material held in the container via an orifice head 38 , which may include a dispensing tube 37 . Dispenser 20 controls the dispensation of the contents, which are preferably dispensed periodically according to user settings. A control panel 30 is preferably situated on a top side of dispenser 20 , to receive user settings of the dispenser's operation, including the frequency of dispensations and the duration of each dispensation. Preferably, the frequency of dispensation may be between once every few seconds to once every few days. Alternatively or additionally, dispenser 20 is operated by an external signal originating, for example, from a sensor or a factory line control.
Preferably, dispenser 20 has three switches 32 , which allow easy selection of the operation settings by the user. In a preferred embodiment of the present invention, a first switch sets the dispensation duration in tenths of seconds; a second switch selects the units in which the interval between durations is measured, e.g., seconds, minutes, hours, days or weeks; and a third switch sets the length of the interval in the selected units. Preferably, the second switch allows choosing other modes of operation including external control, off, constant and a test mode. It is noted that other controls, including various switches and displays, may also be used to set the dispensation timings, as is known in the art.
In some preferred embodiments of the present invention, a wide base 39 is attached to container 22 when it is to be placed on the ground or on another surface. Base 39 prevents container 22 from moving when the material is dispensed therefrom at a high rate. Alternatively, dispenser 20 may be fixed to a pole or wall to prevent turning thereof, as shown for example in FIG. 2 .
FIGS. 2-4 show dispenser 20 with various mounting devices therefor, in accordance with a preferred embodiment of the present invention. It is noted that other mounting methods may be used, including methods allowing dispenser 20 to rotate in various patterns as applied, for example, in the sprinkler industry.
In a preferred embodiment of the present invention, shown in FIG. 2, dispenser 20 is mounted by a fixed holder 33 having a receiving groove 27 which firmly holds a slit 49 located in dispenser 20 close to orifice head 38 . Thus, dispenser 20 is tightly held and prevented from rotating.
FIG. 3 shows another preferred embodiment of the present invention, in which dispenser 20 is mounted on a rotating hanger 31 which rotates together with the dispenser.
In a preferred embodiment of the present invention, shown in FIG. 4, dispenser 20 is hung on a hanger 34 in a manner allowing free turning of the dispenser and container relative to the surroundings. Dispensing tube 37 is bent so that when the contents of container 22 are emitted, dispenser 20 revolves around its axis preferably in the direction of arrow 29 , and the contents of the container are distributed all around the dispenser.
It is noted that the methods of mounting dispenser 20 described above are shown by way of example and other accessories may be used, including hooks, and double sided tape depending on the specific purpose for which dispenser 20 is used. Preferably, the accessories allow positioning dispenser 20 at any desired orientation, since dispenser 20 may operate in substantially any orientation due to its independence from gravity and other external forces in emitting the material. The descriptors top, bottom, upper, lower, etc., which are used in the following description, refer therefore solely to the orientation of dispenser 20 shown in the figures and are used throughout this description only for the purpose of simplicity.
Dispenser 20 forms an air-tight sealed connection with container 22 , such that the contents of container 22 may be dispensed only through dispenser 20 , as described herein. An elastic metal ring 24 at a bottom end 21 of dispenser 20 fits into a groove 26 at the top of container 22 , securing the connection. The connection is preferably released by pressing on handles 25 (FIG. 5) at the edges of ring 24 . Preferably, the connection is capable of withstanding forces of a magnitude of at least 2-4 kg of force to prevent separation of dispenser 20 from container 22 due to the fluid pressure and or inadvertent external pressure.
When dispenser 20 is in connection with container 22 , a plunger, which is preferably an integral part of the bottom of the dispenser, presses on an opening valve 28 of the container, so that the valve is held constantly in the open position. The material in container 22 and the pressure it exerts are thus controlled by dispenser 20 , which is compatible with a wide variety of spray containers without dependence on their specific characteristics. Preferably, when mounting dispenser 20 on container 22 , the plunger presses on valve 28 only after a leak tight connection is formed between valve 28 and dispenser 20 .
The contents of container 22 enter dispenser 20 at bottom 21 of the dispenser, and leave through an orifice 36 (see FIG. 5) at the top of the dispenser. Orifice head 38 is preferably mounted in orifice 36 to direct the contents leaving the dispenser. Orifice head 38 may have a narrow orifice, suitable for long-range dispensing. Preferably, dispensing tube 37 extends from orifice head 38 leading the contents of container 22 to the surroundings of the dispenser. Alternatively, orifice head 38 may have a wide orifice, suitable for covering a large area at a short range. It will be appreciated that various and other orifice heads, as are known in the art, may be used with the dispenser.
FIG. 5 shows an exploded view of dispenser 20 , in accordance with a preferred embodiment of the present invention. Dispenser 20 comprises a case 100 having a cylindrical shape. Preferably, case 100 has a diameter of about 3.9 cm, and a height of about 10 cm. A top piece 102 containing orifice 36 , fits on top of case 100 . Preferably a bulge 43 in top piece 102 defines an upper bore 58 (see FIG. 6) which leads to orifice 36 . Preferably, two slits 103 are defined in case 100 opposite top piece 102 which are sized and positioned to accept ring 24 .
A battery pack 81 , preferably comprising three standard batteries, fits into case 100 and supplies power for the operation of dispenser 20 . The material from container 22 is conveyed to upper bore 58 and orifice 36 through a lower bore 50 defined by three cylinder bolts 110 , 120 and 122 , and a shaft 52 . Preferably, bore 50 and shaft 52 run along the center of dispenser 20 .
Shaft 52 contains a long, hollow core 116 , which communicates between bore 50 and bore 58 . Core 116 is open at its top end, leading to orifice 36 , but is closed at its bottom end 118 . At least one hole 90 , preferably at least three such holes, leading into a central lumen 104 of hollow core 116 , are situated radially near the bottom of core 116 , preferably a few millimeters from bottom end 118 . An O-ring 55 surrounds and seals core 116 within bore 50 , preferably within top bolt 122 , and prevents leakage of the material from container 22 into the interior of dispenser 20 . An additional O-ring 56 is preferably situated around bore 58 to prevent leakage of the material from the bore to the interior of dispenser 20 . Preferably, bolt 122 has a slightly smaller diameter in an area 121 along its length in which it receives O-ring 55 , so that external pressure does not cause damage to the ring. Preferably, shaft 52 comprises a thick section 92 for manipulation of the shaft. Thick section 92 connects to a lever 70 which manipulates shaft 52 , as is described below.
FIGS. 6 and 7 show dispenser 20 in a closed state, in accordance with a preferred embodiment of the present invention. Bottom bolt 110 of bore 50 serves as the plunger which presses down on valve 28 in order to keep container 22 constantly open. Bottom bolt 110 is shaped and sized to receive valve 28 of container 22 at a lower side 105 of the bolt, such that the contents of the container will flow through valve 28 only into bore 50 . In order to accommodate different sizes of valves 28 , a replaceable adapter 112 may be used to seal the connection between valve 28 and bolt 110 . Alternatively or additionally, bolt 110 may be easily replaced to accommodate the different valves. An O-ring 59 preferably aids in sealing the connection. Preferably, the plunger part of bolt 110 is deep enough within bolt 110 so that valve 28 is pressed only when the valve is sealed within bolt 110 . The contents of container 22 enter bore 50 and do not escape due to the tight fit of valve 28 within bolt 110 . Bore 50 is blocked at its upper end by bottom end 118 of core 116 , which in the closed state is situated within bottom bolt 110 . An O-ring 54 aids shaft 52 in preventing the contents of container 22 from passing from bottom bolt 110 to middle bolt 120 . Preferably, an upper side 114 of bottom bolt 110 has an inner diameter which tightly receives core 116 of shaft 52 .
Top bolt 122 preferably has an inner diameter of about the same size as that of upper side 114 of bottom bolt 110 , and likewise prevents leakage of the contents of container 22 when shaft 52 is within the bolt. Preferably, shaft 52 is always held within top bolt 122 , although at varying heights, preventing the aerosol from escaping bore 50 through top bolt 122 , into case 100 .
Middle bolt 120 , has an inner diameter larger than the outer diameter of core 116 . The larger inner diameter defines a cavity 88 which allows passage of the fluid, as is described below. Thus, the fluid entering bore 50 can exit the bore only through holes 90 into central lumen 104 of shaft 52 . However, the fluid enters lumen 104 only when holes 90 are within middle bolt 120 , due to the larger inner diameter of bolt 120 .
Preferably, bottom bolt 110 , middle bolt 120 and top bolt 122 are held within a channel 130 in case 100 . Channel 130 keeps the bolts defining bore 50 tightly in place. Preferably, an O-ring 57 prevents bolt 110 from sliding within channel 130 . Alternatively or additionally, one or more of bolts 110 , 120 and 122 may be formed as an integral part of channel 130 .
Lever 70 is connected on one side to section 92 of shaft 52 and on the other side to a screw 74 , which is coupled to a motor 76 . When dispenser 20 is to be moved between open and closed states, motor 76 rotates screw 74 , and lever 70 is moved from one end of screw 74 to the other. Thus, the distance which lever 70 moves together with shaft 52 is determined by the length of screw 74 , and there is no need to precisely control the number of turns rotated by motor 76 . Precise control of the number of rotations of motor 76 requires relatively expensive apparatus that may be too large for a small dispenser. Stoppers may be used at either end of screw 74 to allow precise control of the distance of movement. The stoppers preferably comprise a suitable non-stick material in order to minimize the possibility of locking of the lever against the stopper.
Preferably, screw 74 is slightly longer than the maximum distance allowed for movement of shaft 52 between the open and closed states. The extra length is compensated for by flexibility of lever 70 , which bends slightly and leans on screw 74 at both open and closed states. Alternatively, screw 74 is substantially longer than the allowed distance, and section 92 serves as a stopper and prevents movement beyond the maximum allowed distance, when section 92 meets the lower surface of top piece 102 . Preferably, section 92 includes a slot 94 for receiving lever 70 . Lever 70 comprises a collar 72 , having approximately one turn of an internal thread, which receives screw 74 . Alternatively, the side of lever 70 which fits on screw 74 comprises a step the size of about half a turn of a thread of screw 74 , which easily fits on the screw. Preferably, collar 72 is flexible and large enough to leave leeway, so as not to require accurate fitting of screw 74 to the collar. In both the closed and open states of dispenser 20 , collar 72 is situated at a respective end of screw 74 and exerts a slight bend pressure on the screw. Thus screw 74 reliably enters collar 72 , and there is substantially no risk of collar 72 not fitting back on screw 74 . Preferably, lever 70 comprises a non-abrasive plastic or any other material having similar characteristics.
Motor 76 preferably comprises a standard DC motor, whose shaft rotates screw 74 . Alternatively, motor 76 may operate on AC power. Motor 76 is controlled by a processor 78 , which operates according to the user's settings on control panel 30 . Processor 78 and motor 76 preferably receive power from batteries 80 within dispenser 20 . Alternatively or additionally, dispenser 20 is connected to a local electric line supply. Further alternatively or additionally, processor 78 receives power from a miniature battery separate from the power supply of the motor. As long as motor 76 is not operated, lever 70 does not move and prevents shaft 52 from moving under pressure from container 22 .
FIGS. 8 and 9 illustrate dispenser 20 in the open position, in accordance with a preferred embodiment of the present invention. When dispenser 20 is to release a spray of aerosol, processor 78 actuates motor 76 . Motor 76 rotates screw 74 clockwise (as indicated by an arrow 79 ) causing lever 70 to elevate relative to screw 74 and reach the top of screw 74 . Shaft 52 is lifted by lever 70 such that its bottom end 118 is located within enlarged cavity 88 in bore 50 . At this stage, the pressure of container 22 pushes some of its contents into cavity 88 . Hole 90 allows the contents to enter hollow shaft 52 and consequently to move out to the atmosphere, through orifice 36 at the top of dispenser 20 .
After the spray has been dispensed for a predetermined time, processor 78 actuates counter clockwise operation of motor 76 , indicated by an arrow 73 , shown in FIG. 7, so as to lower lever 70 . Lever 70 pushes shaft 52 back to the closed state shown in FIGS. 6 and 7, and thus hole 90 is resealed in bottom bolt 110 . Preferably, the movements of screw 74 from one state to another require less than 0.1 seconds. In the closed state, bent lever 70 aids in prevention of shaft 52 from moving.
The force exerted by the pressure of container 22 on shaft 52 is equal to the cross-sectional area of the inner channel in shaft 52 times the pressure of the container. In a preferred embodiment of the present invention, shaft 52 has an inner diameter of about 1.5 mm and the contents of container 22 are generally pressurized to about 5 atmospheres, so that the force exerted is approximately 90 grams of force. The force required to seal the container is about 0.2
kg of force and the force applied by motor 76 to open/close dispenser 20 is preferably approximately between 0.4-0.5 kgs of force. In comparison pressing on the valve to open the container, would require a force of about 2.5 kgs of force. Thus, dispenser 20 generally consumes much less energy than dispensers known in the art. It is noted that the force applied by motor 76 can be adjusted by changing the length of screw 74 and/or the thickness of lever 70 .
The use of rotational movement to move shaft 52 allows the elements of dispenser 20 to be manufactured with relatively low precision. Thus, it is not necessary to use fine mechanical pieces for screw 74 and lever 70 . Also, dispenser 20 does not require gears and cams, which complicate the mechanism and require more accurate design and manufacture.
Preferably, hole 90 (or the aggregate of the plurality of such holes) and orifice 36 have approximately the same cross-sectional area. As gas is known to cool upon expansion, this sizing relation will allow gas entering cavity 88 to exit orifice 36 without freezing inside dispenser 20 .
Container 22 may contain any of a large variety of liquids or gasses including, for example, air, oxygen, fuels, water, oils, sterilizers, cleaning materials, insecticides and deodorants. It is noted that some poisonous materials and fuels must be emitted in small and accurate amounts in order to prevent damage. Therefore, these materials could not generally be used in prior art dispensers. This limitation is overcome by preferred embodiments of the present invention which emit accurate amounts of material and therefore allow use of these materials.
In the above preferred embodiment, dispenser 20 comprises a plurality of parts which are connected together without requirement of screws. For example, slots 106 in battery pack 81 , shown in FIG. 5, facilitate such connection. This embodiment allows easy production and assembling of the dispenser. However, it will be clear to those skilled in the art that the dispenser may comprise fewer or more parts, which may be connected in various manners. For example, as mentioned above, bore 50 may comprise only one piece instead of channel 130 , and separate bolts 110 , 120 , and 122 . Also top piece 102 may be manufactured as part of case 100 .
In a preferred embodiment of the present invention, not shown in the figures, the orifices of a plurality of dispensers 20 are connected in parallel through a common hose to a single emitting opening. Preferably, dispensers 20 are mounted on containers holding different materials and are operated at the same time, mixing the materials together. Alternatively, the dispensers may have different time settings, such that the same opening emits different materials at different times.
In another preferred embodiment of the present invention, also not shown in the figures, dispenser 20 comprises a refill inlet which allows easy refilling of container 22 . FIG. 10 is a schematic illustration showing a dispenser 180 , which operates on a remote container 22 , in accordance with a preferred embodiment of the present invention. A hose 184 connects between container 22 and dispenser 180 . Hose 184 comprises at a first end thereof a connector 186 , which engages valve 28 of container 22 . Preferably, connector 186 is similar to bottom end 21 of dispenser 20 and may include a ring, similar to ring 24 shown in FIG. 1, which strengthens the connection between hose 184 and container 22 . Dispenser 180 is connected to the other end of hose 184 by means of any tube connection known in the art. The use of hose 184 allows the dispenser to be placed in locations where it is not feasible to place container 22 . Thus, it is possible to place large containers 22 in a storage area, while only dispenser 180 is placed in a dispensing area. In a preferred embodiment of the present invention, a plurality of dispensers 180 are connected to container 22 . Alternatively or additionally, a plurality of containers 22 are connected to one or more dispensers 180 via a single hose 184 . Such a set-up provides reliable supply of the contents of container 22 even when one container is empty.
In a preferred embodiment of the present invention, container 22 contains an insecticide, and dispenser 20 is positioned in mosquito habitats, gardens, greenhouses, or any other location where it is desired to periodically spray against insects. Dispenser 20 is set to operate periodically, for example, once a week, to automatically dispense a quantity of insecticide from within container 22 . Preferably, dispenser 20 is covered by a protective plastic which protects it from weather hazards. Dispenser 20 is preferably positioned before the appropriate season, and container 22 contains sufficient material so that it is not necessary to return for refilling until the next season. Using automatic insecticide dispensation is especially advantageous in those areas where access is difficult and/or costly.
FIG. 11 shows an automatic scarecrow 220 , in accordance with a preferred embodiment of the present invention. Scarecrow 220 comprises a pressurized gas container 22 with a dispenser 20 mounted thereon, as described above.
A horn orifice head 222 is mounted on dispenser 20 , so that every time dispenser 20 is operated, a burst of gas is emitted causing a noise which scares off birds and other unwanted creatures. Horn orifice head 222 may comprise a simple horn, a whistle, a siren, a rattle, a kazoo, or any other suitable sound maker. Preferably, the gas includes an insecticide which eliminates insects which may attract the birds. A protective shield 226 preferably covers dispenser 20 and protects it from weather hazards. In a preferred embodiment of the present invention, the gas emission also causes ribbons 224 to wave, so as to enhance the effect on the birds. Alternatively, an additional dispenser may be used to cause the ribbons to wave, or produce other moving effects. Scarecrow 220 may be positioned near fish ponds, gardens, orchards, runways or any other desired location. In a preferred embodiment of the invention, horn head 222 emits sound mainly at frequencies which are perceived by animals, but not by humans.
In other preferred embodiments of the present invention, dispenser 20 may be positioned within a small doll-shaped scarecrow, preferably mounted on a rotatable hanging device, which is hung on a tree in order to scare off pests from the tree.
In some preferred embodiments of the present invention, dispenser 20 is used to maintain a minimal level of a material in its surroundings. Preferably, dispenser 20 operates responsive to a sensor which measures the level of the material in the surroundings. Each time the level goes below a predetermined threshold, dispenser 20 is operated to emit a quantity of the required material from within container 22 . Specific preferred embodiments include maintaining a required smog (for example, to maintain a desired temperature, as is known in the art) or humidity level, particularly within a greenhouse, or an oxygen level in the proximity of a patient.
FIG. 12 schematically shows one way to use dispenser 20 for humidity control, in accordance with a preferred embodiment of the present invention. Dispenser 20 is mounted on container 22 containing pressurized gas, preferably air. The orifice of dispenser 20 is connected through a Venturi jet 234 to a water vessel 230 . Each time the dispenser operates, water from vessel 230 is sprayed into the surrounding air. Preferably, dispenser 20 is operated responsive to a humidity sensor 232 , in order to maintain a minimal humidity level, or a humidity pattern, within the vicinity of dispenser 20 . Alternatively, the water from vessel 230 may be used to periodically automatically water plants.
FIG. 13 shows a cooler 250 , in accordance with a preferred embodiment of the present invention. Cooler 250 comprises dispenser 20 and container 22 , containing a pressurized gas, preferably air, which upon expansion cools and maintains a low temperature within cooler 250 . Preferably, dispenser 20 is operated periodically at intervals set according to the environmental temperature. Alternatively or additionally, a temperature sensor 252 initiates the operation of dispenser 20 when the temperature within cooler 250 is above a predetermined threshold. Preferably, the air is allowed out of cooler 250 through a one-way valve 254 , which is preferably situated such that the air which leaves cooler 250 is relatively warm air, rather than the cold air which was recently emitted by dispenser 20 . It is noted that cooler 250 may be of a variety of sizes, and may similarly comprise a canteen, for cooling water or another drink.
FIGS. 14 and 15 show a cooler 260 , in accordance with another preferred embodiment of the present invention. Cooler 260 is similar to cooler 250 , but the air flow out of cooler 260 , as illustrated in FIG. 15, is planned particularly so as to enhance the cooling effect of the cold gas from dispenser 20 . Cooler 260 comprises double walls 261 which enclose a passage 262 , which provides thermal insulation. When air is emitted from container 22 into cooler 260 , air is not randomly let out of the cooler, but rather the warmest air, near the top of the cooler is pushed out through passage 262 . Preferably, the air which is in the cooler for the longest period is emitted. This air flow scheme is reinforced by having the path to one-way valve 254 run all through passage 262 .
In other preferred embodiments of the present invention, not shown in the figures, gas in container 22 is used to open and close valves or switches in remote locations or otherwise operate remote systems, for example to automatically launch weather balloons. The use of dispenser 20 as a timing device provides a cheap and reliable method of automatic operation of remote systems, reducing the necessity of access to the system.
In some preferred embodiments of the present invention, not shown in the figures, container 22 contains a fuel, and a flare head is mounted on orifice 36 . A spark generator is preferably coupled to dispenser 20 , so that the flare is lit up each time dispenser 20 is operated.
In another preferred embodiment of the present invention, container 22 contains a fire extinguisher. Dispenser 20 is coupled to a temperature sensor or smoke sensor so as to emit the contents of the container if a fire is detected.
In a preferred embodiment of the present invention, container 22 contains an anti-vaporizing material which is emitted periodically in suitable locations.
In some preferred embodiments of the present invention, container 22 contains tear gas or other noxious material, and functions as an anti-intrusion device. Dispenser 20 is positioned within a car, for example, and operates if a theft condition is detected.
In some preferred embodiments of the present invention, container 22 contains a colorful smoke material, which is preferably used for signaling purposes. The smoke is emitted from dispenser 20 according to predetermined time settings. Preferably, the emitted smoke also operates a fog-horn as it is emitted. Thus, dispenser 20 may be used, for example, to mark a destination point in navigation.
It will be appreciated that although in the above embodiments, dispenser 20 is used with a pressurized container the present invention may be implemented with non-pressurized containers, for example, for watering plants. In such embodiments the container is preferably positioned upside-down, so that the contents of the container are released due to gravity.
Other possible arrangements of the elements of the above-described preferred embodiments will also be apparent to those skilled in the art and are included within the scope of the present invention. For example, elements of shaft 52 (FIG. 6) may be reversed so that hole 90 is positioned within upper bore 58 , and controls the outflow of fluid from the shaft, rather than controlling influx into the shaft as described above. It will be appreciated that the preferred embodiments described above are cited by way of example.
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A dispenser for attachment to a container containing a fluid material, including an actuator which keeps the container in a substantially constantly open configuration so as to allow the fluid to pass into the dispenser, and a controllable outlet, through which a portion of the fluid is emitted from the dispenser, substantially independent of the fluid pressure in the container.
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BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention is directed to pin and collar type fasteners and is particularly concerned with an automated assembly for stringing fastener collars onto a magnetically centered mandrel.
2. Description of Prior Developments
U.S. patent application Ser. No. 599,184, incorporated herein be reference, discloses a method and apparatus for loading fastener collars into a fastener installation machine. The method includes the step of stringing individual fastener collars onto an elongated flexible mandrel that extends within a surrounding flexible tube.
Typically, the flexible mandrel and surrounding flexible tube will have a length of about twelve feet. The mandrel can have a diameter ranging from about one eighth inch up to about one half inch, depending on the size fastener collar being strung onto the mandrel. In order to string the annular fastener collars onto the flexible mandrel, the surrounding flexible tube may be suspended in a vertical position from a chute housing associated with a vibratory bowl type collar feeding apparatus.
The collars are sequentially fed from the feeding apparatus into the upper end of a chute. At this point, the collars are allowed to drop down through the chute onto the upper end of the mandrel which is located within the suspended flexible tube. A vacuum pump may be connected to the lower end of the suspended flexible tube to exert a vacuum force on the collars as they descend along the mandrel. The vacuum force helps to ensure a smooth downward flow of the collars along the mandrel, and a relatively tight packing of the collars along the mandrel surface.
Substantially the entire length of the flexible mandrel is utilized for stringing and holding the fastener collars. Each flexible mandrel will hold or support a relatively large number of fastener collars. For example, assuming a collar length of one half inch and a mandrel length of about twelve feet, a single flexible mandrel can serve as a stringer for over two hundred fastener collars.
In order to facilitate collar loading, the upper end of the flexible mandrel should be centered in the chute passage. Otherwise, a given fastener collar may have its end surface strike against the tip end of the mandrel so as to hang up or jam in the chute passage, i.e., not travel downwardly around and along the mandrel surface. Such jams are of course undesirable in that they cause temporary stoppage of the collar stringing process until the particular collar is removed from the chute structure. Centering of the flexible mandrel in the chute passage is made somewhat difficult because of the fact that the entire vertical length of the mandrel should be unconnected to the surrounding tube or chute structure in order to permit the annular fastener collars to freely pass downwardly along and around the mandrel surface.
Accordingly, a need exists for a mandrel centering device which coaxially aligns a mandrel within a chute without physical contact between the mandrel and chute.
SUMMARY OF THE INVENTION
The present invention has been developed to fulfill the needs noted above and is, therefore, directed to a magnetic apparatus for centering the upper end of the flexible mandrel in the chute passage without having any physical structure or connection between the mandrel and the surrounding passage surface. In one form of the invention, the flexible mandrel is connected to a tapered nose piece at its upper end for guiding the fastener collars onto the mandrel. An elongated magnetized rod is carried within the nose piece. A number of segment-shaped magnets are arranged in the chute housing in surrounding relation to the chute passage and to the magnetized nose piece connected to the mandrel. Magnetic polarities of the elongated magnetized rod and surrounding magnets are such that the nose piece is magnetically repulsed or forced away from the surrounding magnets. By arranging the individual magnets symmetrically relative to the passage, the various magnets will exert equalized repulsive forces on the magnetized rod in the nose piece thereby centering the nose piece in the chute passage.
BRIEF DESCRIPTION OF THE DRAWINGS
Various other objects, features and attendant advantages of the present invention will be more fully appreciated from the following detailed description when considered in connection with the accompanying drawings, in which the same reference numbers designate the same or corresponding parts throughout.
FIG. 1 is a sectional view taken through an apparatus embodying features of the invention;
FIG. 2 is a transverse sectional view taken on line 2--2 in FIG. 1; and
FIG. 3 is a fragmentary exploded view of components used in the FIG. 1 apparatus.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The drawings show an apparatus 10 for assembling annular fastener collars 11 into a string configuration on a flexible mandrel 13. The apparatus includes a chute housing 15 constructed to form a vertical chute passage 17. A conventional vibratory bowl feeder mechanism 19, or other conveyor mechanism, may be located to supply fastener collars to the chute passage.
The fastener collars 11 move sequentially in a left-to-right direction within a horizontal channel 21 to enter into the upper end of chute passage 17. As each annular fastener collar leaves channel 21 it begins to fall within passage 17. The gravitational descent of each collar may be augmented by a vacuum force derived from a vacuum pump 23 located at the lower end of a flexible tube 26 that surrounds mandrel 13. The vacuum force is applied within the annular space 25 between the outer surface of the mandrel and the inner surface of tube 26.
A tapered nose piece 27 formed of a low friction plastic material or the like is connected to the upper end of mandrel 13 for guidance of each collar 11 onto the mandrel. The mandrel is unconnected to housing 15 or tube 26, except that the lower end 28 of the mandrel rests against a central bridge wall 30 formed in a vacuum fitting 32. Typically, mandrel 13 will have a length on the order of twelve feet.
Because of its length and flexibility, the mandrel will not necessarily remain exactly centered relative to tube 26 or chute passage 17. Any off-centered disposition of the mandrel may be troublesome, especially at the upper end of the mandrel where the fastener collars initially fall onto and around the mandrel. For example, if the tapered upper end of nose piece 27 were to lay against the surface of passage 17, the fastener collars 11 would tend to pile up on the nose piece without telescoping and moving downwardly along the mandrel surface.
A magnetic assembly is carried by housing 15 and by nose piece 27 for centering the nose piece in chute passage 17. The magnetic centering assembly includes an elongated magnetized rod 29 carried within nose piece 27, with the upper end of the rod having a north polarity and the lower end of the rod having a south polarity or vice versa. The magnetic centering assembly further includes four segment-shaped magnets 31 mounted within housing 15 in surrounding concentric relation to chute passage 17. Each magnet 31 has an inner arcuate surface 33 in axial alignment with the chute passage surface, whereby the magnet inner surfaces form smooth continuations of the chute passage surface.
The four segment-shaped magnets 31 are individual magnetically polarized along radial lines extending from the axis of passage 17, such that each inner arcuate surface 33 of each magnet has a north polarity while each outer arcuate surface 35 of each magnet has a south polarity or vice versa.
When mandrel 13 is positioned so that the nose piece 27 is located within chute passage 17, the upper end portion of rod 29 will be located within the plane of the magnet assembly defined by magnets 31. The north pole of rod 29 will be repulsed from the north poles at the inner surfaces 33 of the segment-shaped magnets 31, thereby magnetically centering the nose piece in the chute passage. Rod 29 is sufficiently elongated that its south pole (at the lower end of the rod) does not magnetically interact with magnets 31.
The four segment-shaped magnets 31 are individually positioned in housing 15 by individual set screws 37. The primary purpose of the set screws is to prevent vibration of the magnets and/or circumferential dislocation thereof. The magnets have segmental configurations in order to increase the magnet mass and magnetic strength, especially at the inner surfaces 33 of the magnets.
Magnets 31 are preferably located so that their radial side edges 39 are in direct engagement with each other, such that the magnet assembly entirely surrounds the nose piece 27. Inner arcuate surfaces 33 of the magnets preferably are in axial alignment with the passage 17 surface so that the magnetic action of each surface 33 will be as close as possible to magnetized rod 29.
When a quantity of fastener collars 11 has accumulated in the annular space 25 between mandrel 13 and tube 26, the mandrel and tube are removed from chute housing 15 in order to attach another similar tube-mandrel assembly to the housing for forming additional collars into another string configuration. It is necessary that tube 26 have a detachable connection with chute housing 15. Any conventional quick-disconnect device ca be provided to form the necessary connection.
As shown in FIG. 1, the disconnect mechanism includes a vertical pipe 40 extending downwardly from housing 15. Two or more plungers 41 are slidably mounted in the pipe for radial movement toward or away from the pipe axis. A manually-rotatable collar 43 is carried on the pipe, with cam lobe elements 45 carried thereon. Each plunger is normally biased radially outwardly by a coil spring 47. However, by manually rotating collar 43, the cam lobe elements are enabled to move the plungers radially inwardly to the FIG. 1 positions.
Flexible tube 26 has a rigid end fitting 48 formed with a circumferential groove 49. When collar 43 rotates to a specific position on pipe 40 the end fitting 47 can be inserted into the lower end of pipe 40, after which collar 43 can be rotated to force plungers 41 into a locked condition on end fitting 48. When mandrel 13 has been loaded with fastener collars 11, collar 43 can be rotated to detach tube 26 from housing 15.
As shown in FIG. 3, nose piece 27 is detachably connected to a tubular mandrel 13 formed of a flexible plastic material. The lower end of magnetized rod 29 extends downwardly from the nose piece for insertion into the mandrel. The nose piece is thus frictionally retained on the mandrel, such that the nose piece can be reused with other similarly constructed mandrels.
The drawings necessarily show a particular embodiment of the invention. However, it will be appreciated that the invention can be practiced in various different constructional configurations and structural assemblies.
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A magnetic means for centering a flexible elongated mandrel within a vertical passage (chute) without any physical connection between the mandrel and the passage surface. The mandrel carries a tapered nose piece that includes an elongated magnetized rod. An array of cooperating magnets is arranged around the perimeter of the passage, so that the magnetic circuits of the rod and perimeter magnets interact to produce a radial repulsion of the rod to a position on the passage axis.
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CROSS REFERENCE TO RELATED APPLICATION
This application claims priority to Korean patent application No. 97-48895, filed Sep. 26, 1997, the content of which is incorporated hereinto by reference.
FIELD OF THE INVENTION
The present invention relates to a method of producing phosphor, more particularly, to a method of producing phosphor of high brightness.
BACKGROUND OF THE INVENTION
Generally, phosphors are classified into white, red, green, yellow and blue phosphors, and among them, red(R), green(G) and blue(B) phosphors are mainly used for display devices such as CRT.
Red phosphor is produced by firing raw materials of the red phosphor, washing the resulting fired material, ball-milling the washed material, coating the material with pigments, drying and then sieving the material.
Green and blue phosphors are produced by firing raw materials, washing the resulting fired material, ball-milling the washed material, surface-treating with various silicate compounds and then sieving the material. That is, in the conventional phosphor producing method, the ball-milling process is indispensably carried out to reduce the amount of aggregated particles and to disperse the phosphor materials. However, there is a problem in that the brightness of the phosphor seriously decreases during the ball-milling process.
SUMMARY OF THE INVENTION
It is an object of the present invention to provide a method of producing phosphor of high brightness, which carries out the ball-milling process during a reduced time interval. In order to achieve this and other objects, the method of producing phosphor of high brightness includes the steps of firing raw materials, washing the resulting fired material, ball-milling the washed material with one or more dispersion agents, coating the ball-milled material with pigments and drying the coated material.
BRIEF DESCRIPTION OF THE DRAWING
A more complete appreciation of the invention, and many of the attendant advantages thereof, will be readily apparent as the same becomes better understood by reference to the following detailed description when considered in conjunction with the accompanying drawing, wherein:
FIG. 1 is a graph showing the light emitting spectrums of phosphors produced by an embodiment of the present invention and by a comparative example.
DETAILED DESCRIPTION OF THE INVENTION
For a better understanding of the present invention, reference will now be made in detail to the following disclosures and appended claims.
In the method of producing phosphor of high brightness according to the present invention, the raw materials of the phosphor are first fired and washed with distilled water. Then, the washed material is ball-milled with one or more dispersion agents, and the ball-milled material is coated with pigment and finally dried. The dispersion agents can be added to the washed phosphor material before or during the ball-milling process.
In the present invention, the dispersion agent is preferably selected from the group consisting of silicate compounds, sodium polycarbonate, and alcohols. One example of a silicate compound is ethyl silicate, and all kinds of alcohols can be used as the dispersion agent. The dispersion agent is preferably a mixture of a silicate compound of 1-10 vol % and an alcohol of 90-99 vol %. Generally, 0.5-5 ml of the dispersion agent is used for dispersing 100 g of the washed phosphor material. However, the amount of the dispersion agent can be variously modified according to the dispersion conditions.
The ball-milling process can be preferably carried out for 3 to 60 minutes to prevent the reduction in brightness of the phosphor. The ball-milling process is carried out to reduce the amount of aggregated particles and to disperse the phosphor materials, and indispensable in producing the phosphor. Since the brightness of the phosphor decreases because the phosphor material is destroyed during the ball milling process, the duration of the ball-milling process should be reduced. In the present invention, by adding one or more dispersion agents during or before the ball-milling process of the washed phosphor material, the ball-milling process can be completed in 3 to 60 minutes compared to the conventional ball-milling time of 5 to 6 hours. Thus, the reduction in brightness can be prevented.
In order to more fully illustrate the preferred embodiments of the present invention, the following detailed examples are given.
EXAMPLE 1
ZnS, AgNO 3 , NaCl, MgCl 2 6H 2 O and S are mixed and fired at 950° C. under an N 2 atmosphere to produce a blue phosphor, and then the fired material is washed with distilled water. With ethyl silicate added as a dispersion agent, the washed material is ball-milled for 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a blue phosphor having high brightness.
EXAMPLE 2
ZnS, AgNO 3 , NaCl, MgCl 2 6H 2 O and S are mixed and fired at 950° C. under an N 2 atmosphere to produce a blue phosphor, and then the fired material is washed with distilled water. With sodium polycarbonate added as a dispersion agent, the washed material is ball-milled for 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a blue phosphor having high brightness.
EXAMPLE 3
ZnS, AgNO 3 , NaCl, MgCl 2 6H 2 O and S are mixed and fired at 950° C. under an N 2 atmosphere to produce a blue phosphor, and then the fired material is washed with distilled water. With ethyl alcohol added as a dispersion agent, the washed material is ball-milled for 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a blue phosphor having high brightness.
EXAMPLE 4
Y 2 O 3 , Eu 2 O 3 , S, Na 2 CO 3 and K 2 PO 4 are mixed and fired at 1250° C. under an N 2 atmosphere to produce a red phosphor, and then the fired material is washed with distilled water. With ethyl silicate added as a dispersion agent, the washed material is ball-milled for 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a red phosphor having high brightness.
EXAMPLE 5
Y 2 O 3 , Eu 2 O 3 , S, Na 2 CO 3 and K 2 PO 4 are mixed and fired at 1250° C. under an N 2 atmosphere to produce a red phosphor, and then the fired material is washed with distilled water. With sodium polycarbonate added as a dispersion agent, the washed material is ball-milled for 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a red phosphor having high brightness.
EXAMPLE 6
Y 2 O 3 , Eu 2 O 3 , S, Na 2 CO 3 and K 2 PO 4 are mixed and fired at 1250° C. under an N 2 atmosphere to produce a red phosphor, and then the fired material is washed with distilled water. With ethyl alcohol added as a dispersion agent, the washed material is ball-milled during 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a red phosphor having high brightness.
EXAMPLE 7
ZnS, Au, Cu and Al are mixed and fired at 950° C. under a CS 2 and H 2 S atmosphere to produce a green phosphor, and then the fired material is washed with distilled water. With ethyl silicate added as a dispersion agent, the washed material is ball-milled for 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a green phosphor having high brightness.
EXAMPLE 8
ZnS, Au, Cu and Al are mixed and fired at 950° C. under a CS 2 and H 2 S atmosphere to produce a green phosphor, and then the fired material is washed with distilled water. With sodium polycarbonate added as a dispersion agent, the washed material is ball-milled for 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a green phosphor having high brightness.
EXAMPLE 9
ZnS, Au, Cu and Al are mixed and fired at 950° C. under a CS 2 and H 2 S atmosphere to produce a green phosphor, and then the fired material is washed with distilled water. With ethyl alcohol added as a dispersion agent, the washed material is ball-milled for 30 minutes. Thereafter, the ball-milled material is coated with a pigment, and then dried at 15° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a green phosphor having high brightness.
Comparative Example 1
ZnS, AgNO 3 , NaCl, MgCl 2 6H 2 O and S are mixed and fired at 950° C. under an N 2 atmosphere to produce a blue phosphor, and then the fired material is washed with distilled water. The washed material is ball-milled for 6 hours. Thereafter, the ball-milled material is coated with a pigment, and then dried at 100° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a blue phosphor.
Comparative Example 2
Y 2 O 3 , Eu 2 O 3 , S, Na 2 CO 3 and K 2 PO 4 are mixed and fired at 1250° C. under an N 2 atmosphere to produce a red phosphor, and then the fired material is washed with distilled water. The washed material is ball-milled for 6 hours. Thereafter, the ball-milled material is coated with a pigment, and then dried at 100° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a red phosphor.
Comparative Example 3
ZnS, Au, Cu and Al are mixed and fired at 950° C. under a CS 2 and H 2 S atmosphere to produce a green phosphor, and then the fired material is washed with distilled water. The washed material is ball-milled for 6 hours. Thereafter, the ball-milled material is coated with a pigment, and then dried at 100° C. The residual aggregated particles and other large particles in the dried material are eliminated by a sieving process to produce a green phosphor.
The light emitting spectrums of phosphors produced by Example 1 and Comparative Example 1 are shown in FIG. 1. In FIG. 1, the reference characters "a" and "b" represent the light emitting spectrums of phosphors produced by Example 1 and Comparative Example 1, respectively. As shown in FIG. 1, the brightness of the phosphor according to Example 1 is more intense than that of the phosphor according to Comparative Example 1. Other Examples show an increase in brightness similar to Example 1.
As described above, the time for the ball-milling process can be reduced from 5 to 6 hours to 3 to 60 minutes by adding a dispersion agent during or before the ball-milling process of the phosphor material. Therefore, the reduction in brightness due to the ball-milling process can be prevented, and the brightness of the phosphor according to the present invention increases by 7-10% compared to that of the conventional phosphor.
While the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art will appreciate that various modifications and substitutions can be made thereto without departing from the spirit and scope of the present invention as set forth in the appended claims.
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A method of producing a phosphor having high brightness is provided, and the method includes the steps of firing raw materials of phosphor, washing the resulting fired material, ball-milling the washed material with one or more dispersion agents, coating the ball-milled material with pigment, and drying the coated material. The dispersion agent is preferably a compound selected from the group consisting of silicate compounds, sodium polycarbonate, and alcohols.
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BACKGROUND OF THE INVENTION
[0001] The present invention is generally directed to a cleaning system for ultraviolet (UV) disinfection modules. More specifically, the present invention is directed to a split wiper or brush, with associated housing, that permits cleaning systems to be quickly and efficiently replaced or adapted to specific treatment conditions.
[0002] Utilization of UV for disinfection of potable and wastewater increases on an ongoing basis. A number of UV disinfection systems are commercially available and utilized for a wide variety of wastewater and potable disinfection process.
[0003] In general, UV light is a portion of the electromagnetic spectrum that has many uses. For example, UV light can be used in a purification or disinfection system to kill bacteria and break down chemicals in a fluid, such as water or air. UV light can also be used to cause chemical reactions in order to break down certain chemicals and make certain chemical compounds.
[0004] In order to harness this ability of UV light, a UV reactor may be utilized. In general, a UV reactor may comprise one or more UV lights, often made from a straight hollow tube of UV transparent material, such as quartz. This tube is filled with a gas such that when an electric current passes through the gas, ultraviolet light is produced. Such UV lamps are often placed in a secondary jacket of UV transparent material, again, such as quartz. The jacket may keep water or wastewater away from the lamp. The lamp and jacket may be referred to as a reactor tube.
[0005] One or more reactor tubes may be placed in a disinfection module so that the water or wastewater flows through and/or around the reactor tubes. However, it has been an ongoing problem in the field of UV disinfection that, over the course of time, the quartz jackets surrounding the individual UV lamps tend to foul due to the slow build-up or accumulation of deposited material on the quartz jackets. Such materials include particulates, fats, oils, greases and the like that are typical of foreign matter contained with the water being disinfected. A number of systems and processes have been developed to remove such accumulations and/or deposits. Such systems include various reciprocating wiper systems which tend to have one problem or another in effectively and economically achieving the task of cleaning quartz jackets for an extended period of time.
[0006] As fouling and scale accumulate on the outer jackets, it increasingly blocks the UV light, thereby reducing the effectiveness of the disinfection module. However, oftentimes, due to the arrangement of multiple reactor tubes, the task of cleaning the jackets is difficult without partially dismantling the disinfection module. This issue has been addressed in the art in various ways, for example by U.S. Pat. No. 6,649,917, owned by Infilco Degremont, Inc., and incorporated herein by reference in its entirety.
[0007] Broadly speaking, U.S. Pat. No. 6,649,917 teaches utilizing a cleaning plate with a multiplicity of holes, and associated wipers. The cleaning plate traverses between two headers along the path of the reactor tubes, and with the reactor tubes traveling through the holes and associated wipers on the cleaning plate. However, issues with the gradual decreasing effectiveness of the wipers or brushes that encircle the reactor tubes may be present. In addition, depending on specific water and/or wastewater conditions, the type of cleaning implement (e.g., a solid wiper or a brush) may vary.
[0008] Changing the wipers or brushes may be a time and manpower intensive task, as a header may need to be removed to slide the cleaning plate and wipers off of the multiplicity of lamps, replace the wipers, and slide the entire unit back on. Such time and manpower requirements reduce the ability to quickly and efficiently change the cleaning implement if the water and/or wastewater conditions change.
[0009] Accordingly, it is desirable to provide a cleaning system for a UV disinfection module that can quickly and efficiently be changed in order to allow for quick and efficient routine maintenance or adaptation to existing or changing water or wastewater conditions.
SUMMARY OF THE INVENTION
[0010] Aspects of some embodiments of the present invention may include a cleaning system for a UV disinfection module having a pair of headers with a multiplicity of UV lamps extending therebetween comprising: a cleaning plate having a multiplicity of openings therein, the openings arranged to substantially coincide with positions of the lamps to permit movement of the plate between the headers; a split wiper assembly comprising a plurality of wiper portions, each wiper portion mounted in a housing, the split wiper assembly connected to the cleaning plate and substantially encircling each opening, sized such that each split wiper assembly has an inner diameter less than the exterior diameter of a corresponding lamp; and a movement device operatively connected to move the plate between the headers.
[0011] Aspects of some embodiments of the present invention may include a cleaning system for a UV disinfection module having a pair of headers with a multiplicity of UV lamps extending therebetween comprising: a cleaning plate having a multiplicity of openings therein, the openings arranged to substantially coincide with positions of the lamps to permit movement of the plate between the headers; a split wiper assembly comprising a plurality of wiper portions that overlap each other in order to fully encircle each opening, each wiper portion mounted in a housing the split wiper assembly connected to the cleaning plate and substantially encircling each opening, sized such that each split wiper assembly has an inner diameter less than the exterior diameter of a corresponding lamp; the split wiper assembly being held in position by one or more mounting plates comprising a first surface and a second surface and wherein the first surface is in contact with the split wiper assembly and the second surface is in contact with the cleaning plate, thereby sandwiching the split wiper assembly between the first surface and the cleaning plate; and a movement device operatively connected to move the plate between the headers.
[0012] Still other aspects of some embodiments of the present invention may include a cleaning system for a UV disinfection module having a pair of headers with a multiplicity of UV lamps extending therebetween comprising: a cleaning plate having a multiplicity of openings therein, the openings arranged to substantially coincide with positions of the lamps to permit movement of the plate between the headers; a split wiper assembly comprising a plurality of wiper portions that overlap each other in order to fully encircle each opening, each wiper portion mounted in a housing the split wiper assembly connected to the cleaning plate and substantially encircling each opening, sized such that each split wiper assembly has an inner diameter less than the exterior diameter of a corresponding lamp; the split wiper assembly being held in position by one or more mounting plates comprising a first surface and a second surface and wherein the first surface is in contact with the split wiper assembly and the second surface is in contact with the cleaning plate, thereby sandwiching the split wiper assembly between the first surface and the cleaning plate; and a rotatable screw operatively connected to move the cleaning plate between the headers.
[0013] Note that other aspects will become apparent from the following description of the invention taken in conjunction with the following drawings, although variations and modifications may be effected without departing from the spirit and scope of the novel concepts of the invention.
BRIEF DESCRIPTION OF THE DRAWING
[0014] The present invention can be more fully understood by reading the following detailed description together with the accompanying drawings, in which like reference indicators are used to designate like elements. The accompanying figures depict certain illustrative embodiments and may aid in understanding the following detailed description. Before any embodiment of the invention is explained in detail, it is to be understood that the invention is not limited in its application to the details of construction and the arrangements of components set forth in the following description or illustrated in the drawings. The embodiments depicted are to be understood as exemplary and in no way limiting of the overall scope of the invention. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The detailed description will make reference to the following figures, in which:
[0015] FIG. 1 illustrates a top view of a UV disinfection module, as known in the prior art.
[0016] FIG. 2 depicts an exemplary cleaning plate, used to clean the reactor tubes in a UV disinfection module, as known in the prior art.
[0017] FIG. 3 illustrates a split wiper design, including the split housing, in accordance with some embodiments of the present invention.
[0018] FIG. 4 illustrates a split wiper and a split brush design, including associated split housings, in accordance with some embodiments of the present invention.
[0019] FIG. 5 illustrates a reactor tube with a split wiper assembly, in accordance with some embodiments of the present invention.
[0020] FIG. 6 illustrates a reactor tube with a split wiper and a split brush assembly, in accordance with some embodiments of the present invention.
[0021] FIG. 7 illustrates a cross section of a split wiper assembly, showing the attachment of the assembly to the cleaning plate, in accordance with some embodiments of the present invention.
[0022] FIG. 8 depicts a cleaning plate mounted in a UV disinfection module, in accordance with some embodiments of the present invention.
[0023] Before any embodiment of the invention is explained in detail, it is to be understood that the present invention is not limited in its application to the details of construction and the arrangements of components set forth in the following description or illustrated in the drawings. The present invention is capable of other embodiments and of being practiced or being carried out in various ways. Also, it is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting.
DETAILED DESCRIPTION OF THE INVENTION
[0024] The matters exemplified in this description are provided to assist in a comprehensive understanding of various exemplary embodiments disclosed with reference to the accompanying figures. Accordingly, those of ordinary skill in the art will recognize that various changes and modifications of the exemplary embodiments described herein can be made without departing from the spirit and scope of the claimed invention. Descriptions of well-known functions and constructions are omitted for clarity and conciseness. Moreover, as used herein, the singular may be interpreted in the plural, and alternately, any term in the plural may be interpreted to be in the singular.
[0025] With reference to FIG. 1 , an ultraviolet disinfection module 10 , as may be known in the prior art will be discussed. UV disinfection module 10 may comprise, among other components, one or more UV lamps 110 that may extend between two headers 150 , 160 . The lamps 110 may be positioned within a transparent jacket 120 , which may be made from UV transparent or resistant materials, such as but not limited to quartz.
[0026] In operation, water or wastewater (or any fluid to be treated, including air or other gases) may travel through the UV lamps 110 . For example, the water or wastewater may travel in a direction parallel to that of the cleaning plate 130 and therefore pass around and/or between the one or more UV lamps 110 . As the water or wastewater passes around and/or between the one or more UV lamps 110 , the UV light emitted by the lamps 110 may disinfect or otherwise treat the water or wastewater.
[0027] In addition, the UV disinfection module 10 may comprise a cleaning plate 130 . A movement device 140 —for example, a threaded rod or screw, a hydraulic piston, an electric or fluid motor, magnetic, a chain drive or other rotary device, etc. may also be present. The movement device 140 may be disposed such that it can effectuate movement of the cleaning plate 130 from one header 150 to the other header 160 . Note that the cleaning plate 150 may or may not contact each header 150 , 160 , but rather may travel substantially between the two.
[0028] The Cleaning plate 130 may include a number of holes or orifices aligned with the UV lamps 110 and jackets 120 , such that as the cleaning plate 130 travels between the headers 150 , 160 , the UV lamps 110 and jackets 120 pass through the holes or orifices.
[0029] With reference to FIG. 2 , a cleaning plate 20 as may be generally known in the prior art is depicted. Cleaning plate 20 may comprise a plate surface with one or more holes or orifices 210 therein. As noted above with regard to FIG. 1 , these holes or orifices 210 may be positioned to align with the UV lamps and jackets utilized by the UV disinfection module. In addition, the cleaning plate 20 may comprise a cleaning apparatus 220 that encircles or surrounds each hole or orifice 210 . The cleaning apparatus 220 may comprise a wiper, a brush, a squeegee, or any other type of cleaning device. The cleaning apparatus 220 may remove build-up and scale present on the lamps and/or jackets through either mechanical contact (e.g., scrubbing, rubbing, or scraping, etc.), or by other means as may be known in the art. In order to provide effective cleaning, the cleaning apparatus 220 generally encircles or surrounds each hole or orifice 210 so that each portion of the UV lamp or jacket is cleaned. In addition, the cleaning apparatus 220 may be sized such that the mechanical interaction between the cleaning apparatus 220 and the UV lamp or jacket is proper to ensure proper cleaning For example, if the cleaning apparatus 220 is a rubber wiper, the rubber wiper 220 will be sized such that as the cleaning plate 20 passes between each header (as discussed above), the rubber wiper 220 will be in sufficient contact with the UV lamp or jacket to effectuate cleaning If the cleaning apparatus 220 is a bristle brush, for example, the sizing of the cleaning apparatus 220 around the hole or orifice 210 may vary.
[0030] As noted above, such prior art systems have several drawbacks and disadvantages. For example, it can be very difficult and time consuming to replace the cleaning apparatus 220 . Cleaning apparatus 220 may be replaced after wear and erosion of the cleaning apparatus 220 reduces its effectiveness, or may be replaced in order to adapt the cleaning apparatus 220 to the specific conditions of the water or wastewater the UV disinfection unit is treating. For example, the characteristics of some water or wastewater may result in scale accumulating on the UV lamps and jackets, which may require a stiff rubber wiper for removal. The characteristics of other water or wastewater treated may result in a layer of sludge or film accumulating on the UV lamps and jackets, which may require a bristle brush for removal.
[0031] Therefore, in accordance with some embodiments of the present invention, a cleaning device that is split into at least two (2) components will now be discussed. With reference to FIG. 3 a split wiper assembly 30 is illustrated. Note that while a split wiper is discussed, the same discussion below may apply to any type of cleaning apparatus—for example a split brush, squeegee, etc. Split wiper assembly 30 may comprise at least two (2) wiper portions 310 , 320 with associated housings 330 , 340 . Each wiper portion may surround a portion of the UV lamp or jacket such that when assembled the split wiper assembly 30 may surround the entirety of the circumference of the UV lamp or jacket. Note that while two (2) portions are illustrated, it is contemplated that the present invention may be adapted to support any number of portions.
[0032] It may be important to maintain uniform friction around the circumference of the UV lamp or jacket. If the friction is greater on one side than the other, the resulting moment may cause the cleaning plate to become askew, which may jam the cleaning plate on the UV lamps or jackets between the headers. In order to maintain such uniform friction, and in accordance with some embodiments of the present invention, the split wiper portions 310 , 320 may each surround more than 180 degrees, thereby providing overlap of coverage. In addition, in order to provide uniform friction—and uniform coverage—the split wiper portions 310 , 320 may be inserted into split housing components 330 , 340 .
[0033] The split housing components 330 , 340 may be designed such that the housing components 330 , 340 may fit together into a single assembly 30 . For example, a first housing component 330 may comprise an extruded portion 331 that may align with the opening in the second housing component 340 . Similarly, the second housing component 340 may comprise an extruded portion that may align with the opening in the first housing component 330 . In order to provide a secure attachment, it is contemplated that the housing portions 330 , 340 may be keyed to mate with each other. For example, the first housing portion 330 may comprise an opening 332 sized and located such that, upon assembly, a raised portion 341 of the second housing component may fit within the opening.
[0034] A side view of the assembled split wiper assembly 350 illustrates how the two wiper and housing portions interlock together. Top view of the assembly 360 illustrates the same. Note how the raised portion from one of the housing components 362 mates with the housing 361 of the other portion. With reference to cross-section A-A—depicted in assembly 370 —the overlapping portions of the wipers 310 and 320 can be seen.
[0035] In accordance with some embodiments of the present invention, it is also contemplated that the split wiper portions 310 , 320 may comprise a lip or ridge 311 , 321 on the wiper portion that may align with a recess (for example, recess 343 in the second housing portion) in the housing portions 330 , 340 . Such design may provide for additional securement of the split wiper portions.
[0036] Moreover, the recess 343 that receives the wiper portion may have an inside diameter slightly smaller than the outside diameter of the wiper portion. Accordingly, even as the wipers wear and tear, friction force between the wiper assembly and the UV lamps or jackets may be maintained—or at least maintained above a minimum value, thereby increasing the useful lifetime of the wiper.
[0037] With reference to FIG. 4 , some embodiments of the present invention may be utilized for both wiping rubber components and wiping brush components. Wiping brush assembly 40 may comprise at least two wiping brush portions 410 and associated housing 420 . Wiping rubber assembly 41 may comprise at least two wiping rubber portions 411 and associated housings 421 .
[0038] Note that FIG. 4 illustrates a slightly different housing design which comprises an post-type protrusion 423 , 425 in each housing portion that inserts into opening 422 , 424 in the opposite housing. Again, having the housings keyed together may provide for additional security and support of the cleaning portions.
[0039] With reference to FIG. 5 , the interaction between a split assembly and the UV lamp or jacket will now be discussed. As noted above, the cleaning apparatus may contact the UV lamp or a jacket. Generally speaking, a jacket is utilized (in order to protect the UV lamp, as well as provide an easier means for changing UV lamps without disassembling the entire module). Accordingly, the discussion below discusses the cleaning apparatus contacting a jacket. Note however, that the same arrangement can be used with the cleaning apparatus contacting the lamp directly.
[0040] FIG. 5 depicts jackets 510 , surrounded by a split wiper assembly 520 . As shown in both cross section B-B and the isometric view, the split wiper assembly 520 may comprise two wiper portions and associated housings 521 , 522 . The wiper portions and associated housings 521 , 522 may be assembled around the jacket 510 (that is, with the jacket in place), or may be assembled and the jacket then introduced between the portions, by for example, moving the cleaning plate along the length of the jacket.
[0041] With continued reference to FIG. 5 , the detail view shows two wiper portions 523 and 526 , each surrounding just over 180 degrees of the jacket. Each wiper portion is supported by a housing—wiper portion 523 is supported by housing 524 ; wiper portion 526 is supported by housing 527 .
[0042] FIG. 6 illustrates, that in accordance with some embodiments of the present invention, a split wiping brush or wiping rubber may be used. Jacket 610 may be surrounded by a wiping brush assembly 630 , comprising at least two wiping brush portions with associated housing 631 , 632 . Jacket 610 may also be surrounded by a wiping rubber assembly 620 , comprising at least two wiping rubber portions with associated housings 621 , 622 .
[0043] FIGS. 7A-7B illustrate various arrangements in which the split wiper assemblies may be attached to the cleaning plate, in accordance with some embodiments of the present invention. With reference to FIG. 7A , a cleaning plate 710 may have a split wiper assembly 720 attached using a “Z” shaped plate 730 . The “Z” shaped plate may comprise a first surface 731 and a second surface 732 , connected by a third plate surface which may be substantially perpendicular to the first and second surfaces 731 , 732 or may connect at an angle, similar to the letter “Z”. The first surface 731 may contact the split wiper assembly 720 , while the second surface 732 may be attached to the cleaning plate 710 . For example, as shown in FIG. 7A (which is a non-limiting example), a bolt 750 may be used to connect the “Z” shaped plate 730 to the cleaning plate 710 . Accordingly, when the “Z” shaped plate 730 is connected to the cleaning plate 710 , the split wiper assembly 720 is sandwiched between, thereby securing the split wiper assembly.
[0044] It is contemplated that various other methodologies, systems, and approaches may be used to attach the split wiper assemblies to the cleaning plate. With reference to FIG. 7B , an “L” shaped plate 740 may also be used. The “L” shaped plate 740 may be used to sandwich, and therefore secure, a split wiper assembly 720 to the cleaning plate 710 . The “L” shaped plate 740 may comprise a first plate surface 741 and a second plate surface 742 . The first plate surface 741 may contact the split wiper assembly, while an edge of the second plate surface 742 may contact the cleaning plate 710 . The “L” shaped plate 740 may be secured to the cleaning plate 710 by the use, for example, of a bolt 750 which may connect the first plate surface 741 to the cleaning plate 710 .
[0045] Note that various other attachment methodologies are contemplated, including but not limited to the use of an interference fit, alternative mechanical connections (e.g. screws, rivets, pins, snap rings etc.), tensile connection (e.g. clamp, spring, bungee, etc.), and/or any other type of connection or attachment.
[0046] With reference to FIG. 8 , an overall UV disinfection module 80 in accordance with some embodiments of the present invention will now be discussed. The UV disinfection module 80 may comprise a cleaning plate 810 with a plurality of holes or orifices aligned with a plurality of UV lamps or jackets 820 . The cleaning plate 810 may further comprise, at each hole or orifice, a split wiper assembly 830 (which in turn, as discussed above, may comprise at least two wiper portions and associated housings). Split wiper assemblies 830 may be attached or secured to the cleaning plate 810 by way of attachment plate 840 . Attachment plate 840 , illustrated in an “L” shaped embodiment, may be in turn attached or secured to the cleaning plate via attachment screws 841 . The entire cleaning plate and split wiper assemblies may be moved along the UV lamps or jackets 810 through a movement device 850 . As shown, movement device 850 may be a threaded rod that interacts with a nut assembly 851 such that rotating the threaded rod 850 causes the nut assembly—and accordingly the cleaning plate 810 —to move laterally along the UV lamps or jackets. However, as noted above, the movement device 850 may comprise for example, a threaded rod or screw, a hydraulic piston, an electric or fluid motor, magnetic, a chain drive or other rotary device, etc. may also be present. The movement device 850 may be disposed such that it can effectuate movement of the cleaning plate 130 along UV lamps or jackets 810 from one header to another.
[0047] Note that while the cleaning plate is discussed as moving along the UV lamps or jackets between two headers, it is contemplated that the cleaning plate may be moved beyond the effective portion of the UV lamps such that the cleaning plate may be stored out of the UV light in order to prevent damage or degradation of the wipers or brushes.
[0048] Moreover, it is contemplated by the present invention that various devices may be included in the housing and wiper portions to ensure certain, specific, or constant pressure between the wiper portions and the UV lamps or jackets. For example, it is contemplated that a spring may be included in the housing, such that the spring may exert pressure on the wiper portion against the UV lamp or jacket. Accordingly, as the wiper portion wears, minimum friction forces may be maintained. In accordance with some embodiments of the present invention, it is contemplated that after assembly of the wiper portions, a spring, band, bungee, or other type device—for example with elastic properties—may be included around the assembly to exert force on the wiper portions against the UV lamps or jackets. Such device may, for example, pull or push the wiper portions towards the center of the UV lamp or jacket.
[0049] It will be understood that the specific embodiments of the present invention shown and described herein are exemplary only. Numerous variations, changes, substitutions and equivalents will now occur to those skilled in the art without departing from the spirit and scope of the invention. Accordingly, it is intended that all subject matter described herein and shown in the accompanying drawings be regarded as illustrative only, and not in a limiting sense, and that the scope of the invention will be solely determined by the appended claims.
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The present invention is directed to a cleaning system for a UV disinfection module. In general, the UV disinfection module may have a pair of headers with a multiplicity of UV lamps extending therebetween. The cleaning system may include a cleaning plate having a multiplicity of openings therein, the openings arranged to substantially coincide with positions of the lamps to permit movement of the plate between the headers; a split wiper assembly including a plurality of wiper portions, each wiper portion mounted in a housing, the split wiper assembly connected to the cleaning plate and substantially encircling each opening, sized such that each split wiper assembly has an inner diameter less than the exterior diameter of a corresponding lamp; and a movement device operatively connected to move the plate between the headers.
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FIELD OF THE INVENTION
The present invention relates to the removal of water from a solution of water and glycol. In particular it relates to a relatively energy efficient system for removing water from a water and glycol solution where the initial weight percent ratio of water to glycol in the solution may be as high as 95% water to 5% glycol.
BACKGROUND OF THE INVENTION
For several years glycol has been used by airports around the world to de-ice the wings of aircraft prior to take-off during poor winter weather conditions. In recent years, the presence of glycol contamination in the ground water table surrounding airports has been discovered. Since the discovery, new controls and regulations have been introduced whereby aircraft are sprayed with glycol at de-icing stations and the sprayed aircraft then taxi for priority take-off. At these stations, glycol that drips off the aircraft is collected along with water melted in the de-icing from freezing rain or snow that may be falling due to poor weather conditions. Since glycol forms a miscible solution with water, the solutions collected may have water contents as high as 95% water to 5% glycol. Currently, the collected solution is removed from the de-icing station for waste management treatment which can involve distillation of the water from the glycol to recover the glycol.
Distillation of water from a water and glycol solution is the most common method used to remove water from a solution of water and glycol. Such distillation systems are used in natural gas treatment systems where the glycol is used to treat natural gas to remove water from natural gas and then the water and glycol solution is distilled by a variety of heating methods to remove the water from the glycol. In such systems the water content in the water and glycol solution is usually well below 10% and the distilled solution ends up being in the order of 99% or better glycol. Examples of these natural gas water removal and subsequent water distillation systems are disclosed in U.S. Pat. Nos. 4,332,643 issued Jun. 1, 1982 to Laurence S. Reid; 4,322,265 issued Mar. 30, 1982 to Harold S. Wood; 4,010,065 issued Mar. 1, 1977 to Carl E. Alleman; 3,841,382 issued Oct. 15, 1974 to Charles K. Gravis, III et al; 3,450,603 issued Jun. 17, 1969 to Charles O. Meyers et al; and, Canadian Patent 807,953 issued Mar. 11, 1969 to Clifford W. Barnhart.
It is also known to purify glycol contaminated by oxidation products by adding small amounts of water and distilling off the water under partial vacuum. Such a method is disclosed in U.S. Pat. No. 3,398,061 issued to Horst Taul et al.
It should be understood that the above methods of distillation involve the use of heat to vaporize the water in glycol solutions having less than 10% initial water content. There is no teaching of using distillation methods to remove water from a glycol and water solution having as much as 95% water content.
It is also known to provide evaporation towers in which human waste, corrosive solutions and saline water are purified by heated packing mediums within the towers. Such evaporation towers are disclosed in U.S. Pat. No. 5,207,869 issued May 4, 1993 to H. David Harmoning et al; Canadian Patent 1,005,746 issued Feb. 22, 1977 to Roger Rat et al; and Canadian Patent 976,866 issued to Melvin H. Brown. However, the application of these evaporation towers is not relevant to the removal of relatively high initial concentrations of water from a water and glycol solution.
There is still a need for a relatively energy efficient apparatus for the removal of water from water and glycol solutions having high initial concentrations of water so that ultimately a reusable water and glycol solution may be obtained.
SUMMARY OF THE INVENTION
In accordance with one aspect of the present invention there is provided a method of removing water from a solution of water and glycol. The method includes the step of circulating a plurality of thin streams of the water and glycol solution generally in a first direction through a packing medium arranged to have a labyrinth. The method further includes the step of circulating air generally in a second direction through the labyrinth of the packing medium over the thin streams of the glycol and water solution to selectively remove water from the solution, to increase relative humidity of the air passing through the labyrinth and to increase the glycol concentration in the water and glycol solution.
Throughout the specification and claims reference is made to glycol and a solution of water and glycol. By glycol it is meant alcohols having two hydroxyl groups attached to the carbon skeleton and, more specifically, ethylene glycol which is dihydroxy alcohol commonly used in antifreeze.
Additionally, the circulating solution step of the above described method may include the step of supplying the solution to the packing medium in the form of a plurality of discrete droplets of water and glycol solution.
From testing it has been determined that the method does not require the introduction of heat and may employ atmospheric air in the air circulating step. It is further contemplated that the first direction in which the solution is circulated through the packing medium is opposite to the second direction in which the air flows through the packing medium.
In accordance with another aspect of the present invention there is provided a glycol concentrator for increasing the concentration of glycol in water and glycol solution. The concentrator includes a tower, a water and glycol solution circulating system, and an air circulating system. The tower supports a packing medium having a labyrinth. The water and glycol solution circulating system includes a solution reservoir positioned below the packing medium, a drip pan supported above the packing medium and a circulating passage running from the reservoir to the drip pan for supplying the water and glycol solution from the reservoir to the drip pan. The drip pan has a plurality of openings though which discrete droplets of the water and glycol solution are distributed over the packing medium to flow in thin streams downwardly though the labyrinth of the packing medium and into the reservoir. The air circulating system circulates air into the reaction tower, through the labyrinth of the packing medium and out of the reaction tower. As the air passes over the thin streams of water and glycol solution in the labyrinth it selectively removes water from the solution and increases the glycol concentration of the solution returning to the reservoir.
It is envisaged that the concentrator may operate without a heat source in ambient weather conditions. The concentrator 10 may be located at ground level with a supply tank and a holding tank located underground. It is also envisaged that the top wall or roof of the concentrator may be transparent allowing the sun light to warm the inside of the tower during daylight hours. Any warming of the air in the tower increases the water absorption properties of the air circulating through the tower. Ambient temperature and humidity sensors may be used to shut the concentrator down when ambient temperatures fall below -35° C. or the relative humidity is above 95%.
Advantage is found in the present invention because of the concentrator's reduced power requirements when compared to a distilling process. It should be further understood that the concentrator has a relatively low energy consumption when compared to that of a distilling process. The concentrator is able to operate 24 hours a day except when it is shut down for cleaning purposes. It is envisaged that when the water to glycol ratio is in the range of 1:1 to 1:2, the solution will be removed from the reservoir for possible further processing depending on the intended use of the solution.
BRIEF DESCRIPTION OF THE DRAWINGS
For a better understanding of the nature and objects of the present invention reference may be had to the accompanying diagrammatic drawings in which:
FIG. 1 is a diagrammatic illustration of a glycol concentrator in which the present invention is embodied;
FIG. 2 is an enlarged diagrammatic view of a randomly packed glass shard configuration for a portion of the packing medium of the glycol concentrator; and,
FIG. 3 is perspective view of the drip pan of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring to FIG. 1 there is shown a glycol concentrator 10 embodying the present invention. It is envisaged that the concentrator 10 can be built as an outdoor station. The concentrator 10 has a tower 12 which supports a packing medium 14 on an expanded metal grid screen 16.
The packing medium 14 is preferably shards of glass 18 that are obtained from smashed recycled glass. As shown in more detail in FIG. 2, the shards of glass 18 provide a network of passages, or a labyrinth 20, through the packing medium 14. Shards of glass 18 are the preferred packing medium 14 because the packing characteristics of the shards of glass have provided the best results to date and the glass can be recycled. The glass shards or bed 18 should not be too fine because the finer the glass bed 18, i.e. the more tightly packed the glass shards, the greater the air pressure drop across the glass bed becomes which decreases the flow of solution and air through the packing medium. It should be understood that the shards of glass 16 may be obtained from other sources. Further, other materials may be used for the packing medium that are inert to the water and glycol solution, such as, for example, plastics or expanded metal wool.
The concentrator 10 has a water and glycol solution circulating system 22. The solution circulating system 22 has a solution reservoir 24 positioned below the packing medium 14 and support screen 16. The solution circulating system has a circulating passage or piping 26, a flow pump 28 operated by a motor 29 (AC or DC) and an ON/OFF float switch 30. The motor 29 and pump 28 operate in ON and OFF conditions controlled by float switch 30 to control flow of solution from the reservoir 24 to a drip pan or headbox 32. The float switch 30 ensures that the pan 32 is not overfilled and is maintained at a predetermined solution level. Alternatively the motor 29 and pump 28 could operate as a variable speed pump with a modern modulating control. The drip pan 32 distributes the water and glycol solution over the packing medium 14. The drip pan 32, shown in more detail in FIG. 3, has openings 34 in its floor 36. The pattern, number and size of the openings 34 determines the distribution of the solution over the packing medium 14 and the size of droplets 38 of solution falling from the drip pan 32. The size of openings 34 should create discrete droplets 38 and not a fine mist that can be carried away by the evaporating air stream 44. As shown in FIG. 3, the openings 34 are arranged on the floor 36 of the drip pan in rows and columns to provide a rectangular matrix of openings.
The concentrator 10 further includes an atmospheric air circulating system that is controlled by a blower or fan 40 located at the top of the tower 12 and an air inlet 42 located to the left side of the tower 12. The inlet 42 has a rain or weather hood 43 to protect the reservoir 24 from rain, sleet or snow. The blower 40 is designed to draw an air flow as shown by arrows 44 circulating below screen 16 and up though the tower and the labyrinth 20 and out the top of the tower 12. The blower outlet is preferably insulated to prevent freezing of condensate leaving the tower. The blower 40 maintains a negative static pressure at the top of the tower 12 of from 1 to 5 inches of water (25 mm to 127 mm of water). It should be understood that the fan pressure depends on the packing configuration and medium used. In FIG. 1 the operation of the blower or fan 40 may be controlled by temperature sensor 67 and humidity sensor 68. Because of the "anti-freeze" characteristic of glycol and water solution, it only becomes necessary to shut down operation of the concentrator 10 when temperature conditions drop below a predetermined temperature such as, for example, -35° C. and the solution in the concentrator starts to turn to slush. Thus, the temperature sensor 67 operates to shut down fan 40 when the temperature becomes too cold. The humidity sensor 68 shuts down the fan 40 when the relative humidity in the air is above a predetermined percentage such as, for example, 95%, since the inherent ability of the ambient air to absorb moisture is low. Otherwise, the concentrator of the present invention can operate 24 hours a day in conditions not sheltered from ambient weather conditions.
Below the concentrator 10 is a supply tank 46 containing a solution of dilute glycol having a water content of up to 95% by weight. This dilute glycol solution is supplied from the tank 46 to the reservoir 24 via supply pipes 48 and pump 50. Pump 50 is controlled by motor 52 and a float control switch 54 located in the reservoir 24 of the concentrator 10 to regulate the supply of dilute solution from tank 46 to reservoir 24.
Also located below the concentrator 10 is a holding tank 56 into which the concentrator 10 feeds a water and glycol solution having a water weight content of 40% to 60%. The concentrator 10 discharges the water and glycol solution to the holding tank 56 via piping 58. The flow of the solution is controlled by hydrometer 60 which preferably measures the specific gravity of the solution in reservoir 24 and sends a control signal via line 62 to normally closed solenoid valve 64. This signal opens solenoid valve 64 allowing solution 100 to drain from the reservoir 24 into the tank 56. The shut off valve 66 also regulates the flow of solution 100 from the reservoir 24 to holding tank 56 to a predetermined maximum flow rate. The shut off valve 66 also allows for maintenance of valve 64.
Those skilled in the art of mechanical design will recognize that the function of hydrometer specific gravity sensing device 60 and solenoid valve 64 acting in concert is to automatically transfer the glycol and water mixture from tank 24 to tank 56 as it is concentrated to the desired density by tower 14. In a practical embodiment, this function can be equally well performed by a simple motor driven domestic sump pump which in response to device 60 raises the water and glycol mixture out of tank 24 and allows it to run by gravity down into tank 56. If the discharge piping of this pump is vented so that it will not siphon liquid from tank 24 to tank 56, the system becomes fail safe in that it will shut down instead of flooding tank 56 with unconcentrated fluid should the pump, motor, or transmitting hydrometer fail. This discharge function becomes the mirror image of the feed function performed by pump 50 and level float switch 54.
The operation of the glycol concentrator 10 of the present invention with reference to FIGS. 1 to 3 will now be described.
The concentrator 10 as shown in FIG. 1 allows for a continuous process. The solution 100 in the reservoir 24 is processed by the concentrator 10 to reduce the water content and increase the glycol content. As the water content in solution 100 is reduced, the level of solution 100 in reservoir 24 drops causing float switch 54 to activate motor 52 and pump 50. Pump 50 supplies solution 110 from supply tank 46 along piping 48 and into reservoir 24. Solution in supply tank 110 is expected to have an initial water to glycol ratio typically in the range of 19:1 to 2:1. The concentration levels of water to glycol of solution 110 in supply tank 46 is dependent on the conditions under which the contaminated solution is collected.
Hydrometer 60 in reservoir 24 controls the draining of solution 100 from reservoir 24. When the specific gravity of solution 100 rises to a predetermined value representing a water to glycol ratio of 1:1 to 1:2, the hydrometer 60 sends a signal on line 62 to solenoid valve 64. This signal opens the solenoid valve 64 allowing solution 100 to drain into holding tank 56 at rate determined by manual shut off valve 58. Holding tank 56 accumulates solution 120 which will have a water to glycol ratio in the range of 1:1 to 1:2. The resultant concentration of water to glycol of solution 120 is dependent on the setting of hydrometer 60 which can be adjusted by the operator.
It should be understood that additional piping and valves will be present in supply tank 46 and holding tank 56 to respectively permit for the loading and removal of solution from these tanks. It should also be understood that separators and filters may be used to remove other contamination from the solution 110 prior to deposit in supply tank 46.
Solution 100 is circulated from the reservoir 24 to the packing medium 14 by pump 28 which supplies solution 100 to drip pan 32. Float switch 30 ensures the dip pan 32 does not overflow by turning on and off pump 28, or alternatively, modulating the pumping rate of pump 28. The openings 34 in the floor 36 of drip pan 32 causes discrete droplets 38 to be distributed over the packing medium 14. While the air flow 44 created by blower 40 draws air about the droplets 38 the droplets are of sufficient size not to be carried away by the air stream. The droplets 38 fall on the packing medium 18 and flow in thin streams 21 of solution down through the labyrinth 20.
The water content in solution 100 is reduced in concentrator 10 by what is believed to be a thin film evaporation process that occurs in the labyrinth 20 of the packing medium 14. The air and solution streams in practice pass over each other. It is believed that as the air passes over the thin streams or sheets of water and glycol on the extended surfaces of the labyrinth, the air selectively removes water from the mixture and progressively increases the concentration of glycol in the mixture. It can be demonstrated that the maximum removal rate of water occurs at a specific water glycol mixture flow rate for a given evaporating tower configuration and conditions. This coupled with the fact that it is most difficult to use known centrifuging art to separate water from glycol, suggest to the inventors that the success of this process depends upon a thin film evaporation process. It is believed that in the labyrinth the glycol water mixture is spread out over the packing medium at 1 or more molecules thick and the air stream selectively removes the water molecules leaving the glycol molecules and other impurities behind. Referring specifically to FIG. 2, the thin steams 21 are shown passing generally down through the labyrinth 20 of the packing medium 14. Air flow is shown by arrows 44 representing air flow generally up through the labyrinth 20. For the purpose of simplifying the illustration, only three air flow streams 44 and two solution streams 21 are illustrated.
It should be understood that the glycol concentrator of FIG. 1 is well adapted to operate in an outdoor environment. While supply tank 46 and holding tank 56 have been previously described as being located below concentrator 10, it should be clear from FIG. 1 that these tanks are located underground below frost line 130. This feature together with temperature sensor 67 and humidity sensor 68, which respectively shut down operation of concentrator 10 when temperature conditions fall below about -35° C. and the relative humidity is above about 95%, allow for an environmentally friendly concentrator able to operate unattended under most weather conditions.
An experimental model of the concentrator 10 was built and tested to determine the evaporation rate of the tower for different packing mediums 14 and to determine the energy consumption per liter of water evaporated. The packing materials tested were shards of glass (coarse broken glass), fine broken glass, and coarse and fine steel wool. The fan or blower 40 had a rating of 1/55 HP which translates to approximately 18 watts, assuming a small motor efficiency of 75%. The drip pan 32 had a length of 30.50 cm and a width of 23.75 cm. The drip pan had 81 holes of 1/32 of an inch diameter (0.79 mm) drilled therein in a 9 by 9 matrix grid. The packing medium 14 had approximately the same length and width dimensions as the drip pan and was packed to a depth of 19 cm. During the experiments no heat was introduced to the tower and the experiments were conducted at an ambient temperature of approximately 22° C. The operating results of the experimental concentrator are shown below in Table 1.
TABLE 1______________________________________ SHARDS FINE COARSE ANDPACKING OF GLASS FINE STEELMEDIUM GLASS PARTICLES WOOL______________________________________Initial Glycol 34 29% 32%ConcentrationInitial Specific 1.046 1.038 1.043Gravity ofSolutionFinal Glycol 64% 59% 47%ConcentrationFinal Specific 1.090 1.084 1.066Gravity ofSolutionElapsed Hrs. 32.5 53.0 26.7Average Water 0.1025 0.0752 0.0922Removal Rate(Liters/Hour)Energy 0.230 kW-Hr 0.314 kW-Hr 0.256 kW-Hrrequired toevaporate1 liter of water______________________________________
Since it is known that the energy required to boil 1 liter of water to vapour is 540 Kilo Calories and that 1 kW-hr=860 Kilo Calories, then 0.628 kW-Hr is required to distill 1 liter of water. Comparing this value with 0.230 kW-Hr required to remove a liter of water in the concentrator demonstrates that the concentrator is more energy efficient by a factor of 2.73.
From the above results it is apparent that the area of the packing tower and the depth of the tower will have to be considerably larger than the experimental model for commercial application. This may involve additional fans being used and the possibility of having a series of towers located one above the other.
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A method and apparatus for removing water from a solution of water and glycol solution. The apparatus finds application in recycling of glycol wherein a water and glycol solution having as much as a 95% water content when introduced to the apparatus leaves the apparatus with a water content in the order of 40% to 60%. The glycol concentrator has a packing medium made from glass shards that provide a labyrinth through which air is circulated in one direction and thin streams of glycol are circulated in generally the opposite direction. It is believed that mixing of the thin streams of solution and air flow steams in the labyrinth results in a thin film evaporation process. The glycol concentrator apparatus has reduced energy requirements when compared with a distilling process.
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CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of U.S. Provisional Application No. 61/129,749, filed Jul. 16, 2008, the entire disclosure of which is hereby incorporated herein by reference.
FIELD OF INVENTION
The present invention is generally related to cancer treatments using electromagnetic energy.
BACKGROUND
Electric fields of endogenous origin have been measured outside the periphery of cultured cells, within multiple tissues and cell types of developing embryos, and at the borders of healing and regenerating tissues. Electrically charged and charge-dependent molecules of cells and tissues are naturally inherent to biologic systems and assist in defining their electro-physiologic and functional properties, thereby permitting them to self-regulate and interact with their associated molecules and related biologic systems. At the molecular level of all cells, tissues and organs, the physiologic and biochemical processes directing cell survival, growth, proliferation, function such as programmed cell death require a complex series of fundamental alterations and modifications in the electrostatic bonding interactions within their given bio-regulatory systems. These charge-dependent cell governing bio-regulatory systems are in fact naturally inherent within all living cells and tissues. Certain exogenously applied electromagnetic fields of low energy have been demonstrated to alter cell membrane signaling systems, cell membrane potentials, oxidative/reductive processes and rates, DNA transcription, thermodynamic and kinetic driven protein folding, ion drift and collision rates, immune cell response, and enzyme activity when applied to biologic systems.
Making use of this phenomena, electromagnetic fields of low energy have been used therapeutically for several years or more to stimulate bone growth and repair, as well as healing of other various tissues in humans and animals.
SUMMARY
In the context of cancer therapeutics, there are physiologic differences between normal cells and cancer cells which render the cancer cells with different sensitivity than normal healthy cells to the electromagnetic field applications described herein. The methods and applications described for electromagnetic field inductive coupling to cancer cells and cancerous tumor tissues are utilized to adversely affect the cancer cell's bio-regulatory growth, proliferation and survival systems without harming, beyond a physiologic lethal tolerance, the bio-regulatory growth, proliferation and survival systems of surrounding non-pathologic normal cells and tissues. That is to say, embodiments of the present invention are directed specifically toward adversely altering the bio-regulatory electrical energies of cancer cells, specifically, the bio-regulatory electrical energies that are involved in the physiologic processes of cancer cell growth, proliferation, and survival.
Embodiments of the present invention accomplish this without lethally affecting the bio-regulatory systems of normal cells and tissues.
Methods are provided for introducing exogenously applied electromagnetic field energy of specific signal parameters into a biological system of cancer cells and cancerous tumor tissues. This provides the ability to induce growth arrest and apoptotic cell death in cancer cells and cancerous tumors via the electromagnetic field's energy affect upon the bio-regulatory electric energies of that cancerous system.
Specifically, in the context of the cancer therapeutic process, methods for electromagnetic field inductive coupling to biologic tissues are utilized for the purpose of adversely affecting, beyond a tolerance of normal biologic homeostasis, the bio-regulatory electric energy interactions that govern the biologic, biochemical, biophysical and physiologic processes of cancer cells and cancerous tumor growth and proliferation. Cancer cell growth arrest and apoptosis are the results demonstrated via applying to cancer cells and cancerous tumor tissue the electromagnetic field energies that are a function of the electromagnetic signal parameters described in this invention.
Embodiments of the present invention are based on investigations which demonstrate an increase in cancer cell and cancerous tumor programmed cell death (apoptosis) as well as an adverse affect on the cancer cells growth and proliferation cycles. These findings are the results of inductive coupling of electromagnetic field energies of specific frequencies, waveforms and intensities to cancer cells grown in an in vitro setting, as well as cancerous tumor tissues residing in living mice during in vivo experimental study model trials.
Embodiments of the present invention are intended for use as a means to induce growth arrest and/or apoptosis in cancer cells and cancerous tumors via the externally applied application of electromagnetic field energies of specific frequency range, waveform and intensity range to the cancer cells and cancerous tumors. An electromagnetic transducer(s) e.g. coil(s) of any design or configuration that is (are) capable of producing said electromagnetic field energy may be employed as the tool for delivery of the electromagnetic field energy to the cancer site of interest. Any of a variety of electrical signal generators can be used to provide alternating (e.g., sinusoidal, square, sawtooth, etc.) current that can be amplified to the desired radio-frequency power levels and modulated to give the desired signal characteristics such as envelope shapes and repetition rates. This signal is used to drive electromagnetic coils with a current that will generate a time varying magnetic field, B. The magnetic field penetrates the biologic tissue and induces an electric field in the tissue.
To optimize the transfer of power from the signal generator and the amplifier into the tissue, a tuner or alike may be used to match the electrical impedances. The electromagnetic field energy is delivered to the cancer site of a patient by anatomically positioning an electromagnetic coil or multiple coil assembly on, around, or about the outer skin surface of the patient. The electromagnetic coil assembly is positioned to deliver the highest quality, in terms of bio-effectiveness, electromagnetic field energy possible to the area of the cancer and or tumor site to be treated.
One aspect of the present invention is to provide a particularly configured electromagnetic field to a cancer site where the electromagnetic field either has or is generated by electrical current having a particular waveform, frequency range and field intensity range. Moreover, embodiments of the present invention utilize electromagnetic field signal parameters which include the harmonics and infinite sub-harmonics of any one or more of the particular signal parameters provided herein, particularly when such parameters have demonstrated cell growth arrest and apoptosis in cancer cells and live cancerous tumors specifically.
One aspect of the present invention is to provide an electromagnetic field energy delivery to a patient via non-invasive electromagnetic field producing instruments that are capable, by way of inductive coupling, to deliver the electromagnetic field energies to the targeted cancer cells and tumor tissues of interest. The electromagnetic field signal parameters described herein are intended to be used specifically as a tool to induce cancer cell growth arrest and apoptosis specifically in the context of cancer therapeutic treatment.
In accordance with at least some embodiments of the present invention, non-invasive methods for the delivery of the electromagnetic field energy to the area of cancer growth in the patient are used. That is to say, the electromagnetic field energy parameters can be delivered via any externally placed electronic device that can serve the purpose of delivering the designated signal by means of electromagnetic field energy to the patient during treatment and attain the desired biologic effect.
In accordance with at least some embodiments the mode of energy transfer between the electronic device and the patient is electromagnetic field/tissue inductive coupling of energy.
It is also one aspect of the present invention to employ electromagnetic transducer(s) such as a coil(s) type of devices for the purpose of delivering electromagnetic field energy via a method of electromagnetic field/tissue inductive coupling to a patient, due to the fact that the electromagnetic field signal parameters used herein are specifically designated to cause growth arrest of cancer cells and death of cancer cells via apoptotic pathways specifically, and not to stimulate or promote tissue growth, or enhance the healing and regeneration of damaged tissues.
As can be appreciated by one skilled in the art, the electromagnetic field signal parameter ranges discussed herein are intended for delivery to a patient via any of the various possible designs of exterior body-positioned electromagnetic transducers, e.g. coils, electromagnetic field producing instruments or device systems, capable of delivering said electromagnetic field energies and attaining the desired biologic effect.
The biological effect to the cancer cells or cancerous tumors resulting from application of the electromagnetic energy signal parameters herein are not a result of excessive levels of heat, radiation, electric current, or high electric voltage that would typically be considered lethal and destructive to both, cancer cells and cancerous tumors as well as normal cells and normal tissues. The electromagnetic energy levels described herein cause adverse growth effects and cell death to cancer cells and cancerous tissues, without causing lethal damage and destruction to normal cells and tissues.
Other past solutions that use similar electromagnetic field signal parameters for the treatment of cancer describe the use of surgically invasive inserted electrodes made of wire or other materials capable of electric conduction.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic representation of a first exemplary transducer placed in a position to treat a tumor site;
FIG. 2 is a schematic representation of a second exemplary transducer (figure eight coil winding) placed in a position to treat a tumor site;
FIG. 3 is a more detailed depiction of a exemplary transducer and its interaction with a tumor site;
FIG. 4 is a block diagram depicting a first exemplary cancer treatment system;
FIG. 5 is a block diagram depicting a second exemplary cancer treatment system;
FIG. 6 is a block diagram depicting a third exemplary cancer treatment system;
FIG. 7 is a block diagram depicting a fourth exemplary cancer treatment system;
FIG. 8 is a block diagram depicting a fifth exemplary cancer treatment system;
FIG. 9 is a block diagram depicting a sixth exemplary cancer treatment system;
FIG. 10 is a block diagram depicting a seventh exemplary cancer treatment system;
FIG. 11 depicts an exemplary waveform used for treating cancer in accordance with at least some embodiments of the present invention; and
FIG. 12 depicts an exemplary waveform used for treating cancer in accordance with at least some embodiments of the present invention.
DETAILED DESCRIPTION
Embodiments of the present invention provide an electrotherapeutic system of employing electromagnetic field energies to a human or animal for the purpose of inducing growth arrest and cell death in cancer cells and cancerous tumors that reside in the body of animals or humans. The electromagnetic fields can be synthesized by any type of the many varieties of signal generators, signal amplifiers, and geometrically configured electromagnetic coil designs. For example, with reference to FIGS. 1-3 , these diagrams represent three different types of electromagnetic coil configurations that can be selected and used to apply the signal by means of electromagnetic field for treating cancer.
The exemplary embodiment depicted in FIG. 1 represents the solenoid design type that utilizes wire windings of various circular dimensions to carry electric current and induce electromagnetic fields. The induced electric fields are strongest at the wires and inside the perimeters of the coil boundaries where the targeted cancer tissue can be located during patient treatment.
FIG. 2 depicts another exemplary embodiment where a figure eight design type is used whereas the wire windings are configured in the shape of the number eight and these wire windings carry electrical current used to induce electromagnetic fields. The induced electric fields are typically the strongest perpendicular to the center area of the figure eight coil at a point where the windings cross one another and thus it is this area that would be most effective during treatment of a cancerous tumor in a patient.
FIG. 3 depicts another exemplary embodiment where a solid ferrite core type design is used and is electrically energized via wire wrappings around a solid iron or ferrite core. The current induces a magnetic field in the iron core and the magnetic field is transmitted across the open gap. The induced electric field is substantially oriented at a right angle to the magnetic field and the targeted cancer cells and cancerous tumor tissues are placed such that they are exposed to these fields. The coil depicted in FIG. 3 may be placed such that the targeted area of interest on the patient would fall adjacent to the gap in the iron core.
FIGS. 4-6 depict examples of various types of portable coil apparatuses and systems that can be used during treatment application for the delivery of an electromagnetic field to the patient. In accordance with at least some embodiments of the present invention, the coil apparatuses may be secured to the patient via a non-conductive means, such as by using fabric or other non-conductive materials. Alternatively, or in addition, the coils may be placed on the patient and held in place by gravity. As another alternative, the coils may be secured to the patient with a preconfigured device that is capable of conducting electricity and generating its own electromagnetic field, which can be used to supplement or direct the electromagnetic field generated by the primary coil apparatus.
As an alternative to using portable coils, or in addition to using such coils, embodiments of the present invention also contemplate the use of a stationary coil or set of coils that can be configured to have a patient moved into and about such coils. Such exemplary embodiments are depicted in FIGS. 7-10 where it is shown that the stationary table design types of coil assemblies can be used for application of electromagnetic energy to a patient in the clinical setting, where the patient is resting on the table during the electromagnetic field delivery. More particularly, embodiments of the present invention may be adapted to employ a clam-shell coil configuration ( FIG. 7 ), a full coil configuration ( FIG. 8 ), one or two opposing figure eight coils ( FIG. 9 ), and/or a c-shaped coil ( FIG. 10 ). One or more of such exemplary electromagnetic energy delivery systems may be described in further detail in one or more of the following patent documents, each of which are hereby incorporated herein in their entirety: U.S. Pat. No. 7,160,241; U.S. Pat. No. 6,060,293; U.S. Pat. No. 5,723,001; U.S. Pat. No. 4,998,532; U.S. Pat. No. 4,454,882; U.S. Pat. No. 5,014,699; U.S. Pat. No. 4,674,482; U.S. Pat. No. 6,208,892; U.S. Pat. No. 6,856,839; US 2001/0021868.
The electromagnetic energy field generated by a coil and applied to a patient in accordance with at least some embodiments of the present invention is composed of current and voltage (i.e., is generated in a coil or similar conductor at a particular voltage and current level) to induce a particular magnetic field. The electromagnetic field may be synthesized by one or multiple electrically energized electromagnetic coils that are connected via terminals and cables to an electric signal source. That is to say, a single coil or multiple coils are driven by a signal source from a suitable or commercially available signal generator with an output current that is amplified by a suitable or commercially available amplifier. The amplified signal is then delivered to a coil which can be made of various electric conducting materials (e.g., steel, copper, aluminum, gold, silver, etc.), and that may be configured the same, similar, or different from the coils referred to FIGS. 1-3 , and whereby the current traveling through the coil material produces a magnetic field.
The magnetic field is adapted to induce an electric field, thus the electromagnetic field is produced. During treatment applications on a patient, and with a coil assembly as described above positioned on, about, or around the tissue area of choice, the electromagnetic field then inductively couples to the dielectric pathways of the targeted cell or tissue of interest, thereby inducing electrical potential in the targeted cell or tissue, and inducing the desired biophysical event. To optimize the uniformity of the electromagnetic field lines and induced voltage in the targeted tumor tissues, it is recommended that the size of the coil that is used for treatment of the tumor be determined with consideration to the anatomical location and size of the tumor area being treated. Situations can arise where impedance miss-match between the coil and tissues can occur as a result of coil placement on, about or around the body. The coil/tissue inductive coupling event can be optimized to deliver the most appropriate and required electromagnetic energy via a process of impedance-matching. Impedance-matching is made possible with the use of an impedance-matching transformer that is typically located between the output of the amplifier and input of the coil structure.
One of the embodiments of this invention includes a signal comprised of modulated-bursts of a sine wave (or similar type of wave), and this electromagnetic energy is delivered to the area of cancer growth at a pre-determined amplitude range. The amplitude of the electromagnetic wave is set by controlling the current output from the current source to the amplifier. The electromagnetic signal parameters found to be effective in reducing cancer cell proliferation and inducing cancer cell apoptosis are within a particular range. However, the biology of cancer is such that cancer cells and cancerous tumors demonstrate a wide heterogeneous biologic nature, and it is recognized scientifically that widespread histological diversities exist among the various anatomical regions in the body where cancer may be located. Therefore, the electromagnetic field signal parameters that can be altered to optimally treat a cancerous cell but not harm a normal cell include, but are not limited to, waveform, peak field strength, carrier frequency, duty cycle, burst duration time, rise and/or fall times, and burst repetition rate. The particular combination of values for each parameter may vary across a certain range depending upon certain mentioned biologic factors. These biologic factors include, but are not limited to, specific cancer cell genotype, phenotype, cell sensitivity, and variables within the biologic, physiologic, biophysical and biochemical properties of the specific cancer cells or cancerous tissues being treated. The absorption of the signal by the biologic material occurs over a range of frequencies so that it is expected there will be a range for frequencies corresponding to the line width of the absorption spectra of the biologic processes being excited or activated by the applied signal. Accordingly, the impedance matching transformer may be employed and may have as an input to its control mechanism one or more sensors connected to the patient that are adapted to measure one or more of the biologic factors of interest.
The variation of electromagnetic field signal properties within the electromagnetic field signal parameter range that are necessary to address the above biologic factors includes, but is not limited to, waveform type, carrier frequency, burst duration and width, duty cycle, burst repetition rate, rise and/or fall time, and peak amplitude. These electromagnetic field signal parameters are expected to range over the bandwidth of the response time for the biologic tissue being addressed. This can be done in order to demonstrate effectiveness in terms of cancer cell growth arrest and the induction of cancer cell and tumor apoptosis. The electromagnetic field signal parameters found to be effective for cancer cell growth arrest and apoptosis induction are multiple signal components to include any Fourier components within the spectral parameters of the pulsed-modulated bursts of sinusoidal bipolar radio-frequencies described in this invention.
As can be appreciated by one skilled in the art, electromagnetic field signal parameters used can be inclusive within the parameters or range of parameters discussed herein for use relative to the treatment of cancer and cancerous tumors in animals or humans.
As one example, and as can be seen in FIG. 11 , about a 100 kHz to about 1 GHz bipolar sinusoidal waveform, or preferably a 1 MHz to 100 MHz bipolar sinusoidal waveform, or more preferably about a 10 MHz bipolar sinusoidal waveform (where the frequency of the waveform is maintained low enough to avoid tissue heating), when properly gaited using a signal control unit, and when delivered to the tissue site of interest as a pulse modulated burst width of between about 0.2 microseconds and about 20 microseconds, or preferably between about 1 microsecond and about 10 microseconds, or more preferably about 2 microseconds duration, (20 cycles/burst) and at a burst repetition rate of between about 100 and 300 kHz, or preferably between about 150 kHz and 250 kHz, or more preferably about 200 kHz has demonstrated successful biological effectiveness in the context of arresting cancer cell growth and proliferation, and inducing cancer cell apoptosis in cancerous tumors of living mice. This particular waveform may be applied with any of the coil devices or system described herein. For instance, any suitable portable or stationary electromagnetic coil device or electric field producing device thereof, capable of delivering the electromagnetic energy signal to the cancerous tumor site, and within the guidelines, parameters, and specifications as described in this invention, can be employed.
As another example, and as can be seen in FIG. 12 , about a 100 kHz to about 1 GHz bipolar sinusoidal waveform, or preferably a 1 MHz to 100 MHz bipolar sinusoidal waveform, or more preferably about a 10 MHz bipolar sinusoidal waveform that is properly gaited by using a signal control unit, and when delivered to the tissue site of interest as a pulse modulated burst width of between about 0.015 milliseconds and about 150 milliseconds, or preferably between about 0.15 milliseconds and about 15 milliseconds, or more preferably about 1.5 milliseconds duration, (15,000 cycles/burst), and a burst repetition rate of between about 0.15 Hz and about 1.5 kHz, or preferably between about 1.5 Hz and about 150 Hz, or more preferably about 15 Hz has demonstrated successful biologic effectiveness in the context of cancer cell growth arrest and apoptosis induction in cancerous tumors of living mice. This particular waveform may be applied with any of the coil devices or system described herein. For instance, any suitable portable or stationary electromagnetic coil device or electric field producing device thereof, capable of delivering the electromagnetic energy signal to the cancerous tumor site, and within the guidelines, parameters, and specifications as described in this invention, can be employed.
The solid ferrite type of coil may be used to optimize certain frequencies used in this invention, thereby helping to reduce the power required to drive this coil. The electromagnetic field peak amplitude levels for both of the pulse-modulated radio-frequency burst signals described above that demonstrate decreased cancer cell growth, proliferation, and apoptosis, when applied to cancer cells or tumors during the time points and vulnerable cell cycle periods as described below, are in a range of about 1 to 300 V/cm, or peak amplitudes that are less than that which causes significant or sustained damage to (most) normal cells or tissues. More specifically, embodiments of the present invention contemplate that some damage may occur to some normal cells around a targeted region of cancer cells, but such damage should be limited in terms of the size and scope (e.g., if a tumor is being treated in a liver or similar internal organ, then some healthy tissues in the internal organ and surrounding areas may be damaged, but the extent of such damage should be limited by properly controlling the characteristics of the electromagnetic field). The current density of these fields would be in the range of several amps per meter squared, and this value is dependent on the tissue impedance being targeted and exposed during patient treatment.
In the context of the cancerous tumor environment, the growth and division regulatory cell cycles of cancerous tumor cells typically are not collectively synchronized with one another. In terms of cell sensitivity to the electromagnetic field energies, many of the diverse cancer cell genotypes and or phenotypes that make up the tumor proper have individual critical points in their growth and division cell cycles as a function of biological timing and molecular vulnerability. It is therefore clarified that in order to attain success in arresting cancer cell growth and/or inducing cancer cell or cancerous tumor cell apoptosis, the electromagnetic field energies described herein and used in accordance with at least some embodiments of the present invention should be presented and/or delivered to any tumor cell of therapeutic treatment interest during at least one or more critical cell cycle biological time points or molecular vulnerability points or relevantly sensitive points within that given tumor cell.
The final effect from the electromagnetic field energies delivered to the area of cancer is inhibition of the cancer cells growth cycle, decreased cancer cell growth rate, and cancer cell apoptosis. It has been determined that the outcomes of applying electromagnetic field signals to cancer growth in tumors residing in living mice that the above electromagnetic signal parameters are effective in arresting cancer cell growth and inducing cancer cell apoptosis.
EXAMPLES
To insure adequate tumor development the immuno-compromised mouse strain ICR-scid was chosen for these experiments. Four male mice were injected with a human pancreatic cancer cell line for the purpose of inducing tumor development. Ample time was allowed for tumor development in each mouse. Two mice were used for electromagnetic field exposure application and two were used as a non-exposed control group.
Three different coil configurations as shown in FIGS. 1-3 were individually tested as part of this study. Individual coils were applied directly over the tumor site of the mouse in a manner that allowed for inductive coupling of the electromagnetic field signal into the area of the mouse tumor. The two mice were exposed individually throughout all periods of the tumor growth cycle. The electromagnetic signal parameters described in the detail section of this invention were applied for each individual mouse that was exposed. The tumors of all four mice were surgically removed five days after the finish of the last exposure application and preserved in formalin. Each individual tumor was then sectioned into three individual areas and the tumor tissues processed and mounted on glass slides for histo-chemical study. The tissues of the tumor samples were stained using TUNEL staining which is one of the current standards for detection of apoptosis. The slides were read using fluorescence microscopy and six photographs of each tissue section were acquired. The TUNEL staining was quantified in the following manner. All images were acquired with the same exposure and gain settings. For each field, the total TUNEL fluorescence per nucleus was quantified. Nuclei were defined by thresholding the DAPI signal. The threshold image was used as a mask on the TUNEL image to define nuclear TUNEL labeling. The masked TUNEL image was thresholded and the integrated intensity was calculated. Nuclei were counted manually in each field using DAPI labeling. Total apoptotic activity was calculated as nuclear TUNEL integrated intensity.
Experiment results demonstrate a substantial increase of up to and above 50% in the level of apoptotic related cell death in the electromagnetic field exposed mouse group when compared to the unexposed mouse control group when using certain exposure parameters, numerical differences in terms of the level of cell apoptotic activity vary between the two exposed mice on an individual basis, and there is a numerical variation of cell apoptosis measured among individual tissue sections corresponding to anatomical depth within the same tumor. This most likely reflects electromagnetic field differences in terms of field amplitude relative to distance from various sections of the tumor. This experiment was repeated with similar results.
While embodiments of the present invention have been described in connection with particular apparatuses, methods, systems, and system components, the invention is not so limited. Moreover, one skilled in the art will appreciate that each feature of the present invention described herein may be separately claimable. Furthermore, embodiments of the present invention are not necessarily limited to the treatment of cancerous cells, although experimental data has been produced showing positive results when used on such cells. Rather, embodiments of the present invention may also be used to target any particular type of cell (whether cancerous or not) based on its characteristics and to impart a particular reaction from that cell or group of cells having the common characteristic. The reaction imparted may be controlled by intelligently adjusting the parameters of the electromagnetic field applied thereto.
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A non-invasive method of using electromagnetic field energies to reduce or arrest the growth rate and proliferation of cancer cells, and induce apoptosis in cancer cells, relatively without significantly harming normal cells beyond their physiologic threshold of survival are provided. The methods described herein are intended to be used toward the treatment of cancer in human or animals within the context of cancer therapeutics.
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The present invention relates to a nutritional or therapeutic composition for oral administration which comprises a naturally occurring precursor that is metabolised to a compound having anandamide activity for use as a medicament or nutritional product, a method of production of the composition, use of the composition in the manufacture of a nutritional or therapeutic composition for the treatment or prevention of a behavioural disorder; and a method of treatment or prevention of a behavioural disorder which comprises administering an effective amount of the composition.
Within the context of this specification the word “comprises” is taken to mean “includes, among other things”. It is not intended to be construed as “consists of only”.
Standard nomenclature for fatty acid compounds is used. For example, the number of carbon atoms and number and position of double bonds is typified by “20:4(5,8,11,14)” for arachidonic acid: the number preceding the colon is the total number of carbon atoms, the number immediately following the colon is the number of double bonds, and the numbers in parentheses are the position of the double bonds, starting from the end of the chain bearing the carboxylic acid group. In all compounds referred to in this manner, except where otherwise indicated, all double bonds are cis.
Standard nomenclature for classes of fatty acid compounds is used indicating the location of the double bond closest to the methyl end group, typified by “n-3” or “n-6”: the number following the dash denotes the position of the double bond closest to the methyl end of the molecule, counting from the methyl end. Thus, arachidonic acid is in the n-6 class, as is linoleic acid (18:2(9,12)), whereas eicosapentaenoic acid (20:5(5,8,11,14,17)) is in the n-3 class. This nomenclature is equivalent to “omega or ω” nomenclature in the literature, “ω” and “n” being interchangeable.
Anandamide (also referred to as N-arachidonylethanolamine) is an example of an N-acyl ethanolamine (hereinafter referred to as NAE). Both NAEs and N-acyl amines (hereinafter referred to as NAAs), an example of the latter of which is oleamide, are naturally occurring in the human body. They have been found in the hippocampus, striatum, cerebellum, spleen, heart, plasma and cerebral spinal fluid as well as in human milk.
The term “anandamide activity” is used within the context of this specification to mean an activity selected from the group which comprises an activity attributed to the drug 9-tetrahydrocannabinol (THC), as well as affects specific to anandamide and 1- and 2-monoarachidonylglycerol isomers (hereafter denoted AG), and unique from THC. It has been suggested that anandamide and AG activities are typically, but not necessarily, mediated by binding to the receptor class, known as CB1 and CB2 receptors. These anandamide activities include, but are not limited to: antinociception, catalepsy and inhibition of locomotor activity in vivo and displacement of 9-tetrahydrocannabinol (THC), inhibition of adenylate cyclase, inhibition of calcium channels, activation of phospholipase A 2 , release of intracellular calcium in vitro and inhibition of twitch response ex vivo.
The term anandamide, as used within the context of this specification, refers to an NAE, NAA or MAG having anandamide activity (as defined above). Accepted scientific nomenclature will be used in this specification when reference is made to specific acyl moieties of an NAE, NAA or MAG.
It is well known that pharmaceutical compounds have wide application for their calming effects and they may be used in the treatment of patients suffering from conditions such as hypertension, glaucoma, insomnia, pain, inflammation, migraine headaches, convulsions, loss of appetite, nausea, cramps, diarrhea, asthma, nervousness, aggressive behaviour, excessive timidity, inability to sleep, catalepsy, low mood, depression, gut upsets, or spasms, poor motor control, tics, excessive stress, spasticity or multiple sclerosis. However, a number of these compounds are not naturally occurring in nature and in view of this, patients may be reluctant to be administered them. In the light of this there is a need for the provision of new products which include naturally occurring precursors of compounds that have a nutritive or therapeutic effect, when metabolised endogenously to active compounds with anandamide activity.
Furthermore, a problem with most commercially available drugs is that they give rise to side affects such as nausea, bloating, cramping, etc. Clearly there is a need for a composition which does not give rise to these side effects.
The method of administration of a nutritive or therapeutic compound is an important consideration. Intravenous or subcutaneous administration of drugs requires expertise, and compared to oral administration it is not as safe, convenient or acceptable to the patient. In the light of these concerns it is clear that there is a need for new nutritive or therapeutic products which may be administered orally.
In addition to the problems set out above, infant formulae are generally constructed so that they resemble human milk as closely as possible, however a plurality of components in human milk are bioactive and, because of synergies among the components, the inclusion of only one or a few of them may not reproduce the bioactivity of human milk. In view of this, a problem which presently faces researchers lies in the formulation of infant formulae or weaning foods which have components that are present in human milk and which have an equivalent activity to human milk. The problem is compounded in view of the fact that not all of the components in human milk have been identified and there are variations in the concentration of components which are present, possibly due to variations of mother's diets.
A further problem which faces nutritionists lies in the field of pet nutrition. Whereas some pets are aggressive, others are excessively timid. Muzzles have been provided which fit over the heads of aggressive animals and cover their mouths. This may not be a good solution in view of the fact that a muzzle may serve to aggravate the animal. In the light of this, there is a need for alternative solutions for calming excessively aggressive or timid pets.
U.S. Pat. No. 5,874,459 discloses that anandamide may act as a ligand which interacts with cannabinoid receptors in the central nervous system and gut (CB1 receptors) and/or immune cells and tissues such as spleen, thymus and lymphocytes (CB2 receptors). Furthermore, this document indicates that interactions between anandamide and these two types of cannabinoid receptors have been shown to induce physiological effects. It is described that non-arachidonoyl NAEs and NAAs have been shown to inhibit anandamide inactivating enzyme. This inhibition has the net effect of potentiating the effect of anandamide.
It has been suggested that a family of NAEs and NAAs as well as sn-1 and sn-2 monoarachidonyl glycerides are agonists of anandamide receptors (here anandamide receptor refers to a receptor that anandamide might bind to, including CB1, CB2, non-CB receptors) and elicit responses analogous to that elicited by anandamide. The chemical structures of NAEs and NAAs are based on fatty acids and depending on the specific fatty acids esterified they have been shown to have different activities. For example, whereas anandamide interacts with both the CB1 receptor of the central nervous system and the CB2 receptor of the immune system, palmitolyethanolamide may interact with the CB2 receptor but not the CB1 receptor and has an anti-inflammatory effect but no known neural effect.
Nature, vol 396, page 636, (1998) discloses the results of an analysis wherein NAEs and 2 arachidonylglycerol (2-AG) were identified from foods including human, bovine and goat milk and cocoa at various stages of processing. The document suggests that anandamide (300 mgkg body weight −1 ) and 2-arachidonoyl glycerol (400 mgkg body weight −1 ) have bioactivity when taken orally in mice, however the compounds were active only at very high concentrations relative to the concentrations normally present in foods and the results obtained show that the amounts of anandamide, 2-AG and oleamide in foods, including milk and cocoa, are several orders of magnitude below those required if administered by mouth, to reach the blood and cause observable “central effects”. However, the document indicates that pure doses of anandamide, 2-AG and oleamide have calming effects and effects on the immune system when injected into animals. Calming effects are characterised by lessened activity, decreased nociception and greater propensity for sleep.
U.S. Pat. No. 5,689,55 discloses that synthetically produced polyunsaturated fatty acid amides and their derivatives are able to mimic the effect of naturally occurring anandamides in the brain and bind to the canabinoid receptor. The compounds described exhibit physiological activity and are reported as being useful active ingredients in pharmaceutical compositions for treatment of inflammation, migraines, spasticity, glaucoma and multiple sclerosis.
Remarkably it has now been found that a composition for oral administration may be provided which includes a precursor that is metabolised endogenously to form a compound having anandamide activity. It is particularly surprising that a dietary precursor is selectively taken up by the CNS and selectively incorporated into the NAE pool to serve as a CB receptor-binding ligand. In addition, it is remarkable that a dietary precursor induces only a small change in the phospholipid acyl composition but induces a large change in the NAE composition.
The invention addresses the problems set out above.
SUMMARY OF THE INVENTION
The present invention provides improved nutritional and therapeutic compositions.
Accordingly, in a first aspect the invention provides a nutritional or therapeutic composition for oral administration which comprises a naturally occurring precursor that is metabolised to a compound having anandamide activity for use as a medicament or nutritive product.
In a second aspect the invention provides a method of production of a nutritional or therapeutic composition for oral administration which comprises the steps of identifying, purifying or synthesising a naturally occurring precursor that is metabolised to a compound having anandamide activity.
In a third aspect the invention provides use of a precursor which is metabolised to a compound having anandamide activity in the manufacture of a nutritional or therapeutic composition for the treatment or prevention of an anandamide-mediated ailment selected from the group which comprises hypertension, glaucoma, insomnia, pain, inflammation, migraine headaches, loss of appetite, nausea, cramps, diarrhea, gut upsets, intestinal motility disturbances, asthma, nervousness, aggressive behaviour, excessive timidity, inability to sleep, catalepsy, low mood, depression, spasms, poor motor control, tics, excessive stress, spasticity, multiple sclerosis and vocalization, poor language acquisition, skin inflammation and excess nociception.
Vocalization is taken to mean disturbances in vocalization and vocalization related to bonding behaviour, for example between an infant and mother. Such vocalizations are important in animal husbandry and in successful nurturing of the offspring by the mother in household pets. Further, such behaviours as chronic sustained crying in human infants may be treatable by oral administration of an embodiment of a composition according to the invention.
Oral administration of an embodiment of a composition according to the invention may also be used to treat or prevent inflammation in superficial mammal tissues (e.g., skin) by modulating levels of compounds with anandamide-like activity in these tissues.
In a forth aspect the invention provides a method of treatment of an anandamide-mediated ailment selected from the group which comprises hypertension, glaucoma, insomnia, pain, inflammation, migraine headaches, loss of appetite, nausea, cramps, diarrhea, gut upsets, intestinal motility disturbances, asthma, nervousness, aggressive behaviour, excessive timidity, inability to sleep, catalepsy, low mood, depression, spasms, poor motor control, tics, excessive stress, spasticity, multiple sclerosis and vocalization, poor language acquisition, skin inflammation and excess nociception which comprises administering an effective amount of an embodiment of the composition according to the invention.
Preferably the precursor that is metabolised to a compound having anandamide activity comprises a long chain polyunsaturated fatty acid (LCPUFA) or derivative thereof. More preferably it comprises a compound of the general formula X:
wherein R is the alkenyl moiety of a LCPUFA of total chain length 16-28 carbon atoms with 2-6 double bonds, with the first double bond at the c-1, c-3 c6, c7, c9 c12 position, counting from the non carboxyl (methyl) part of the molecule; and where R″ is selected from —H, lower alkyl, —OH, NH 3 , and NHCH 2 CH 2 OH, or an acid addition salt or complex thereof.
More preferably the precursor comprises a plurality of the formula X. Preferably 1-3 X molecules are esterified to a glycerol backbone, in the following stereochemical configurations: sn-1,2,3; sn-1,2; sn-1,3; sn-2,3; sn-1; sn-2; sn-3.
In an alternative embodiment the LCPUFA is a polyunsaturated fatty acid of 16-28 carbon atoms with 2-6 double bonds, having methylated-, branched-, cyclic-, conjugated-, non-methylene interrupted-, epoxy-, furanoid-, hydroxyl-, allylic-, trans-, and seleno-moieties.
More preferably the fatty acid is selected from the group which comprises arachidonate (20:4n-6 AA), linoleate (18:3n-6), gamma linolenate (18:3n-6), dihomogamma-linolenate (20:3n-6 DGLA), adrenic acid (22:4n-6), linolenate (18:3n-3), stearidonic (18:4n-3), eicosatetraenoic (20:4n-3), eicosapentaenoate (20:5n-3), docosahexaenoate (22:6n-3DHA), docosapentaenoate (22:5n-3 or 22:5n-6), tetracosapentaenoate (24:5n-3 or 24:5n-6), tetracosahexaenoate (24:6n-3) or the Mead acid (20:3n-9).
Preferably, an embodiment of a composition according to the invention includes an inhibitor of anandamide inactivating enzyme (also known as amidase). Preferably the inhibitor is selected from the group which comprises oleate and oleamide, palmitate, palmitoylethanolamide, linoleylethanolamide, 2 palmitoylglycerol, 2-linoleylglycerol.
Preferably an embodiment of a composition according to the invention comprises a mixture of a saturated molecule in combination with an unsaturated precursor that is metabolised to a compound having anandamide activity. Preferably, the saturated molecule is palmitate or palmitoylethanolamide. Preferably the unsaturated precursor is arachidonic acid. This provides the advantage that the anandamide activity of the metabolite formed endogenously is potentiated by both inhibiting the breakdown of a metabolite having anandamide-like activity and by the saturated NAE compound binding to the CB2 receptor.
Preferably, an embodiment of a composition according to the invention comprises a mixture of a compound which reacts with a CB receptor in combination with a precursor that is metabolised to a compound having anandamide activity and an inhibitor of the amidase. This provides the advantage of synergy between the active molecules and potentiation of their effect by inhibiting the breakdown of a metabolite having anandamide-like activity.
Preferably, the precursor that is metabolised to a compound having anandamide activity is a free fatty acid, fatty acid ester of an alcohol, or a triacylglycerol. More preferably it is a triacylglycerol having an active fatty acid at the sn-1 and sn-2 position. This provides the advantage that it leads to particularly effective CB receptor agonism. Most preferably, the triacylglycerol comprises both the active precursor compounds (e.g. arachidonate) and the potentiator compounds (e.g. palmitate). This provides the advantage of a particularly effective mixture.
Preferably, an embodiment of a composition according to the invention comprises a structured triacylglycerol prepared by the interesterification of triacylglycerols with active fatty acids so that a bioactive fatty acid is found in the sn-2 position of the triacylglycerol. This provides the advantage of optimising delivery of the active FA to body tissues, particularly the brain.
Preferably an embodiment of a composition according to the invention comprises a physiologically acceptable carrier diluent or adjuvant.
Preferably an embodiment of a composition according to the invention comprises a combination of a naturally occurring precursor that is metabolised to a compound having anandamide activity together with a typical steroidal or non-steroidal anti-inflammatory drug (NSAID). This provides the advantage that synergy occurs since the combination has the ability to diminish inflammation via different pathways.
Preferably, an embodiment of a composition according to the invention comprises a precursor of a CB1 receptor agonist (e.g. anandamide) in combination with a precursor of a CB2 receptor agonist (e.g. palmitoylethanolamide). This provides the advantage that the anti-pain effect of the metabolites is about 100 times stronger than the effect provided by the metabolites of either precursor individually.
Additional features and advantages of the present invention will be described in and apparent from the detailed description of the presently preferred embodiments and the figures.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows the chemical structure of N-arachidonoyl ethanolamine (anandamide), 2-AG, and oleamide.
FIG. 2 shows the effects of oral cannabimimetic lipids on ambulation, rearing, immobility and analgesia.
FIG. 3 shows the effects of oral administration of olive oil, anandamide, 2-AG, THC and oleamide on ambulation, rearing, immobility and analgesia. Ambulation, rearing, and immobility parameters were statistically, significantly different between the treatment groups and the control group, p<0.01-0.05, ANOVA, Newman-Keuls; Only THC statistically, significantly increased analgesia.
FIG. 4 shows the effect of olive oil, anandamide, 2-AG, THC and oleamide on body temperature. All groups were statistically, significantly different from the control group, p<0.01-0.05, ANOVA, Newman-Keuls.
FIG. 5 shows the effect of olive oil, anandamide, 2-AG, THC and oleamide on fecal output. Only the THC group was statistically, significantly different from the control.
FIG. 6 shows the changes in piglet brain N-acylethanolamines following dietary fatty acid modification with a scale of 0 to 250 on the axis labelled pmols/mg piglet brain lipid extract. Bars within a group of three not denoted with a letter in common are statistically significant from one another (p<0.01-0.05, ANOVA, Newman-Keuls). Adeq, adequate.
FIG. 7 shows the changes in piglet brain N-acylethanolamines following dietary fatty acid modification with a scale of 0 to 70 on the axis labelled pmols/mg piglet brain lipid extract. Bars within a group of three not denoted with a letter in common are statistically significant from one another (p<0.01-0.05, ANOVA, Newman-Keuls). Adeq, adequate.
DETAILED DESCRIPTION OF THE INVENTION
The present invention provides improved nutritional compositions. These compositions provide therapeutic benefits. The compositions include a naturally occurring precursor that is metabolized to a compound having anandamide activity.
By way of example and not limitation, examples of the present invention will now be set forth.
Piglets were fed using two different kinds of adapted infant formulations supplemented with low levels of arachidonate and docosahexaenoate (approximately the same levels as found in human breast milk) and obtained from different sources (see Table 1). The levels of NAE, MAG (monoacylglycerol) and primary amides were evaluated in their brains.
In this study piglets were fed from birth to 18 days with diets comprising embodiments of a composition according to the invention with or without 0.5% 20:4n-6 from single cell oils and 0.4% 22:6n-3 in formula, with either low (deficient) 18:2n-6(1.6%) and 18:3n-3(0.1%), or with adequate 18:2(n-6)(15.6%) and 18:3n-3(1.5%).
The diet compositions are shown in table 1.
TABLE 1
Formulas varied in n-3 and n-6 fatty acid content
18:2n-6-18:3n-3 deficient
18:2n-6-18:3n-3 adequate
Egg +
Egg +
single
Fatty
No
fish
Single
No
fish
cell
Sow
Acid
LCP
Oil
cell oil
LCP
oil
oil
milk
g/100g fatty acids
8:0
8.0
7.0
7.4
17.2
15.5
14.9
10:0
6.7
5.9
6.5
13.5
12.6
13.0
12:0
44.2
39.7
42.9
1.0
0.3
0.3
0.1
14:0
17.1
15.6
16.8
0.8
0.6
0.6
2.4
16:0
9.5
10.5
9.5
11.3
12.1
10.9
28.1
18:0
3.4
4.0
3.5
3.2
3.5
3.3
5.6
16:1
0.1
0.34
0.1
0.1
0.3
0.2
4.7
18:1
8.1
10.4
9.3
33.3
33.4
35.1
32.6
18:2n-6
1.6
3.8
1.9
15.6
16.0
16.4
20.4
18:3n-6
—
0.6
0.1
—
0.4
0.1
0.2
20:2n-6
—
—
—
—
—
—
0.4
20:3n-6
—
—
—
—
—
—
0.2
20:4n-6
—
0.1
0.4
—
0.1
0.4
0.7
22:4n-6
—
—
—
—
—
—
0.1
18:3n-3
0.1
0.5
0.1
1.5
1.8
1.6
2.3
20:5n-3
—
0.1
—
—
0.1
—
0.1
22:5n-3
—
—
—
—
—
—
0.6
22:6n-3
—
0.3
0.3
—
0.3
0.3
0.1
Changes in individual brain phospholipid classes that occurred after feeding were analysed.
The results showed that the addition of 20:4n-6 and 22:6n-3 to diets containing adequate levels of essential fatty acids (18:2n-6 and 18:3n-3) lead to an increase in 22:6n-3 in phosphatidyl choline; a decrease in 22:5n-6 in phosphatidyl ethanolamine; and no change in arachidonate (20:4n-6) in any of the phospholipid classes.
Thus, the small, unsubstantial increase seen in 22:6n-3 in phosphatidyl choline is consistent with the fact that the relevant diet had added 22:6n-3; however the lack of significant increase in arachidonate in any of the phospholipid classes examined indicates that added arachidonate is not incorporated into these phospholipid classes, but rather is metabolised or inadequately transported to the brain.
The primary amides, oleamide and arachidonamide, and 18:3 NAE were not detected and are omitted from table 2, which shows the changes in levels of MAG and NAE expressed as pmols/mg lipid that occurred following feeding of the diets.
TABLE 2
Monacyl glycerols (MAG)
Group
C20:4n-6
C22:4n-6
C22:6n-3
Adequate
66.0
3.53
3.87
adequate + SCO
44.4
6.23
5.93
Sow fed
44.1
6.13
6.67
TABLE 3
N-acyl-ethanolamines (NAE)
Group
C16:0
C18:0
C18:1n-9
C18:2n-6
Adequate
114.87
27.90
27.00
8.57
adequate + SCO
149.93
63.87
15.97
2.90
Sow fed
95.07
3.13
1.40
9.80
TABLE 4
N-acyl-ethanolamines (NAE)
Group
C20:4n-6
C20:5n-3
C22:4n-6
C22:5n-3
C22:6n-3
Adequate
6.10
32.87
14.80
3.63
3.80
adequate + SCO
23.77
172.37
23.07
33.67
36.10
Sow fed
19.97
165.63
29.30
28.00
15.77
MAG levels were not statistically significant for 20:4n-6 MAG, 22:4n-6 MAG and 22:6n-3 MAG in animals fed essential fatty acid sufficient diets (sn-1 and 2 isomers combined). This is an important finding because specific MAGs, such as 2-AG are known to bind to CB receptors and have bioactivity.
In animals fed the 18:2n-6/18:3n-3 sufficient diets, supplementation with AA and DHA led to increases in 20:4n-6 NAE and 22:4n-6 NAE (22:4n-6 is the 2-carbon elongation product of AA), 22:6n-3 NAE, 20:5n-3 NAE and 22:5n-3 NAE (the latter two are retroconversion products of 22:6n-3). The levels of these NAE products were similar to that found in sow milk fed piglets. Thus, it is a remarkable feature of the invention that when sufficient essential fatty acids are provided in the diet, the supplementation of AA and DHA to levels found in breast milk, has the effect of increasing corresponding NAE products to levels found in sow milk.
The results obtained indicate that supplementation with AA and DHA to formulae having sufficient essential fatty acid had minimal effects on brain phospholipid acyl moieties. However, in striking contrast, the same level of supplementation led to a 4-fold increase in the level of 20:4n-3 NAE present, a 5.2 fold increase in 20:5n-3 NAE, and a 9.5 fold increase in 22:5n-3 and 22:6n-3 NAE.
In order to show the biological activity of the composition of the present invention on animal's behaviour the effect of dietary poly-unsaturated fatty acids with and without a CB-1 receptor antagonist on anxiolytic-like responses in mice were tested. To this end, the ELEVATED PLUS MAZE TEST was applied (adapted after Handley and Mithani (Naunyn. Schmied. Arch. Pharmacol. 327: 1-5, 1984).
For the experiments male Rj:NMRI mice, obtained from Elevage Janvier, Le Genest-Saint-Isle France and weighing 10-11 g at delivery and 33-51 grams on day 42 were used. The mice were housed 10 per cage in wire cages with bedding and normal light cycle. They received ad libitum quantities of bottled distilled water and purified powdered diets (7.5 g/mouse) in ceramic cups (10/group) for 42 days. The Food was maintained at −80° C. in daily aliquots under nitrogen, thawed each afternoon before administration to mice. Uneaten food was discarded daily.
The principle of the test resides in that anxiolytic agents increase the number of entries into the open and often the closed arms of the elevated Consequently, mice should want to move and explore the spaces of the open and closed arms rather than staying still in the middle).
Mice were given the following agents intraperitoneally 60 minutes before the Plus Maze test:
Tween 80 as placebo;
the anxiolytic agent Clobazam at a non-sedative dose for test validation; or
validated amounts of AM251 (Tocris Cookson LTD., UK), a CB-1 receptor antagonist, to inhibit binding of endogenous NAEs to the CB-1 receptor.
All diets contained 90% fat-free AIN93G rodent diet in powder form (Lot 9350-5, Dyets, Inc., Bethlehem, Pa.), 0.4% milk fat, 1.2% palm olein, 1.9% Trisun sunflower oil, 1.5% soybean oil and 2.1-5.1% medium chain triacylglycerol oil. Parts of the medium chain triacylglycerol oil were replaced with 1.1% algal oil (providing 0.5 dietary wt.-% arachidonic acid) in diet D, 1.9% fish oil (providing 0.5 dietary wt.-% docosahexaenoic acid) in diet E, and with 1.1% algal oil and 1.9% fish oil in diets F and G. Dietary groups are summarized in the table below:
Diet Agent given Code Diet Description before Plus Maze Test A Control Diet Tween 80, 1% distilled water solution B Control Diet Clobazam, 32 mg/kg body weight C Control Diet AM 251, 64 mg/kg body weight D Diet AA Tween 80, 1% distilled water solution E Diet DHA Tween 80, 1% distilled water solution F Diet AA + DHA Tween 80, 1% distilled water solution G Diet AA + DHA AM 251, 64 mg/kg body weight
Abbreviations: AA, Arachidonic Acid; DHA, Docosahexaenoic Acid
The body weight, weight gain and the food intake of the mice was monitored throughout the experiment. These parameters were not significantly affected by ingestion of the various diets using classical one way analysis of variance (ANOVA). This indicates that differences in the behavioral tests as found can only be attributed to the components in the diet that were varied, namely dietary polyunsaturated fatty acids. To assess changes in the Plus Maze test, generalized Linear Models (GLM) and the Poisson family were used because the obtained response data are non-normally distributed counts.
Number of Entries in the Closed Arms
A vs. B: Average entries were 3.6 and 6.3, respectively, and the difference is at the limit of statistical significance (p-value=0.053). This result establishes that the anxiolytic agent Clobazam, under the present conditions, can increase closed arm entries.
A vs. C
There was no significant difference (p-value = 0.19).
A, D, E and F
overall, the p-value is 0.06. The fitted average
entries are respectively 3.6, 6.4, 6.0 and 6.8. In
group D, there is one mouse with 16 entries,
which is unusally high. Omitting this mouse,
the p-value becomes significant (0.02) and the
prediction for group
D
decreases to 5.3. This result establishes that the
combination of dietary AA and DHA may induce
anxiolytic (Clobazam-like) effects.
F vs. G
Average entries are respectively 6.8 and 4.6, and
the difference is at the limit of statistical
significance (p-value = 0.11). This result indicates
that the anxiolytic effects of the combination
of dietary AA and DHA may be transduced via
CB-1 receptor binding, i.e., via binding of
PUFA-derived NAEs.
C vs. G
Average entries are respectively 2.3 and 4.6, and
the difference is close to statistical significance
(p-value = 0.08). This result indicates that CB-1
receptors are not the only receptors that mediate
responses in the PLUS MAZE TEST, i.e., non-CB-1
receptors may partially mediate the actions of
dietary PUFA and (PUFA-derived) NAEs.
Additionally, the drug AM251 may not
fully antagonize CB-1 receptor binding.
In summary, the results from the number of entries into the closed arms in the ELEVATED PLUS MAZE TEST show that dietary AA and DHA and the combination of the two, have anxiolytic-like effects that seem to be mediated via their conversion to NAEs, and these NAEs in turn bind to CB-1 receptors located in brain regions known to induce behavioral responses in the PLUS MAZE TEST, such as the hippocampus.
It should be understood that various changes and modifications to the presently preferred embodiments described herein will be apparent to those skilled in the art. Such changes and modifications can be made without departing from the spirit and scope of the present invention and without diminishing its attendant advantages. It is therefore intended that such changes and modifications be covered by the appended claims.
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A nutritional or therapeutic composition for oral administration which comprises a naturally occurring precursor that is metabolised to a compound having anandamide activity for use as a medicament or nutritive product. In addition the invention includes a method of production of the composition, use of the composition in the manufacture of a nutritional composition for the treatment or prevention of a behavioral disorder; and a method of treatment or prevention of a behavioral disorder which comprises administering an effective amount of the composition. In a preferred embodiment the composition comprises a triacylglycerol having palmitate and arachidonate attached to its backbone wherein arachidonate is at the sn-1 and sn-2 positions.
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This application is a 371 of PCT/JP96/00602 filed Mar.11, 1996.
TECHNICAL FIELD
This invention is concerned with a peroxide bleach product with excellent bleaching activity. The bleach product of this invention is characterized by its content of cyanourea as the bleach activating agent and is used for bleaching of fabrics. The bleach product of this invention is preferably used for bleaching of mold developed on the walls of a house or furniture.
BACKGROUND ART
Bleaches and mold removers are classified into chlorine bleach and peroxide bleaches. Chlorine bleaches with the main component of sodium hypochlorite have been used for bleaching fabric and mold developed on the walls of a house or furniture because of its strong bleach activity. However, despite the excellent bleaching effectiveness, chlorine bleach products are fraught with weaknesses such as discoloration of the fabric, making its use inappropriate for colored fabric, unpleasant characteristic odor due to the chlorine molecule during use and the possible danger of poisoning due to chlorine gas.
On the other hand, peroxide bleaches have been used more frequently in the general household because of the wide applicability as a bleach compared to the chlorine type and the absence of malodor. However, the bleaching effectiveness of peroxide bleaches is inferior, if used alone, compared to chlorine bleaches, resulting in poor bleaching performance when used for fabrics at low temperatures and when used for bleaching mold on the surface of household walls or furniture, especially mold which develops on the sink in the kitchen and on the walls and ceiling of the bathroom and tile joints.
Consequently, attempts have been made to increase the bleaching activity by addition of N-acyl compounds such as tetraacetylethylenediamine (TAED) or tetraacetyl glycoluryl (TAGU) or esters such as glucose pentaacetate or saccharose octaacetate to peroxide compounds such as hydrogen peroxide, hydrogen peroxide adduct of sodium carbonate or sodium perborate. Various proposals have been made to use nitrile compounds as the activating agent for improved bleaching activity of peroxide compounds. United Kingdom Patent Application No. 802,035 described use of various nitrile compounds and U.S. patent application Ser. No. 3,882,035 described a bleach product containing iminodiacetonitrile as the activating agent. Japanese Kokai Patent Application No. Sho 52 1977!-52880 described nitriles such as p-chlorobenzoylcyanamide.
However, insufficient bleaching activity was obtained for fabrics at low temperatures and for removal of household mold by bleaching. There is another weakness in such bleach in that malodor, specifically peracetic acid was generated as the result of reaction of hydrogen peroxide in the use of activators such as N-acyl compounds, for example, TAED, and esters, for example, glucose pentaacetate.
DISCLOSURE OF INVENTION
This invention offers a bleach product with excellent bleaching activity on fabric as well as excellent activity for removal of mold on household walls and furniture by bleaching without malodor.
After intense studies for the solution of aforementioned problems, we discovered that a marked improvement can be made in bleaching of fabrics and removal of mold on household furniture and walls by bleaching without generation of malodor by the use of a bleach product composed of hydrogen peroxide or a peroxide which gives rise to hydrogen peroxide in aqueous solution, cyanourea and an alkaline agent, under the condition that alkalinity is achieved when the product is dissolved in water. The invention is the result of this discovery.
The invention offers a bleach product characterized by its content of (A) hydrogen peroxide or peroxide compounds which generate hydrogen peroxide in aqueous solution, (B) cyanourea and (C) an alkaline agent under the provision that pH 8 or higher is achieved in the aqueous solution of the product.
As (A) hydrogen peroxide or a peroxide which generates hydrogen peroxide in aqueous solution, one can use an aqueous solution of hydrogen peroxide or hydrogen peroxide with added sodium carbonate with a molar ratio between sodium carbonate and hydrogen peroxide of 2:3 or sodium perborate mono- or tetrahydrate.
As (B) cyanourea, one can use the solid or an alkaline aqueous solution of this compound.
As (C) an alkaline agent, one can use hydroxides of alkali metals or silicate salts of alkali metals. Among them, it is preferable to use silicate salts of alkali metal such as sodium and potassium silicate, because the bleaching activity is markedly improved by these compounds.
The bleach product of this invention can be used by sprinkling the components of the product, (A) hydrogen peroxide or a peroxide which generates hydrogen peroxide in aqueous solution, (B) cyanourea and (C) an alkaline agent, over the material to be bleached. Or the product can be used with the cleanser during washing. Also one can use an aqueous solution prepared beforehand by dissolving (A) hydrogen peroxide or a peroxide which generates hydrogen peroxide in aqueous solution, (B) cyanourea and (C) an alkaline agent in water.
In the use of the bleach product of this invention, it is preferable to use the aqueous solution of the product previously prepared to carry out the bleach process smoothly. In such a case, the content of hydrogen peroxide is 0.5-60 wt %, or preferably 0.5-30 wt %, or most preferably 0.5-10 wt % and practically 1-6 wt %. If the content is lower than this range, the bleaching activity is too low, and if its content is more than this range, handling becomes difficult. The content of (B) cyanourea is 0.2-30 wt %, or preferably 0.5-10 wt %, or most preferably 0.5-5 wt %. The content of (C) an alkaline agent is 0.1-20% so that the pH of the aqueous solution is 8 or higher, or preferably in the range of 9-13. It is necessary to use the alkaline agent to attain a high bleaching activity in the bleach product of this invention. The bleach product of this invention can be in the form of a homogeneous solution and of a slurry, in order to carry out the bleaching activity. When the bleach product of this invention is used for mold removal, such a previously prepared aqueous solution is convenient for easy application.
It is possible to improve the bleaching and cleaning effect by addition of a surfactant to the bleach product of this invention. As such a surfactant, one can cite polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters and amine oxides as nonionic surfactants, soap, alkyl sulfate salts and alkylbenzenesulfonate salts as anionic surfactants. It is preferable to add the surfactant at 0.1-5 wt % of the bleach product.
DESCRIPTION OF PREFERRED EMBODIMENTS
The invention is explained with application examples, but the invention is not limited by these examples.
APPLICATION EXAMPLE 1
A bleach product was prepared by dissolving hydrogen peroxide at 3 wt %, cyanourea at 3 wt % and sodium metasilicate at 5 wt % in water at 10.9 pH.
With the bleach product thus obtained, the following tests were performed as described below: bleach test of fabric stained with black tea, bleach test of mold and evaluation of odor. The results are shown in Table I.
Test method and evaluation for bleach test of fabric stained with black tea
1) Preparation of fabric stained with black tea
10 g of black tea leaves wrapped in gauze were boiled for 5 min in 1000 mL water placed in a 1000 mL beaker followed by removal of tea leaves for preparation of black tea. A 50-g prewashed cotton broadcloth (#100) was soaked in the tea, which was continuously boiled for 30 min. The fabric was wrung by hand after cooling and was dried without exposure to sunlight.
2) Test method for bleaching fabric stained with black tea
Tea-stained fabric (5×5 cm) was placed in a crystallization dish (external circumference 12 cm, height 6 cm) and 20 g of the bleach product were added and left for 30 min. The fabric was taken out to be washed with tap water and dried without exposure to sunlight.
3) Method of evaluation
Reflectance the fabric was measured before staining with black tea, after staining with black tea and after bleaching using a colorimeter (differential colorimeter) and the bleaching rate was calculated using the following equation:
Bleaching rate (%) =(Rw-Rs)/(Ro-Rs) ×100
Ro: reflectance of fabric before staining with black tea
Rw: reflectance of fabric after bleaching
Rs: reflectance of fabric after staining with black tea.
Test method and evaluation of bleaching of mold
1) Mold culture method
Autoclaved agar culture medium was poured into sterile petri dishes to be seeded with black mold (Aureobasidium pullulans) and the dish was incubated in an incubator at 35° C. for 10 days.
2) Test method of bleaching of mold
A glass tube was placed over the agar plate on which mold had grown and the test solution was placed in the glass tube. 30 min later, the degree of bleaching of the black mold was measured.
3) Evaluation method
The degree of bleaching was classified in 3 stages, described below by macroscopic observation.
Degree of bleaching: completely bleached
Degree of bleaching: bleached to some degree
Degree of bleaching: almost or completely unbleached
Test method and evaluation of door
1) Odor test method
10 panel members were asked to sniff the bleach product for the sensory evaluation.
2) Evaluation of odor
Odor was classified as follows:
o: No irritating odor or malodor was sensed by almost all or all panel members.
Δ: About half of the panel members sensed an irritating odor or malodor.
x: Almost all or all panel members sensed an irritating odor or malodor.
Application Examples 2-7
Bleach products were prepared with altered components and contents as shown in Table I, where the term % indicates wt %. The pH of solution is shown in Table I.
Similar to above, the bleach test on black tea-stained fabric, the bleach test on mold and the evaluation of odor were performed with the results listed in Table I.
Application Examples 8-9
Bleach products were prepared using hydrogen peroxide with added sodium carbonate and sodium perborate hydrate instead of hydrogen peroxide. The hydrogen peroxide content with added sodium carbonate or sodium perborate monohydrate was expressed in terms of the hydrogen peroxide contained in these substances. Table II shows the results of the bleach test for fabric stained with black tea, the bleach test for mold and the evaluation of the odor, using these products.
Application Example 10
A bleach product was prepared similar to Application Example 1 except with added alkylamine oxide (trademark Aromox, Lion Akuzo transliteration! K.K.) as the surfactant. The pH of the product is shown in Table II, in which the term % indicates wt %.
A bleach test of fabric stained with black tea, bleach test of mold and the evaluation of the odor were performed similar to above using the product and the results are shown in Table II.
Comparative Example 1
A bleach product was prepared using sodium hypochlorite as shown in Table III. The term % indicates wt %. Table III shows the pH of the product and the results of a bleach test of fabric stained with black tea, a bleach test of mold and an evaluation of the odor carried out with this product. The bleaching activity was excellent, but the malodor of chlorine was markedly sensed.
A bleach product was prepared similarly to Application Example 1, except for the use of cyanourea. Table III shows the pH of the product and the results of a bleach test for fabric stained with black tea, a bleach test for mold and the evaluation of the odor with this bleach product. The bleaching activity decreased.
Comparative Example 3
A bleach product was prepared with a content of sodium metasilicate at 2.5 wt % and using tetraacetylethylenediamine instead of cyanourea. Table III shows the pH of the product and the results of a bleach test for fabric stained with black tea, a bleach test for mold and the evaluation of the odor with this bleach product. The bleaching activity was slightly reduced with a strong malodor of peracetic acid.
Comparative Example 4
A bleach product was prepared similarly to Application Example 1, except for the addition of an alkaline agent. The pH of the product was 2.3, and the bleaching activity was reduced.
Comparative Example 5
A bleach product was prepared similarly to Application Example 1, except using iminodiacetonitrile instead of cyanourea. Table III shows the pH of the product and the results of a bleach test for fabric stained with black tea, a bleach test for mold and evaluation of odor. The bleaching activity was reduced.
Comparative Example 6
A bleach product was prepared with hydrogen peroxide with added sodium carbonate. Table III shows the pH of the product and the results of a bleach test for fabric stained with black tea, a bleach test for mold and the evaluation of the odor using this bleach product. The bleaching activity was reduced.
Application Example 11
A washing test was carried out on fabric stained with black tea using the mixture of a marketed detergent (trademark Hi-top, Lion K.K.) and hydrogen peroxide with added sodium carbonate, cyanourea and sodium metasilicate as the prescribed contents. Table IV shows the content of each component and the results.
Washing test and evaluation methods
1) Preparation of fabric stained with black tea
A similar method was used as in the bleach test for fabric stained with black tea.
2) Standard washing
0.75 g detergent and prescribed amounts of bleach and/or bleach product were dissolved in 900 mL tap water at 25° C. and 10 pieces of fabric stained with black tea (5×5 cm) and 30 pieces of cotton fabric for underwear (5×5 cm) were placed in the solution for washing in a targotometer transliteration! (product of Daiei Kagaku Seiki Seisakusho) for 10 min followed by rinsing, water removal and drying.
3) Washing after soaking
0.75 g detergent and prescribed amounts of bleach product were dissolved in 150 mL tap water at 25° C. 10 pieces of fabric stained with black tea (5×5 cm) were soaked in the solution for 1 h at 25° C. Then 30 pieces of cotton fabric for underwear (5×5 cm) and 750 mL tap water at 25 C. were added for washing in a targotometer for 10 min followed by rinsing, removal of water and drying.
4) Method of evaluation
The bleach rate was calculated similarly to the bleach test for fabric stained with black tea and the mean was obtained for 10 pieces of fabric stained with black tea as the bleach rate.
Comparative Example 7
A washing test was carried out with detergent and hydrogen peroxide with added sodium carbonate as the bleach. The amounts added and the results are shown in Table IV. The bleach rate was reduced in the standard washing test and the washing test after soaking.
Comparative Example 8
A washing test was carried out with hydrogen peroxide with added sodium carbonate as the bleach and tetraacetylethylenediamine as the bleach activator. The amounts added and the results are shown in Table IV. The bleach rate was somewhat reduced in the washing test after soaking and bleaching the fabric stained with black tea resulted in a speckled condition.
Comparative Example 9
A washing test was carried out with hydrogen peroxide with added sodium carbonate as the bleach and iminodiacetylnitrile as the bleach activator. The amounts added and the results are shown in Table IV. The bleach rate was reduced in standard washing test and the washing test after soaking.
TABLE I______________________________________Application Example 1 2 3 4 5 6 7______________________________________Hydrogen peroxide 3% 3% 3% 3% 3% 1% 18%Cyanourea 3% 3% 3% 5% 1% 3% 3%Sodium metasilicate 5% 5% 5% 5% 5%Sodium orthosilicate 5%Sodium hydroxide 5%Water Rem* Rem* Rem* Rem* Rem* Rem* Rem*pH 10.9 11.3 13.0 11.1 11.4 11.5 9.6Bleach test for mold III III III III III II IIIBleaching rate** 94% 95% 92% 96% 90% 86% 96%Evaluation of odor ◯ ◯ ◯ ◯ ◯ ◯ ◯______________________________________ *remainder **of fabric stained with black tea
TABLE II______________________________________Application Example 8 9 10______________________________________Hydrogen peroxide 3%SPC*** 3%PB**** 2%Cyanourea 3% 3% 3%Sodium metasilicate 5% 5% 5%AAO***** 1%Water Remainder Remainder RemainderpH 10.6 12.0 10.9Bleach test for mold II II IIIBleaching rate** 84% 82% 95%Evaluation of odor ◯ ◯ ◯______________________________________ **of fabric stained with black tea ***hydrogen peroxide with added sodium carbonate (concentration expressed as the concentration of hydrogen peroxide) ****sodium perborate monohydrate (concentration expressed as the concentration of hydrogen peroxide) *****surfactant, alkylamine oxide
TABLE III______________________________________Comparative Example 1 2 3 4 5 6______________________________________Hydrogen peroxide 3% 3% 3% 3%SPC*** 3%Sodium hypochlorite 3.5%Cyanourea 3%TAED****** 3%Iminodiacetonitrile 3%Sodium metasilicate 5% 2.5% 5%Water Rem* Rem* Rem* Rem* Rem* Rem*pH 13.1 11.5 10.8 2.3 10.9 9.6Bleach test for mold III I II I II IBleaching rate** 93% 81% 82% 18% 85% 65%Evaluation of odor X ◯ Δ ◯ ◯ ◯______________________________________ *remainder **of fabric stained with black tea ***hydrogen peroxide with added sodium carbonate (concentration expressed as the concentration of hydrogen peroxide) ******tetraacetylethylene diamine
TABLE IV______________________________________ Ap. Ex. 11 Co. Ex. 7 Co. Ex. 8 Co. Ex. 9______________________________________Detergent 0.75 g 0.75 g 0.75 g 0.75 gSPC*** 0.075 g 0.075 g 0.075 g 0.075 gCyanourea 0.038 gTAED****** 0.038 gIDAN******* 0.038 gSodium metasilic. 0.075 gBleach rateStandard washing 10% 4% 10% 6%Soaking/Washing 34% 16% 29% 24%______________________________________ ***hydrogen peroxide with added sodium carbonate (concentration expressed as the concentration of hydrogen peroxide) ******tetraacetylethylene diamine *******iminodiacetonitrile
This invention offers bleach product with excellent bleaching activities and washing without irritating odor. The bleach product of this invention can be used effectively for removal of mold.
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A bleach product comprising an aqueous solution at a pH of 8 or more is disclosed that has an excellent bleaching activity without an irritating odor. The aqueous solution comprises: (A) from 0.5 to 60 weight percent of a compound selected from the group consisting of hydrogen peroxide and peroxide compounds which generate hydrogen peroxide in aqueous solution, (B) cyanourea and (C) an alkaline agent has. The product can be used for removal of mold with excellent results.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application claims priority of German patent application No. 10 2009 037 315.2 filed on Aug. 14, 2009, the content of which is incorporated herein by reference.
FIELD OF THE INVENTION
[0002] The present invention relates to a device for receiving of disposable items.
BACKGROUND OF THE INVENTION
[0003] Disposal items include, in particular, surgical instruments, expendable medical items, and sterile packagings, that is, containers in which a sterile material remains until its immediate use.
[0004] A device for receiving of disposable items for an operating room is disclosed in patent DE-OS 2146823.
[0005] Surgical instruments and sterile materials such as swabs and surgical cloths required in operations, after use, are deposited directly into such a disposal container or are placed in other receptacles such as sieve baskets. For medical documentation it is then customary to document the used articles in an OR documentation list. This task is performed entirely manually. It is very laborious and time-consuming, and therefore requires highly specialized nursing staff who are familiar with the individual instruments, expendable materials, and sterile supplies and can perform the manual documentation without transmission errors.
[0006] The complexity of handling sterile materials, in the meantime, requires a sterile materials management that is capable of rapidly capturing and mastering all procedures connected with sterility in a hospital. The principle of identification and retraceability is just one of the essential tasks.
[0007] It is the object of the present invention to perfect a device for receiving of disposable items in such a way that improved documentation becomes possible.
SUMMARY OF THE INVENTION
[0008] This object is achieved by means of a device for receiving of disposable items, with the traits of claim 1 . The subsidiary claims indicate elaborations of the invention.
[0009] The inventive device includes a container equipped with an opening and an identification unit, which is positioned in the area of the container's opening.
[0010] On the basis of the inventive device it is possible securely to acquire an object equipped with one or more data carriers and to read out data from the data carrier when said carrier is subjected to the detection area of the identification unit. The primary advantages that result from this are: time saving in acquiring the objects, fewer errors in documentation, and the fact that the device can be used easily and intuitively and consequently requires no specialized training of personnel.
[0011] The inventive identification unit advantageously comprises at least one reader head, which shows a continuing detection area that completely covers the container's opening and acquires it while extending horizontally in particular, preferably parallel to the surface of the container's opening, and corresponds to the profile of the perimeter of the opening of the container. The area of detection here corresponds in particular to the container's opening. This ensures that every object that is equipped with a data carrier and is inserted into the container is reliably acquired and the data of the data carrier can be correspondingly read out. In addition, thanks to the selected configuration of the identification unit, the possibility of erroneous detection is also excluded, that is, the risk of unwittingly capturing objects that are found outside the container and are conducted along the identification unit in close proximity to it. Thus, thanks to the identification unit, one can ensure the acquisition exclusively of the objects that in fact are to be disposed of, and in a preferred embodiment, in addition, they are also identified. In addition to the acquired data, in addition and alternatively, other data can be documented for the identified objects and subjected to an additional evaluation.
[0012] In another preferred embodiment of the inventive device, the identification unit comprises two or more reader heads. These are preferably positioned and oriented in such a way that the respective detection areas of the mutually adjoining and/or facing reader heads overlap and together form a continuous detection area. Such a configuration has the advantage of ensuring the reliable acquisition of objects equipped with data carriers. According to the invention, a secure record is nevertheless achieved, in particular with objects whose data carrier is found in a non-readable position for an individual reader head and/or objects that comprise screening components that disturb the process.
[0013] One or more of the reader heads of the inventive device can preferably be configured as barcode scanners and/or RFID reader devices. These devices are appropriate for their ability to read out information without contact from data carriers, such as barcode labels or RFID data carriers—also known as RFID tags. This occurs largely independently of the soiling of the objects that are to be removed. Additional advantages of RFID data carriers and RFID laser devices consist in the higher storage capacity, and greater speed of reading and identification in comparison with other conventional data carriers and related reader devices such as barcode systems. Data can also be acquired directly and precisely. The data, in particular, can be taken from the data group product name, article designation, lot number, usability/expiration date, or series number.
[0014] In addition, such reader devices constitute standardized components with a high capturing precision, thanks to which it is possible to produce an economical device. The advantage of a barcode or barcode scanner system resides, in particular, in the fact this technology in the field of automatic recognition systems has matured and has already been widely used in many fields for several years. The objects that are to be removed can also be labeled in simple and reliable manner and thus can be especially simply acquired and subjected to documentation.
[0015] By means of the reader heads, which preferably are configured as barcode scanners and/or RFID reader devices, data can be read out as an object to be removed from its data carrier and later can be documented. In the framework of an additional evaluation, these data can then be complemented with additional data, in particular from a database, and correspondingly subjected to an additional evaluation and documentation. This can lead, for instance, to material flow information. In the framework of an optional identification by means of the identification unit, it is possible on the basis of the acquired data also to make an identification by comparison with previously stored material data, where these data are filed in a remote database or in a database associated with the identification unit. In the latter case the database is updated regularly or, depending on the situation, on the basis of a remote database, in particular in the hospital's central computer. As a result, a very current and reliable documentation can be maintained.
[0016] An additional configuration of the inventive device provides that the identification unit is connected by means of a communication link with an evaluation unit that is remote from it, and the data read out by the identification unit are transmitted to the evaluation unit preferably over this communication link. To achieve a local data transfer, the identification unit in this case can be physically connected with the evaluation unit by a data cable. The use of a data cable, however, involves the risk of stumbling over the cable or of unintended severing of the cable from the identification unit and/or the evaluation unit by an impact or pulling motion.
[0017] Alternatively and preferably, the data transfer should occur wirelessly, for instance by means of an IR or Bluetooth connection, which proves especially useful with frequent changes of location for the inventive device.
[0018] Transmission of data can proceed in real time, that is, during an ongoing identification and the reading of an object directed to a reader head and equipped with a data carrier, without substantial delay. Consequently it is possible in advantageous manner to dispense with particular data storage systems for intermediate storage within the identification unit and to keep said unit correspondingly small and economical to produce.
[0019] Alternatively, it is also possible in the area of the identification unit or of the communication link to produce data storage devices by which the data can first be stored and then, or at least with a time delay, read and forwarded.
[0020] It is also possible to conduct a simple pre-processing of the acquired data still in the area of the identification unit. Thus, in the context of this pre-processing, these data can be standardized for a simple processing later.
[0021] In an advantageous embodiment of the inventive device, the evaluation unit here can be, for instance, a PC workplace with a monitor and keyboard or a mobile hand device. Thus, by means of the keyboard, for instance, patient identification information can additionally be entered, ensuring an unequivocal allocation of the acquired objects to the patient.
[0022] In an especially useful and preferred configuration of the inventive device, the evaluation unit is connected with a touch screen to form a single unit that makes possible the processing of the scanned information in connection with an input by touching the display surface and/or by corresponding entry of operating and control commands.
[0023] The evaluation unit can be positioned inside the operating room, preferably in immediate proximity to the operating table and/or in an area of the operating room. Thus, the materials to be removed can be subjected to evaluation and further documentation immediately after, or even during, the operation to reach the acquisition and expanded documentation by a short route.
[0024] In a particularly advantageous embodiment, the evaluation unit is positioned outside the operating room. This has the advantage that the acquisition and documentation can be conducted in a non-sterile area and consequently, because of the decreased risk of contamination, by the support personnel, who are not required to wear protective clothing for hygienic reasons as required for an operating room. In addition, the evaluation unit is not required to be made of specialized, complex, and thus expensive sterilizable materials.
[0025] It is expected that the evaluation unit first receives the raw data and/or raw data sets from an identification unit and that the data are then entered and stored, for instance in a standard tabular calculation program, so that the data sets contain information from the group product name, article designation, lot number, usability/expiration date, series number, which are selectively arranged in the tabular fields. After the data distribution is complete, evaluation data can then be automatically generated. For instance, an inventory file or material flow information can be produced.
[0026] An inventory file, stored in the evaluation unit, thus contains for instance the number of objects that were provided and used or applied for the patient during the operation. The generated inventory file can then be compared with a previous one, which was produced at the start of the procedure. Depending on the queries used, information can be provided, for instance by an OR documentation list, on whether and/or how many objects were actually used during the procedure. In particular, this allows a determination of whether all instruments and other materials applied were listed in complete and updated manner at the end of the operation. This information is important in the patient's interest.
[0027] In a preferred embodiment, the evaluation unit is connected electronically, for instance via GPRS/WLAN, with the central database, preferably of the hospital, also known as hospital information system (HIS). The evaluation results generated in the evaluation unit can then be controlled, for instance regularly or depending on the situation, particularly after a procedure is completed, sent to the central database of the hospital and/or called up by it and stored in the computer of the central database and/or further processed.
[0028] Thanks to the data acquisition which is constantly possible, material flow information within the hospital can be called up at any time, communicated, and/or displayed.
[0029] Because decisive data on every object are regularly registered in the central computer database at the moment of its entry into the hospital's sterile storage system and also at the time of acquisition in the operating room, it is particularly possible to conduct a permanent balance sheet of the stored inventory by using an electronic quantity and value recording method.
[0030] Thus the respective current inventory level and changes in inventory, for instance, can be displayed at any time by means of a graph or inventory list. In addition it is also possible to automatically deduct the depleted and/or applied objects and to allocate them to certain usage categories such as individual operating rooms, in order finally to produce a corresponding patient-based cost record.
[0031] The inventive device regularly comprises a container with an opening pointed upward, a base surface, and an interior space into which the conveyed objects are introduced using gravitational force. The container here can be produced from various materials. It is especially effective to select materials in such a way that they are autoclavable, that is, capable of withstanding water pressure treatment under pressures up to about 134 degrees C. without damage. Autoclavability is particularly essential and therefore of great advantage for the inventive device if the container for instance should be contaminated with blood and/or germs. In this case autoclaving allows a reuse of the container and thus a greater lifetime for the receptacle altogether, while non-autoclavable containers must be removed expensively as special medical waste after every contamination with germs.
[0032] In an additional advantageous embodiment, the container can be slid with respect to the storage and/or work space, for instance on rollers, or for example it should be capable of pivoting or tipping by means, for instance, of a weighing frame, by about 10 to 15 degrees. Thus the container can be moved, for instance placed first on rollers, totally without problems to the utilization site and there can be brought into the particular operating or moving position by the user according to need or preference, without any problems, making comfortable and ergonomic operation possible. This ensures that the inventive device is always available at the desired location and thereby an efficient documentation of the objects can be achieved.
[0033] An additional advantageous embodiment of the inventive device consists in the fact that the interior space of the container comprises dividing walls and, depending on the number of dividing walls, the interior space is divided into at least two compartments. In this manner this container makes it possible that at least two categories of object can be sorted out and, in keeping with their sorting criteria, can be directed to one of the compartments. Thus just about all objects made of plastic, such as catheters and tubes, can be sorted, collected, and finally conveyed to the recycling facility. Objects thus removed and sorted into various compartments are documented, preferably selectively, so that a detailed evaluation becomes possible, for instance according to the size of the objects by category.
[0034] In another preferred embodiment an individual compartment can be configured so that an adaptation to various application requirements becomes possible on the basis of the prescribed objects used during the procedure. Thus, a compartment for the selective depositing of syringes can be configured with a particularly puncture-resistant wall to prevent possible injury during removal of the compartment. In addition, there can be differentiations in the capacity of compartments' volume or in the cross-sections of their openings.
[0035] This can be achieved either through differentiated combinations of modular components in the manufacturing process or through subsequent adjustments, or a combination of both. Thus, for instance, objects such as reusable surgical instruments can be collected by the sorting process so that they are subjected finally to a sterilization process in the course of instrument reconditioning.
[0036] In another practical embodiment, the containers and/or a compartment in the interior can be lined with a removable plastic sack. The sack is preferably provided with individualized markings that make documentation possible and/or improve logistics and/or removal.
[0037] In addition, a compartment an also be produced as a plastic sack or synthetic pouch and thus be used for objects that are not recyclable and are to be conveyed to refuse removal.
[0038] Another configuration of the inventive device concerns a container with an opening that faces upward and is provided with a lid to cover the opening. In any case, the opening of the container can be provided with a lid to cover the opening. It can also be arranged that several compartments each have a lid or cover and thus not all compartments require lids. This ensures a controlled insertion into the container or compartments, reducing erroneous deposits and thus improving the data quality of the documentation.
[0039] The one or more lids can be opened and closed manually. As a preferred alternative, lids can be opened and closed by electronic switches on the basis of a signal, received by the identification unit, for detecting objects to be removed. The control is configured in such a way that the container and/or compartment is closed after insertion of the object, thus preventing any unintended additional dropping or steering of a non-sorted object into the container and/or the compartment.
[0040] The inventive device is also preferably provided with a sorting device, which is positioned in the area of the container's opening and controlled as necessary, and which can use the information from the identification unit to control the device. Thus data are culled from the data carrier of the object by the identification unit, allowing in particular data on the specific sorting of an object. Thus the sorting destination is determined on the basis of such criteria as size, shape, material, type, and so on.
[0041] Then, in accordance with the sorting assignment, the object is mechanically transported away, for instance, and directed to a corresponding compartment. Thus the object itself transmits to the sorting device the data required for optimal removal. It is possible in this preferred manner to automatically document, sort, and unequivocally collect objects that resemble one another in the form and/or type of recycling they undergo, such as opened product packaging or surgical instruments.
[0042] Mechanical conveyance and/or sorting of objects can thus be effected by an alterable switch, for instance, which is mounted around a pivot axis and, by the position it assumes, determines into which compartment the sorted products are sent. Another possibility is a pivotable, sloping chute by which the sorted objects are selectively removed on the basis of gravity and finally fall into a compartment. In addition, an ejector or blowing nozzle can be provided for conveyance on a chute. This allows a very reliable selection of the objects, in particular with respect to logistics and removal, and consequently an informative documentation.
[0043] In another preferred embodiment of the inventive device, the device comprises a hand device that is connected by a connecting device, in particular with wireless support, with the identification unit. This makes it possible to read out the acquired, evaluated, or stored data, in particular, from the identification unit. In addition, object-related data that are necessary or helpful for the identification can be entered by the hand device and forwarded for instance, to the identification unit, and these data can be used in additional identification or evaluation.
[0044] It is also possible to connect a hand scanner for acquiring and reading from data carriers by means of the connection device. The connection between the hand device, hand scanner, and connection device should preferably be wireless. These embodiments are marked by the mobility of the hand devices or hand scanners, which allow for better data quality thanks to improved handling for the user.
[0045] According to an especially advantageous embodiment of the inventive device, it should be provided with a filling-level detection device in order to improve the additional logistical process of disposal with intermediate storage, transport, and final, especially thermal, disposal, on the basis of acquired filler-level data and its documentation.
[0046] The weight and/or volume of inserted objects is determined by the filler-level detection device. In addition the weight and volume of a container and/or compartment can be measured by means of a filler-level detection device upon insertion into the container and/or into a compartment. Also, depending on the case, the total weight and/or total volume of all inserted objects can be computed from these data. The measured weight and/or volume value can then be conveyed to a display unit. The filler level can thus be recognized and, for instance, stored and/or displayed, if and when the maximum filler volume of the container and/or compartment has been reached and consequently the container and/or compartment needs to be emptied or replaced.
[0047] Inserted refuse can be weighed, for instance, by a weighing platform that is positioned below the container and/or compartment and is equipped with a weight recorder/sensor to detect changes in weight. This configuration can be especially advantageously used when the refuse exceeds a drop height after it is inserted into the interior space of the container and/or compartment. In another advantageous embodiment, the weighing platform is constructed so that it comprises several force transducers corresponding to the number of compartments, each being positioned under one compartment. This has the advantage that the change in a compartment's weight can be individually measured and displayed, especially when an object is directed to this compartment.
[0048] Another preferred embodiment provides that the container and/or compartment has at least one distance sensor available for detecting volume. It is particularly advantageous if the distance sensor is positioned immediately below the predetermined filler height of the container and/or compartment, so that the filler height of the container and/or of a compartment is measurable with its help automatically and continuously, and also any overfilling of the container and/or compartment is reliably prevented. In addition, identified objects can be verified against stored object profiles by weighing them. This permits a clear increase in security.
[0049] Even without weighing or determining volume, information on the weight or volume of the identified objects can be determined by object profiles stored in the database and from that the filler status of the container is determined. Thus it is possible to reliably document which objects are present in the container, particularly a filled container, and which are jointly removed in a sack. The sacks removed from the container are preferably provided with individualized markers that make the additional documentation possible.
[0050] In another practical configuration of the invention, the identification unit is a component of a cap, particularly a ring-shaped one, that can be positioned so that it can be removed from and applied to a container. This cap is preferably in a single piece and self-supporting. Thus the ring opening of the cap continues into the opening of the container and thus allows a clear identification by means of the cap. With this inventive structure, the container can be emptied in especially simple and rapid manner by removing the cap. In addition the cap can also be mounted on other containers without problem and/or can be subjected to a sterilization process after acquisition of objects, thus increasing the operational readiness of the invention.
[0051] An additional especially advantageous embodiment of the inventive device concerns a video camera whose field of vision includes the area of the container's opening and which is capable of clearly identifying objects that are conducted to the area of the opening of the container and/or compartment, for instance on the basis of their formal properties. Thus it is also possible and advantageous to acquire and document objects which, for instance, are not equipped with a data carrier. In addition it is possible, nevertheless, to identify objects whose data carrier for instance has been damaged and which thus can no longer be scanned by a given reader head. The likelihood that an object equipped with a data carrier cannot be read is additionally reduced by this refinement, further improving the quality of the documentation.
BRIEF DESCRIPTION OF THE DRAWINGS
[0052] FIG. 1 shows an operating room including a device for receiving of disposable items.
DETAILED DESCRIPTION OF THE INVENTION
[0053] An exemplary embodiment of the inventive device and of the technical environment of the invention is now further described with reference to FIG. 1 . The invention is not restricted to this illustrated embodiment.
[0054] Here FIG. 1 shows an operating room 20 whose sterile area is separated by a wall 25 from the non-sterile area 30 . In addition, FIG. 1 shows a device, standing on the floor of the operating room, for receiving objects for an operation room 20 that are to be removed. The device shows and comprises a two-chamber container 1 with an identification unit 2 positioned in the area of the opening of the container 1 along with a sorting device 6 . This device's positioning is selected below the identification unit 2 .
[0055] The identification unit 2 is positioned on the upper edge of the container 1 and integrated into a removable ring-shaped cap, so that its opening continues into the opening of the container 1 . The unit comprises a first reader head 3 , a second 4 . 1 , and a third reader head 4 . 2 . They are configured for the detection of objects that are to be removed and for the reading of information from data carriers connected with the objects as soon as they are brought into their detection areas. The data carriers contain information that serves for individual identification and are applied on the respective object.
[0056] The reader heads 4 . 1 and 4 . 2 are positioned with respect to one another so that their detection areas overlap in FIG. 1 in a manner not shown in closer detail and cover the entire area of the opening of the container 1 .
[0057] On the basis of this arrangement of two reader heads in facing position, it is guaranteed that if one reader head cannot acquire and read the data carrier, for instance if the data carrier is covered up, then at least the other reader head is capable of doing so.
[0058] The illustrated reader heads 3 , 4 . 1 , and 4 . 2 read the barcode and/or RFID identification data as a rule from data carriers that are brought into the range of their detection areas and are accordingly configured as barcode or RFID scanners.
[0059] In addition, FIG. 1 shows a two-chamber container that comprises an essentially trapezoidal-shaped longitudinal section. The interior of the container 1 is divided in its lower area into two compartments 7 . 1 and 7 . 2 , separated from one another by a dividing wall 6 that extends from the floor of the container upward. The deposited objects are sorted with the help of a sorting unit 6 . The first 7 . 1 and second 7 . 2 compartments serve to receive selectively sorted objects, which differ in their product characteristics, for instance their material and/or function. The separating wall 6 ensures that the objects sorted in the container according to differing product characteristics can no longer be mingled together.
[0060] Mounted downstream of the identification unit 2 is the sorting unit 5 , which is positioned in the area of the opening but is smaller in dimension. The position of a conductor element determines in which compartment the sorted objects end up. The sorting of objects here can be done for instance by means of an angular profile alterable switch as conductor element, which is mounted to pivot around an axis. The sorting device 5 thus receives information that has been read out by the identification unit 2 from the data carriers of the objects and contains or admits indications on the sorting categories of an object. The object is then diverted and removed according to the sorting assignment.
[0061] The container 1 comprises two compartments 7 . 1 and 7 . 2 , positioned side by side. The diverted objects, according to their sorting category, by which they are sorted, are fed toward the left into the first compartment 7 . 1 or toward the right into the second compartment 7 . 2 .
[0062] The identification unit 2 and the evaluation unit 9 are connected to one another by a communication link 8 for the exchange of data. The data transfer here can occur through a cable between the identification unit 2 and the evaluation unit 9 or through an IR connection or Bluetooth connection.
[0063] All of the data ascertained and read out by the identification unit 2 run together in the evaluation unit 9 . The transmitted data are first stored, so that they can be read out again and further evaluated or processed.
[0064] Evaluation of the entered data can be processed, for instance on the basis of evaluation procedures that may require no additional particular input operations by the user. Thus, after arrival of the data, total information on the conveyed objects is for instance determined or objects are grouped and/or displayed in tables according to their sorting categories. It is possible to continually modify and document the displays on the basis of a running input of data.
[0065] Entered data can be displayed on the monitor 9 . 1 of the evaluation unit 9 as a raw data set and/or in their evaluated form.
[0066] The final step is the indication of what type of surgical instrument or which medical expendable material is primarily present. Other acquired data such as the date and time of the data acquisition can also be displayed as needed, of course.
[0067] These data can be supplemented on the evaluation unit 9 by manual and/or speech-activated input of additional data such as patient identification data or indications on the operating room 20 . Thus, data acquired in the area of the identification unit 2 and stored in the evaluation unit 9 can be unequivocally associated with a patient and/or an operating room 20 from which they were obtained. This is particularly important when an evaluation unit 9 is associated with various operating rooms 20 and/or used in a number of procedures.
[0068] Data and evaluation results processed by the evaluation unit 9 are then made available on a central computer 11 of the hospital, which is installed in a non-sterile area 30 of the hospital. The communication line 10 between the evaluation unit 9 and the central computer 11 of the hospital is configured here as a fiberglass cable. The data transmission can also be processed here with link-up to the Internet as data transfer system. In this case an update of the company/software of the evaluation unit and/or of the identification unit can be conducted by the evaluation unit, so that the user can use the current software versions in each case. The care and expansion of the data acquisition and/or data evaluation possibility in the context of the existing hardware is thus simple, reasonable in price, and rapid.
[0069] Positioned on the central computer 11 of the hospital is a database in which, in addition to the acquired and/or supplemented data, additional data are stored and contained, by means of which, in particular, the material flow in an operating room 20 can be depicted.
[0070] With the arrival of an object in the hospital's sterile storage unit, various identifying data on each object are registered and filed in the database. This occurs either manually or semi- or completely automatically. Thus, from these data on registered objects an allocation data set can then be produced. This allocation data set allows, among other things, a later allocation of raw data and evaluation results for a particular operating room 20 or the identification of objects acquired by the inventive device that are to be disposed of on the basis of the read-out data from data carriers. On the basis of this documentation it is possible to depict the material flow within the hospital thanks to the ongoing use of objects, and to simplify the removal logistics, the utilization or removal of the object.
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A system for receiving of disposable items in an operating room, where the objects that are to be disposed of and which are equipped with a data carrier are automatically acquired and electronically registered in databases. The data carrier on the objects can be RFID tags or a barcode. The data read out are used in particular to individually recognize the type, quantity, and value of an object and to be able to document and display the type, quantity, and value of an object by using an electronic inventory and value determination process.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] The present application is a divisional of application Ser. No. 13/248,865 filed Sep. 29, 2011.
BACKGROUND OF THE INVENTION
[0002] The present invention is generally directed to farm implements and, more particularly, to a method and apparatus for remotely controlling the hydraulics of a tractor or other implement towing vehicle.
[0003] Increasingly, farm implements have been designed to have frames that can be folded between field-working and transport positions. One such type of farm implement is a stack-fold planter, such as the 1230 Stackerbar planter from Case New Holland, LLC. Stack-fold planters generally consist of a center frame section and a pair of wing frame sections. In the field-working position, the wing frame sections are evenly aligned with the center frame section. In the transport position, however, the wing sections are lifted to a position directly above the center frame section, i.e., to a “stacked” position. In the stacked position, the width of the implement is generally that of the center frame section, thus making the implement better suited for transport along roads and between crops.
[0004] Openers are mounted to the frame sections at equal intervals, with each of the wing sections typically carrying one-half the number of openers mounted to the center frame section. The openers are designed to a cut a furrow into a planting surface, deposit seed and/or fertilizer into the furrow, and then pack the furrow. In this regard, each opener will have a seed box that is manually loaded with seed and/or fertilizer. Since the size of the seed box determines how much particulate matter the box can retain, there is generally a desire to have larger seed boxes for each of the openers. Since the larger seed boxes can hold more material, fewer refilling stops are needed when planting a field.
[0005] Larger seed boxes, however, have drawbacks. The additional material that can be carried by larger seed boxes adds to the overall weight of the openers, including those mounted to the wing sections. This additional weight can stress the lifting/lowering system that stacks the wing sections, or require a more robust system, which can add to the overall size, mass, complexity, and cost of the implement. Larger spacing between seed trenches lower per acre crop yields. Further, it can be problematic and time consuming to individually fill each of the seed boxes, whether using bags or a conveyor system.
[0006] Accordingly, bulk fill systems have been designed for stack-fold planters that generally consist of one or more bulk fill tanks mounted to a frame or toolbar that can be coupled to the frame of the stack-fold planter. The frame for the bulk fill system is supported above the ground by a lift wheel assembly that is designed to raise the frame when the stack-fold planter is in transport. Oftentimes, an operator will also raise the bulk fill system frame at headland turns when the gull wings are also raised to provide additional implement stability.
[0007] Raising the gull wings and the frame for the bulk fill hopper(s) at headland turns poses one of the challenges that is faced by an operator when making a headland turn onto a new swath. More particularly, as the operator of a planter arrives at the headland of a field, the operator has to perform numerous tasks to reposition the planter in the next swath. Many of these tasks require the operator to attempt simultaneous control of three or more operations. For stack-fold planters equipped with lift assist wheels and/or gull wings, the operator needs to retract the gull wings to prevent the wings from drooping when lifted from the ground, elevate the three-point hitch that connects the stack-fold planter to the towing vehicle, e.g., tractor, and extend the lift wheel assembly to raise the bulk fill system. The operator will also need to slow the tractor by shifting and/or reducing engine speed. By requiring the operator to perform these tasks substantially simultaneously, the operator can become mentally and physically fatigued, require an enhanced skill level to operate the stack-fold planter, increase the likelihood that the operator may make an error, or reduce the performance of the stack-fold planter at headland turns.
SUMMARY OF THE INVENTION
[0008] The present invention directed to a method and apparatus for automating some of the tasks that heretofore required operator action at headland turns or similar events. For example, in one embodiment, the present invention automates operation of lift assist wheels and/or gull wings, such as those found on a stack-fold implement, based On the position of the tractor hitch to which the implement is coupled. Accordingly, an operator may control the position of the implement, such as at a headland turn, by raising and lowering the tractor hitch using a conventional remote control. The invention enables the planter to compare the tractor hitch position relative to an implement position and control operation of the implement accordingly without additional user inputs.
[0009] In accordance with one aspect of the invention, a farm implement has a toolbar configured to be coupled to a towing vehicle and a bulk till hopper mounted to a frame that is supported by a lift wheel assembly. The farm implement further has a connector for coupling the toolbar to a hitch of the towing vehicle. A first electrical input receives a hitch position signal from the towing vehicle and a second electrical input receives a frame position signal. The implement further has an electronic control unit (ECU) that receives the hitch position and the frame position signals and automatically activates the lift wheel assembly to maintain the frame in a level position as the vertical position of the connector changes.
[0010] In accordance with another aspect of the invention, a farm implement having a frame supported by a lift wheel assembly comprises a connector for coupling the toolbar to the ISOBUS hitch of a towing vehicle, a first electrical input that receives a hitch position signal from the tractor, an electric over hydraulic valve that controls hydraulic fluid flow from the hydraulic system to the lift wheel assembly, and an electronic control unit (ECU). The ECU receives the hitch position signal and provides a command signal to the electric over hydraulic valve to control hydraulic fluid flow in the hydraulic system to raise the frame when the hitch is in a raised position.
[0011] The present invention is also embodied in a method for automatically leveling a farm implement having a frame and being towed by a tractor that is coupled to the farm implement by a hitch. The method, which is preferably carried out automatically using various electronics, includes receiving a hitch position signal from the tractor and receiving a frame position signal from a sensor that detects a position of the frame. The method further includes the step of automatically raising or lowering the frame in response to changes in hitch position of the tractor.
[0012] Other objects, features, aspects, and advantages of the invention will become apparent to those skilled in the art from the following detailed description and accompanying drawings. It should be understood, however, that the detailed description and specific examples, while indicating preferred embodiments of the present invention, are given by way of illustration and not of limitation. Many changes and modifications may be made within the scope of the present invention without departing from the spirit thereof, and the invention includes all, such modifications.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] Preferred exemplary embodiments of the invention are illustrated in the accompanying drawings in which like reference numerals represent like parts throughout.
[0014] In the drawings:
[0015] FIG. 1 is a pictorial view of an agricultural planting system comprised of a stack-fold planter coupled to a tractor;
[0016] FIG. 2 is an isometric view of the stack-fold planter of FIG. 1 in a field-working (float) position;
[0017] FIG. 3 is a rear elevation view of the stack-fold planter of FIG. 1 in a stacked, transport position;
[0018] FIG. 4 is an isometric view of the central bulk fill system of FIG. 1 in a lowered, field working position;
[0019] FIG. 5 is a schematic block diagram of a hydraulic control system according to one embodiment of the invention; and
[0020] FIG. 6 is a schematic block diagram of a hydraulic control system according to another embodiment of the invention.
DETAILED DESCRIPTION
[0021] As will be made apparent from the following description, the present invention provides an apparatus that automatically adjusts the position of an implement in response to changes in the position of the hitch of a tractor towing the implement. For purposes of description, the invention will be described with respect to a stack-fold planter, such as that shown in FIGS. 1-4 , but it is understood that the invention is applicable with other types of implements. The invention, which can also be embodied in an automated method, is designed to reduce the number of user inputs that were heretofore required to command movements of the implement, such as at headland turns.
[0022] Turning now to FIGS. 1-4 , a planting system 10 includes a stack-fold implement 12 , shown in a field working position, coupled to a prime mover 14 , e.g., tractor, in a known manner. For purposes of illustration, the stack-fold implement 12 is a row crop planter, which as shown in FIG. 2 . includes a frame 16 generally comprised of a center section 18 and wing sections 20 , 22 on opposite lateral sides of the center section. The center section 18 includes a tongue (not shown) that extends forwardly of the center section 18 for hitching the implement 12 to the prime mover 14 . As will be described more fully below, the implement 12 is coupled to a three-point hitch of the prime mover 14 . Gauge wheels 24 on the frame sections 18 , 20 , and 22 set the seeding or cutting depth for the implement.
[0023] In the illustrated embodiment, sixteen openers 26 are mounted to the frame 16 at equally spaced intervals, but it is understood that more than or fewer than sixteen openers could be mounted to the frame 16 . As known in the art, the wing sections 20 , 22 may be raised to a transport position, as shown in FIG. 3 , in which the openers earned by the wing sections 20 , 22 are stacked over the center section 18 . As also known in the art, the openers 26 are designed to cut a furrow into the soil, deposit seed and/or fertilizer into the furrow, and then pack the furrow. Seed boxes or “mini-hoppers” 28 are optionally mounted to each of the openers 26 . The mini-hoppers 28 are preferably smaller than conventional mini-hoppers used with stack-fold crop row planters and thus hold less material than conventional seed boxes.
[0024] The smaller mini-hoppers are flow-coupled to a central bulk fill assembly 30 that delivers material, such as seed and/or fertilizer, to the openers 26 and/or the mini-hoppers 28 . The central bulk fill assembly 30 preferably includes a pair of bulk fill hoppers 32 and 34 supported adjacently to one another on a frame 36 . The frame 36 is coupled to the center section 18 by a set of rearwardly extending frame members 38 , 40 , and 42 connected to a crossbar 44 . In a preferred embodiment, the frame members 38 , 40 , 42 are removably coupled to center frame section 18 which allows the bulk fill assembly 30 to be removed from the implement 12 or added as an after-market add-on to an existing stack-fold implement.
[0025] The frame 36 is supported above the work surface (or transport surface) by a pair of wheels 46 , 48 that are each connected to the frame by a wheel lift assembly 50 , which in the illustrated embodiment includes a pair of parallel linkages 52 , 54 . Each linkage includes upper links 56 , 58 and lower link 60 , 62 . respectively. In addition to the links 56 - 62 , a pair of lift arms 64 , 66 are provided. Lift arm. 64 is coupled to frame member 42 at a knuckle 68 to which parallel linkage 52 is also connected. in a similar manner, lift arm 66 is coupled to frame member 38 at a knuckle 70 to which parallel linkage 54 is also connected. As shown particularly in FIG. 4 , the frame 36 further includes a Y-beam 72 that is pivotally coupled to the center frame member 40 . As is customary for most central bulk fill assemblies, an air blower 74 is mounted beneath the bulk fill hoppers and is operable transfer particulate matter from the hoppers 32 , 34 to the individual mini-hoppers 28 or directly to the openers 26 in a forced air stream.
[0026] As known in the art, central bulk fill hoppers, such as those described above, provide the convenience of a central fill location rather than having to fill the individual seed boxes. Also, the central fill hoppers have greater capacity than the seed boxes, which reduces the number of fill iterations that must be taken when planting. Simply mounting a central bulk fill assembly to a stack-fold planter, such as planter 12 , can create stability issues, especially when the stack-fold planter is in the transport position. In this regard, the present invention provides a mechanism for raising the bulk fill assembly 30 when the stack-fold planter 10 is in the folded, transport position. Raising the bulk assembly 30 provides greater stability during transport as well provides increased clearance between the bulk fill assembly 30 and the roadway.
[0027] A pair of hydraulic lift cylinders 76 and 78 are operable for lifting the frame 36 , and thus the bulk fill assembly 30 . Cylinder 76 is interconnected between forward knuckle 68 and a rearward knuckle 80 . As shown in FIG. 4 , the rearward knuckle 74 includes, or is coupled to, a mounting arm 82 that is coupled to axle 84 about which wheel 46 rotates. Cylinder 76 includes a ram 86 that is coupled to the rearward knuckle 80 whereas cylinder 76 is coupled to the forward knuckle 68 . In a similar fashion, cylinder 78 includes a ram 88 connected to a rearward knuckle 90 whereas the cylinder 78 is connected to the forward knuckle 70 . It will be appreciated that a mounting arm 92 is connected to, or formed with, the rearward knuckle 90 , and the mounting arm 92 is connected to an axle (not shown) about which wheel 48 rotates.
[0028] As known in the art, central bulk fill hoppers, such as those described above, provide the convenience of a central fill location rather than having to fill the individual seed boxes. Also, the central fill hoppers have greater capacity than the seed boxes, which reduces the number of fill iterations that must be taken when planting. Simply mounting a central bulk fill assembly to a stack-fold planter, such as planter 12 , can create stability issues, especially when the stack-fold planter is in the transport position. In this regard, the present invention provides a mechanism for raising the bulk fill assembly 30 when the stack-fold planter 10 is in the folded, transport position. Raising the bulk assembly 30 provides greater stability during transport as well provides increased clearance between the bulk fill assembly 30 and the roadway.
[0029] Turning now to FIG. 5 , the present invention provides a communications apparatus 94 for use with a prime mover equipped with ISO 11783 technology. The communications apparatus 94 includes datalink 96 that communicatively links an implement electronic control unit (ECU) 98 with electronics 100 of the prime mover 14 . The datalink 96 may be a wireless connection or, as shown in FIG. 5 , a wired communication consisting a connector 102 tethered by cable 104 to the electronics 100 and a receiver 106 tethered by cable 108 to ECU 98 . In a preferred embodiment, the connector 102 and the receiver 106 are ISO 11783 components that permit the transfer of data between the prime mover electronics 100 and the ECU 98 . Thus, it will be appreciated that the datalink 96 provides an ISOBUS connection between the prime mover 14 and the stack-fold implement 12 .
[0030] The ISOBUS connection enables the transmission of various data between the stack-fold implement 12 and prime mover 14 . One type of data is hitch position information. The prime mover 14 has a hitch position sensor 110 that provides feedback to the electronics 100 of the prime mover 14 as to the vertical position of the coupling between the stack-fold implement 12 and the prime mover 14 . In one embodiment, this coupling is a three-point hitch. The prime mover electronics 100 provides a data signal to the ECU 98 via datalink 96 containing hitch position information. In accordance with one aspect of the invention, the ECU 98 adjusts the vertical position of the stack-fold implement 12 accordingly.
[0031] More particularly, the stack-fold implement 12 has a frame position sensor 112 that measures the vertical position of the central bulk fill assembly 30 . In one preferred embodiment, the vertical position is determined from the angle between frame 36 and the wheel lift assembly 50 . It is contemplated that a number of sensors may be used to measure this angle including, but not limited to, rotary potentiometers, displacement sensors, optical sensors, strain gauges, pressure sensors, and the like. For example, in one embodiment, the frame position sensor 112 measures the displacement of either hydraulic lift cylinder 76 or hydraulic lift cylinder 78 .
[0032] The ECU 98 receives the frame position signal from the frame position sensor 112 and compares the frame position of the stack-fold implement 12 with the vertical position of the hitch, as provided in the hitch position signal. From this comparison, the ECU 98 raises or lowers the central bulk fill assembly 30 to level the central bulk fill assembly 30 in light of the changes in vertical position of the prime mover hitch.
[0033] In one embodiment of the invention, the central bulk fill assembly 30 is raised or lowered by ECU 98 controlling operation of an electric over hydraulic valve 114 . The hydraulic valve 114 is interconnected between the hydraulics 115 of the prime mover 14 and the hydraulics of the stack-fold implement 12 , which include the pair of hydraulic lift cylinders 76 , 78 . Thus, the hydraulic valve 114 , upon receipt of a corresponding command signal from the ECU 98 , can increase or decrease the pressure in the pair of hydraulic lift cylinders 76 , 78 to raise or lower, respectively, the central bulk fill assembly 30 . It is highly desirable to increase the elevation of the central bulk fill assembly 30 when the hitch is raised and, conversely, lower the elevation when the hitch is lowered.
[0034] In a further embodiment of the invention, also shown schematically in FIG. 5 , the wing sections 20 , 22 are moved automatically based on the vertical position of the three-point hitch. As known in the art, the hydraulic components, including lift actuators 116 , 118 , are used to raise and lower the left wing section 22 (“left side gull wing”) and the right wing section 20 (“right side gull wing”), respectively. In this further embodiment, the ECU 98 also provides command signals to the left and right lift actuators, which can be of conventional design. In a preferred embodiment, the lift actuators are hydraulic cylinders whose operation is controlled by a valve, such as hydraulic valve 114 . As such, the ECU 98 provides control commands to the hydraulic valve 114 which in turn controls operation of the lift actuators preferably in synchrony with the wheel lift assembly 50 .
[0035] It will be appreciated that the wing sections are movable between a field working position, such as illustrated in FIG. 2 and a retracted or raised position, such as illustrated in FIG. 3 . In the field working position, the wing sections (as well as the center section) are free to float so to respond to changes in surface contours. In this regard, the ECU 98 commands the electric over hydraulic valve 114 to control hydraulic fluid flow in the hydraulic system to move the wing sections to the float position when the hitch is in a fully lowered position.
[0036] It will also be appreciated that in the embodiment illustrated in FIG. 5 , the operator of the tractor, i.e., towing vehicle, using conventional hydraulic remotes, pressurizes the tractor's hydraulic system to which the hydraulics of the implement are flow-coupled and thus also pressurized. As such, the operator must manually operate the hydraulic remotes to supply the hydraulic power needed to operate the lift actuators for the gull wings and the central bulk fill assembly.
[0037] In contrast, and referring now to FIG. 6 , a communications apparatus 120 according to an alternate embodiment of the invention controls operation of the hydraulic remotes automatically, i.e., uses the tractor hydraulics 122 to directly control operation of the wheel lift assembly 50 and the lift actuators 116 , 118 rather than control an electronic-over-hydraulic valve 114 . More particularly, the hitch position sensor 110 provides hitch position data to the implement ECU 98 across ISOBUS connection 96 . The implement ECU 98 uses the hitch position information together with frame position data read from the frame position sensor 112 and provides control commands to the hydraulic remote(s) 124 , which are connected to the tractor hydraulics 122 in a known manner. The tractor hydraulics are flow-coupled to the actuators of the wheel lift assembly 50 and the lift actuators 116 , 118 . It is understood that the actuators could be independently flow coupled to the tractor hydraulics, but preferably, a single supply conduit 126 and return conduit 128 that are coupled to a manifold 130 or similar distribution device to which the actuators for the wheel assembly and the lift actuators are flow coupled in a conventional manner, It will thus be appreciated that in the embodiment illustrated in FIG. 6 , the implement controls the hydraulics of the tractor based on commands transmitted to the tractor via the ISOBUS connection.
[0038] It will be appreciated that in one embodiment of the invention, the position of the tractor hitch is used to adjust the vertical position of the implement frame. It is understood however that in another embodiment, the vertical position of the implement frame could be monitored to cause automatic adjustment of the tractor hitch.
[0039] Many changes and modifications could be made to the invention without departing from the spirit thereof. The scope of these changes will become apparent from the appended claims.
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A method and apparatus for automating some of the tasks that heretofore required operator action at headland turns or similar events are provided. The present invention automates operation of lift assist wheels and/or gull wings, such as those found on a stack-fold implement, based on the position of the tractor hitch to which the implement is coupled. An operator may control the position of the implement, such as at a headland turn, by raising and lowering the tractor hitch using a remote control. The invention enables the planter to compare the tractor hitch position relative to an implement position and control operation of the implement accordingly without additional user inputs.
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[0001] This patent application claims priority of provisional patent application Ser. No. 60/438,457 filed Jan. 8, 2003 and provisional patent application No. 60/409,042 filed Sep. 9, 2002.
FIELD OF INVENTION
[0002] The field of the invention is water filtration devices.
BACKGROUND OF THE INVENTION
[0003] The demand for pure water continues to grow rapidly due to increasing concerns about the quality and safety of tap water, the popularity of water as a beverage (instead of soda and alcohol) and the growing awareness that most people do not drink enough water as prescribed by the medical community.
[0004] Water is supplied from municipal water systems (many of which are aging), private water systems and wells in the United States. Frequently, this water has poor taste, particulates, unwanted odors and in many cases contaminants contained in it. Municipal water is commonly treated with chlorine to eliminate bacterial contaminants. Chlorine adds what most people feel is an unpleasant taste and odor. Water conditions vary greatly according to the geographic area and therefore travelers may also experience these problems as they visit hotel and motel rooms around the country. It is desirous to remove bad tastes, odors, sediment and contaminants before ingesting the water or using it for cooking food.
[0005] Water treatment devices of many varieties have proven effective in accomplishing water purification. Generally these devices work through chemical and mechanical actions that remove contaminants and impurities from water. These filters have a finite life. Sediment can eventually clog a filter and chemical reactions realized through adsorption (carbon media) and ion exchange (cation resin) have a limited capacity.
[0006] U.S. Pat. No. 5,989,425 to Yonezawa et al. discloses a multi-way valve and water purifier. The multi-way valve is disclosed as a small-sized one which may be used with a small-sized water purifier. The device disclosed in the '425 patent is a faucet mounted filter and it is designed for removing and exchanging valve bodies.
[0007] U.S. Pat. No. 5,017,286 to Heiligman and U.S. Pat. No. Re. 35667 to Heiligman disclose a vertical filter enclosed in a housing and the housing is supported by a duct. The vertical filter may be permanently secured to the filter by hot melt adhesive which renders the filter non-removable. Further, the vertical filter may be pre-wrapped with a porous paper pre-filter. The device disclosed in the '286 patent is a faucet mounted filter. If the filter is glued to the filter housing the filter housing must be removed and discarded together with the filter. A new filter housing (and filter) must then be mounted onto the duct of the diverter valve each time the filter housing is replaced. This involves time consuming labor in the case of each embodiment disclosed in the '286 patent. In one embodiment of the '286 patent, the filter housing is secured by a retaining clip. In another embodiment disclosed in the '286 patent, the male duct of the filter housing is press-fit into an opening in the diverter valve. Alternatively, the male duct of the filter housing may be affixed to the diverter valve by a U-clip, cotter pin or the like. The filter housing as disclosed in the '286 patent is disclosed as residing vertically in front of the faucet. In short, it is not a simple matter to change the filter housing of the device disclosed in the '286 patent.
[0008] U.S. Pat. No. 5,527,451 to Hembree et al. discloses a faucet mounted filter utilizing a replacement filter cartridge. The replacement filter cartridge resides within a larger rotatable housing which channels water flow either into the filter or through the diverter valve assembly. Hembree et al. also discloses a very complicated flow totalization mechanism which includes porting water to a turbine driven mechanism prior to filtering thereof.
[0009] U.S. Pat. No. 6,571,960 B2 to Williamson et al. discloses a faucet-mounted water filtration device whose filter housing includes a valve therein and whose filter housing extends longitudinally rearwardly from the point of attachment to the faucet. The filters in Williamson et al. are replaceable filter cartridges.
[0010] U.S. Pat. No. 6,284,129 B1 to Giordano et al. discloses a rotating a magnetized impeller actuating a reed switch.
[0011] In each of the foregoing disclosures, the devices disclosed therein are designed for disassembly of some sort as a matter of maintenance of the filtration device. This requires labor and attendant time. Complex flow totalization mechanisms such as the one disclosed in Hembree et al. '451 present maintenance problems. The need to change the filter and/or the filter housing and/or the diverter valve all require labor and attendant time.
[0012] In each of the foregoing disclosures, the devices disclosed therein are designed for disassembly of some sort as a matter of maintenance of the filtration device. Filtration devices customarily employ replaceable filter cartridges of some type. These arrangements require either a coupling arrangement for attaching and detaching a replacement filter cartridge or a large chamber to entirely enclose the replacement filter cartridge. Both approaches require additional components and materials that add to the manufactured cost and complexity of the device. Furthermore, each of the foregoing disclosures, by requiring the replacement of the filter element, cause great inconvenience to the user by having him search for and procure replacement filter elements at considerable cost. This arrangement, while lucrative for the manufacturer, is a well documented nuisance for the consumer. In addition, most of the devices in the related art, owing to their need for easy access and maintenance are relatively large and obtrusive partially blocking the sink basin. Finally, the devices noted above and most others despite the availability of high capacity filter media are not designed for long life so as to maximize the frequency with which users must purchase replacement filter elements.
[0013] It is therefore desirable to have a small faucet-mounted water filtration device which is a single-use, long-life water filtration device which includes an indicator of filter performance. By single use it is meant that it is discarded when its performance indicator reveals that the efficacy of the filter has been diminished. It is also desirable to have the filter housing of the water filtration device mounted behind the connection to the faucet to enable full access to the sink basin beneath the faucet.
SUMMARY OF THE INVENTION
[0014] A single-use faucet-mounted water filtration device is provided. The device is of uni-body construction and has no removable or replaceable parts yet provides long life operation. This arrangement makes the device more convenient to use compared with other devices that require frequent replacement of filter cartridges. The device is constructed with a minimum of components making it relatively small in size and less costly to manufacture. While compact, the device is able to hold enough filter media to allow for long life operation. The life of the water filtration device is dependent upon the type of filter media used, sizing and geometry of the filter media, and the sizing and geometry of water flow paths. For instance, water filtration devices having a useful life of 300 gallons or more can be made utilizing the teachings of the instant invention. Water filtration devices having useful lives smaller than 300 gallons may also be made utilizing the teachings of the instant invention. Performance indications as a function of integrated flow are indicated by a light emitting diode.
[0015] The main housing of the devices resides beneath the faucet neck and rearward of the water discharge point thus not obstructing the sink basin. A single-use device is provided for use in a kitchen sink and a device is provided for use in a bathroom sink. Unlike devices in the related art the bathroom embodiment of the single-use faucet filter is scaled to the small size of bathroom sinks and therefore practical for use in bathrooms. The bathroom filter device allows residential users to have the benefit of filtered water in close proximity to the bedroom avoiding the inconvenience of going to a kitchen sink for water during the night. In addition, because the bathroom device is small and disposable it may be taken with a traveler and installed in a hotel or motel room. Further, as travelers readily discern the differences between water and its tastes from one place to another it is highly desirable that the water filter be portable.
[0016] The invention includes a front housing connectable to a water faucet and a filter housing having an inlet and an outlet. An end cap of the filter housing completes the filter housing. The front housing is non-removably affixed to the filter housing and the water filter is non-removably contained within the water filter housing. The water filter housing includes a chamber in communication with the water filter. The filter is preferably activated carbon and includes a filter pre-wrap. Other filter media may be used. The outlet resides in the chamber. Alternatively, a second outlet may also reside in the chamber in the embodiment of the bathroom filter.
[0017] The single use water filtration device is small. The embodiment designed for bathroom use has a filter diameter less than or equal to 1.6 inches. The embodiment designed for kitchen use has a filter diameter less than or equal to 2.2 inches. The water filtration devices disclosed herein, namely the bathroom and kitchen embodiments, reside substantially rearwardly with respect to the water faucet. Other diameters and sizes of the water filtration devices disclosed herein may be made using the teachings hereof.
[0018] The filter includes ends thereof each secured to an end cap. The end caps have peripheral seal portions which seal against the interior of the filter housing.
[0019] A housing end cap is ultrasonically welded to the filter housing. Other welding methods such as microwave, radio frequency (RF), heat and induction welding may be employed to weld various portions of the water filtration devices disclosed herein together.
[0020] The second outlet includes a valve seat and a valve interposed in the filter housing being operable against the valve seat of the second outlet for controlling the flow out of the second outlet. The valve includes a plunger having a foot and an elastomeric ball valve or boot residing over the foot. The foot of the plunger and the elastomeric ball valve reside within the housing. A handle is pivotally connected to the end cap of the filter housing and engages the plunger such that when the plunger is depressed the elastomeric ball valve moves inwardly toward the center of the housing and away from the seat of the second outlet. A fountain head is rotatably secured in the plunger and lever for communication with a passageway in the plunger.
[0021] A spring is interposed between the plunger and the filter housing urging the elastomeric ball valve against the valve seat of the second outlet.
[0022] A front housing having first and second passageways is non-removably affixed to the filter housing. The front housing includes a directional valve residing within the front housing and movable therein for directing water into the filter for filtering or through the front housing for direct use of the unfiltered water. The filter housing includes three protrusions which interengage corresponding apertures in the front housing. The front housing also includes a continuous periphery welded to the filter housing by one of the aforementioned methods. The filter housing includes a recess whose shape is the reciprocal of the continuous periphery of the front housing and the continuous periphery of the front housing fits snugly within the recess in the filter housing. The end cap of the filter housing is welded to the filter housing. Three parts or pieces, the filter housing, the front housing and the end cap of the filter housing are welded together to provide a unibody or integral construction.
[0023] A gate having a magnet affixed therein resides in the chamber and swings between a first position and a second position. Spacers extending from the end cap serve to ensure that the gate remains in alignment with respect to the earth. These spacers also serve to ensure that the filter subassembly remains in proper position. The first end cap of the filter includes a first hinge member and the gate includes a second hinge member which coacts with the first hinge member to enable the gate to swing between first and second positions. A gate position sensor resides in a dry portion of the end cap of the water filter housing and is actuated when the gate swings to the second position and the magnet is in proximity to the sensor.
[0024] An electronic package and a light emitting diode reside in the dry portion of the end cap of the water filter housing. The electronic package outputs a signal to the light emitting diode which indicates the performance of the water filtration device. The electronic package outputs three discrete signals to the light emitting diode to indicate three performance levels of the filter.
[0025] A method of making a water filtration device is also disclosed and comprises the steps of: attaching end caps to the filter; inserting the filter within a filter housing; aligning the filter within the filter housing; inserting a portion of a gate into corresponding receptacles on one end of one of the end caps previously affixed to the filter; inserting a sensor and electronic package into an open end of a filter housing end cap; affixing the filter housing end cap to the filter housing forming a chamber between a closed end of the filter housing end cap and the one end of one of the end caps; and, affixing a front housing to the filter housing. The step of attaching end caps to said filter may be performed with adhesive. And, the steps of affixing the end cap of the filter housing, affixing the filter housing end cap to the filter housing and affixing the front housing to the filter housing may be performed by an ultrasonic welding process or one of the other welding processes identified herein.
[0026] It is an object of the present invention to provide a water filtration device which is disposable and provides an indication as to when the filter should be disposed.
[0027] It is a further object of the present invention to provide a water filtration device which is small in size and which resides substantially rearwardly with respect to the faucet to which it is mounted.
[0028] It is a further object of the present invention to provide a water filtration device which is self-contained and which does not require maintenance and, in fact, which cannot be maintained because the parts thereof are non-removably affixed together or non-removably contained therein.
[0029] It is an object of the present invention to provide a water filtration device at reasonable cost which is disposable and which is faucet mounted.
[0030] It is an object of the present invention to provide a water filtration device which includes a swinging gate having a magnet therein which in combination with a sensor and an electronic package provides a visual indication as to the status or performance of the filter.
[0031] It is an object of the present invention to provide a water filtration device which includes two filtered outlets.
[0032] It is an object of the present invention to provide a water filtration device which includes a valved outlet with the valve operated by a lever.
[0033] It is an object of the present invention to provide a water filtration device which includes an outlet having a rotatably mounted fountain head.
[0034] It is an object of the present invention to provide a water filtration device which includes a lever actuated fountain.
[0035] These and additional objects will become apparent when reference is made to the Brief Description of the Drawings, Description of the Invention and Claims which follow hereinbelow.
BRIEF DESCRIPTION OF THE DRAWINGS
[0036] FIG. 1 is an exploded assembly view of a first embodiment of the water filtration device.
[0037] FIG. 2 is a perspective view of a first embodiment of the water filtration device.
[0038] FIG. 2A is a perspective view of a first embodiment of the water filtration device with the handle of the valve pulled forward.
[0039] FIG. 3 is a cross-sectional view of the first embodiment of the water filtration device taken along the lines 3 - 3 of FIG. 2 . In FIG. 3 the filter is not operating as no water is being directed into it.
[0040] FIG. 3A is an enlargement of a portion of FIG. 3 .
[0041] FIG. 3B is a cross-sectional view of the first embodiment of the water filtration device with the fountain lever depressed and with water flowing through the filter.
[0042] FIG. 3C is an enlargement of a portion of FIG. 3B .
[0043] FIG. 3D is a cross-sectional view of the first embodiment of the water filtration device similar to FIG. 3 with an O-ring used as an additional seal for the filter subassembly.
[0044] FIG. 4 is an enlargement of the front housing of the first embodiment of the water filtration device.
[0045] FIG. 4A is a cross-sectional view of the front housing taken along the lines 4 A- 4 A of FIG. 4 .
[0046] FIG. 4B is a cross-sectional view of the front housing taken along the lines 4 B- 4 B of FIG. 4 .
[0047] FIG. 4C is a top view of the front housing of the first embodiment.
[0048] FIG. 4D is an enlarged rear perspective view of the front housing of the first embodiment.
[0049] FIG. 4E is a cross-sectional view of the rotatable collar (faucet adapter) and the lock collar which is secured to the front housing.
[0050] FIG. 4F is a cross-sectional view of the aerator mounted into the front housing.
[0051] FIG. 4G is a cross-sectional view taken along the lines 4 G- 4 G of FIG. 2 with the flow diverter valve inserted in the front housing in a first position, bypass position.
[0052] FIG. 4H is a cross-sectional view taken along the lines 4 H- 4 H of FIG. 2A with the flow diverter valve inserted in the front housing in a second position which directs flow into the filter.
[0053] FIG. 5 is a front perspective view of the filter housing of the first embodiment of the water filtration device.
[0054] FIG. 5A is a front view of the filter housing of the first embodiment of the water filtration device.
[0055] FIG. 5B is a cross-sectional view of the filter housing taken along the lines 5 B- 5 B of FIG. 5A .
[0056] FIG. 5C is a cross-sectional view of the filter housing taken along the lines 5 C- 5 C of FIG. 5A .
[0057] FIG. 5D is a cross-sectional view of the filter housing taken along the lines 5 D- 5 D of FIG. 5A .
[0058] FIG. 5E is a bottom view of the filter housing of the first embodiment of the water filtration device.
[0059] FIG. 5F is a left side view, the open end view, of the filter housing of the first embodiment of the water filtration device.
[0060] FIG. 6 is a perspective view of the valve and its handle which are used in both the first embodiment and the second embodiment of the water filtration device.
[0061] FIG. 6A is a perspective view of the other side of the valve and its handle of FIG. 6 .
[0062] FIG. 7 is a perspective view of the electronic package (electric circuit), sensor and light emitting diode used in the first and second embodiments of the water filtration device.
[0063] FIG. 7A is a side view of the electronic package (electric circuit), sensor and light emitting diode package of FIG. 7 .
[0064] FIG. 8 is a side view of the housing end cap.
[0065] FIG. 8A is a perspective view of the other side, i.e., the wetted side, of the housing end cap illustrated in FIG. 8 .
[0066] FIG. 9 is a front view of the gate of the first embodiment.
[0067] FIG. 9A is a cross-sectional view taken along the lines 9 A- 9 A of FIG. 9 .
[0068] FIG. 10 is a front view of the left end cap of the filter.
[0069] FIG. 10A is cross-sectional view of the left end cap of the filter taken along the lines 10 A- 10 A of FIG. 10 .
[0070] FIG. 11 is a perspective view of the plunger used in conjunction with the lever and elastomeric ball valve.
[0071] FIG. 11A is a another perspective view of the plunger used in conjunction with the lever and elastomeric ball valve.
[0072] FIG. 11B is a top view of the plunger.
[0073] FIG. 11C is a cross-sectional view of the plunger taken along the lines 11 C- 11 C of FIG. 11B .
[0074] FIG. 11D is a cross-sectional view taken along the lines 11 D- 11 D of FIG. 11B .
[0075] FIG. 12 is a front view of the ball valve.
[0076] FIG. 12A is a cross-sectional view taken along the lines 12 A- 12 A of FIG. 12 .
[0077] FIG. 13 is a top view of the lever used to operate the plunger of the first embodiment.
[0078] FIG. 13A is a cross-sectional view of the lever taken along the lines 13 A- 13 A of FIG. 13 .
[0079] FIG. 13B is a perspective view of the underside of the lever of FIG. 13 .
[0080] FIG. 14 is a front view of the fountain head.
[0081] FIG. 14A is a cross-sectional view taken along the lines 14 A- 14 A of the fountain head of FIG. 14 .
[0082] FIG. 15 is an exploded perspective view of a second embodiment of the invention.
[0083] FIG. 16 is a perspective view of a second embodiment of the water filtration device.
[0084] FIG. 16A is a perspective view of a second embodiment of the water filtration device with the valve handle pulled forward.
[0085] FIG. 17 is a cross-sectional view of the second embodiment of the water filtration device taken along the lines 17 - 17 of FIG. 16 .
[0086] FIG. 17A is a cross-sectional view of the second embodiment of the water filtration device similar to FIG. 17 except the gate is shown rotated clockwise in the flow condition.
[0087] FIG. 18 is a perspective view of the front housing of the second embodiment.
[0088] FIG. 18A is a cross-sectional view taken along the lines 18 A- 18 A of FIG. 18 .
[0089] FIG. 18B is a cross-sectional view taken along the lines 18 B- 19 B of FIG. 18 .
[0090] FIG. 18C is a top view of the front housing of the second embodiment.
[0091] FIG. 18D is a rear perspective view of the front housing of the second embodiment of the water filtration device.
[0092] FIG. 18E is a cross-sectional taken along the lines 18 E- 18 E of FIG. 16 with the flow diverter valve inserted in the front housing in a first position, bypass position.
[0093] FIG. 18F is a cross-sectional view taken along the lines 18 F- 18 F of FIG. 16A with the flow diverter valve inserted in the front housing in a second position which directs flow into the filter.
[0094] FIG. 19 is a front perspective view of the filter housing of the second embodiment of the water filtration device.
[0095] FIG. 19A is a bottom view of the of the filter housing of the second embodiment of the water filtration device.
[0096] FIG. 19B is a cross-sectional view taken along the lines 19 B- 19 B of FIG. 19A .
[0097] FIG. 19C is a cross-sectional view taken along the lines 19 C- 19 C of FIG. 19C .
[0098] FIG. 19D is a left side view, the open end view, of the filter housing of the second embodiment of the water filtration device.
[0099] FIG. 20 is a front side view of the end cap of the housing of the second embodiment of the water filtration device.
[0100] FIG. 20A is a right side view of the end cap of FIG. 20 .
[0101] FIG. 20B is a perspective view of the end cap of FIG. 20 .
[0102] FIG. 20C is a view of the left side of the end cap of FIG. 20 .
[0103] FIG. 20D is another perspective view of the end cap.
[0104] A better understanding of the drawings will be had when reference is made to the Description of the Invention and Claims which follow hereinbelow.
DESCRIPTION OF THE INVENTION
[0105] Referring to FIG. 1 , an exploded assembly view of a first embodiment of the water filtration device 100 , the various components of the single-use faucet mounted water filter are shown. Filter 113 is illustrated having a longitudinal bore 129 therethrough. Filter 113 is illustrated without a filter pre-wrap in this view but such a pre-wrap 495 is specifically within the scope of this invention and is illustrated in FIGS. 4G and 4H . The filter is preferably a carbon block but may be a fiber bundle or granular activated carbon. Further, the carbon block may include bacteriastic materials, ion exchange resins and zeolites to assist in its filtration activity. End caps 114 and 115 are affixed to said filter with a hot melt adhesive applied to the entire mating surfaces of end caps 114 and 115 including but not limited to the dowel portions thereof such as dowel 130 A on right end cap 130 . Once filter 113 is affixed to end caps of filter 114 , 115 , the subassembly is inserted into the filter housing 101 . End caps 114 , 115 include peripheral seal portions which seal annulus 301 . See FIG. 3 for example. O-rings 375 , 376 ensure that water entering annulus 301 flow through filter 113 and does not bypass the end caps 114 , 115 and migrate into chamber 350 . See, FIG. 3D . To ensure that the subassembly is properly oriented, gate hinges 132 , 132 A must be aligned in relation to a mark 160 on the filter housing as the subassembly is inserted into the filter housing 101 . Gate hinges 132 , 132 A are properly positioned when their axis is parallel to the earth or parallel to a tangent of the earth's surface.
[0106] Referring to FIG. 5F , the left side view (open end view) of the filter housing 101 of the first embodiment of the water filtration device, the concave right side wall 508 of the filter housing 101 is illustrated along with molded ribs 515 . In this the first embodiment the diameter of the filter housing 101 is approximately 1.6 inches and the length of the filter housing as viewed, for example, in FIGS. 5 and 5 A, is approximately 4.2 inches. Other dimensions may be utilized in the construction of water filtration devices as taught herein without departing from the spirit and scope of the invention. When the filter subassembly is inserted into the filter housing the right end cap abuts ribs 515 .
[0107] Gate 118 is rotatably affixed to gate hinges 132 , 132 A by inserting prongs or knobs 133 , 133 A in the hinges. Knobs or prongs 133 , 133 A are snap-fit into apertures in the hinges 132 , 132 A enabling rotation of the gate 118 when water pushes against it as it exits the filter. As will be explained in more detail hereinafter, gate 118 swings (rotates) in a clockwise direction about its axis of rotation (see FIGS. 3B and 3C ) upon the application of pressure caused by water flow through the filter 113 and the longitudinal bore 129 therein.
[0108] Referring to FIGS. 1 and 3 , gate 118 includes a magnet 117 which is press fit into a recess 134 in the gate and hermetically sealed with either hot melt adhesive or potting compound. FIG. 3 is a cross-sectional view 300 of the first embodiment of the water filtration device taken along the lines 3 - 3 of FIG. 2 . Presence or absence of magnet 117 is sensed by reed switch (reed relay) 135 . Housing end cap 102 includes spacers 142 and 143 . See FIG. 8A , a perspective view of the end cap to best view the spacer 142 which is not well illustrated in the exploded assembly view of FIG. 1 . Spacers 142 , 143 assist in correctly spacing the housing end cap 102 with respect to the left end cap 114 of the filter. Once housing end cap 102 is inserted into the filter housing 101 , spacers 142 , 143 ensure that the filter subassembly comprising the filter 113 , left end cap 114 and right end cap 115 does not migrate leftwardly (See FIG. 3 ) too far and remains in proximity to the mold ribs 515 of the interior of the housing. Housing end cap 102 includes a tapered portion 190 for insertion into the filter housing 101 . A chamber is formed between the end cap 114 and the closed end 803 A of the housing end cap 102 . See, FIG. 3 . Water is expelled from passageway 141 in the left end cap 114 of the filter housing and exerts a force against gate 118 causing it to rotate in a clockwise direction. As gate 118 rotates in the clockwise direction the magnet 117 is urged toward the reed switch 135 (reed relay) causing it to effectively close which starts the electronic timer within electronic package 112 to continuously measure the time when the magnet 117 is in proximity to the switch. The electronic package (electric circuit or integrated circuit) measures the cumulative time of flow through the filter and outputs signals to the light emitting diode (LED) indicating filter performance. The LED indicates three colors representative of cumulative filter usage one of which indicates that the water filtration device should be discarded. The electric circuit outputs three discrete signals to the light emitting diode.
[0109] The electronic package is secured in a dry well 170 which in turn is secured and closed by end plate 116 . After the housing end cap 102 is installed it is welded to the filter housing 101 . The end plate 116 is glued or ultrasonically welded to the housing end cap 102 . That is, the housing end cap 102 is welded to the filter housing and the end plate 116 is welded or glued to the housing end cap 102 . Reference numeral 139 represents the raised portions of the end plate 116 which are ultrasonically welded or glued to the housing end cap 102 .
[0110] Referring to FIG. 3 again, reference numerals 302 , 303 , 130 , 131 signify peripheral edges or portions of the end caps 114 , 115 of the filter which slidingly engage and seal against the interior walls of the filter housing 101 . Referring to FIG. 3D , elastomeric seal 375 acts as an additional optional seal which resides between peripheral edge portions 302 and 131 and elastomeric seal 376 acts as an additional optional seal which resides between peripheral edge portions 303 and 130 .
[0111] Still referring to FIG. 1 , aperture 137 permits light emitting diode 136 which stems from the electronic package 112 to pass therethrough. A small amount of potting compound may be used around the light emitting diode to seal any space between the diode and the aperture 137 when the light emitting diode is installed in place. The electronic package 112 and the substrate upon which the electronics are mounted are housed in a dry space in the housing end cap 102 .
[0112] Referring to FIGS. 1 and 5 , the filter housing 101 including its inlet 125 , filtered outlet 107 A, and filtered outlet 180 are illustrated. Filtered outlet 107 A always expels filtered water whenever water enters the filter housing inlet 125 . See, FIG. 4H . Inlet 125 is generally cylindrically shaped and includes a recess 126 for receiving an O-ring seal 502 and a passageway 505 for conducting unfiltered water to the interior of the filter housing so that it can be filtered by filter 113 . Filter 113 is a carbon block filter and it is necessary that the water to be filtered have a certain residence time in contact with the filter so that impurities therein can be removed.
[0113] The preferred materials of the front housing 103 , filter housing 101 and housing end cap 102 are ABS (acrylonitrile butadiene styrene) plastic although other plastics may be used. The preferred adhesive to be used for securing the end caps 114 , 115 to the filter is a hot melt adhesive. The gate material is HDPE (high density polyethylene). End caps 114 , 115 are also HDPE and the material used for sealing. Lever 122 is preferably an acetyl material.
[0114] FIG. 5 is a front perspective view 500 of the filter housing 101 of the first embodiment of the water filtration device, i.e., a bathroom filter. FIG. 5 illustrates an inlet surface 504 adapted to receive a corresponding mating surface 190 from the housing end cap 102 . See, FIG. 1 to identify the corresponding mating surface 190 on the housing end cap 102 .
[0115] Referring again to FIG. 5 , the filter housing 101 includes a recessed region 501 for receiving the front housing 103 as best seen in FIGS. 1, 2 and 4 G. Engagement pins 127 , 128 assist in positioning the front housing 103 with respect to the recessed region 501 for ultrasonic welding thereto. It is the ultrasonic welding of the front housing 103 to the filter housing which secures the parts together and makes them into an integral unit.
[0116] Pins 127 , 128 fit snugly into corresponding receptacles 420 , 419 in the front housing. Referring to FIG. 4D , a rear perspective view 400 D of the front housing of the first embodiment (bathroom filter) is illustrated along with the receptacles 420 , 419 . Reference numerals 415 , 417 and 418 indicate mold cavities which are formed as a part of the molding process of the front housing 103 . Joint 421 is welded to the filter housing 101 . Further, referring to FIGS. 4G and 5 , O-ring seal 502 which resides in recess 126 mates with cylindrical recess 410 in the front housing 103 as illustrated in FIG. 4D to prevent leakage of water as it is being directed into the filter housing as will be explained hereinbelow.
[0117] FIG. 5A is a front view 500 A of the filter housing 101 of the first embodiment of the water filtration device. The right end 508 is closed and is convexly shaped when viewed from the outside of the filter housing. Viewing the interior of the right end 508 as in FIG. 5F , it is shaped concavely. During assembly of the device, the water filter 113 with end caps attached thereto is inserted from the left side, the open side, of the filter housing 101 .
[0118] FIG. 5B is a cross-sectional view 500 B of the filter housing taken along the lines 5 B- 5 B of FIG. 5A . FIG. 5B provides a good illustration of recess 126 in inlet 125 and of pin 128 . Outlets 180 and 107 A are also illustrated in FIG. 5B .
[0119] FIG. 5C is a cross-sectional view 500 C of the filter housing taken along the lines 5 C- 5 C of FIG. 5A . Outlet port 180 is illustrated in cross-section as having two diametrical sections 503 and 506 . Likewise, outlet port 107 A is illustrated as having two diametrical sections 519 and 507 .
[0120] FIG. 5D is a cross-sectional view 500 D of the filter housing taken along the lines 5 D- 5 D of FIG. 5A . FIG. 5D illustrates the recessed region 501 in filter housing 101 . Also illustrated in FIG. 5D is the inlet 125 having passageway 505 therein.
[0121] FIG. 5E is a bottom view 500 E of the filter housing of the first embodiment of the water filtration device illustrating diametrical portions 507 , 519 of outlet 107 A. FIG. 5E illustrates that outlet 107 A resides generally forwardly in the filter housing. Outlet 107 A includes spout 107 which is affixed through an ultrasonic weld or by gluing same to the filter housing 101 . See, FIG. 1 .
[0122] FIG. 2 is a perspective view 200 of a first embodiment of the water filtration device. Referring to FIGS. 1, 2 , 4 , and 4 E, collar lock 105 is inserted within collar 104 and is welded to surface 401 of front housing 103 . FIG. 4 is an enlargement 400 of the front housing of the first embodiment of the water filtration device. FIG. 4E is a cross-sectional view 400 E of the collar 104 , collar lock 105 and screen 110 . Screen 110 includes an elastomeric generally circular periphery and a convexly shaped screen portion 110 A. Collar 104 may rotate with respect to collar lock 105 in the connection and disconnection process with a faucet. The faucet (not shown) seals on the elastomeric portion of the screen 110 . Screen 110 assists in removing large particulate matter.
[0123] Referring still to FIG. 2 , front housing 103 is illustrated in its assembled condition welded to the filter housing 101 . Valve and valve handle 108 are illustrated in the first or bypass position. FIG. 4G is a cross-sectional view 400 G taken along the lines 4 G- 4 G of FIG. 2 with the flow diverter valve 108 inserted in the front housing in a first position, bypass position. Flow arrow 470 indicates the path flow will take through the front housing when the water bypasses the filter. FIG. 4H is a cross-sectional view 400 H taken along the lines 4 H- 4 H of FIG. 2A with the flow diverter valve 108 inserted in the front housing in a second position which directs flow into the filter. Flow arrow 471 indicates the path of flow through the front housing when the diverter valve 108 is rotated counterclockwise when viewing FIG. 4H to a second position. Referring to FIG. 2A , valve and valve handle 108 are pulled forward to the second position when it is desired to filter the water.
[0124] Referring again to FIGS. 4G and H, elastomeric seal 450 is illustrated as sealing passageways 603 and 610 in valve 108 . Passageway 610 is formed by wall 611 and passageway 603 is formed by wall 605 which is horn shaped. See, FIG. 6 , a perspective view 600 of the valve and its handle 108 which are used in both the first embodiment and the second embodiment of the water filtration device. The handle portion of the valve includes an insert 109 which may glued to a corresponding recess 109 A in the handle. See, FIG. 1 .
[0125] FIG. 4A is a cross-sectional view 400 A taken along the lines 4 A- 4 A of FIG. 4 illustrating the generally cylindrical wall 401 to which the collar lock 105 is welded. FIG. 4E is a cross-sectional view 400 E illustrating the collar lock 105 secured to the wall 401 with the collar 104 being rotatable and movable slightly vertically for engagement with a faucet. Screen 110 is also illustrated in FIG. 4A .
[0126] Referring again to FIG. 4A , valve 108 is not shown therein so as to view the valve stop 407 which controls the rotation of the valve between its first (bypass position) and its second (filter) position. Valve cavity 430 is tapered as it extends inwardly as indicated by circular lines 412 and 431 . See, FIGS. 4A and 4B . Ports 403 and 408 join to form a water inlet to the valve cavity 430 . Water outlet 409 conveys water to be filtered when the front housing is nonremovably affixed to the filter housing 101 and the valve 108 is in its second position. FIG. 4B is a cross-sectional view 400 B taken along the lines 4 B- 4 B of FIG. 4 and also illustrates the taper of valve cavity 430 .
[0127] Referring again to FIGS. 4A and 4B , recess 416 is illustrated for receiving a seal 640 on the valve 108 illustrated in FIG. 6 . Bypass port or passageway 414 is illustrated in FIGS. 4A and 4B . Stop 407 is also illustrated in FIG. 4B as is recess 410 for receiving inlet 125 of the filter housing 101 . Referring to FIG. 4A mold aperture 415 from the molding process is illustrated in cross section. FIG. 4C is a top view 400 C of the front housing 103 of the first embodiment and also illustrates the ports 403 and 408 .
[0128] FIG. 4 is an enlargement 400 of the front housing 103 of the first embodiment of the water filtration device illustrating wall 401 to which the collar lock 105 is welded. Ports. 403 , 408 in floor 404 are shown in the top of the housing as are mold openings 402 . Recess 416 in valve cavity 431 is shown as is rim 406 which is welded to the filter housing 101 . Recess 416 receives seal 640 on valve 108 so as to prevent leakage about valve 108 .
[0129] Referring again to FIGS. 1 and 4 A, bottom portion 103 A of the front housing is illustrated along with bore 422 having stepped portions 429 and 413 . Bore 422 receives aerator assembly 111 / 111 A and spout 106 secures the aerator assembly in place as it is welded to the bottom portion 103 A of the housing 103 . See, FIG. 4F , a cross-sectional view 400 F of the aerator assembly 111 / 111 A mounted into the front housing.
[0130] Referring to FIGS. 3-3D , reference numerals 302 , 303 , 131 , and 130 indicate sliding engagement of the filter end caps 114 , 115 with the filter housing 101 . Referring again to FIGS. 1 and 3 , second outlet 180 in the filter housing 101 is disclosed. Alignment mark 160 is also illustrated well in FIG. 1 and it is this mark which is used during assembly to ensure that the left filter end cap 114 and hinges 132 / 132 A are positioned such that the axis of the hinges are parallel to the earth enabling gate 118 to swing freely upon the application of pressure thereto and not to bind. Plunger 120 having a passageway 120 A therein fits somewhat snugly within second outlet 180 and is slidingly movable therein. Lever 122 resides in engagement with the plunger 120 such that the plunger 120 and lever 122 move together. Referring to FIG. 2 , lever 122 is hinged and pivotal on prongs or protrusions 138 of the housing end cap 102 . Like lever 108 , lever 122 has a decorative insert 123 which resides in a corresponding recess. Fountain head 119 resides in and through passageway 122 A in lever 122 . Fountain 119 includes a passageway 119 A in communication with passageway 120 A in plunger 120 . Passageway 120 A is exposed to fluid under pressure in chamber 350 when the plunger is depressed by lever 122 .
[0131] Plunger 120 includes a shoe portion 1104 . FIG. 11 is a perspective view 1100 of the plunger 120 used in conjunction with the lever 122 and elastomeric ball valve 121 . Plunger 120 includes a cylindrical portion 1103 and a shaft 1105 with a shoe 1104 on the end thereof. A flat extending portion 1101 of the plunger resides against a corresponding surface of the lever 122 . A taper 1102 leads to passageway 120 A.
[0132] FIG. 11A is a another perspective view 1100 A of the bottom side of the plunger 120 used in conjunction with the lever 122 and elastomeric ball valve 121 . Contoured side edge portion 1150 of plunger 120 engages lever 122 . Passageway 120 A and bottom side 1106 of the flat extending portion 1101 are best viewed in FIG. 11A . Spring 124 is operable between the bottom side 1106 of plunger and a lip 570 of the filter housing. See FIG. 3 , a cross-sectional view 300 of the first embodiment of the water filtration device taken along the lines 3 - 3 of FIG. 2 . In FIG. 3 , the filter is not operating meaning that the diverter valve 108 is in the bypass (first) position.
[0133] FIG. 11B is a top view 1100 B of the plunger 120 illustrating the passageway 120 A. FIG. 11C is a cross-sectional view 1100 C of the plunger 120 taken along the lines 11 C- 11 C of FIG. 11B . FIG. 11D is a cross-sectional view 1100 D taken along the lines 11 D- 11 D of FIG. 11B .
[0134] FIG. 12 is a front view 1200 of the ball valve 121 . FIG. 12A is a cross sectional view 1200 A taken along the lines 12 A- 12 A of FIG. 12 . Shoe 1104 is covered by elastomeric valve 121 which includes a cavity which is substantially reciprocally shaped to the shape of the shoe. Elastomeric valve of boot 121 includes a surface 1202 which engages the interior of the filter housing around passageway 506 . See, FIGS. 5C and 3 .
[0135] FIG. 3A is an enlargement 300 A of a portion of FIG. 3 illustrating the valve 121 engaged with the inner wall of housing 101 . Spring 124 is operable between filter housing 101 and plunger 120 and urges the plunger and the lever upwardly when viewing FIGS. 3 and 3 A.
[0136] Still referring to FIG. 3 , an annular space 301 between the filter 113 and the filter housing 101 is illustrated. Water occupies this annular space 301 during operation of the filter. Water resides in this annulus and flows through filter 113 into passageway 129 and out port 141 impinging upon gate 118 rotating it clockwise. When the water filtration device of the first embodiment is operable, water will be expelled from both outlets 107 A and 180 if lever 122 is depressed. If the lever is not depressed then elastomeric valve 121 is seated against the curved inner surface of the filter housing 101 and water will be expelled just from the outlet 107 A. Valve 121 is preferably elastomeric but may be made of other materials such as metal. Similarly, the filter housing may be made of metal if desired and the valve can be made of metal as well. FIG. 3 illustrates spacer 142 extending from the closed end 803 A of housing end cap 102 near the filter left end cap 114 . FIG. 8 is a side view 800 of housing end cap 102 . Closed end 803 is a wall or boundary between the wetted chamber 350 and the electronic package 112 and sensor 135 . Guide ribs 801 , 802 and 810 enable placement of the generally-rectangularly shaped electronic package within the drywell 811 of the housing end cap 102 . End plate 116 fits over the opening 811 of the end cap and is either welded or glued 139 to the end cap for hermetic sealing thereof. During assembly the light emitting diode 136 is carefully placed within the aperture 137 first followed by the electronic package 112 which is placed within opening 811 . FIG. 8A is a perspective view 800 A of the other side, i.e., the wetted side, of the end illustrated in FIG. 8 . Sloped surface 190 which is welded to filter housing 101 is illustrated in FIG. 8A .
[0137] FIG. 3B is a cross-sectional view 300 B of the first embodiment of the water filtration device with the fountain lever 122 depressed and valve 121 off its seat. It will be noticed that plunger 120 bends slightly when lever 122 is depressed. This bending tends to seal the passageway denoted by reference numeral 506 . Gate 118 is shown rotated clockwise due to water flow out of passageway 141 . In this position, gate 118 and magnet 117 are in proximity to reed switch 135 . FIG. 3C is an enlargement 300 C of a portion of FIG. 3B and illustrates the flow path 391 of water past valve 121 , through passageway 120 A of plunger 120 and through passageway 199 A of fountain 119 . It will be noticed in FIGS. 3, 3A , 3 B and 3 C that outlet 107 A is not shown therein as it is located fore (ahead) with respect to the cross-section of these drawing figures.
[0138] FIG. 6 is a perspective view 600 of the valve 108 and its handle which are used in both the first embodiment and the second embodiment of the water filtration device. FIG. 6 illustrates the underside (the side that is not exposed) when viewing FIG. 2 . Reference numeral 612 illustrates a cavity from the molding process. Reference numeral 609 indicates the handle portion of the valve 108 and reference numeral 608 indicates the other or second end of the valve 108 . Ridges 602 engage stop 407 to limit the rotation of the valve between its first bypass position and its second filter position. A horn shaped passageway 603 is formed by wall 605 . Wall 606 creates an annulus 604 in which a seal (not shown in FIG. 6 ) is positioned. A seal 450 is positioned in annulus 604 as indicated in FIGS. 4G and 4H . A groove 607 resides in the valve 108 for receiving a seal (not shown in FIG. 6 ) which prevents leakage of water from the valve 108 when it inserted in the front housing 103 . FIG. 6A is a perspective view 600 A of the exposed side of the valve and its handle 108 as viewed in FIG. 2 . FIG. 6A illustrates seal 640 in groove 607 for sealing the valve 108 which is snap fit in the front housing.
[0139] FIG. 7 is a perspective view 700 of the electronic package 112 , battery 701 , sensor 135 , leads 702 , 703 and light emitting diode 136 used in the first and second embodiments of the water filtration device. In the preferred embodiment sensor 135 is a reed switch also known as a reed relay. However, those skilled in the art will readily recognize that different, sensors based on capacitance principles, piezoelectric principles, or induction principles may be employed with some modifications. FIG. 7A is a side view 700 A of the electronic package illustrated in FIG. 7 .
[0140] FIG. 9 is a front view 900 of gate 118 of the first embodiment. Recess 134 receives magnet 117 which actuates reed switch 135 when in proximity therewith. Prongs or knobs 134 interengage corresponding hinges 134 as illustrated in FIGS. 1 and 3 . FIG. 9A is a cross-sectional view 900 taken along the lines 9 A- 9 A of FIG. 9 . FIG. 9A illustrates the contour of the gate 118 which includes front 903 and rear 902 surfaces. Sloping surface 904 diverges to body 905 having recess 134 in which magnet 117 is housed. Locks 901 secure magnet 117 in place. The magnet is installed by simply pushing on the magnet to orient it past the locks 901 which are plastic and somewhat malleable enabling insertion of the magnet into the plastic. The magnet is then hermetically sealed with potting compound.
[0141] FIG. 10 is a front view 1000 of the left end cap 114 of the filter 113 . Hinges 132 / 132 A are illustrated in FIGS. 10 and 10 A. FIG. 10A is cross-sectional view 1000 A of the left end cap of the filter taken along the lines 10 A- 10 A of FIG. 10 illustrating the hinges 132 / 132 A, passageway 141 , dowel 1001 , and protrusions 1002 and 1003 which slidingly seal with respect to the filter housing. Peripheral end portion such as the one denoted by reference numeral 131 are relatively soft and seal against the interior of the filter housing.
[0142] FIG. 13 is a top view 1300 of the lever 122 used to operate the plunger 120 of the first embodiment. Reference numeral 1301 indicates a recess in which insert 123 is secured by adhesive. Apertures or hinges 140 / 140 A engage prongs or protrusions 138 for pivoting as previously described. FIG. 13A is a cross-sectional view of the lever 122 taken along the lines 13 A- 13 A of FIG. 13 also illustrates the aperture 140 A. Cavities 1302 and 1303 are illustrated in FIG. 13A . Cavity 1303 fits over flat portion 1101 of plunger 120 . See, FIG. 11 .
[0143] FIG. 13B is a perspective view 1300 B which illustrates the underside of the lever 122 of FIG. 13 . Cavity 1303 and wall 1304 of cavity 1303 are illustrated. Flat portion 1101 of plunger 120 fits into cavity 1303 .
[0144] FIG. 14 is a front view 1400 of the fountain head 119 illustrating flanges 1401 and 1402 . FIG. 14A is a cross-sectional view 1400 A taken along the lines 14 A- 14 A of the fountain head 119 of FIG. 14 . Flange 1402 is snap-fit into place in lever 122 as is best seen in FIG. 3 . Fountain head 119 is made of plastic. Spring 124 is illustrated in FIG. 1 as operable between seat 570 and surface 1106 . See, FIGS. 3, 5C and 11 C. FIG. 3 illustrates valve 121 seated against seat 330 .
[0145] FIGS. 1-14 are directed toward the first embodiment of the invention. Some of the uses of the first embodiment of the invention are in bathrooms, hotel and motel rooms. The device disclosed is small and convenient for storage on vacations and business trips. FIGS. 15-20 are directed toward the second embodiment of the invention. Use of the second embodiment include kitchen and bar uses. Both embodiments are designed such that the filter sits rearwardly with respect to the faucet so that access to the faucet and the filter is permitted.
[0146] The reference numerals used in FIG. 15 correspond generally to the reference numerals used in FIG. 1 such that for example reference numerals 101 and 1501 both indicate filter housings.
[0147] FIG. 15 is an exploded perspective view 1500 of a second embodiment of the invention. Filter housing 1501 may have, for example, a diameter of 2.40 inches and a length of approximately 3.90 inches. One of the principal differences in the kitchen filter of the second embodiment is that it has only one filtered outlet 1507 A whereas the bathroom unit has two filtered outlets 107 A and 180 . Filters 1513 and 113 may be pre-wrapped 495 using a hot seal method. See, FIGS. 4G and 4H . Adhesive is applied to the filter end caps 1514 , 1515 , then attached to the filter after which the subassembly is inserted into the filter housing. Peripheral seal portions of end caps 1514 , 1515 seal the filter. Optionally, O-rings 375 , 376 may be used to seal the filter so as to prevent unfiltered water from entering chamber 1750 . See, FIG. 17 . As in the case of the bathroom filter, the aerator assembly 1511 and spout 1506 are affixed in the front housing 1503 as previously illustrated. As also in the case of the bathroom filter, the collar lock 1505 is welded to the front housing 1503 and collar 1504 is permitted to rotate with respect to the collar lock. The screen assembly is inserted into the assembly atop the collar lock. Gate 1518 is slightly dimensionally different than the gate 118 previously described but it functions in the same way as gate 118 . Spacers 1542 and 1543 extend from end cap 1502 and serve to ensure that gate 1518 remains in alignment.
[0148] Electronic package 112 is the same package used in the first embodiment. Reed switch 135 (or reed relay as it sometimes known) senses the proximity of magnet 1517 and the electronic package measures the total time of flow. Instead of a reed switch which is a magnetically coupled device, a capacitance based device or a pressure-sensitive device may be used instead. The pressure sensitive device would have to mounted in the closed end of the housing end cap 1502 .
[0149] Valve 108 illustrated in FIG. 15 is the same valve used in the bathroom filter of the first embodiment. Spacers 1542 , 1543 of the housing end cap 1502 assist in ensuring that the filter subassembly is in place. Referring to FIG. 17 , a gap (unnumbered) exists between the spacer 1543 and the end cap 1514 of the filter. Spacer limits the movement of the filter subassembly such that it cannot move leftwardly too far before engaging the spacers. End plate 1516 is glued or welded to the housing end cap 102 . Housing end cap 102 is glued or welded to the filter housing 1501 .
[0150] FIG. 16 is a perspective view 1600 of the second embodiment of the water filtration device. FIG. 17 is a cross-sectional view 1700 of the second embodiment of the water filtration device taken along the lines 17 - 17 of FIG. 16 . FIG. 17A is a cross-sectional view 1700 A of the second embodiment of the water filtration device similar to FIG. 17 except the gate 1518 is shown rotated clockwise in the flow condition. Annulus 1701 is illustrated in FIG. 17A . Water resides in this annulus and flow thru filter 1513 into passageway 1529 and out port 1541 impinging upon gate 1518 rotating it clockwise.
[0151] Referring to FIGS. 15 and 17 , filter end caps 1514 and 1515 have peripheral end portions (i.e., 1531 and 1530 ) which are seals which seal against the interior diameter of the filter housing 1501 . Although not shown in FIG. 17 , optional elastomeric O-ring seals similar to 375 , 376 may be used between the peripheral end seals as illustrated in FIG. 3D .
[0152] FIG. 18 is a perspective view 1800 of the front housing of the second embodiment. FIG. 18 employs reference numerals like FIG. 4 . FIG. 18A is a cross-sectional view taken along the lines 18 A- 18 A of FIG. 18 . Reference numeral 1801 indicates the wall to which the collar lock 1505 is welded and reference numeral 1804 indicates the floor upon which the collar lock 1804 sits at the time it is welded. Mold recesses 1802 are from the molding process. Groove or recess 1816 receives the seal from the valve 108 . Cavity 1831 receives the valve 108 . Referring to FIG. 18A , stop 1807 A is illustrated which engages ridges 602 on valve 108 . Stop 1807 A is also illustrated in FIG. 18B , a cross-sectional view taken along the lines 18 B- 18 B of FIG. 18 . Tapered bore 1812 is illustrated by the circular lines in FIG. 18A .
[0153] Bore 1822 includes stepped portions 1813 and 1829 . Inlet 1808 is shown leading to valve cavity 1831 . Outlet 1814 and outlet 1809 are also shown in FIG. 18A . When valve 108 is positioned as illustrated in FIG. 18E inlet 1808 is connected to outlet 1814 and the water passes through front housing 1503 and is expelled unfiltered. Flow arrow 1870 depicts the path of flow through front housing 1503 . When the valve 108 is positioned as illustrated in FIG. 18F inlet 1808 is connected to outlet 1809 where it is directed into the filter by inlet 1525 of the filter housing 1501 . See, FIG. 16A a perspective view of a second embodiment of the water filtration device with the valve handle pulled forward. Flow arrow 1871 depicts the path of flow through front housing 1503 and into inlet 1525 of the filter housing.
[0154] Referring to FIG. 18B , valve cavity 1831 is illustrated as is stop 1807 A and the cross-sectional portion 1807 of the stop. Unfiltered outlet 1814 is also depicted. FIG. 18C is a top view 1800 C of the front housing 1503 of the second embodiment. FIG. 18D is a rear perspective view 1800 D of the front housing of the second embodiment of the water filtration device. FIG. 18D illustrates receptacles 1819 and 1820 of the front housing which engage pins 1528 and 1527 respectively. Mold recesses from the molding process are indicated by reference numerals 1817 , 1818 , 1823 , 1824 and 1825 . Joint 1821 is welded to the filter housing.
[0155] FIG. 19 is a front perspective view 1900 of the filter housing of the second embodiment of the water filtration device. Surface 1904 engages the corresponding surface on the housing end cap 1502 . Recess 1901 engages the perimeter of the front housing. FIG. 19A is a bottom view 1900 A of the of the filter housing 1501 of the second embodiment of the water filtration device. FIG. 19B is a cross-sectional view 1900 B taken along the lines 19 B- 19 B of FIG. 19A illustrating port 1907 from which filtered water is expelled.
[0156] FIG. 19C is a cross-sectional view 1900 C taken along the lines 19 C- 19 C of FIG. 19C illustrating passageway 1905 in inlet 1525 of the filter housing 1501 . FIG. 19D is a left side view 1900 D, the open end view, of the filter housing 1501 of the second embodiment of the water filtration device illustrating mold prongs in the end housing. These prongs or ribs 1906 restrict the insertion depth of the filter sub assembly.
[0157] FIG. 20 is a front side view 2000 of the end cap of the housing 1502 of the second embodiment of the water filtration device. Surface 2007 of the housing end cap engages surface 1904 of the filter housing and is welded or glued thereto. FIG. 20A is a right side view 2000 A of the end cap of FIG. 20 illustrating the closed end 2003 . FIG. 20B is a perspective view 2000 B of the end cap of FIG. 20 illustrating the closed end and spacers 1543 , 1542 . FIG. 20C is a view 2000 C of the left side of the end cap of FIG. 20 illustrating supports 2001 , 2002 and 2010 which restrict the movement of the electronic package in place. FIG. 20D is another perspective view 2000 D of the end cap illustrating the housing 2011 in which the electronic package resides.
[0158] To assemble the water filtration devices, insert the aerator into the through spout and then insert the through spout and ultrasonically weld the aerator/spout assembly to the front housing. Place the threaded collar into the seat on top of the front housing and press the lock collar through the threaded collar and seat the lock collar into the housing. Clamp and ultrasonically weld the lock collar to the front housing.
[0159] Insert the filtered spout into the filter housing and clamp and weld it to the filter housing. Insert the front housing into position with respect to the filter housing and then clamp and ultrasonically weld it to the filter housing.
[0160] A prefilter may be wrapped around the filter and sealed using the hot seal method. Next, the left and right end caps with adhesive applied to the contact surfaces thereof are inserted in the filter. Uniform pressure is applied to the left and right filter end caps 114 , 115 , 1514 , 1515 to spread the adhesive and allow it to set. Approximate time for applying pressure is 2-5 seconds. The magnet is installed into the gate under the pressure of a person's finger or a tool such as pliers or the equivalent then hermetically sealed in place.
[0161] Next, the gate 118 , 1518 is snapped into the hinges with the magnet facing outwardly. Indicia on the left end cap of the filter subassembly is aligned with a mark or other indicia on the filter housing and the filter subassembly is inserted into the filter housing. Indicia on the housing end cap 102 , 1502 is aligned with indicia on the filter housing and inserted therein. Once the housing end cap is in place it is clamped and ultrasonically welded to the filter housing non-removably retaining the filter within the filter housing.
[0162] The lever is installed by snapping it into place in the valve cavity. To install the end of life electronic package, the light emitting diode is inserted into and through the aperture 137 . Optionally, adhesive may be used when installing the diode in the aperture 137 to secure it into position and to ensure that the diode is hermetically sealed. The electronic package is installed into the reservoir in the open end of the housing end cap with the glass reed switch facing inwardly. End plate 116 , 1516 is next snap-fit into place to hermetically seal the electronic package. Optionally, adhesive may be used around the perimeter of the end plate to ensure a hermetic seal. Or, the end plates may be welded to the housing end caps.
[0163] The materials which are ultrasonically welded should be amenable to welding such as ABS or other plastics.
[0164] The invention has been described herein by way of example only. Those skilled in the art will readily recognize that changes and modifications may be made to the invention without departing from the spirit and scope of the appended claims which follow hereinbelow.
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Single-use long-life faucet mounted water filtration devices are disclosed. A bathroom water filtration device having two outlets for filtered water is disclosed. Additionally, a fountain head is included for use in the bathroom water filtration device. The water filtration device is of unibody construction formed by ultrasonically welding certain parts thereof together. Since the devices disclosed are disposable, no filter replacement or other maintenance is performed. A gate, magnet, sensor and electronics provide an indication of filter performance enabling disposal of the water filtration device and installation of a new device. A kitchen water filtration device is larger than the bathroom device. Both the kitchen and bathroom water filtration devices are small and are mounted behind the faucet connection so as to facilitate full utilization of the sink or wash basin.
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TECHNICAL FIELD
[0001] The present invention relates to packaging machines and more particularly to apparatus that deliver to packaging machines strip material which is formed into bags by the packaging machine.
BACKGROUND OF THE INVENTION
[0002] One form of packaging includes a bag of generally of square or rectangular configuration having flanges at each longitudinal corner. Typically such bags have a “block bottom” so that they stand upright with the flanges extending upwardly.
[0003] Machinery that produces the above discussed bags are intermittent in motion. More particularly, the flanges are formed by halting movement of the film and welding the flanges while the film is stationary.
[0004] The above discussed apparatus have a number of disadvantages including slow operation as the dwell time for the welding process is time consuming. A further disadvantage is the complexity of the machinery and problems associated with the heaters that form the welds. A still further problem is that frequently the seals in these bags fail as product dropping into the bags ruptures the flanges.
[0005] In the above mentioned apparatus it should be noted that the bag material is formed into a tube and then subsequently formed so as to have longitudinally extending flanges. Accordingly, the flanges are formed downstream (after) the bag material has passed the former.
[0006] Described in UK Patent Application 2357991 is a bag in which folds are disposed inwardly of the bag to reinforce the bag. A folding apparatus forms folds in the strip bag material, with the folded strip bag material being delivered to a former so that the folds are located internally of the former and do not engage the forming surface of the former. The bags so formed have the disadvantage of reduced area available for printing. A still further disadvantage is that the folds project inwardly of the former and can inhibit the delivery of product to the interior of the tubular bag material. When forming bags with longitudinal flanges, correctly locating the flanges is difficult. This problem is exacerbated when the flanges are inside the bag material. A still further disadvantage is the problem of transversely sealing the bag material. With the folds inside the bag material the sealing jaws engage a layered construction consisting of six layers. Accordingly, the probability of a defective seal being formed is increased. This problem will be exacerbated where stripping is required as product may be difficult to move from the scaled area due to the layered construction.
OBJECT OF THE INVENTION
[0007] It is the object of the present invention to overcome or substantially ameliorate at least one of the above disadvantages.
SUMMARY OF THE INVENTION
[0008] There is disclosed herein an assembly including folding apparatus, through which strip material passes along a predetermined path to be longitudinally folded, and a former to which the strip material is delivered to font the strip material into a tube having longitudinally extending folds, the apparatus including:
[0009] a plurality of transversely spaced folding slots extending generally parallel to said path and through which portions of the strip material to be folded are moved;
[0010] a press member operatively associated with each slot to press each strip portion into a respective one of the slots to form a fold;
[0011] a fold former associated with each slot to engage the folds passing therethrough to deform the folds so that the folds maintain their configuration; and wherein
[0012] said former is operatively associated with said folding apparatus so that said folds are on the exterior of said tube.
[0013] Preferably, said former has a forming surface over which the strip passes, and wherein said folds contact the former surface
[0014] Preferably, each press member is of a circular configuration that rotates as it presses the strip material into the associated slot.
[0015] In an alternative preferred form, each press member is a blade that extends into a respective one of the slots to press the strip material into the slot.
[0016] Preferably, each fold former is a heated block having a longitudinal slot along which the folds pass to be heated there by.
[0017] Preferably, each fold former further includes rollers to engage the folds to secure portions to the folds together so that the folds maintain their configuration.
[0018] Preferably, the apparatus forms four generally parallel co-extensive folds.
[0019] There is further disclosed herein a combination to form tubular bag material having longitudinally extending flanges, said combination including:
[0020] a folding station through which strip bag material passes so as to he longitudinally folded so that the strip material leaving the station has longitudinally extending folds; and
[0021] a packaging machine former, operatively associated with the folding station, to receive the bag material with the longitudinally extending folds so that the former provides tubular bag material having longitudinally extending external flanges.
[0022] Preferably, said former has a forming surface that engages the strip material to form the tubular bag material, with said folding station being associated with said former so that said folds contact said former surface.
[0023] Preferably, the folding station includes a plurality of transversely spaced folding slots extending generally parallel to said path and through which portions of the strip material to be folded are moved; and a press member operatively associated with each slot to press each strip portion into a respective one of the slots to form a fold.
[0024] There is further disclosed herein a method of providing tubular bag material having longitudinally extending flanges, said method including the steps of:
[0025] providing a supply of strip material to be used to form bags;
[0026] moving the strip material from said supply and longitudinally folding the strip material so that the strip material has longitudinally extending folds; and
[0027] passing the strip with folds over a packaging machine former so as to provide tubular bag material having external longitudinally extending flanges.
[0028] Preferably, the former has a forming surface that contacts the folds.
BRIEF DESCRIPTION OF THE DRAWINGS
[0029] Preferred forms of the present invention will now be described by way of example with reference to the accompanying drawings wherein:
[0030] FIG. 1 is a schematic perspective view of a bag formed from flexible strip material;
[0031] FIG. 2 is a schematic side elevation of an apparatus to provide film for a packaging machine which forms the bag of FIG. 1 ;
[0032] FIG. 3 is a schematic end elevation of the apparatus of FIG. 2 ;
[0033] FIG. 4 is a schematic side elevation of a modification of the apparatus of FIG. 2 ;
[0034] FIG. 5 is a schematic end elevation of the apparatus of FIG. 4 ;
[0035] FIG. 6 is a schematic top plan view of the apparatus of FIGS. 2 and 3 ;
[0036] FIG. 7 is a schematic end elevation of the strip produced by the apparatus of FIGS. 2 to 6 ; and
[0037] FIG. 8 is a schematic perspective view of a packaging machine former to which the strip of FIG. 7 is being delivered so that the former produces tubular bag material having longitudinally extending flanges.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0038] In U.S. Pat. Nos. 4,663,917, 3,522,689, 3,070,931, 4,516,379, 3,629,987 and 4,524,567 there are various packaging machines described. These packaging machines have jaws which from discreet bags from tubular bag material. The tubular bag material is formed from strip material delivered to a former 30 ( FIG. 8 ). The strip leaving the former 30 is of a tubular configuration. Typically, the strip is plastics material and is longitudinally scaled and transversely sealed to form discreet bags. Product to be contained in the bags passes through the centre of the former 30 to be delivered to the interior of the tubular bag material.
[0039] The strip material delivered to the former 30 comes from a roll.
[0040] In FIG. 1 there is a schematically depicted a bag 10 . The bag 10 has a “block bottom” in that it will stand in a stable manner on its bottom surface 11 . The bag 10 has four side panels 12 and may be of a square or rectangular transverse cross-section. Joining the side panels 12 are external flanges 13 . The upper end of the bag 10 has sloping portions 14 extending to a top seal 15 . The bag 10 also has a bottom seal 16 .
[0041] The bag 10 is formed from strip material that passes through a packaging machine such as the above mentioned packaging machines.
[0042] The bag 10 is formed from a strip 17 shown in end elevation in FIG. 7 . The strip 17 has longitudinally extending folds 18 that form the external flanges 13 of the bag 10 . The strip 17 is preferably formed of plastics material. The folded strip is delivered to a packaging machine former 30 as shown in FIG. 8 .
[0043] The strip 17 is longitudinally folded at a folding station by means of a folding apparatus 20 . The apparatus 20 receives unfolded strip 19 from a roll and forms the longitudinally extending folds 18 so as to provide the strip 17 .
[0044] The apparatus 20 includes a plurality of elongated members 21 each with a longitudinally extending slot 22 . Associated with each slot 22 is a relatively narrow roller 23 that projects inwardly of its associated slot 22 .
[0045] The strip 19 / 18 passes along a predetermined path through the apparatus 20 . The slots 22 and form folds 18 extend parallel to the longitudinal direction of extension of the strip 17 / 19 and therefore generally parallel to the path along which the strip 17 / 19 passes.
[0046] As the strip 19 approaches the slots 22 it is deflected into the slots 22 by the rollers 23 . More particularly rollers 23 rotate about a generally horizontal axis 24 that extends generally normal to the strip 17 / 19 and slots 22 .
[0047] After exiting the slots 22 the strip 17 passes over heating blocks 25 . The heating blocks 25 have longitudinally extending slots 26 , each slot 26 being aligned with a respective one of the slots 22 so as to receive a respective fold 18 . As the strip 17 passes through the blocks 25 , the folds 18 are heated to a desired temperature. Upon leaving the heating blocks 25 each fold 18 is engaged by a pair of rollers 27 so that each fold 18 is compressed therebetween so that the plastics material fuses (welds) to thereby ensure that each fold 18 retains its configuration. The rollers 27 rotate about generally vertical axis 28 . The axis 28 are generally normal to the strip 17 .
[0048] As is best seen in FIGS. 2 and 3 , the rollers 23 are movable between a first position at which the rollers 23 are spaced from the slots 22 , and a second position projecting inwardly of the slots 22 to form the folds 18 .
[0049] In this embodiment there are four slots 22 and four associated rollers 23 and four heating blocks 25 each having a slot 26 .
[0050] In the embodiment of FIGS. 4 and 5 the rollers 23 are replaced by blades 29 . The blades 29 are movable in the same manner as the rollers 23 but further includes a ramp surface to aid in moving the strip 19 into the slots 22 .
[0051] As best seen in the accompanying drawings (particularly FIG. 7 ) the folds 18 after being formed are subsequently engaged by rollers so that they are applied to a major surface of the strip 17 , that is they lay flat on a major surface (bottom) of the strip 17 . This facilitates movement of the strip 17 over the former of the packaging machine. The folds 18 are of a “U” shaped configuration in transverse cross-section.
[0052] As best seen in FIG. 8 , the former 30 receives the strip 17 with the longitudinally extending folds 18 . The Strip 17 passes a roller 31 to be delivered to the former 30 . The former 30 forms tubular bag material 32 having longitudinally extending external flanges 13 . In particular the folds 18 contact the former surface 33 over which the strip 17 passes to be formed into the tubular bag material 32 with the folds 18 on the exterior.
[0053] In another embodiment one or more opposing pairs of heated rollers 34 are located in the block 25 . The folds 18 pass between the rollers 34 of each opposing pairs 34 to weld the folds 18 so that the folds 18 maintain their configuration.
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An assembly and method for forming bags ( 10 ) having a “block bottom” with external flanges ( 13 ). The method and apparatus includes forming folds ( 18 ) in a strip ( 17 ) and delivering the strip ( 17 ) to a former ( 30 ) so that the folds ( 18 ) engage the forming surface ( 33 ) to thereby locate the flanges ( 18 ) on the exterior of the tubular bag material ( 32 ).
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BACKGROUND OF THE INVENTION
The present invention pertains to an over-center spring hinge mechanism for mounting a cover to a vehicle accessory and particularly one for use in connection with an automotive visor.
Automotive visors have incorporated an illuminated vanity mirror for several years. U.S. Pat. No. 4,227,241 discloses one such construction in which a cover is mounted to the mirror frame utilizing a pivot arm and an over-center spring arrangement for providing snap-open and closed operation of the cover. Other cover arrangements have also been employed including those shown in U.S. Pat. No. 4,213,169 which discloses a cover having a cam-shaped stub axle which cooperates with a socket in the mirror frame for camming the cover into an open or closed position. More recently, flat spring-type controls have been used with snap-on covers as disclosed for example in U.S. Pat. No. 4,760,503.
While all of these mounting configurations provide the desired cover control, they typically are used in connection with visors in which a molded polymeric frame is incorporated as part of the mirror construction. In such construction, the frame typically integrally must include the provision of a socket or axle for the cover mounting arrangement.
As cost and weight reduction becomes increasingly a more important design goal in the automotive industry, and in the design of automotive visors, and particularly visors incorporating high-end features such as a covered illuminated vanity mirror package, the utilization of a separate mirror frame and its associated mold tooling and materials costs, have made such construction, although attractive and functional, less desirable. Also, with modern vehicles, a cleaner appearance can be achieved by a cover with a so-called "close-on cloth" look and feel which is provided by a mirror cover which closes directly on an upholstered visor body. Further, some visors are now made with fiberboard cores as opposed to molded polymeric cores, to further reduce cost and weight.
The mounting of a cover to a fiberboard visor body which includes a covered but frameless illuminated vanity mirror package for the visor becomes problematic since there can be no socket for receiving a cover pivot axle. One solution to this problem has been proposed in U.S. patent application entitled MULTIPLE FUNCTION VISOR, Ser. No. 383,542, filed July 24, 1990, in which mounting posts are employed with configured ends to attach to the body of the visor which can be a molded polymeric material or any planar substrate material.
SUMMARY OF THE INVENTION
The system of the present invention improves upon the above-noted structure by providing a combined cover hinge and spring mechanism in which the cover can be mounted to a planar visor core member utilizing a relatively inexpensive spring-clip hinge which receives an axle extending from a cover to provide snap-open and closed operation of the cover against the visor to which the spring member is attached.
Apparatus embodying the present invention include a vehicle accessory with a cover and a spring-clip hinge for pivotally attaching the cover to the body of the accessory such that the cover is urged toward an open or a closed position. In a preferred embodiment of the invention the spring-clip hinge is an integral member which is a generally S-shaped member defining opposed sockets with one socket receiving the accessory body for mounting the hinge to the body, and the remaining socket cooperatively receiving the cover for urging the cover between open and closed positions. In one embodiment of the invention the accessory is a visor with a planar core and a pair of the hinge spring clips each includes arm means for attaching said spring clip to said visor core. In this embodiment the visor includes a mirror mounted to the core and a cover including pivot axles which snap-fit within the sockets of a pair of spaced hinges and cooperating with said axles for urging said cover between a closed position substantially parallel with and adjacent the visor body to an open position pivoted outwardly from said visor body. Such construction provides a relatively inexpensive and effective coupling of a visor cover to a planar visor core member with improved performance at a reduced cost.
These and other features, objects and advantages of the present invention, will become apparent by reading the following description thereof together with reference to the accompanying drawings in which:
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a fragmentary, perspective view of a vehicle accessory such as a visor embodying the present invention;
FIG. 2 is a fragmentary, perspective view of the visor shown in FIG. 1, showing the cover in an open position;
FIG. 3 is a fragmentary right side perspective view of the mounting structure for the cover to the visor core member;
FIG. 4 is a rear elevational view of the assembled structure shown in FIG. 3, shown with the cover in the closed position;
FIG. 5 is the right side elevational view of the structure shown in FIG. 4;
FIG. 6 is a rear elevational view of the structure shown in FIG. 4 with the cover in an open position;
FIG. 7 is a right side elevational view of the structure shown in FIG. 6;
FIG. 8 is a fragmentary plane view of a portion of the core structure showing the apertures for receiving the spring-clip hinge embodying the present invention;
FIG. 9 is a front elevational view of the spring-clip hinge;
FIG. 10 is a bottom plane view of the structure shown in FIG. 9;
FIG. 11 is a right side elevational view of the structure shown in FIG. 9;
FIG. 12 is a rear elevational view of the structure shown in FIG. 9;
FIG. 13 is a cross-sectional view of the structure shown in FIG. 9 taken along section line XIII--XIII of FIG. 9;
FIG. 14 is a cross-sectional view of the structure shown in FIG. 9 taken along section line XIV--XIV of FIG. 9;
FIG. 15 is a cross-sectional view of the structure shown in FIG. 9 taken along section line XV--XV of FIG. 9;
FIG. 16 is a front elevational view of the spring-clip hinge shown installed on a visor core member; and
FIG. 17 is a rear elevational view of the structure shown in FIG. 16.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring initially to FIGS. 1-3, there is shown a vehicle accessory such as a visor 10 embodying the present invention and installed in a vehicle such as an automobile 11 at the right front area adjacent the windshield 12 and the "A" pillar 13. The visor 10 includes a mounting assembly 25 for mounting the visor to the roof 26 of the vehicle for movement between a lowered use position illustrated and a raised stored position adjacent the roof. Conventionally, the mounting assembly also allows the visor to pivot from the windshield position shown to a position adjacent the side window 17. The visor includes a central core 14 (FIG. 3) which can be a folded planar material made of a polypropylene or, as in the preferred embodiment, a fiberboard material of the type disclosed in U.S. patent application Ser. No. 07/439,451, filed on Nov. 20, 1989 and entitled VISOR AND METHOD OF MAKING THE SAME; the disclosure of which is incorporated herein by reference. Core 14 includes a rectangular aperture 15 (FIGS. 2-4) for receiving an illuminated vanity mirror assembly 20 which includes a mirror and mirror frame 24 and 23, respectively, (FIG. 2), a pair of lenses 27 mounted with an aperture 26 on opposite sides of mirror 24, and a light control means such as a dimming switch 28 for controlling the intensity of light which is directed outwardly from the visor and focuses inwardly toward the face of a user. The assembly 20 includes lamp means positioned behind the lenses 27 and electrical wiring (not shown) for coupling the lamps and switch 28 to the vehicle's electrical system as disclosed in the above identified U.S. Pat. No. 4,760,503, the disclosure of which is incorporated herein by reference. The visor core 14 covered by suitable upholstery fabric 16 and the lighted mirror assembly 20 is covered by an independently mounted cover 30. The mounting of the mirror assembly 20 to the visor core 14 and within aperture 15 can be conventional such as by using mounting tabs which extend from around the mirror frame 23 toward the panel 78 (FIG. 3) forming one half of the folded core 14 and which engage the peripheral edge of aperture 15 to snap-fit the assembly 20 to the visor.
The cover 30 is independently mounted to the core 14 as best seen in FIGS. 3-7 by a pair of spring-clip hinges 40 which are mounted to the core 14 in spaced alignment with a pair of arms 32 on cover 30 and adjacent the upper edge of aperture 15 as viewed in FIG. 2 so it can be installed independently of the illuminated vanity mirror assembly 20. The pair of curved cover arms 32 (FIGS. 2-7) are snap-in received by the spring-clip hinges 40 of the present invention which are pre-installed on the visor core 14. Once hinges 40 are installed on the visor core, as described in greater detail below, the arms 32 of cover 30 snap-fit within the hinges which biases the cover 30 toward a snap-closed or snap-opened position as illustrated in FIGS. 1 and 2 respectively. Before describing the coupling of the cover to the spring-clip hinges 40, a description of one of the identical hinges 40 is presented in detail in connection with FIGS. 9-15.
Each spring-clip hinge 40 is generally S-shaped as viewed from the side as best seen in FIG. 11 which defines a pair of generally U-shaped opposing sockets 42 and 44 facing in opposite directions. The hinge integrally includes a central body 41 which is generally rectangular and which integrally includes a lower front U-shaped section including a pair of lower front arms 43 and 44' integrally joined to body 41 at base 45 as best seen in FIGS. 9 and 11 to define socket 42. The tips 46 of arms 43 and 44' are upwardly and inwardly curved in a semicircular configuration as best seen in FIG. 11 to assist in mounting the hinge to core 14 and securing it thereto as described below and shown in FIG. 16. The upward end of section 41 also includes a pair of spaced arms 48 and 49 which, as best seen in FIG. 15, extend outwardly and upwardly in an L-shaped bend 50 to lie in a plane substantially parallel with and in alignment with the plane of legs 43 and 44' for mounting the spring-clip hinges 40 to the core 14 as shown in FIGS. 3- 8, described below.
The second or rear leg 44' of the generally S-shaped hinge 40 defines in cooperation with a curved central integral arm 60 extending upwardly from the lower edge of an inverted T-shaped cutout 57 in section 41 (as best seen in FIGS. 9, 11, and 12), a cover arm receiving socket 44. This socket is also defined in part by the surface 47 (FIG. 12) of section 41 and integral downwardly and outwardly curved generally U-shaped arm 52 integrally formed with section 41 at bend 53, as best seen in FIGS. 12 and 14. U-shaped arm 52 includes a pair of legs 54 and 56 which terminate in outwardly bent and downwardly inclined tips 58 for facilitating the insertion of the cover arms 32 within the socket 44 so defined.
As can be seen by reference to FIGS. 16 and 17, hinge 40 compressibly engages the planar core member 14 with the tips 46 of arms 43 and 44 overlying an edge portion 70 (FIG. 8) of core 14. The generally rectangular aperture 15 includes at its upper corners a curved recess 72 and notch 78 for lockably receiving the spring-clip hinges 40. The tips 46 of arms 43 and 44' extend within and lockably engaging the lower edges 73 of a pair of rectangular apertures 75 formed in core member 14 in spaced relationship above notch 78 as best seen in FIGS. 8 and 16. The remaining legs 48 and 49 of hinge 40 extend under and behind section 70 of the core member 14 and upwardly through the rectangular apertures 75 with their tip as best seen in FIGS. 16 and 17 with the tip ends 48 and 49 overlying the surface 71 of core member 14 above apertures 75 near the fold line 76 of the folded core member 14, as best seen in FIG. 16. This effectively locks the spring clip to the planar visor core in secure relationship with respect thereto. To further secure the hinge however, the tip 59 of arm 60, as best seen in FIG. 17, engages the rear surface 77 of core member 14 near the edge of the rectangular notch 78 (FIG. 8). This also stabilizes the spring clip 40 hinge in place on the visor core.
Each hinge 40 is mounted to the visor core as shown in FIGS. 16 and 17 by aligning the U-shaped socket 42 with legs 48 and 49 extending upwardly through apertures 75 formed in the core member 14 at each of the two spaced locations to align the hinge 40 with the corresponding cover arm 32. The lower arms 43 and 44' are then slid over the section 72 of the core member 14 until the L-shaped bend 50 of arms 48 and 49 engage and set against the upper edge 80 of slot 75 as seen in FIGS. 16 and 17. With the spring-clip hinges 40 mounted to the visor core 14, the cover 30 can be snap-fitted within the remaining U-shaped socket 44 of the spring clip as described in connection with FIGS. 3-5. Before describing this operation however, a description of the cover arms 32 which serve as cam members in cooperation with the hinges 40, is presented.
As seen in FIGS. 2 and 3, the cover 30 includes a pair of arcuately curved arms 32, which curve upwardly and inwardly from the front surface 31 of the cover, which surface may include a decorative upholstered fabric 33 matching that of fabric 16 of the visor. Each arm 32 terminates in a cam member tip 34, which as best seen in FIGS. 3-7 comprises a somewhat elongated curved body as viewed from the side. The cover 30 is installed once clip 40 is mounted to the core member 14 by pushing the arm 32 in a direction indicated by arrow A in FIG. 3, under the surface 71 of the core and into the sockets 44 which guideably receives the cam 34 with the assistance of the upwardly curved tips 58. It is noted, for purposes of illustrating this assembly, FIG. 3 is inverted from the structure shown in FIGS. 4-6 to show the front side of the visor during the installation process. The cover is pushed inwardly until the rounded cam member 34 snap-locks and nests within the curved cam receiving socket 62 of the center arm 60 extending upwardly from base 45 as best seen in FIGS. 11 and 12. In this position, the cam member is compressibly gripped between the legs 54 and 56 and section 41 to provide a significant compressive force against the cam member tending to hold it in a cover-closed position as shown in FIG. 5 or cover-open position as shown in FIG. 7. In the cover-closed position, surface 37 of cam 34 engages the surface member 41 facing arms 54 and 56 while the opposite surface 39 of cam 34, engages the inner surface of arms 54 and 56 as best seen in FIG. 5. The spring bias force of arms 54 and 56 with the left end 37 of cam member 34 engaging member 41 as shown in FIG. 5 and the right end of member 34 spaced from end 37 provides a camming action holding the cover in a closed position with the edges of the cover 30 engaging the upholstery 16 of the visor as shown in FIG. 1. As can be appreciated, the pivot axis for the cover is aligned generally with the center line of the socket 62 formed in arm 60. As the cover is opened as illustrated by arrow B in FIG. 7, the position of cam member 34 reverses with surface 39 now engaging section 41 of plane 40 while the surface 37 of cam 34 engages arm 56. Again, the contact point at opposite ends of the curvilinear cam member 34 provides the torque in connection with the compressive force of arms 54 and 56 against cam member 34 for holding the cover in an open position as illustrated in FIGS. 2 and 7.
Thus the spring-clip hinge of the present invention, cooperates with the planar visor core member 14 and the snap-in cover 30 to provide an over-center biasing force on the cover for holding it in a closed or open position. Once the cover has been snapped into the pair of spaced hinges 40, mounted in a pair of spaced configured apertures on each edge of the rectangular aperture 15 of the visor core member 14, the mirror package can be installed utilizing suitable snap-in fasteners. The core member 14 is covered with a suitable upholstering such as padded fabric 16 applied to the visor and the core folded and locked together to complete the visor in a manner as described in the above-identified U.S. patent application Ser. No. 439,451.
The spring-clip hinge employed in the present invention is made by a progressive die and stamped into the configuration shown utilizing a suitable spring steel material which can be treated for rust inhibition in a conventional manner. In the preferred embodiment of the invention, the spring member 40 was a 1074 steel having a thickness of about 0.014 inches and which was conventionally heat and surface treated to a Rockwell C hardness of 45-50. Thus the system of the present invention provides an easily assembled relatively inexpensive covered visor construction in which the hinge and camming mechanism is an integral spring clip which can be lockably attached to a configured aperture in a planar core member. The hinge defines a spring biased socket which snap receives a cover having a cam means thereon for camming the cover in snap-open or snap-closed position in response to the spring clip bias force.
It will become apparent to those skilled in the art that various modifications to the preferred embodiment described herein can be made without departing from the spirit or scope of the invention as defined by the appended claims.
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The present invention includes a spring clip hinge for pivotally attaching a cover to the body of a vehicle accessory such as a visor such that the cover is urged toward an open or a closed position. In a preferred embodiment of the invention the spring-clip hinge is an integral S-shaped member defining opposed sockets with one socket receiving the accessory body for mounting the hinge to the body, and the remaining socket cooperatively receiving the cover for urging the cover between open and closed positions.
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BACKGROUND OF THE INVENTION
The present invention relates to fluid delivery systems. In one particular aspect, it relates to enteral fluid delivery systems utilizing closure devices for connection between an enteral fluid container and a patient feed line.
SUMMARY OF THE INVENTION
Broadly, the present invention provides a closure device for connection to a fluid container which has an opening for receiving the device. The closure device has a base section which may sealably cover the container opening. The base section has a spike receiving opening passing there through with at least one aperture, e.g., an air vent on the base section which is spaced from the spike receiving opening. An air filter e.g., hydrophobic air filter, is associated with the air vent. Adjoining the base section is an internal cover, which lies over the aperture, covering it and the base section. The internal cover has a pierceable portion e.g., a weakened section, which is in alignment with the spike receiving opening of the base section.
In a preferred embodiment of the invention, the closure device has a threaded wall portion projecting from the base section which wall portion is adapted to threadly receive a threaded connection of the fluid container. The fluid container may also have a pierceable seal covering the opening.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is an isometric view of a closure device of this invention.
FIG. 2 is a perspective view of the closure device of FIG. 1, showing the device in connection with a fluid container.
FIG. 3a, b, c and d are perspective views showing additional positions of the hydropholic air filter.
FIG. 4 is a perspective view showing a gasket assembly of the closure device of this invention.
FIG. 5 is a perspective view showing the internal operation of a spike.
FIG. 6 is a perspective view showing the spike of FIG. 4 fully inserted in the device.
FIG. 7 is a Top View along the line 7--7 of FIG. 6 showing the rupture of seal 27.
FIG. 8 is a perspective view showing a snap-fit assembly of the closure device on a container.
FIG. 9 is a perspective view showing the closure device sealed across a container opening.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIGS. 1 and 2, the closure device 10 generally comprises a base section 11 and a threaded wall portion 12. The base section 11 has a spike receiving opening 13, and an air inlet aperture 14. There may be one or more air inlet apertures 14.
A hydrophobic air filter is associated with the air inlet apertures 14. The position and configuration of the filter may be varied depending upon the number of apertures 14. When multiple apertures are used, the filter may consist of a disk-like filter 16 as shown in FIG. 1. This filter 16 is preferably positioned on the inside of the closure device 10 (as shown in FIG. 1). It may also be positioned over the apertures on the outside of the closure device 10 (not shown).
One or more apertures 14 may also be covered by individual filters which may cover the apertures on the outside of the closure device 10, the inside of the closure device, or may lie within the apertures. These filter positions 16a, 16b, 16c and 16d are shown in FIG. 3a, b, c and d. Filter position 16d differs from position 16b, in that it is raised from the base section 11. The preferred filter position is on the inside of the closure device (16b). The individual filter may be secured to the closure device by any suitable means e.g., sonic welding, so that it will remain in position in relation to the aperture. Suitable hydrophobic air filters may be obtained from Pallflex Products Corp. (Pallflex EMFAB E01008E).
A spike receiving cylindrical member 17, aligned with the spike receiving opening 13, extends outwardly from the base section 11. The opening 13 and the cylindrical member 17 are adapted to receive a piercing spike 18.
An internal cover 19 lies over the filter 16 and the base section 11. The cover 19 may have a plurality of rib members 20, to support and maintain the integrity of the cover. The cover may have a raised edge section 21 which may be adhered to the base section 11; and may have a center portion 22 which is in alignment with the spike receiving opening 13, and the cylindrical member 17, of the base section 11. Preferably, the internal cover 19 is concave in hape on its external surface, e.g., the surface facing away from the base section (see FIG. 2).
As shown in FIG. 2, the wall portion 12 of the closure device is threaded 23, to threadably receive the threaded neck 24 of a fluid container 26, e.g., an enteral fluid container. The container 26 has a seal 27, e.g., a foil seal, across the container opening. When the closure device 10 is attached to the container 26 (as shown in FIG. 2), the foil seal 27 contacts the cover 19.
In a preferred embodiment, the foil seal 27 may be adhesively sealed 25 to the cover 19. Preferably, the foil 27 is adhesively hot sealed (aseptically sealed) to the cover 19, by flowing a heated foodgrade hot melt adhesive between the foil seal 27 and the cover 19. The concave shape of the internal cover 19 insures that a thin layer of adhesive is placed between the cover and the foil seal. The cover 19 protects the apertures 14, and filters 16 from the adhesive, and also insures an open passage through the spike receiving opening 13. Suitable food contact adhesives which may be used are ethylene vinyl acetate based adhesive, (H. B. Fuller HL 7434); and polyethylene based adhesive, (H. B. Fuller HM 1002)
In an additional embodiment of the invention, a gasket 36 may be used in place of the hot melt adhesive (see FIG. 4). The gasket 36 may be formed in situ, or may be preformed, and is aseptically installed in the closure device 10.
The center portion 22 of the cover 19 is surrounded by a weakened area 28. It is preferred that the diameter of the weakened area 28 be larger than the piercing spike 18. The weakened area 28 breaks when the spike 18 is urged against it. As the spike 18 moves against the weakened area 28, the part closest to the tip 29 of the spike 18 breaks first (see FIG. 5). The weakened area 28 continues to break as the spike moves in the spike receiving opening 13.
As shown in FIG. 6, the weakened area 28 does not sever completely from the cover 19, but forms a hinge 31 on the side opposite the tip 29 of the spike 18. The hinge 31 and the center 22, thus form a flap 32 in the cover 19. As the flap 32 is raised by the spike 18, the seal 27 is ruptured, and the spike 18 enters the container 26. The flap 32 keeps the ruptured seal 27 away from the spike 18, insuring that air from the filter has access to the container 26. The spike 18 should penetrate sufficiently far into the container 26 so as not to draw air into the conventional central enteral fluid pathway of the spike. In a preferred embodiment of the flap 32, the innersurface of the center portion 22 e.g., the side facing the base section 11, is convex in shape 33. Thus, only the convex portion of the flap 32 rests on the spike 18, insuring that a sufficient air opening is maintained into the container, see FIG. 7. Though the cover 19 has been preferably described as having a center portion 22, with a circular weakened area 28, other spike penetrating weakened areas may be employed. For example, a weakened area in the form of a cross, triangle and the like, may be used. These alternate weakened areas sections are also pierceable by a spike, and provide air access to the container.
A cap 34 may be placed over the external end of the cylindrical member 17, to prevent contamination of the closure device 10 prior to use. The cap may be teathered to the cylindrical member (not shown).
It is also within the scope of this invention, to use a snap-fit assembly of the closure device 10 and the container 26, thus, eliminating the threaded assembly. As shown in FIG. 8, a circumferential tab section 37 projecting from the base section 11, engages a rim 38 on the container 26, securing the closure device 10 to the container 26. After engagement, the closure device 10 may be further adhered to the container 26 by e.g., sonic welding.
The closure device 10 may also be sealed across a container opening without a threaded assembly, or snap-fit assembly by sealing e.g., sonic welding the base section 11 across the container opening, as shown in FIG. 9.
The closure device 10 of this invention when connected to an enteral fluid container, may be sterilized as a unit with the container. Alternately, the structure of the closure device 10 allows for it to be sterilized separate from an enteral fluid container. The internal cover 19 and cap 34, protects the internal portions of the device from contamination after sterilization.
To administer enteral fluid to a patient using the closure device of this invention, the cap 35 is removed, and a spike 18 (attached to an enteral delivery set) is plunged into the cylindrical member 17 and spike receiving opening 13 breaking the weakened area 28, and the container foil seal 27 as described above, thus releasing the enteral fluid to the patient, and allowing the fluid container to properly vent to the atmosphere.
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A closure device for connection to a fluid container which has an opening for receiving the device. The closure device has a base section which may sealably cover the container opening. The base section has a spike receiving opening passing there through with at least one air vent on the base section which is spaced from the spike receiving opening. A hydrophobic air filter, is associated with the air vent. Adjoining the base section is an internal cover, which lies over the aperture, covering it and the base section. The internal cover has a pierceable portion which is in alignment with the spike receiving opening of the base section.
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BACKGROUND OF THE INVENTION
[0001] This invention is directed toward a portable, directional, ballistic resistant vehicle tray for personal protection. More specifically, and without limitation, this invention relates to a multi-layer, molded ballistic resistant vehicle tray that is configured to operate as a durable interior floor mat in vehicles and in emergency situations which is immediately and easily accessed for use as a tactical personal protection device.
[0002] With the rising levels of terroristic events, school and office campus emergencies, general levels of gun violence, and readily accessible firearms such as handguns, rifles, and similar weaponry, first responder personnel to such events are frequently exposed to great danger from shootings, stabbings, injury due to projection of blunt force objects, assaults, and attacks from both known and unknown threats as they carry out their daily duties. According to a Federal Bureau of Investigation statistical analysis, there was an increase of law enforcement deaths of almost eighty-nine percent within just one year. Within that same year, out of forty-one law enforcement deaths, thirty-eight resulted from firearms.
[0003] Many first responders often remain in a defensive location while under gunfire or similar threat while waiting for a SWAT team or other agency to arrive to offensively address the emergency. Alongside the rise in violence, there is also an increased expectation for first responder personnel to engage a threat immediately to reduce fatalities. This expectation, however, has not been accompanied by additional personal protection for the first responders.
[0004] Portable personal protective devices for first responders are well known in the art. One advancement that has taken place is a wearable protective device commonly known as a bullet proof vest. This design, however, has its deficiencies. Bullet proof vests are non-directional, are not used by all personnel, and do not cover the entire body for needed protection. Also, personnel do not always wear vests at all times because the vests may be bulky, heavy, limit the range of motion, and are hot. As such, they are not immediately available in emergency situations.
[0005] One solution to this problem, however, is either a portable hand held shield or ground level staged shield, or “wall.” Similarly, ballistic resistant attachments for vehicle doors have been suggested in the art.
[0006] Despite these advances and others, problems still remain. In particular, emergency events require quick action and many advancements require various steps to access and utilize the protective device. Additionally, many current devices do not provide a personal protective device that is dual purpose within a vehicle that can also be used offensively during a tactically complicated situation.
[0007] Thus it is a primary objective of this invention to provide a portable personal protection device for first responder personnel that improves upon the current state of the art.
[0008] Another objective of this invention is to provide a ballistic resistant vehicle tray that can be used as a both a durable floor tray and a portable directional personal protection device.
[0009] Yet another objective of this invention is to provide a ballistic resistant vehicle tray that is seamlessly integrated into existing emergency military, medical services, and police vehicles.
[0010] Another objective of this invention is to provide a ballistic resistant vehicle tray that accommodates both drivers and passengers of emergency response vehicles.
[0011] Yet another objective of this invention is to provide a ballistic resistant vehicle tray that is within close proximity to first responder personnel for quick removal upon exiting the vehicle.
[0012] Another objective of this invention is to provide a ballistic resistant vehicle tray that can provide tactical support enabling a first responder to actively engage a threat.
[0013] Yet another objective of this invention is to provide a ballistic resistant vehicle tray that withstands multiple rounds during up to a threat level IV event.
[0014] Another objective of this invention is to provide a ballistic resistant vehicle tray that is cost effective.
[0015] These and other objectives, features, and advantages of the invention will become apparent from the specification and claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] FIG. 1 a is a front view of a ballistic resistant vehicle tray;
[0017] FIG. 1 b is a back view of a ballistic resistant vehicle tray;
[0018] FIG. 2 is an exploded perspective view of a ballistic resistant vehicle tray; and
[0019] FIG. 3 is a perspective view of a ballistic resistant vehicle tray positioned within a vehicle.
SUMMARY OF THE INVENTION
[0020] In general, the invention relates to a ballistic resistant vehicle tray system 10 positioned within close proximity to the user and seamlessly positioned to engage the interior flooring of the vehicle. The ballistic resistant vehicle tray system includes a shell having a rigid molded top layer and rigid molded bottom layer with a ballistic resistant layer positioned within the shell. The invention further includes first and second handles rotatably connected by connection members to the top layer of the shell and positioned such that the first handle provides for easy removal from a vehicle, and the second handle provides for immediate directional use as a portable personal protection device. The first and second handles are also positioned on the top layer such that the first and second handles lie flush with the top layer. The invention may include an opening extending through each layer of the shell that receives a ballistic resistant viewing window. The invention may also include identification indicia that can be either removably attached or permanently affixed to the bottom layer of the shell by attachment members.
DETAILED DESCRIPTION
[0021] For the purpose of the specification and the claims:
[0022] The terms “terroristic”, “emergency” and “violent threat” event refers to occurrences involving known or unknown violent acts or acts dangerous to human life that are in violation of the criminal laws of the United States or of any State, events requiring an immediate response from emergency personnel such as police, EMS, or soldiers, acts involving civilian or governmental population intimidation or coercion requiring immediate response from emergency personnel, an assassination or assassination attempt, kidnapping, and other general violent events where gunfire or explosives are used during the assault.
[0023] The term “ballistic resistant” refers to materials that are resistant to at least one round of either high power and lower power weaponry including but not limited to rifles and handguns up to a level IV threat.
[0024] The term “close proximity” refers to the location of the invention in relation to a user where the invention is located within the user's reach without exiting the vehicle.
[0025] With reference to the Figures, a portable ballistic resistant vehicle tray system 10 is shown positioned within a vehicle 12 and having a durable shell 14 having a molded top layer 16 and molded bottom layer 18 . The shell 14 may be comprised of any weather resistant, durable materials that provide for easy cleaning and are of a light weight. The molded top layer 16 and molded bottom layer 18 are, in one arrangement, connected along and outer edge 20 to form the shell 14 . In one embodiment, the shell is equal to or less than three-quarters of an inch thick.
[0026] The molded top layer 16 is rigidly molded generally concave to seamlessly accommodate the contour of a user's feet and an interior foot well of a vehicle 22 . The molded top layer 16 has a top end 24 , a bottom end 26 , a first side 28 and a second side 30 . The molded top layer 16 has treading 32 to engage a user's feet and to enable the shell 14 to be used as a floor mat. In one embodiment, the molded top layer 16 has a pair of recesses 34 , 36 with a first recess 34 that receives a first handle 38 and a second recess 36 that receives the second handle 40 . The recesses 34 , 36 are of a depth providing for no interference in driving between a user, at least one pedal 42 of a vehicle 12 and the handles 38 , 40 .
[0027] The first handle 38 , in one embodiment, is positioned in close proximity to a user and positioned on the molded top layer 16 near the first side 28 of the molded top layer 16 such that the first handle 38 does not interfere with a user's foot or vehicle pedals 42 and such that the tray system 10 may be easily removed from the vehicle 12 for immediate use as a portable personal protection device. In one embodiment, a first handle 38 , may be located at a midpoint 44 between the top end 24 and bottom end 26 of the molded top layer 16 . In the present invention, the first handle 38 is rotatably connected to the shell 14 by a plurality of connection members 46 that extend through the tray system 10 via a plurality of apertures 48 in the tray system 10 . In one embodiment, the first handle 38 provides for gripping and manipulating the system 10 in order to immediately and quickly remove the system 10 from a vehicle 12 .
[0028] Also in the as shown in FIG. 2 , a second handle 40 is positioned on the molded top layer 16 adjacent a notch 50 that is positioned adjacent a corner 52 of the system 10 . The notch 50 is positioned such that a user may place a weapon 54 (not shown) on notch 50 and return gunfire. The present invention anticipates that the notch 50 may be positioned throughout the system 10 for use as an effective offensive tactical weapon support. Further, the second handle 40 is positioned adjacent the top end 24 such that the second handle 40 lies flush with the molded top layer 16 and does not interfere with the vehicle foot pedals 42 or impede a user driving the vehicle 12 . In one embodiment, the second handle 40 is positioned adjacent the top end 24 such that a user may immediately manipulate the tray system 10 as a directional portable personal protective device upon encountering a known or unknown threat and to actively engage such threat. The second handle 40 , in one embodiment, is rotatably connected to the shell 14 by a plurality of connection members 56 which extend through the system 10 via a plurality of apertures 58 within the system 10 .
[0029] As shown in FIG. 2 , below the molded top layer 16 and positioned within the shell 14 , is a ballistic resistant layer 60 . The ballistic resistant layer 60 may be comprised of light weight, cost effective ballistic resistant materials such as gels, Kevlar, polymers, fiberglass, and the like that can withstand threat level IV assaults such as multiple ammunition rounds from handguns, rifles, and blast cannons and the like. In one embodiment, a cloth pocket 62 , sealed at its ends, encloses the ballistic resistant layer 60 between the molded top layer 16 and the molded bottom layer 18 .
[0030] The molded bottom layer 18 is rigidly molded generally concave to seamlessly form to the contour of an interior floor well of a vehicle 22 and to directly engage the floor of a vehicle 64 as shown in FIG. 3 . The bottom layer 18 has a top end 66 , a bottom end 68 , a first side 70 , and a second side 72 . The bottom layer 18 may be comprised of durable, soil and water resistant materials that provide easy cleaning and are of a light weight. In the present invention, bottom layer is a heavy duty plastic and rubber mixture. In one embodiment, as shown in FIG. 1 b , the bottom layer 18 has identification indicia 74 connected positioned adjacent the middle of the shell 14 via attachment members 76 . The attachment members 76 may be temporarily or permanently affixed to the molded bottom layer 18 and may be comprised of Velcro, glue, snaps, buttons, tape, string, screws, or the like. In another embodiment, the indicia may be directly written on the molded bottom layer 18 or embossed upon the molded bottom layer 18 . In yet another embodiment, as shown in FIG. 1 a , the shell 14 has an opening 78 extending through and positioned adjacent the middle of the shell 14 that receives a bullet resistant transparent viewing window 80 . In another embodiment, the opening 78 with the bullet resistant transparent viewing window 80 is positioned such that identification indicia 74 may be attached to the shell 14 either above or below the window 80 .
[0031] In the present invention, the portable ballistic resistant vehicle tray system 10 is configured to accommodate a foot well 22 and floor 64 contour as well as accommodate a user's use of the system 10 by positioning the handles 38 , 40 in positions easily accessed by the user while not interfering with driving. The present invention may also be configured substantially the same as the user side arrangement but certain features such as the notch 50 , first and second handles 38 , 40 and molded top and bottom layers 16 , 18 are positioned such that a passenger's use is accommodated for. In this embodiment, the molded top and bottom layers 16 , 18 are molded to the contours of a passenger's vehicle foot well 82 and floor 84 . This provides the unique benefit of placing the invention in close proximity to both the driver and at least one passenger when engaging a threat in order to access additional protection without exiting the vehicle.
[0032] In operation, a portable ballistic resistant vehicle tray system 10 is provided with a ballistic resistant layer 60 encased within a shell 14 . The tray system 10 is inserted into a vehicle 12 such that the molded bottom layer 18 of the tray system 10 engages the contouring of a vehicle floor 64 . Using a first handle 38 positioned on a first side 28 of a molded top layer 16 of the tray 10 , a user may quickly remove the tray 10 from the vehicle 12 . Using a second handle 40 , a user may immediately hold the tray 10 as a portable directional personal protective device interposed between a user and a threat. A user may then maneuver the tray 10 offensively and directionally toward a threat in order to engage in an immediate tactical response. In the present invention, the system 10 is located in close proximity to the user and is of a size such that the majority of the user's body is protected.
[0033] Therefore, a ballistic resistant vehicle tray system 10 has been provided that provides a lightweight, cost effective, portable directional personal protection device, and improves upon the art.
[0034] From the above discussion and accompanying Figures and claims it will be appreciated that the ballistic resistant vehicle tray 10 offers many advantages over the prior art. It will be appreciated further by those skilled in the art that other various modification could be made to the device without parting from the spirit and scope of this invention. All such modifications and changes fall within the scope of the claims and are intended to be covered thereby. It should be understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in the light thereof will be suggested to persons skilled in the art and are to be included in the spirit and purview of this application.
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The present invention relates to a device and method for providing immediate additional ballistic resistant portable personal protection for first responders, such as Police, Fire, EMS, and military personnel, during an emergency event. The device, configured for insertion into either the driver or passenger interior floor of an emergency vehicle is comprised of a molded shell with layers comprising a ballistic resistant layer that both provides vehicle floor matting and fits seamlessly into the contours of the emergency vehicle foot well and interior floor. For easy removal and immediate use as a directional portable personal protection device, handles are provided on the shell such that the handles do not interfere with driving.
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BACKGROUND OF THE INVENTION
[0001] 1. Technical Field
[0002] This invention generally relates to vehicles for lifting and transporting materials. More particularly, the invention relates to power-driven walk-behind vehicles that are used to move loads both horizontally over a surface and vertically with respect to the surface. Specifically, the invention relates to a vehicle which includes a suspension system connecting the drive wheel to the frame of the vehicle and which enables the vehicle to travel over an uneven surface.
[0003] 2. Background Information
[0004] Power-driven walk-behind vehicles, such as powered pallet jacks, powered material transfer trucks and powered pallet stackers are commonly used in the manufacturing and retailing industries for moving heavy loads from one location to another within a factory or store and for stacking products on top of each other. When the powered vehicle travels across even terrain, all of its wheels remain in contact with the ground surface and the weight of the vehicle is distributed across all of the wheels. The vehicle is, therefore, able to move forward at a relatively constant speed. If, however, the vehicle travels over uneven terrain, one of the wheels may enter a small hole or depression in the surface and this may cause other wheels to be temporarily lifted off the ground surface. This causes a hesitation in the forward motion of the vehicle and causes the drive wheel to lose traction and the operator momentarily loses control of steering, acceleration and braking. Similarly, if the vehicle travels over a small bump in the terrain, some of the wheels may lift off the ground causing additional force to be placed on the drive wheel and additional strain on the motor. This is particularly problematic if the drive wheel of the vehicle is the wheel which travels over the bump and some or all of the side wheels are temporarily lifted off the ground. This greatly increases the strain on the motor and thereby reduces the motor's life and greatly increases the operator's steering effort. Furthermore, powered vehicles are designed to carry heavy loads and these loads have to be positioned correctly in order to maintain the vehicle's center of gravity in a particular location for safe operation. If wheels are lifted off the ground, the vehicle's center of gravity may be shifted to an unsafe position and the vehicle may tip over putting the vehicle, operator and load at risk.
[0005] There is therefore a need in the art for a material handling lift vehicle that is able to negotiate both even and uneven terrain without being prone to having some of its wheels lift off the ground and which can therefore maintain substantially constant traction and continuous operator control, i.e., steering, acceleration and braking, regardless of surface conditions or weight of load being carried.
SUMMARY OF THE INVENTION
[0006] It is therefore an object of the present invention to provide a material handling lift vehicle with a suspension system connecting its drive wheel to the vehicle frame. The suspension system adjusts the drive wheel's relative position when the vehicle travels over uneven terrain so that the vehicle's wheels are all kept in contact with the ground. The suspension system also holds the steering rod, onto which the drive wheel is mounted, in a substantially vertical position when the vehicle is traveling over uneven terrain.
[0007] The material handling lift vehicle includes a frame that has side wheels mounted on it to travel over the ground surface. At least a portion of the frame holds the load thereon. A drive wheel is received on an axle mounted at one end of a steering column. A parallelogram type suspension connects the steering column to the frame. The parallelogram type suspension includes at least one pair of swing arms that extend outwardly from the frame and are pivotally connected thereto, a stabilizer bar fixedly connected between the swing arms and at least one shock absorber or dampener connected at one end to the frame and pivotally connected at the other end to the swing arms. A plate extends between the stabilizer bar and the steering column and is fixedly connected thereto. When the drive wheel travels over the uneven surface, rotational movement in the suspension system causes a vertical movement in the steering column and thus any shocks to the system are dampened. Consequently, all the wheels of the vehicle tend to remain in contact with the surface over which the vehicle is traveling regardless of the condition of that surface.
BRIEF DESCRIPTION OF THE DRAWINGS
[0008] The preferred embodiments of the invention, illustrative of the best mode in which applicant has contemplated applying the principles, are set forth in the following description and are shown in the drawings and are particularly and distinctly pointed out and set forth in the appended claims.
[0009] FIG. 1 is a side elevational view of a material handling lift vehicle in accordance with the present invention;
[0010] FIG. 2 is a partial cross-sectional side elevational view of the material handling lift vehicle with the hood removed to show the suspension system of the present invention connected to the steering column;
[0011] FIG. 3 is a partial front elevational view of the material handling lift vehicle and suspension system shown in FIG. 2 ;
[0012] FIG. 4 is a partial top view of the material handling lift vehicle and suspension system;
[0013] FIG. 5 is a partial cross-sectional side elevational view through line 5 - 5 of FIG. 4 , showing the shock dampener in greater detail;
[0014] FIG. 6 is a partial cross-sectional side elevational view through line 6 - 6 of FIG. 4 , showing the stabilizer bars and their connection to the outer surface of the steering column housing;
[0015] FIG. 7 is a partial cross-sectional side elevational view through line 7 - 7 of FIG. 4 , showing the connection of the housing to the steering column;
[0016] FIG. 8 is a partial cross-sectional front elevational view through line 8 - 8 of FIG. 4 , showing the stabilizer bars in greater detail;
[0017] FIG. 9 is a partial cross-sectional front elevational view through line 9 - 9 of FIG. 4 , showing the connection of the upper and lower swing arms to the bracket mounted on the frame;
[0018] FIG. 10 is a partial top view of the material handling lift vehicle moving toward a depression in the ground surface;
[0019] FIG. 11 is a partial cross-sectional side elevational view of the material handling lift vehicle as shown in FIG. 10 , showing the suspension system in its rest position as it travels over a relatively flat surface;
[0020] FIG. 12 is a partial cross-sectional side elevational view of the material handling lift vehicle showing the drive wheel entering a depression in the ground surface and showing the related movement in the positions of the suspension system components;
[0021] FIG. 13 is a partial cross-sectional side elevational view of the material handling lift vehicle after it has exited the depression in the surface and showing the suspension system returning to its rest position;
[0022] FIG. 14 is a partial cross-sectional side elevational view of the material handling lift vehicle approaching a bump in the surface over which it is traveling;
[0023] FIG. 15 is a partial cross-sectional side elevational view of the material handling lift vehicle showing the drive wheel riding over the bump in the surface and showing the related movement in the suspension system; and
[0024] FIG. 16 is a partial cross-sectional side elevational view of the material handling lift vehicle with the suspension system returning to its rest position after negotiating the bump in the ground surface.
DETAILED DESCRIPTION OF THE INVENTION
[0025] Referring to FIGS. 1-9 , there is shown a material handling lift vehicle, generally indicated at 10 . Material handling lift vehicle 10 includes a frame, generally indicated at 12 , onto which is mounted a power unit (not shown), a support 16 and a load carrying platform 18 . Two pairs of laterally spaced side wheel assemblies 19 and 21 , having wheels 20 and 22 respectively, are provided on the underside of frame 12 . A non load-bearing drive wheel assembly 24 is connected to a steering column 26 and is positioned intermediate side wheel assemblies 19 and 21 . Drive wheel 24 is provided with a parallelogram-style suspension system, generally indicated at 27 . Both the power unit (not shown) and suspension system 27 are covered by a hood 28 for protection and to make material handling lift vehicle 10 more aesthetically pleasing.
[0026] Still, referring to FIGS. 1-9 , frame 12 includes a horizontal portion 12 a and a vertical portion 12 b ( FIG. 2 ). A plurality of pairs of support brackets 30 , 32 and 34 are mounted on vertical section 12 b and extend outwardly therefrom at substantially ninety degrees thereto. Brackets 30 and 32 connect frame 12 and steering column 26 together via components of suspension system 27 as will be hereinafter described. Brackets 34 connect the side wheel assemblies 19 , 21 to frame 12 .
[0027] Steering column 26 is an elongated tubular member having a longitudinal axis indicated by line X-X′ ( FIG. 2 ). A steering column cap 36 is screwed onto one end of steering column 26 and a handle 37 extends outwardly from cap 36 to enable an operator to move stacker 10 . A mount plate 38 is welded onto the opposite end of steering column 26 . An axle support flange 40 extends downwardly from mount plate 38 and supports an axle 42 which extends outwardly from mount plate 38 and through the bore (not shown) of drive wheel 24 . Axle 42 lies substantially at ninety degrees to the longitudinal axis X-X′ of steering column 26 . A housing 44 , having a central bore 46 ( FIG. 4 ), is coaxially disposed around a portion of steering column 26 intermediate cap 36 and mount plate 38 . Housing 44 is spaced a distance above mount plate 38 and between a pair of collars 48 and 50 ( FIG. 7 ) and is connected to steering column 26 at bearing assemblies 52 .
[0028] In accordance with one of the main features of the invention and referring to FIGS. 2-9 , suspension system 27 includes a pair of laterally spaced upper swing arms 54 , a pair of laterally spaced lower swing arms 56 , an upper stabilizer bar 58 , a lower stabilizer bar 60 and a pair of shock dampeners 62 . When these components are connected together and to frame 12 , they are arranged to form a parallelogram-style suspension system for maintaining steering column 26 substantially vertical and to reduce the tendency of steering column 26 to move from a vertical position when drive wheel 24 travels over an uneven surface. Steering column 26 is disposed within the parallelogram formed by upper and lower swing arms 54 , 56 ; stabilizer bars 58 , 60 and frame 12 .
[0029] Upper and lower swing arms 54 , 56 are of substantially the same length and each arm has a longitudinal axis extending from a first end 54 a and 56 a to a second end 54 b and 56 b , respectively. In FIG. 2 , the longitudinal axis of upper swing arm 54 is indicated by the line Y-Y′ and the longitudinal axis of lower swing arm 56 is indicated by the line Z-Z′. First end 54 a of each upper swing arm 54 is provided with an aperture 64 ( FIG. 9 ). A sleeve 66 is received through aperture 64 and a pin 68 pivotally connects first end 54 a of each upper swing arm 54 between a pair of brackets 30 , such as pair 30 a or 30 b ( FIG. 9 ). Similarly, first end 56 a of each lower swing arm 56 is provided with an aperture 70 and a sleeve 72 and pin 74 are received therethrough to pivotally connect each lower swing arm 56 to a pair of brackets 30 a or 30 b . Upper swing arms 54 are disposed vertically above lower swing arms 54 on brackets 30 .
[0030] FIG. 8 shows that upper stabilizer bar 58 is positioned between the second ends 54 b of upper swing arms 54 . Upper stabilizer bar 58 includes a tubular member 76 , a rod 78 and bearing assemblies 80 . Tubular member 76 includes annular shoulders 77 for engaging bearing assemblies 80 . Rod 78 has threaded ends 78 a and 78 b which extend outwardly from tubular member 76 . Each threaded end 78 a , 78 b is received through an aperture 82 in second end 54 b of one of upper swing arms 54 . A nut 84 is screwed onto each threaded end 78 a , 78 b to pivotally connect upper swing arms 54 to upper stabilizer bar 58 . Lower stabilizer bar 60 is substantially identical in structure and function to upper stabilizer bar 58 . Lower stabilizer bar 60 is disposed between lower swing arms 56 and the threaded ends 86 a , 86 b of rod 86 are each received through an aperture 88 in second end 56 b of one of lower swing arms 56 and are secured therein by a nut 90 . Tubular member 92 is pivotally connected between second ends 56 b of lower swing arms 56 via bearing assemblies 93 . Tubular member 92 includes annular shoulders 95 which engage bearing assemblies 93 . Upper and lower swing arms 54 , 56 lie substantially parallel to each other when upper and lower stabilizer bars 58 , 60 are secured thereto. Upper and lower swing arms 54 , 56 are connected to brackets 30 in such a way that they are separated from each other by a small gap 94 . Upper and lower stabilizer bars 58 , 60 lie substantially parallel to each other and at right angles to the longitudinal axes Y-Y′, Z-Z′, of the upper and lower swing arms 54 , 56 .
[0031] Referring to FIGS. 4, 7 and 8 , a pair of laterally spaced plates 96 are provided to connect upper stabilizer bar 58 to housing 44 . A second pair of laterally spaced plates 98 are provided to connect lower stabilizer bar 60 to housing 44 . Plates 96 and 98 each have an arcuate first end complementary sized and shaped to engage the outer surfaces of tubular members 76 , 92 , respectively. The first ends of plates 96 and 98 are welded to tubular members 76 , 92 , respectively. Plates 96 and 98 abut the outer surface of housing 44 ( FIG. 4 ) and are welded thereto. Plates 96 , 98 lie substantially parallel to the longitudinal axes Y-Y′, Z-Z′, of upper and lower swing arms 54 , 56 . Upper and lower stabilizer bars 59 , 60 are therefore rigidly connected to steering column 26 and, consequently, when steering column 26 moves vertically up and down as drive wheel 24 travels over a surface 100 , upper and lower stabilizer bars 58 , 60 move in unison with steering column 26 about bearing assemblies 80 .
[0032] Referring to FIGS. 2-5 , shock dampeners 62 are provided to dampen the reciprocating motion of steering column 26 and to maintain constant traction and steering effort and control when drive wheel 24 travels over uneven areas of surface 100 . A first end 62 a of each shock dampener 62 is pivotally connected, via a spacer 102 and pin 104 , through an aperture (not shown) in one of upper swing arms 54 . The second end 62 b of each shock dampener 62 is pivotally connected between a pair of brackets 32 by a pin 106 . Shock dampeners 62 preferably are of the type having a spring biased piston rod 63 that reciprocates in and out of a cylinder 65 , but could equally be of any other known type of shock dampener without departing from the spirit of the present invention.
[0033] Referring to FIGS. 10-13 , in use, material handling lift vehicle 10 may be driven over surface 100 in the direction of the arrow “A”. FIG. 11 shows the position of upper and lower swing arms 54 , 56 when surface 100 is flat and even and all wheels of vehicle 10 engage surface 100 in the same plane. Upper and lower swing arms 54 , 56 extend outwardly from and generally normal to frame 12 b and lie substantially normal to the longitudinal axis X-X′ of steering column 26 . As vehicle 10 continues to move in the direction of the arrow “A”, drive wheel 24 enters a small depression 108 in surface 100 . If steering column 26 was not provided with suspension system 27 , drive wheel 24 would lose contact with surface 100 and traction, control and forward motion of vehicle 10 would be impeded. However, steering column 26 is provided with suspension system 27 and, consequently, when drive wheel 24 enters depression 108 , steering column 26 moves vertically downwardly in the direction of arrow “B” toward surface 100 ( FIG. 12 ) causing drive wheel 24 to remain in contact with the surface 110 of depression 108 . As upper and lower stabilizer bars 58 , 60 are rigidly attached to housing 44 , they move downwardly in the direction of arrow “B” when steering column 26 moves downwardly in the direction of arrow “B”. This causes second ends 54 b and 56 b of upper and lower swing arms 54 , 56 , respectively, to move in an arc “C”, thereby moving first end 62 a of each shock dampener 62 downwardly. This, in turn, drives piston rods 63 into cylinders 65 in the direction of arrow “D”. As vehicle 10 continues to move in the direction of the arrow “A”, drive wheel 24 exits depression 108 and steering column 26 moves upwardly in the direction of arrow “E” ( FIG. 13 ). The upward motion of steering column 26 is transferred to upper and lower stabilizer bars 58 , 60 and thereby to second ends 54 b and 56 b of upper and lower swing arms 54 , 56 , causing them to begin to move in an arc indicated by arrow “F”. The release of the downward thrust on piston rods 63 allows them to rebound in the direction of arrow “G” and this allows upper and lower swing arms 54 , 56 to return to their rest position. Wheels 20 and 22 remain in contact with surface 100 when drive wheel 24 travels into and out of depression 108 . The forward motion of vehicle 10 in the direction of the arrow “A” is therefore not interrupted or impeded, traction and control are not lost and no additional stress is placed upon the power unit (not shown) even though vehicle 10 is traveling over an uneven surface.
[0034] Referring to FIGS. 14-16 , suspension system 27 is also useful for assisting vehicle 10 to negotiate bumps 114 in surface 100 without wheels 20 , 22 lifting off surface 100 and stressing power unit (not shown) and increasing steering effort. Vehicle 10 moves in the direction of arrow “H”. When vehicle 10 is traveling over a flat or even section of surface 100 , upper and lower swing arms 54 , 56 are in the rest position where their longitudinal axes lies at ninety degrees to the longitudinal axis of steering column 26 . As vehicle 10 continues in the direction “H”, drive wheel 24 travels upwardly onto bump 114 and, as it does so, it causes steering column 26 to be forced upwardly in the direction of the arrow “I”. Upper and lower stabilizer bars 58 , 60 move upwardly in the direction of the arrow “I” with steering column 26 . Second ends 54 b and 56 b of upper and lower swing arms 54 , 56 are moved in an arc “J”, causing piston rod 63 to be drawn out of cylinder 65 in the direction of arrow “K”. This allows the wheels 20 and 22 to remain in contact with surface 100 while drive wheel 24 moves over bump 114 . Drive wheel 24 is therefore not carrying any additional weight of vehicle 10 as it travels over bump 114 and power unit (not shown) is therefore not additionally stressed and traction is maintained and steering effort remains constant. When drive wheel 24 rolls off bump 114 and returns back to the flat even surface 100 , steering column 26 moves downwardly in the direction of arrow “L” ( FIG. 16 ). The movement in steering column 26 causes downward movement in upper and lower stabilizer bars 58 , 60 , and thereby causes upper and lower swing arms 54 , 56 to move in an arc “M”. Piston rods 63 consequently rebound in the direction of arrow “N”. This returns upper and lower swing arms 54 , 56 to their rest position. The entire time that drive wheel 24 is traveling over bump 114 the wheels 20 , 22 remain in contact with surface 100 .
[0035] It will be understood that modifications may be made to vehicle 10 without departing from the spirit of the present invention. Material handling lift vehicle 10 is shown to include a motor to raise and lower the load carrying platform and to move the vehicle across the terrain. Vehicle 10 may, alternatively, be provided with a hand-cranked winch, to raise and lower platform, and a handle used to push the unit across the terrain by hand. Additionally, the shock dampener is shown as being attached to the upper swing arm, but it could alternatively be connected to the lower swing arm by inserting a pin (not shown) through aperture 116 . Upper and lower stabilizer bars may be manufactured with a pair of laterally spaced slots therein to receive plates instead of having a concavely shaped front edge for receiving the convexly shaped stabilizer bar. Furthermore, while the bolt passing through the stabilizer bar is shown as having threaded ends that are secured with nuts to the swing arms, it will be understood that other rods and fasteners could be utilized, such as a pin with a cooperating cotter pin. It will also be understood that while the suspension system is disclosed as connecting the drive wheel to the frame, such a system could also be mounted on any or all of the side wheels.
[0036] In the foregoing description, certain terms have been used for brevity, clearness, and understanding. No unnecessary limitations are to be implied therefrom beyond the requirement of the prior art because such terms are used for descriptive purposes and are intended to be broadly construed.
[0037] Moreover, the description and illustration of the invention is an example and the invention is not limited to the exact details shown or described.
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A material handling lift for moving a load horizontally over a surface and vertically with respect to that surface and a suspension system for the material handling lift. The material handling lift includes a frame with wheels for traveling over the surface. At least one of the wheels is a drive wheel mounted on a vertically-oriented steering column. The steering column is connected to the frame by a parallelogram type suspension system which includes swing arms that are pivotally connected to the frame. A stabilizer bar is connected between the free ends of the swing arms and a shock dampener is connected between the frame and a swing arm. The suspension system helps dampen the shock of traveling over uneven terrain, helps to keep the steering column vertical and the wheels of the vehicle on the ground thereby helping to maintain constant traction with the surface and control of the steering, braking and acceleration of the vehicle. Furthermore, the suspension system aids in providing constant steering effort for the vehicle, regardless of the weight of the load carried.
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BACKGROUND OF THE INVENTION
This invention relates to nuclear magnetic resonance (NMR) imaging and, more particularly, to methods and compositions for enhancing NMR imaging.
The recently developed technique of NMR imaging encompasses the detection of certain atomic nuclei utilizing magnetic fields and radio-frequency radiation. It is similar in some respects to x-ray computed tomography (CT) in providing a cross-sectional display of the body organ anatomy with excellent resolution of soft tissue detail. As currently used, the images produced constitute a map of the proton density distribution and/or their relaxation times in organs and tissues. The technique of NMR imaging is advantageously non-invasive as it avoids the use of ionizing radiation.
While the phenomenon of NMR was discovered in 1945, it is only relatively recently that it has found application as a means of mapping the internal structure of the body as a result of the original suggestion of Lauterbur (Nature, 242, 190-191 (1973)). The fundamental lack of any known hazard associated with the level of the magnetic and radio-frequency fields that are employed renders it possible to make repeated scans on vulnerable individuals. In addition to standard scan planes (axial, coronal, and sagittal), oblique scan planes can also be selected.
In an NMR experiment, the nuclei under study in a sample (e.g. protons) are irradiated with the appropriate radio-frequency (RF) energy in a highly uniform magnetic field. These nuclei, as they relax, subsequently emit RF at a sharp resonance frequency. The resonance frequency of the nuclei depends on the applied magnetic field.
According to known principles, nuclei with appropriate spin, when placed in an applied magnetic field (B, expressed generally in units of gauss or Tesla (10 4 gauss)) align in the direction of the field. In the case of protons, these nuclei precess at a frequency, f, of 42.6 MHz at a field strength of 1 Tesla. At this frequency, an RF pulse of radiation will excite the nuclei and can be considered to tip the net magnetization out of the field direction, the extent of this rotation being determined by the pulse duration and energy. After the RF pulse, the nuclei "relax" or return to equilibrium with the magnetic field, emitting radiation at the resonant frequency. The decay of the emitted radiation is characterized by two relaxation times, i.e., T 1 , the spin-lattice relaxation time or longitudinal relaxation time, that is, the time taken by the nuclei to return to equilibrium along the direction of the externally applied magnetic field, and T 2 , the spin-spin relaxation time associated with the dephasing of the initially coherent precession of individual proton spins. These relaxation times have been established for various fluids, organs and tissues in different species of mammals.
In NMR imaging, scanning planes and slice thicknesses can be selected. This selection permits high quality transverse, coronal and sagittal images to be obtained directly. The absence of any moving parts in NMR imaging equipment promotes a high reliability. It is believed that NMR imaging has a greater potential than CT for the selective examination of tissue characteristics in view of the fact that in CT, x-ray attenuation coefficients alone determine image contrast, whereas at least five separate variables (T 1 , T 2 , proton density, pulse sequence and flow) may contribute to the NMR signal. For example, it has been shown (Damadian, Science, 171, 1151 (1971)) that the values of the T 1 and T 2 relaxation in tissues are generally longer by about a factor of 2 in excised specimens of neoplastic tissue compared with the host tissue.
By reason of its sensitivity to subtle physicochemical differences between organs and/or tissues, it is believed that NMR may be capable of differentiating different tissue types and in detecting diseases which induce physicochemical changes that may not be detected by x-ray or CT which are only sensitive to differences in the electron density of tissue.
As noted above, two of the principal imaging parameters are the relaxation times, T 1 and T 2 . For protons (or other appropriate nuclei), these relaxation times are influenced by the environment of the nuclei (e.g., viscosity, temperature, and the like). These two relaxation phenomena are essentially mechanisms whereby the initially imparted radiofrequency energy is dissipated to the surrounding environment. The rate of this energy loss or relaxation can be influenced by certain other nuclei which are paramagnetic. Chemical compounds incorporating these paramagnetic nuclei may substantially alter the T 1 and T 2 values for nearby protons. The extent of the paramagnetic effect of a given chemical compound is a function of the environment within which it finds itself.
In general, paramagnetic divalent or trivalent ions of elements with an atomic number of 21 to 29, 42 to 44 and 58 to 70 have been found effective as NMR image contrasting agents. Suitable such ions include chromium (III), manganese (II), manganese (III), iron (III), iron (II), cobalt (II), nickel (II), copper (II), praseodymium (III), neodymium (III), samarium (III) and ytterbium (III). Because of their very strong magnetic moments, gadolinium (III), terbium (III), dysprosium (III), holmium (III) and erbium (III) are preferred. Gadolinium (III) ions have been particularly preferred as NMR image contrasting agents.
Typically, the divalent and trivalent paramagnetic ions have been administered in the form of complexes with organic complexing agents. Such complexes provide the paramagnetic ions in a soluble, non-toxic form, and facilitate their rapid clearance from the body following the imaging procedure. Gries et al., U.S. Pat. No. 4,647,447, disclose complexes of various paramagnetic ions with conventional aminocarboxylic acid complexing agents. A preferred complex disclosed by Gries et al. is the complex of gadolinium (III) with diethylenetriaminepentaacetic acid ("DTPA"). This complex may be represented by the formula: ##STR4##
Paramagnetic ions, such as gadolinium (III), have been found to form strong complexes with DTPA. These complexes do not dissociate substantially in physiological aqueous fluids. The complexes have a net charge of -2, and generally are administered as soluble salts. Typical such salts are the sodium and N-methylglucamine salts.
The administration of ionizable salts is attended by certain disadvantages. These salts can raise the in vivo ion concentration and cause localized disturbances in osmolality, which in turn, can lead to edema and other undesirable reactions.
Efforts have been made to design non-ionic paramagnetic ion complexes. In general, this goal has been achieved by converting one or more of the free carboxylic acid groups of the complexing agent to neutral, non-ionizable groups. For example, S. C. Quay, in U.S. Pat. Nos. 4,687,658 and 4,687,659, discloses alkylester and alkylamide derivatives, respectively, of DTPA complexes. Similarly, published West German applications P 33 24 235.6 and P 33 24 236.4 disclose mono- and polyhydroxyalkylamide derivatives of DTPA and their use as complexing agents for paramagnetic ions.
The nature of the derivative used to convert carboxylic acid groups to non-ionic groups can have a significant impact on tissue specificity. Hydrophilic complexes tend to concentrate in the interstitial fluids, whereas lipophilic complexes tend to associate with cells. Thus, differences in hydrophilicity can lead to different applications of the compounds. See, for example, Weinmann et al., AJR, 142, 679 (March 1984) and Brasch et al., AJR, 142, 625 (March 1984).
Thus, a need continues to exist for new and structurally diverse non-ionic complexes of paramagnetic ions for use as NMR imaging agents. There is further a need in the art to develop highly stable complexes with good relaxivity characteristics.
SUMMARY OF THE INVENTION
The present invention provides novel complexing agents and complexes of complexing agents with paramagnetic ions. The complexes are represented by the following formula: ##STR5## wherein A is --CHR 2 --CHR 3 -- or ##STR6## M +Z is a paramagnetic ion of an element with an atomic number of 21-29, 42-44 or 58-70, and a valence, Z, of +2 or +3; R 1 groups may be the same or different and are selected from the group consisting of --O - and ##STR7## wherein R 4 , R 5 , and R 6 may be the same or different and are hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl or acylaminoalkyl wherein the carbon-containing portions contain from 1 to about 6 carbon atoms, or R 5 and R 6 can together with the adjacent nitrogen form a heterocyclic ring of five, six or seven members, wherein 0 or 1 members other than the nitrogen are --O--, --S--, ##STR8## and which members are unsubstituted or substituted by hydroxy, alkyl, aryl, hydroxyalkyl, aminoalkyl, aminoaryl, alkylamino, or carbamoyl Wherein the substituents contain from 1 to about 6 carbon atoms, or R 4 and R 5 can together with the nitrogens to which each is attached form a hetercyclic ring of five, six or seven members, wherein 0 to 1 members other than the nitrogens are ##STR9## and which members are unsubstituted or substituted by hydroxy, alkyl, aryl, hydroxyalkyl, aminoalkyl, aminoaryl, alkylamino, or carbamoyl wherein the substituents contain from 1 to about 6 carbon atoms;
R 2 and R 3 may be the same or different and are hydrogen, alkyl having from 1 to about 6 carbon atoms, phenyl or benzyl;
R 7 is hydrogen, alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl or acylaminoalkyl wherein the carbon-containing portions contain from 1 to about 6 carbon atoms;
and wherein 2 or 3 of the R 1 groups are --O - and the remainder of the R 1 groups are ##STR10##
In one embodiment, R 5 and R 6 together form a heterocyclic ring of the formula ##STR11## wherein X is a single bond, ##STR12## In other embodiments, wherein R 4 and R 5 together with the nitrogens to which each is attached form a heterocyclic ring, the heterocyclic ring may have the formula ##STR13## wherein R 6 is as defined above.
Also disclosed is a method of performing an NMR diagnostic procedure which involves administering to a warm-blooded animal an effective amount of the above-described complex and then exposing the warm-blooded animal to an NMR imaging procedure, thereby imaging at least a portion of the body of the warm-blooded animal.
DETAILED DESCRIPTION OF THE INVENTION
The complexing agents employed in this invention are derivatives of well-known polyaminocarboxylic acid chelating agents, such as DTPA and ethylenediaminetetraacetic acid ("EDTA"). In these derivatives, some carboxylic acid groups of the polyaminocarboxylic acid are converted to hydrazide groups, such as those of the formula, ##STR14## Thus, if the paramagnetic ion is trivalent and the chelating agent is DTPA, two of the carboxylic acid groups will be derivatized to the hydrazide form. Likewise, if the paramagnetic ion is divalent, three of the carboxylic acid groups of DTPA or two of the carboxylic acid groups of EDTA will be derivatized to the hydrazide form. When reacted with a divalent or trivalent paramagnetic ion, the resulting complexes are substantially non-ionic as evidenced by very low electrical conductivity.
The hydrazide derivatives of the chelating agents are prepared in a conventional manner. One process for preparing hydrazide derivatives is set forth in U.S. Pat. No. 3,787,482. In general, they are prepared by reacting a stoichiometric amount of a mono-, di-, or tri-substituted hydrazino compound of the formula ##STR15## with a reactive derivative of the polyaminocarboxylic acid chelating agent under hydrazide-forming conditions. Such reactive derivatives include, for example, anhydrides, mixed anhydrides and acid chlorides. As noted above, R 5 and R 6 together with the adjacent nitrogen may form a heterocyclic ring of five, six or seven members. This embodiment results in compounds containing a hydrazide functional group external to the ring structure. In another embodiment, R 4 and R 5 together with the nitrogens to which each is attached form a heterocyclic ring of five, six or seven members. In this embodiment, the hydrazide functional group is internal to the ring structure. This ring can be saturated or unsaturated and substituted or unsubstituted. If the heterocyclic ring is substituted, the total number of substituents typically is 1 to 3. Examples of suitable heterocyclic rings include pyrrolidinyl, pyrrolyl, pyrazolidinyl, pyrazolinyl, pyridyl, piperidyl, piperazinyl, morpholinyl, etc.
In one embodiment, the reactions for preparing the hydrazide derivatives of the present invention are conducted in an organic solvent at an elevated temperature. Suitable solvents include those in which the reactants are sufficiently soluble and which are substantially unreactive with the reactants and products. Lower aliphatic alcohols, ketones, ethers, esters, chlorinated hydrocarbons, benzene, toluene, xylene, lower aliphatic hydrocarbons, and the like may advantageously be used as reaction solvents. Examples of such solvents are methanol, ethanol, n-propanol, isopropanol, butanol, pentanol, acetone, methylethyl ketone, diethylketone, methyl acetate, ethyl acetate, chloroform, methylene chloride, dichloroethane, hexane, heptane, octane, decane, and the like. If a DTPA or EDTA-type acid chloride is used as the starting material, then the reaction solvent advantageously is one which does not contain reactive functional groups, such as hydroxyl groups, as these solvents can react with the acid chlorides, thus producing unwanted by-products.
The reaction temperature may vary widely, depending upon the starting materials employed, the nature of the reaction solvent and other reaction conditions. Such reaction temperatures may range, for example, from about 20° C. to about 85° C., preferably from about 25° C. to about 50° C.
Following reaction of the reactive polyaminocarboxylic acid derivatives with the hydrazine compound, any remaining anhydride or acid chloride groups can be hydrolyzed to the carboxylate groups by adding a stoichiometric excess of water to the reaction mixture and heating for a short time.
The resulting hydrazide is recovered from the reaction mixture by conventional procedures. For example, the product may be precipitated by adding a precipitating solvent to the reaction mixture, and recovered by filtration or centrifugation.
The paramagnetic ion is combined with the hydrazide under complex-forming conditions. In general, any of the paramagnetic ions referred to above can be employed in making the complexes of this invention. The complexes can conveniently be prepared by mixing a suitable oxide or salt of the paramagnetic ion with the complexing agent in aqueous solution. To assure complete complex formation, a slight stoichiometric excess of the complexing agent may be used. In addition, an elevated temperature, e.g., ranging from about 20° C. to about 100° C., preferably from about 40° C. to about 80° C., may be employed to insure complete complex formation. Generally, complete complex formation will occur within a period from a few minutes to a few hours after mixing. The complex may be recovered by precipitation using a precipitating solvent such as acetone, and further purified by crystallization, if desired.
The novel complexes of this invention can be formulated into diagnostic compositions for enteral or parenteral administration. These compositions contain an effective amount of the paramagnetic ion complex along with conventional pharmaceutical carriers and excipients appropriate for the type of administration contemplated. For example, parenteral formulations advantageously contain a sterile aqueous solution or suspension of from about 0.05 to 1.0M of a paramagnetic ion complex according to this invention. Preferred parenteral formulations have a concentration of paramagnetic ion complex of 0.1M to 0.5M. Such solutions also may contain pharmaceutically acceptable buffers and, optionally, electrolytes such as sodium chloride. The compositions may advantageously contain a slight excess, e.g., from about 0.1 to about 15 mole % excess, of the complexing agent or its complex with a physiologically acceptable, non-toxic cation to insure that all of the potentially toxic paramagnetic ion is complexed. Such physiologically acceptable, non-toxic cations include calcium ions, magnesium ions, copper ions, zinc ions and the like. Calcium ions are preferred. A typical single dosage formulation for parenteral administration has the following composition:
______________________________________Gadolinium DTPA-bis(hydrazide) 330 mg/mlCalcium DTPA-bis(hydrazide) 14 mg/mlDistilled Water q.s. to 1 mlpH 7.0______________________________________
Parenteral compositions may be injected directly or mixed with a large volume parenteral composition for systemic administration.
Formulations for enteral administration may vary widely, as is well-known in the art. In general, such formulations are liquids which include an effective amount of the paramagnetic ion complex in aqueous solution or suspension. Such enteral compositions may optionally include buffers, surfactants, thixotropic agents, and the like. Compositions for oral administration may also contain flavoring agents and other ingredients for enhancing their organoleptic qualities.
The diagnostic compositions are administered in doses effective to achieve the desired enhancement of the NMR image. Such doses may vary widely, depending upon the particular paramagnetic ion complex employed, the organs or tissues which are the subject of the imaging procedure, the NMR imaging equipment being used, etc. In general, parenteral dosages will range from about 0.01 to about 1.0 MMol of paramagnetic ion complex per kg of patient body weight. Preferred parenteral dosages range from about 0.05 to about 0.5 MMol of paramagnetic ion complex per kg of patient body weight. Enteral dosages generally range from about 0.5 to about 100 MMol, preferably from about 1.0 to about 20 MMol of paramagnetic ion complex per kg of patient body weight.
The novel NMR image contrasting agents of this invention possess a unique combination of desirable features. The paramagnetic ion complexes exhibit an unexpectedly high solubility in physiological fluids, notwithstanding their substantially non-ionic character. This high solubility allows the preparation of concentrated solutions, thus minimizing the amount of fluid required to be administered. The non-ionic character of the complexes also reduces the osmolality of the diagnostic compositions, thus preventing undesired edema and other side effects. As illustrated by the data presented below, the compositions of this invention have very low toxicities, as reflected by their high LD 50 values.
The diagnostic compositions of this invention are used in the conventional manner. The compositions may be administered to a warm-blooded animal either systemically or locally to the organ or tissue to be imaged, and the animal then subjected to the NMR imaging procedure. The compositions have been found to enhance the magnetic resonance images obtained by these procedures. In addition to their utility in magnetic resonance imaging procedures, the complexing agents of this invention may also be employed for delivery of radiopharmaceuticals or heavy metals for x-ray contrast into the body.
The invention is further illustrated by the following examples, which are not intended to be limiting.
EXAMPLE I ##STR16## Preparation of [N,N"-Bis(2,2-dimethylhydrazino)carbamoylmethyl]diethylene-triamine-N,N',N"-triacetic acid:
A mixture of DTPA-dianhydride (10 g) and N,N-dimethylhydrazine (3.7 g) in isopropanol (25 mL) was stirred at 50° C. (water bath) for 18 hours. The gummy residue was dissolved by the addition of 50 mL of methanol and the solution filtered through a fine porosity sintered glass funnel to remove undissolved impurities. The solvent was removed under reduced pressure and the solid was recrystallized from 95% ethanol/isopropanol to give 5.3 g of colorless solid (m.p. 142°-144° C.). Anal. Calcd. for C 18 H 35 N 7 O 8 ×1.5 H 2 O: C, 42.86; H, 7.54; N, 19.44. Found: C, 43.03; H, 7.52; N, 18.91.
Preparation of [N,N'-Bis(2,2-dimethylhydrazino)carbonylmethyl]diethylenetriamine-N,N',N"-triaceto]gadolinium (III) hydrate (MP-1291).
A mixture of the ligand (9.4 g) and gadolinium oxide (3.3 g) in deionized, distilled water (50 mL) was heated at 65°-70° C. for 20 hours. The pale green solution was filtered through a fine porosity sintered glass funnel to remove undissolved impurities. The clear filtrate was then poured onto acetone (1 L) and the solid was collected and dried. The off white solid was redissolved in water (25 mL) and purified by flash chromatography over reverse phase (octadecylsilane derivatized silica gel) sorbent to give almost colorless solid. Yield 10.3 g (88%). Anal. Calcd. for C 18 H 32 N 7 O 8 Gd×H 2 O. C, 31.79; H, 4.91; N, 11.58; Gd, 26.01. Found: C, 31.89; H, 4.89; N, 11.45; Gd, 25.70.
EXAMPLE II
The acute intravenous toxicity of the compound of Example 1 was determined as follows: ICR mice, at 1 to 4 per dose level, received single intravenous injections of the test substance via a lateral tail vein at the rate of approximately 1 ml/minute. The test substances were at concentrations chosen to result in dose volumes of 5 to 75 ml/kg body weight. Dosing began at a volume of 10 ml/kg. Dose adjustments up or down were made to closely bracket the estimated LD 50 with 4 animals per group (2 males and 2 females). Observations of the mice were recorded at times 0, 0.5, 1, 2, 4 and 24 hours and once daily thereafter for up to 7 days post injection. On the 7th day post injection, the mice were euthanized, weighed and necropsied. Abnormal tissues were noted. At this time a decision was made as to whether any histopathology was to be performed and whether or not the tissues should be retained. Necropsies were also performed on mice expiring after 24 hours post-injection, except for dead mice found on the weekends. The LD 50 values, along with 95 % CI were calculated using a modified Behrens-Reed-Meunch method. The results for the complex of Example 1 are reported below:
LD 50 : 11.5 mmol/kg
95% Confidence Limits: 6.8-19.6 mmol/kg
Sex and Weight Range of Mice: Males (15.5-22.7 g) Females (19.6-20.3 g)
EXAMPLE III
T 1 relaxation times were measured using spin-echo sequence on the JEOL FX90Q (90 MHz) FT-NMR spectrometer/Twenty millimolar solution of the complex in Example 1 was prepared in H 2 O/D 2 O (4:1) mixture and was serially diluted to lower concentrations (10, 5, 2.5, 1.25, 0.526 mM) with H 2 O/D 2 O (4:1) mixture. T 1 measurements were made at each of these 6 concentrations. The relaxivity (R 1 ) was determined by applying least-square fit to the plot of 1/T 1 versus concentration. The relaxivity of the complex in Example 1 was 4.85+0.06 mM -1 sec -1 . The correlation coefficient for the least squares analysis was 0.9994.
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Novel magnetic resonance imaging agents comprise complexes of paramagnetic ions with hydrazide derivatives of polyaminocarboxylic acid chelating agents. The complexes are represented by the formula of: ##STR1## wherein A is --CHR 2 --CHR 3 -- or ##STR2## M +Z is a paramagnetic ion of an element with an atomic number of 21-29, 42-44 58-70, and a valence, Z, of +2 or +3; R 1 groups may be the same or different and are selected from the group consisting of --O - and ##STR3## The R 4 , R 5 and R 6 groups are as defined in the disclosure. These novel imaging agents are characterized by excellent NMR image-contrasting properties and by high solubilities in physiological solutions. A novel method of performing an NMR diagnostic procedure involves administering to a warm-blooded animal an effective amount of a complex as described above and then exposing the warm-blooded animal to an NMR imaging procedure, thereby imaging at least a portion of the body of the warm-blooded animal.
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FIELD OF THE INVENTION
[0001] This invention generally relates to isotopically labeled neurochemical agents, uses thereof for spin hyperpolarized magnetic resonance spectroscopic imaging, and for diagnosing of conditions and disorders, including neurological conditions and disorders.
BACKGROUND OF THE INVENTION
[0002] The following publications are considered relevant for describing the state of the art in the field of the invention:
[0003] WO 2007/052,274
[0004] U.S. Pat. No. 6,466,814
[0005] U.S. Pat. No. 6,574,495
[0006] WO 2007/044,867
[0007] U.S. Pat. No. 7,102,354
[0008] U.S. Pat. No. 6,311,086
[0009] U.S. Pat. No. 6,278,893
[0010] US2005/0232864
[0011] The reference in this specification to any prior publication (or information derived from it), or to any matter which is known, is not, and should not be taken as an acknowledgement or admission or any form of suggestion that that prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavor to which this specification relates.
[0012] Magnetic resonance imaging and spectroscopy (MRI/MRS) has become an attractive diagnosing technique in the last three decades. Due to its non-invasive features and the fact that it does not involve the exposure of the diagnosed patient to potentially harmful ionizing radiation, MRI has become the leading diagnosing procedure implemented in all fields of medicine.
[0013] The underlying principle of MRI and MRS is based on the interaction of atomic nuclei with an external magnetic field. Nuclei with spin quantum number I=½ (such as 1 H, 13 C, and 15 N) can be oriented in two possible directions: parallel (“spin up”) or anti-parallel (“spin down”) to the external magnetic field. The net magnetization per unit volume, and thus the available nuclear magnetic resonance (NMR) signal, is proportional to the population difference between the two states. If the two populations are equal, their magnetic moments cancel, resulting in zero macroscopic magnetization, and thus no NMR signal. However, under thermal equilibrium conditions, slightly higher energy is associated with the “spin down” direction, and the number of such spins will thus be slightly smaller than the number of spins in the “spin up” state.
[0014] An artificial, non-equilibrium distribution of the nuclei can also be created by hyperpolarization NMR techniques for which the spin population differences is increased by several orders of magnitudes compared with the thermal equilibrium conditions. This significantly increases the polarization of the nuclei thereby amplifying the magnetic resonance signal intensity.
[0015] The enhancement of the hyperpolarized magnetic resonance signal is limited by the relatively fast decay of the hyperpolarization due to spin-lattice relaxation (termed as T 1 relaxation time). This decay determines the temporal window of ability to detect the hyperpolarized nuclei. Known techniques of enriching the proton positions with deuterium were shown to prolong the T 1 relaxation times of compounds in a manner that is dependant on the compound's conformation in solution. The prolongation of T 1 values is attributed to a decrease in dipolar interaction that a particular nucleus experiences. However, because the dipolar interaction is only one of several relaxation mechanisms that affect the overall T 1 relaxation time, it is not possible to predict the extent of this effect for a particular nucleus in specific molecule within a specific medium (for example in the blood). Moreover, prolongation of T 1 in itself at times does not allow for practical and effective in vivo magnetic resonance detection of a compound or its metabolic fate when administered to a subject, since the sensitivity of detection is limited due to the low natural abundance of 13 C nuclei, thereby yielding signals which are below the threshold of detection.
[0016] There is a need for isotopically labeled compounds capable of being hyperpolarized giving rise to high T 1 relaxation time values and higher sensitivity of detection, thereby enabling practical and useful non-invasive diagnosing techniques of conditions and disorders in the human body.
SUMMARY OF THE INVENTION
[0017] The present invention provides a neurochemical agent comprising at least one isotopically labeled carbon atom directly bonded to at least one deuterium atom.
[0018] In a further aspect the invention provides a neurochemical agent comprising an isotopically labeled carbon atom directly bonded to at least one deuterium atom.
[0019] The term “neurochemical agent” as used herein is meant to encompass any agent participating in neurological biochemical pathways, in generation and/or degradation of neurotransmitters and in neuro-energetic pathways. Such agents may cross the blood-brain-barrier by passive or active transport, and be taken up and processed by the cellular system of the nervous system. It is noted that neurochemical agents of the invention may also participate in other metabolic events in the blood circulation in other organs, which are not only limited to cellular events within the nervous system, such as for example in pathological processes within and outside the nervous system such as cancer.
[0020] In some embodiments of the invention said neurochemical agent is selected from the following non-limiting list consisting of choline, dopamine, L-DOPA, acetylcholine, tyrosine, N-acetylaspartate, creatine, L-arginine, L-citrulline, L-tryptophan, 5-hydroxy-tryptophan, 5-hydroxy-tryptamine (5-HT, serotonin), glutamate, gamma-aminobutyric acid, norepinephrine, epinephrine, vanillylmandelic acid (VMA), homovanillic acid (HVA), 3-O-methyldopamine (3OMD), 3-O-methylnorepinephrine (3OMN), 3-O-methylepinephrine (3OME), dopaquinone, 5-hydroxyindole acetaldehyde (5-HIA), 5-hydroxyindole acetic acid (5-HIAA), melatonin, rivastigmine tartrate, rasagiline (N-propargyl-1-(R) aminoindan, methylphenidate (methyl 2-phenyl-2-(2-piperidyl)acetate), amphetamine (alpha-methyl-phenethylamine), (S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid, 2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid and 2-amino-5-(diaminomethylidene imino)pentanoic acid, N-acetylcitrulline, argininosuccinate, kynurenic acid (KYNA), 7-chlorokynurenic acid (7-Cl-KYNA), kynurenine, and 4-chlorokynurenine, tacrine, donepezil, metrifonate, fluoxetine, sertraline, paroxetine, fluvoxamine, citalopram, escitalopram, venlafaxine, nefazodone, mirtazapine, bupropion, cianopramine, femoxetine, ifoxetine, milnacipran, oxaprotiline, sibutramine, viqualine, clozapine, fenclonine, dexfenfluramine, chlorpromazine, methamphetamine, prazosin, terazosin, doxazosin, trimazosin, labetalol, medroxalol, tofenacin, trazodone, viloxazine, riluzole or any metabolite or salt thereof.
[0021] In other embodiments of the invention said neurochemical agent is selected from group consisting of choline, betaine, acetylcholine, N-acetylaspartate, L-DOPA, dopamine, norepinephrine, epinephrine, homovanillic acid, 3-O-methyldopamine, 3-O-methylnorepinephrine, 3-O-methylepinephrine, dopaquinone, vanillylmandelic acid, 5-hydroxyindole acetaldehyde, 5-Hydroxyindole acetic acid, melatonin, rivastigmine tartrate, rasagiline (N-propargyl-1-(R)aminoindan), amphetamine (alpha-methyl-phenethylamine), methylphenidate (methyl 2-phenyl-2-(2-piperidyl)acetate), (2-hydroxyethenyl)trimethylammonium, (S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid, (S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid, L-citrulline, 2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid and 2-amino-5-(diaminomethylidene imino)pentanoic acid and any methanolites thereof.
[0022] A neurochemical agent of the invention comprises at least one isotopically labeled carbon atom which is directly bonded to at least one deuterium atom (commonly marked as D or 2 H).
[0023] The term “isotopically labeled atom” is meant to encompass an atom in a compound of the invention for which at least one of its nuclei has an atomic mass which is different than the atomic mass of the prevalent naturally abundant isotope of the same atom. Due to different number of neutrons in the nuclei, the atomic mass of a isotopically labeled atoms is different. The total number of neutrons and protons in the nucleus represents its isotopic number.
[0024] In some embodiments an isotopically labeled atom is 13 C (having 7 neutrons and 6 protons in carbon nucleus). In other embodiments an isotopically labeled atom is 2 H (having 1 neutron and 1 proton in hydrogen nucleus). In other embodiments an isotopically labeled atom is 15 N (having 8 neutrons and 7 protons in nitrogen nucleus). As will be appreciated by the description below, the isotopic labeling of specific atoms in a compound of the invention is achieved by techniques known to a person skilled in the art of the invention, such as for example synthesizing compounds of the invention from isotopically labeled reactants or isotopically enriching specific nuclei of a neurochemical agent.
[0025] When referring to a neurochemical agent comprising at least one isotopically labeled atom, it should be understood to encompass agents having isotopically labeled atoms above the natural abundance of said at least one isotopically labeled atom. Thus, in some embodiments when said isotopically labeled atom is deuterium, said isotopical enrichment of said deuterium in a specific position in a compound of the invention, may be between about 0.015% to about 99.9%. Thus, in other embodiments when said isotopically labeled atom is 13 C, said isotopical enrichment of said carbon in a specific position in a compound of the invention, may be between about 1.1% to about 99.9%. Thus, in some other embodiments when said isotopically labeled atom is 15 N, said isotopical enrichment of said nitrogen in a specific position in a compound of the invention, may be is between about 0.37% to about 99.9%. Thus, a compound or a composition of the invention may have different degrees of enrichment of isotopically labeled atoms.
[0026] In some embodiments of the invention, the neurochemical agent comprises one, two, three, four or more 13 C atoms each one directly bonded to one, two, three or four 2 H atoms.
[0027] In some embodiments a neurochemical agent of the invention has T 1 relaxation time values for 13 C nucleus of between about 5 to about 500 sec.
[0028] In other embodiments of the invention, said neurochemical agent further comprises at last one isotopically labeled nitrogen atom. In some embodiments said at least one isotopically labeled nitrogen atom may be directly bonded to said at least one isotopically labeled carbon atom. In other embodiments said at last one isotopically labeled nitrogen atom may be adjacent (on a neighboring atom) to said at least one isotopically labeled carbon atom.
[0029] In other embodiments a neurochemical agent of the invention further comprises at least one additional isotopically labeled carbon atom. In some embodiments said at least one additional isotopically labeled carbon atom may be directly bonded to said at least one isotopically labeled carbon atom. In other embodiments said at least one additional isotopically labeled carbon atom may be adjacent to said at least one isotopically labeled carbon atom.
[0030] In yet further embodiments of the invention said neurochemical agent further comprises, at least one additional isotopically labeled hydrogen atom. In some embodiments said at least one additional isotopically labeled hydrogen atom may be bonded to at least one adjacent to said at least one isotopically labeled carbon atom.
[0031] In another one of its aspects, the invention provides a neurochemical agent selected from the following list:
[1,1,2,2-D 4 ,2- 13 C]-choline; [1,1,2,2-D 4 ,1- 13 C]-choline; [1,2-D 2 ,1- 13 C]-choline; [1,2-D 2 ,2- 13 C]-choline; [D 13 ,1- 13 C]-choline; [D 13 ,2- 13 C]-choline; [1,2-D 2 ,2- 13 C, trimethylamine-D 9 ]-choline; [1,2-D 2 ,1- 13 C, trimethylamine-D 9 ]-choline; [1,1,2,2-D 4 ,2- 13 C, 15 N]-choline: HO-CD 2 - 13 CD 2 - 15 N + (CH 3 ) 3 [1,2-D 2 ,2- 13 C, 15 N]-choline: HO—CHD- 13 CHD- 15 N + (CH 3 ) 3 [D 13 ,2- 13 C, 15 N]-choline: HO-CD 2 - 13 CD 2 - 15 N + (CD 3 ) 3 [2- 13 C, D 11 ]-betaine: HO—CO- 13 CD 2 -N + (CD 3 ) 3 ; [2- 13 C,2,2-D 2 ]-betaine: HO—CO- 13 CD 2 -N + (CH 3 ) 3 ; [1,2- 13 C 2 , D 11 , 15 N]-betaine: HO— 13 CO- 13 CD 2 - 15 N + (CD 3 ) 3 [2- 13 C, D 11 , 15 N]-betaine: HO—CO- 13 CD 2 - 15 N + (CD 3 ) 3 [2- 13 C,2,2-D 2 ]-betaine aldehyde: H—CO- 13 CD 2 -N + (CH 3 ) 3 ; [1- 13 C,2,2-D 2 ]-betaine aldehyde: H- 13 CO-CD 2 N + (CH 3 ) 3 ; [1- 13 C, D 11 ]-betaine aldehyde: H- 13 CO-CD 2 -N + (CD 3 ) 3 ; [1- 13 C, D 11 , 15 N]-betaine aldehyde: H- 13 CO-CD 2 - 15 N + (CD 3 ) 3 ; [1,1,2,2-D 4 ,2- 13 C]-acetylcholine; [D 13 ,2- 13 C]-acetylcholine; [7,7,8-D 3 ,7- 13 C]-L-tyrosine; [7,7,8-D 3 ,8- 13 C]-L-tyrosine; [D 7 ,7- 13 C]-tyrosine; [D 7 ,8- 13 C]-L-tyrosine; [7,7,8-D 3 ,7- 13 C]-L-DOPA; [7,7,8-D 3 ,8- 13 C]-L-DOPA; [2,5,6,7,7,8-D 6 ,8- 13 C]-DOPA; [2,5,6,7,7,8-D 6 ,7- 13 C]-L-DOPA; [2,5,6,7,7,8-D 6 ,7,8- 13 C 2 , ring- 13 C 6 ]-DOPA; [D 7 , 13 C 8 ]-dopamine; [D 7 ,7- 13 C]-dopamine; [D 7 ,8- 13 C]-dopamine; [D 7 , 13 C 6 ring]-dopamine; [1,2-D 2 ,1- 13 C]-(2-hydroxyethenyl)trimethylammonium; [1,2,D 2 ,2- 13 C]-(2-hydroxyethenyl)trimethylammonium; [7-D,7- 13 C]S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid: 3-HO-,4HO—C 6 H 3 13 CDC(NH 2 )COOH; [7-D,8- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid 3-HO-,4HO—C 6 H 3 CD 13 C(NH 2 )COOH; [6,5,2,7-D 4 ,8- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid 3-HO-,4HO—C 6 D 3 CD 13 C(NH 2 )COOH; [6,5,2,7-D 4 ,7- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid; [6,5,2,7-D 4 , 13 C 6 ring]-(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid; [6,6,6-D 3 ,6- 13 C]-N-acetylaspartate: HOOCCH(NH(CO 13 CD 3 ))CH 2 COOH [1,2,2-D 3 ,1- 13 C]-N-acetylaspartate: HOOC 13 CD(NH(COCH 3 ))CD 2 COOH [2,2-D 2 ,2- 13 C]-creatine: H 2 N + C(NH 2 )N(CH 3 ) 13 CD 2 CO 2 [2,2,6,6,6-D 5 ,2,6- 13 C 2 - 15 N]-creatine: H 2 N + C(NH 2 ) 15 N( 13 CD 3 ) 13 CD 2 CO 2 [2,2,6,6,6-D 5 ,2,6- 13 C 2 ]-creatine: H 2 N + C(NH 2 )N( 13 CD 3 ) 13 CD 2 CO 2 [2,3,3,4,4,5,5-D 7 ,2- 13 C]-arginine: + NH 2 C(NH 2 )NHCD 2 CD 2 CD 2 13 CD(NH 2 ) CO 2 H [2,3,3,4,4,5,5-D 7 ,3- 13 C]-arginine: + NH 2 C(NH 2 )NHCD 2 CD 2 13 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5,5-D 7 ,4- 13 C]-arginine: + NH 2 C(NH 2 )NHCD 2 13 CD 2 CD 2 CD(NH 2 ) CO 2 H [2,3,3,4,4,5,5-D 7 ,5- 13 C]-arginine: + NH 2 C(NH 2 )NH 13 CD 2 CD 2 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5,5-D 7 ,2- 13 C]-citrulline: NH 2 CONHCD 2 CD 2 CD 2 13 CD(NH 2 )CO 2 H [2,3,3,4,4,5,5-D 7 ,3- 13 C]-citrulline: NH 2 CONHCD 2 CD 2 13 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5,5-D 7 ,4- 13 C]-citrulline: NH 2 CONHCD 2 13 CD 2 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5,5-D 7 ,5- 13 C]-citrulline: NH 2 CONH 13 CD 2 CD 2 CD 2 CD(NH 2 )CO 2 H [9,9,10-D 3 ,10- 13 C]-L-tryptophan: C 6 H 4 C(CD 2 - 13 CD(NH 2 )COOH)CH—NH [9,10-D 2 ,10- 13 C]-tryptophan: C 6 H 4 C(CDH- 13 CD(NH 2 )COOH)CH—NH [9,9,10-D 3 ,9- 13 C]-L-tryptophan: C 6 H 4 C( 13 CD 2 -CD(NH 2 )COOH)CH—NH [9,9,10-D 3 ,10- 13 C]-5-hydroxy-tryptophan: 5-OH—C 6 H 3 C(CD 2 - 13 CD(NH 2 )COOH)CH—NH [9,10-D 2 ,10- 13 C]-5-hydroxy-tryptophan: 5-OH—C 6 H 3 C(CDH- 13 CD(NH 2 )COOH)CH—NH [9,9,10-D 3 ,9- 13 C]-5-hydroxy-tryptophan: 5-OH—C 6 H 3 C( 13 CD 2 -CD(NH 2 )COOH)CH—NH [9,9,10,10-D 4 ,10- 13 C]-serotonin: 5-OH—C 6 H 3 C(CD 2 - 13 CD 2 (NH 2 )CH—NH [9,10-D 2 ,10- 13 C]-serotonin: 5-OH—C 6 H 3 C(CDH- 13 CDH(NH 2 )CH—NH [9,9,10,10-D 4 ,9- 13 C]-serotonin: 5-OH—C 6 H 3 C( 13 CD 2 -CD 2 (NH 2 )CH—NH [2,2,3,3,4-D 5 ,2- 13 C]-glutamate: HOOC 13 CD 2 CD 2 CD(NH 2 )COOH [2,2,3,3,4-D 5 ,3- 13 C]-glutamate: HOOCCD 2 13 CD 2 CD(NH 2 )COOH [2,2,3,3,4-D 5 ,4- 13 C]-glutamate: HOOC 13 CD 2 CD 2 13 CD(NH 2 )COOH [2,2,3,3,4-D 5 ,5- 13 C]-glutamate: HOOCCD 2 CD 2 CD(NH 2 ) 13 COOH [2,2,3,3,4-D 5 ,1- 13 C]-glutamate: HOO 13 CCD 2 CD 2 CD(NH 2 )COOH [2,2,3,3,4,4-D 6 ,2- 13 C]-gamma-aminobutyric acid: H 2 N-CD 2 -CD 2 - 13 CD 2 -COOH [2,2,3,3,4,4-D 6 ,3- 13 C]-gamma-aminobutyric acid: H 2 N-CD 2 - 13 CD 2 -CD 2 -COOH [2,2,3,3,4,4-D 6 ,4- 13 C]-gamma-aminobutyric acid: H 2 N- 13 CD 2 -CD 2 -CD 2 -COOH [5,6,2,7,8,8-D 6 , 13 C 6 ]-norepinephrine: 3-HO-,4HO— 13 C 6 D 3 CD(OH)CD 2 -NH 2 (phenyl- 13 C 6 ) [5,6,2,7,8,8-D 6 , 13 C 6 ]-epinephrine: 3-HO-,4HO— 13 C 6 D 3 CD(OH)CD 2 -NH(CH 3 ) (phenyl- 13 C 6 ) [9,9,9-D 3 ,9- 13 C]-epinephrine: 3-HO-,4HO—C 6 H 3 CH(OH)CH 2 —NH( 13 CD 3 ) (phenyl- 13 C 6 ) [5,6,2,7-D 4 , 13 C 6 ]-VMA: 3-HO-,4HO— 13 C 6 D 3 CD(OH)CO 2 H (phenyl- 13 C 6 ) [5,6,2,7-D 4 ,7- 13 C]-VMA: 3-HO-,4HO—C 6 D 3 13 CD(OH)CO 2 H [5,6,2,7,7-D 5 , 13 C 6 ]-HVA: 3-HO-,4HO— 13 C 6 D 3 CD 2 CO 2 H (phenyl- 13 C 6 ) [5,6,2,7,7-D 5 ,7- 13 C]-HVA: 3-HO-,4HO—C 6 D 3 13 CD 2 CO 2 H [5,6,2,7,7,8,8,9,9,9-D 10 , 13 C 6 ]-3OMD: 3-CD 3 O-,4HO— 13 C 6 D 3 CD 2 CD 2 NH 2 (phenyl- 13 C 6 ) [5,6,2,7,7,8,8,9,9,9-D 10 ,9- 13 C]-3OMD: 3-CD 3 O-,4HO— 13 C 6 D 3 CD 2 CD 2 NH 2 (3-O-methyl- 13 C) [5,6,2,9,9,9,7,8,8-D 9 ,9,7- 13 C 2 ]-3OMN: 3- 13 CD 3 O-,4HO—C 6 D 3 13 C 3 CD(OH)CD 2 NH 2 [9,9,9,10,10,10,2,5,6,7,8,8-D 6 ,9,7,10- 13 C 2 ]-3OME: 3-CD 3 O-,4HO—C 6 D 3 CD(OH)CD 2 NH(CD 3 ) [2,5,6,7,7,8-D 6 ,8- 13 C]-dopaquinone: 30-,40-C 6 D 3 CD 2 13 CD(NH 2 )COOH [2,5,6,7,7,8-D 6 ,7- 13 C]-dopaquinone: 30-,40-C 6 D 3 13 CD 2 CD(NH 2 )COOH [9,9,-D 2 ,9- 13 C]-5-HIA: 5-OH—C 6 H 3 C( 13 CD 2 CHO)CH—NH [9,9,-D 2 ,9- 13 C]-5-HIAA: 5-OH—C 6 H 3 C( 13 CD 2 CO 2 H)CH—NH [13,13,13,9,9,10,10,12,12,12-D 10 ,9,12,13- 13 C]-melatonin: 5- 13 CD 3 O—C 6 H 3 C( 13 CD 2 CD 2 NHCO 13 CD 3 )CH—NH [13,13,13,9,9,10,10,12,12,12-D 10 ,10,12,13- 13 C]-melatonin: 5-CD 3 O—C 6 H 3 C(CD 2 13 CD 2 NHCO 13 CD 3 )CH—NH [9,9,10,10-D 4 ,9- 13 C]-melatonin: 5-CH 3 O—C 6 H 3 C( 13 CD 2 CD 2 NHCOCH 3 )CH—NH [9,9,10,10-D 4 ,10- 13 C]-melatonin: 5-CH 3 O—C 6 H 3 C(CD 2 13 CD 2 NHCOCH 3 )CH—NH [1,1,1,2,2-D 5 ,1- 13 C]-rivastigmine tartrate: (S)—N-Ethyl-D 5 , 13 C—N-methyl-3-[1-(dimethylamino)ethyl]-phenyl carbamate [16,16,16-D 3 ,16- 13 C 2 ]-rivastigmine tartrate (S)—N-Ethyl-N-methyl-3-[1-(dimethylamino-D 3 , 13 C)ethyl]-phenyl carbamate [13,13,13,12-D 4 ,13- 13 C]-rivastigmine tartrate (S)—N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl-D 4 , 13 C]-phenyl carbamate [13,13,13,12-D 4 ,12- 13 C]-rivastigmine tartrate (S)—N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl-D 4 , 13 C]-phenyl carbamate [16,16,16,15,15,15-D 6 ,15,16- 13 C 2 ]rivastigmine tartrate (S)—N-Ethyl-N-methyl-3-[1-(dimethylamino-D 6 , 13 C 2 )ethyl]-phenyl carbamate [3,3-D 2 ,3- 13 C]-rasagiline (R)—N-(D 2 -prop-2-ynyl)-2,3-dihydro-1H-inden-1-amine [14,14,14-D 3 ,14- 13 C]-methylphenidate methyl-[1) 3 , 13 C]phenyl(piperidin-2-yl)acetate [D 18 ,2- 13 C]-methylphenidate D 18 -methyl-[ 13 C]phenyl(piperidin-2-yl)acetate- 13 C [D 18 ,14- 13 C]-methylphenidate D 18 -methyl-[ 13 C]phenyl(piperidin-2-yl)acetate- 13 C [9,9,9-D 3 ,9- 13 C]-amphetamine 1-phenylpropan-2-amine,3,3,3-D 3 ,3- 13 C [9,9,9,1,2,2-D 6 ,1- 13 C]-amphetamine 1-phenylpropan-2-amine,1,1,2,3,3,3-D 6 ,2- 13 C [9,9,9,1,2,2-D 6 ,2- 13 C]-amphetamine 1-phenylpropan-2-amine,1,1,2,3,3,3-D 6 ,1- 13 C [9,9,9,1,2,2,4,5,6,7,8-D 11 ,1- 13 C]-amphetamine 1-phenylpropan-2-amine,D 11 ,2- 13 C [9,9,9,1,2,2,4,5,6,7,8-D 11 ,2- 13 C]-amphetamine 1-phenylpropan-2-amine,D 11 ,1- 13 C [9-D,9- 13 C]—(S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid: 5-OHC 6 H 3 C( 13 CDC(NH 2 )COOH)CHNH [9-D,10- 13 C]—(S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid: 5-OHC 6 H 3 C(CD 13 C(NH 2 )COOH)CHNH [6,4,3,1,9-D 5 ,10- 13 C]—(S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid: 5-OHC 6 D 3 C(CD 13 C(NH 2 )COOH)CDNH [6,4,3,1,9-D 5 ,8- 13 C]—(S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid: 5-OHC 6 D 3 13 C(CDC(NH 2 )COOH)CDNH [3,4,4,5,5-D 5 ,3- 13 C]-2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid: + NH 2 —C(NH 2 )NHCD 2 CD 2 13 CDC(NH 2 )CO 2 H [3,4,4,5,5-D 5 ,4- 13 C]-2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid: + NH 2 ═C(NH 2 )NHCD 2 13 CD 2 CDC(NH 2 )CO 2 H [3,4,4,5,5-D 5 ,5- 13 C]-2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid: + NH 2 ═C(NH 2 )NH 13 CD 2 CD 2 CDC(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,2- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid + NH 2 C(NH 2 )NCDCD 2 CD 2 13 CD(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,3- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid + NH 2 C(NH 2 )NCDCD 2 13 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,4- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid + NH 2 C(NH 2 )NCD 13 CD 2 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,4- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid + NH 2 C(NH 2 )N 13 CDCD 2 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,5- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid: + NH 2 C(NH 2 )N 13 CDCD 2 CD 2 CD(NH 2 )CO 2 H
[0163] including any metabolite, salt or derivative thereof.
[0164] In some embodiments a neurochemical agent of the invention is in a hyperpolarized state.
[0165] As noted above in order to acquire an NMR signal of a particular nucleus of a compound there has to be a significant difference between the spin population energy levels of said nucleus. The strength of the NMR signal is linearly dependent on the number of nuclei at the low energy level. The difference between the population of a nucleus at high and low nuclear energy levels is the “polarization” of the nuclei, which is defined as P=CB 0 /T, where C is a nucleus specific constant, B 0 is the magnetic field strength, and T is the absolute temperature. Under thermal equilibrium conditions, the polarization is relatively low thereby resulting in a very weak signal under standard clinical MRI scanners (at body temperature of about 37° C. for a magnetic field of 1.5 T, P (for 1 H)≈5×10 −6 ratio and P (for 13 C)≈×10 −6 ratio).
[0166] In order to increase the polarization of a specific nucleus in a compound consequently creating an artificial, non-equilibrium distribution of the spin population of a nucleus, i.e. a “hyperpolarized” state, where the spin population difference is increased by several orders of magnitudes compared with the thermal equilibrium, the hyperpolarized state can be created ex vivo by means of dynamic nuclear polarization (DNP) techniques, such as the Overhauser effect, in combination with a suitable free radical (e.g. TEMPO and its derivatives). Hyperpolarization may also be performed ex-vivo using the Para-hydrogen Induced Polarization technique, and ortho-deuterium induced polarization. Ex-vivo hyperpolarization may also be performed by interaction with a metal complex and reversible interaction with para-hydrogen without hydrogenation of the organic molecule. These techniques have been described in U.S. Pat. No. 6,466,814, U.S. Pat. No. 6,574,495, and U.S. Pat. No. 6,574,496, and in Adams R. W. et al. (Science, 323, 1708-1711, 2009), the contents of which are incorporated herein by reference.
[0167] Ex vivo hyperpolarization of a compound of the invention is performed in order to reach a level of polarization sufficient to allow a diagnostically effective contrast enhancement of said agent. In some embodiments, said level of hyperpolarization may be at least about a factor of 2 above the thermal equilibrium polarization level at the magnetic field strength at which the MRI is performed. In some embodiments, said level of hyperpolarization is at least about a factor of 10 above the thermal equilibrium polarization level at the magnetic field strength at which the MRI is performed. In other embodiments, said level of hyperpolarization is at least about a factor of 100 above the thermal equilibrium polarization level at the magnetic field strength at which the MRI is performed. In yet further embodiments, said level of hyperpolarization is a factor of at least about 1000 above the thermal equilibrium polarization level at the magnetic field strength at which the MRI is performed. In other embodiments said level of hyperpolarization is a factor of at least about 10000 above the thermal equilibrium polarization level at the magnetic field strength at which the MRI is performed. In further embodiments said level of hyperpolarization is a factor of at least 100000 above the thermal equilibrium polarization level at the magnetic field strength at which the MRI is performed.
[0168] A hyperpolarized neurochemical agent of the invention comprises nuclei capable of emitting magnetic resonance signals in a magnetic field (e.g. nuclei such as 13 C and 15 N) and capable of exhibiting T 1 relaxation times between about 5 to 500 sec (at standard MRI conditions such as for example at a field strength of 0.01-5 T and a temperature in the range 20-40° C.). In some embodiments, said hyperpolarized neurochemical agent of the invention has T 2 relaxation times of 13 C nucleus of between about 10 to 10,000 msec.
[0169] In other one of its aspects the invention provides a neurochemical agent of the invention for use in the manufacture of a composition for diagnosing and evaluating a condition or disease.
[0170] The term “diagnosing and evaluating a condition or disease” is meant to encompass any process of investigating, identifying, recognising and assessing a condition, disease or disorder of the mammalian body (including its brain). A diagnosis according to the present invention using a neurochemical agent of the invention includes, but is not limited to the objective quantitative diagnosis of a condition or disease, prognosis of a condition or disease, genetic predisposition of a subject to have a condition or disease, efficacy of treatment of a therapeutic agent administered to a subject (either continually or intermittently), quantification of neuronal function, diagnosis and evaluation of a psychiatric, neurodegenerative, and neurochemical diseases and disorders, affirmation of a therapeutic agent activity, determination of drug efficacy, strategic planning of the location of deep brain stimulation electrodes and other neurostimulators, characterization of masses, tumors, cysts, blood vessel abnormalities, and internal organ function; quantification of brain, kidney, liver, and other organs' metabolic function; evaluation and determination of the level of anesthesia, comatose states, and the brain regions affected by stroke or trauma and their penumbra, kidney, liver, and muscle function, examination of the action, response or progress of therapy (involving medicinal and non-medicinal treatment) aimed at alleviating or curing psychiatric, neurodegenerative, and neurochemical diseases and disorders, selection of patients for clinical trials to allow for homogenous groups of patients in terms of neuromodulator activity, especially when the clinical trial is carried out in order to evaluate the efficacy of drugs that are aimed at modifying the level of neuromodulators in the brain and monitoring neuromodulator activity in laboratory animals and in pre-clinical trials, especially when the clinical trial is carried out in order to evaluate the efficacy of drugs that are aimed at modifying the levels of neuromodulators in the brain.
[0171] In some embodiments said condition or disease is selected from the following non-limiting list: Alzheimer's disease, Parkinson's diseases, depression, brain injury, dementia, mild cognitive impairment, affective disorders, serotonin syndrome (or hyperserotonemia), neuroleptic malignant syndrome, schizophrenia, addiction, atherosclerosis, and cancer (including brain cancer breast cancer, prostate cancer, pancreatic cancer, ovary cancer, lymphoma and kidney cancer).
[0172] The invention further provides a use of a neurochemical agent of the invention for the preparation of a composition for diagnosing and evaluating a condition or disease. The invention further provides a use of a neurochemical agent of the invention for diagnosing and evaluating a condition or disease.
[0173] In another one of its aspects the invention provides a use of a neurochemical agent comprising an isotopically labeled carbon atom directly bonded to at least one deuterium atom for the manufacture of a composition for diagnosing and evaluating a condition or disease. In a further aspect the invention provides a use of a neurochemical agent comprising an isotopically labeled carbon atom directly bonded to at least one deuterium atom for diagnosing and evaluating a condition or disease.
[0174] In some embodiments of the use of a neurochemical agent of the invention, said neurochemical agent is selected from a group consisting of: choline, betaine, acetylcholine, aspartate, N-acetylaspartate, L-DOPA, dopamine, norepinephrine, epinephrine, homovanillic acid (HVA), 3-O-methyldopamine (3OMD), 3-O-methylnorepinephrine (3OMN), 3-O-methylepinephrine (3OME), dopaquinone, vanillylmandelic acid (VMA), 5-hydroxyindole acetaldehyde (5-HIA), 5-Hydroxyindole acetic acid (5-HIAA), melatonin, rivastigmine tartrate, rasagiline (N-propargyl-1-(R)aminoindan), amphetamine (alpha-methyl-phenethylamine), methylphenidate (methyl 2-phenyl-2-(2-piperidyl)acetate), (2-hydroxyethenyl)trimethylammonium, (S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid, (5)-2-amino-3-(3,4-dihydroxyphenyppropenoic acid, L-citrulline, 2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid, 2-amino-5-(diaminomethylidene imino)pentanoic acid, aspartatic acid, creatine, L-tyrosine, L-tryptophan, 5-hydroxy-tryptophan, 5-hydroxy-tryptamine (5-HT, serotonin), glutamic acid, gamma-aminobutyric acid and L-arginine.
[0175] In other embodiments a use according to the invention relates to neurochemical agents selected from the following list:
[1,1,2,2-D 4 ,2- 13 C]-choline; [1,1,2,2-D 4 ,1- 13 C]-choline; [1,2-D 2 ,1- 13 C]-choline; [1,2-D 2 ,2- 13 C]-choline; [D 13 ,1- 13 C]-choline; [D 13 ,2- 13 C]-choline; [1,2-D 2 ,2- 13 C, trimethylamine-D 9 ]-choline; [1,2-D 2 ,1- 13 C, trimethylamine-D 9 ]-choline; [2- 13 C,2,2,3,3,3-D 5 ]-betaine; [2- 13 C,2,2-D 2 ]-betaine; [1,1,2,2-D 4 ,2- 13 C]-acetylcholine; [7,7,8-D 3 ,7- 13 C]-L-tyrosine; [7,7,8-D 3 ,7- 13 C]-tyrosine; [7,7,8-D 2 ,7- 13 C]-L-DOPA; [7,7,8-D 3 ,8- 13 C]-L-DOPA; [2,5,6,7,7,8-D 6 ,8- 13 C]-L-DOPA; [2,5,6,7,7,8-D 6 ,7- 13 C]-L-DOPA; [2,5,6,7,7,8-D 6 ,7,8- 13 C 2 , ring- 13 C 6 ]-DOPA; [5,6,2,7,7,8,8-D 7 , 13 C 6 ]-dopamine; [1,2-D 2 ,1- 13 C]-(2-hydroxyethenyl)trimethylammonium; [1,2,D 2 ,2- 13 C]-(2-hydroxyethenyl)trimethylammonium; [7-D,7- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid; [7-D,8- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid; [6,5,2,7-D 4 ,8- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid; [6,5,2,7-D 4 ,7- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid; [6,5,2,7-D 4 ,1- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid; [1,2,2-D 3 ,1- 13 C]-aspartate: HOOC- 13 CD(NH 2 )CD 2 COOH [1,2,2-D 3 ,2- 13 C]-aspartate: HOOC-CD(NH 2 )— 13 CD 2 COOH [1,2-D 2 ,1,2- 13 C]-aspartate: HOOC- 13 CD(NH 2 )— 13 CDHCOOH [6,6,6-D 3 ,6- 13 C]-N-acetylaspartate: HOOCCH(NH(CO 13 CD 3 ))CH 2 COOH [1,2,2-D 3 ,1- 13 C]-N-acetylaspartate: HOOC 13 CD(NH(COCH 3 ))CD 2 COOH [2,2-D 2 ,2- 13 C]-creatine: H 2 N + C(NH 2 )N(CH 3 ) 13 CD 2 CO 2 [2,2-D 2 ,2,6- 13 C 2 ,6,6,6-D 3 , 15 N]-creatine: H 2 N + C(NH 2 ) 15 N( 13 CD 3 ) 13 CD 2 CO 2 − [2,2-D 2 ,2,6- 13 C 2 ,6,6,6-D 3 ]-creatine: H 2 N + C(NH 2 )N( 13 CD 3 ) 13 CD 2 *CO 2 − [2,3,3,4,4,5,5-D 7 ,2- 13 C]-arginine: + NH 2 C(NH 2 )NHCD 2 CD 2 CD 2 13 CD(NH 2 ) CO 2 H [2,3,3,4,4,5,5-D 7 ,3- 13 C]-arginine: + NH 2 C(NH 2 )NHCD 2 CD 2 13 CD 2 CD(NH 2 ) CO 2 H [2,3,3,4,4,5,5-D 7 ,4- 13 C]-arginine: + NH 2 C(NH 2 )NHCD 2 13 CD 2 CD 2 CD(NH 2 ) CO 2 H [2,3,3,4,4,5,5-D 7 ,5- 13 C]-arginine: + NH 2 C(NH 2 )NH 13 CD 2 CD 2 CD 2 CD(NH 2 ) CO 2 H [2,3,3,4,4,5,5-D 7 ,2- 13 C]-citrulline: NH 2 CONHCD 2 CD 2 CD 2 13 CD(NH 2 )CO 2 H [2,3,3,4,4,5,5-D 7 ,3- 13 C]-citrulline: NH 2 CONHCD 2 CD 2 13 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5,5-D 7 ,4- 13 C]-citrulline: NH 2 CONHCD 2 13 CD 2 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5,5-D 7 ,5- 13 C]-citrulline: NH 2 CONH 13 CD 2 CD 2 CD 2 CD(NH 2 )CO 2 H [9,9,10-D 3 ,10- 13 C]-L-tryptophan: C 6 H 4 C(CD 2 - 13 CD(NH 2 )COOH)CH—NH [9,10-D 2 ,10- 13 C]-L-tryptophan: C 6 H 4 C(CDH- 13 CD(NH 2 )COOH)CH—NH [9,9,10-D 3 ,9- 13 C]-L-tryptophan: C 6 H 4 C( 13 CD 2 -CD(NH 2 )COOH)CH—NH [9,9,10-D 3 ,10- 13 C]-5-hydroxy-tryptophan: 5-OH—C 6 H 3 C(CD 2 - 13 CD(NH 2 )COOH)CH—NH [9,10-D 2 ,10- 13 C]-5-hydroxy-tryptophan: 5-OH—C 6 H 3 C(CDH- 13 CD(NH 2 )COOH)CH—NH [9,9,10-D 3 ,9- 13 C]-5-hydroxy-tryptophan: 5-OH—C 6 H 3 C( 13 CD 2 -CD(NH 2 )COOH)CH—NH [9,9,10,10-D 4 ,10- 13 C]-serotonin: 5-OH—C 6 H 3 C(CD 2 - 13 CD 2 (NH 2 )CH—NH [9,10-D 2 ,10- 13 C]-serotonin: 5-OH—C 6 H 3 C(CDH- 13 CDH(NH 2 )CH—NH [9,9,10,10-D 4 ,9- 13 C]-serotonin: 5-OH—C 6 H 3 C( 13 CD 2 -CD 2 (NH 2 )CH—NH [2,2,3,3,4-D 5 ,2- 13 C]-glutamate: HOOC 13 CD 2 CD 2 CD(NH 2 )COOH [2,2,3,3,4-D 5 ,3- 13 C]-glutamate: HOOCCD 2 13 CD 2 CD(NH 2 )COOH [2,2,3,3,4-D 5 ,4- 13 C]-glutamate: HOOC 13 CD 2 CD 2 13 CD(NH 2 )COOH [2,2,3,3,4-D 5 ,5- 13 C]-glutamate: HOOCCD 2 CD 2 CD(NH 2 ) 13 COOH [2,2,3,3,4-D 5 ,1- 13 C]-glutamate: HOO 13 CCD 2 CD 2 CD(NH 2 )COOH [2,2,3,3,4,4-D 6 ,2- 13 C]-gamma-aminobutyric acid: H 2 N-CD 2 -CD 2 13 CD 2 -COOH [2,2,3,3,4,4-D 6 ,3- 13 C]-gamma-aminobutyric acid: H 2 N-CD 2 - 13 CD 2 -CD 2 -COOH [2,2,3,3,4,4-D 6 ,4- 13 C]-gamma-aminobutyric acid: H 2 N- 13 CD 2 -CD 2 -CD 2 -COOH [5,6,2,7,8,8-D 6 , 13 C 6 ]-norepinephrine: 3-HO-,4HO— 13 C 6 D 3 CD(OH)CD 2 -NH 2 (phenyl- 13 C 6 ) [5,6,2,7,8,8-D 6 , 13 C 6 ]-epinephrine: 3-HO-,4HO— 13 C 6 D 3 CD(OH)CD 2 -NH(CH 3 ) (phenyl- 13 C 6 ) [9,9,9-D 3 ,9- 13 C]-epinephrine: 3-HO-,4HO—C 6 H 3 CH(OH)CH 2 —NH( 13 CD 3 ) (phenyl- 13 C 6 ) [5,6,2,7-D 4 , 13 C 6 ]-VMA: 3-HO-,4HO— 13 C 6 D 3 CD(OH)CO 2 H (phenyl- 13 C 6 ) [5,6,2,7-D 4 ,7- 13 C]-VMA: 3-HO-,4HO—C 6 D 3 13 CD(OH)CO 2 H [5,6,2,7,7-D 5 , 13 C 6 ]-HVA: 3-HO-,4HO— 13 C 6 D 3 CD 2 CO 2 H (phenyl- 13 C 6 ) [5,6,2,7,7-D 5 ,7- 13 C]-HVA: 3-HO-,4HO—C 6 D 3 13 CD 2 CO 2 H [5,6,2,7,7,8,8,9,9,9-D 10 , 13 C 6 ]-3OMD: 3-CD 3 O-,4HO— 13 C 6 D 3 CD 2 CD 2 NH 2 (phenyl- 13 C 6 ) [5,6,2,7,7,8,8,9,9,9-D 10 ,9- 13 C]-3OMD: 3-CD 3 O-,4HO— 13 C 6 D 3 CD 2 CD 2 NH 2 (3-O-methyl- 13 C) [5,6,2,9,9,9,7,8,8-D 9 ,9,7- 13 C 2 ]-3OMN: 3- 13 CD 3 O-,4HO—C 6 D 3 13 C 3 CD(OH)CD 2 NH 2 [9,9,9,10,10,10,2,5,6,7,8,8-D 6 ,9,7,10- 13 C 2 ]-3OME: 3-CD 3 O-,4HO—C 6 D 3 CD(OH)CD 2 NH(CD 3 ) [2,5,6,7,7,8-D 6 ,8- 13 C]-dopaquinone: 30-,40-C 6 D 3 CD 2 13 CD(NH 2 )COOH [2,5,6,7,7,8-D 6 ,7- 13 C]-dopaquinone: 30-,40-C 6 D 3 13 CD 2 CD(NH 2 )COOH [9,9,-D 2 ,9- 13 C]-5-HIA: 5-OH—C 6 H 3 C( 13 CD 2 CHO)CH—NH [9,9,-D 2 ,9- 13 C]-5-HIAA: 5-OH—C 6 H 3 C( 13 CD 2 CO 2 H)CH—NH [13,13,13,9,9,10,10,12,12,12-D 10 ,9,12,13- 13 C]-melatonin: 5- 13 CD 3 O—C 6 H 3 C( 13 CD 2 CD 2 NHCO 13 CD 3 )CH—NH [13,13,13,9,9,10,10,12,12,12-D 10 ,10,12,13- 13 C]-melatonin: 5-CD 3 O—C 6 H 3 C(CD 2 13 CD 2 NHCO 13 CD 3 )CH—NH [9,9,10,10-D 4 ,9- 13 C]-melatonin: 5-CH 3 O—C 6 H 3 C( 13 CD 2 CD 2 NHCOCH 3 )CH—NH [9,9,10,10-D 4 ,10- 13 C]-melatonin: 5-CH 3 O—C 6 H 3 C(CD 2 13 CD 2 NHCOCH 3 )CH—NH [1,1,1,2,2-D 5 ,1- 13 C]-rivastigmine tartrate: (S)—N-Ethyl-D 5 , 13 C—N-methyl-3-[1-(dimethylamino)ethyl]-phenyl carbamate [16,16,16-D 3 ,16- 13 C]-rivastigmine tartrate (S)—N-Ethyl-N-methyl-3-[1-(dimethylamino-D 3 , 13 C)ethyl]-phenyl carbamate [13,13,13,12-D 4 ,13- 13 C]-rivastigmine tartrate (S)—N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl-D 4 , 13 C]-phenyl carbamate [13,13,13,12-D 4 ,12- 13 C]-rivastigmine tartrate (S)—N-Ethyl-N-methyl-3-[1-(dimethylamino)ethyl-D 4 , 13 C]-phenyl carbamate [16,16,16,15,15,15-D 6 ,15,16- 13 C 2 ]-rivastigmine tartrate (S)—N-Ethyl-N-methyl-3-[1-(dimethylamino-D 6 , 13 C 2 )ethyl]-phenyl carbamate [3,3-D 2 ,3- 13 C]-rasagiline (R)—N-(D 2 -prop-2-ynyl)-2,3-dihydro-1H-inden-1-amine [14,14,14-D 3 ,14- 13 C]-methylphenidate methyl-[D 3 , 13 C]phenyl(piperidin-2-yl)acetate [D 18 ,2- 13 C]-methylphenidate D 18 -methyl-[ 13 C]phenyl(piperidin-2-yl)acetate- 13 C [D 18 ,14- 13 C]-methylphenidate D 18 -methyl-[ 13 C]phenyl(piperidin-2-yl)acetate- 13 C [9,9,9-D 3 ,9- 13 C]-amphetamine 1-phenylpropan-2-amine,3,3,3-D 3 ,3- 13 C [9,9,9,1,2,2-D 6 ,1- 13 C]-amphetamine 1-phenylpropan-2-amine,1,1,2,3,3,3-D 6 ,2- 13 C [9,9,9,1,2,2-D 6 ,2- 13 C]-amphetamine 1-phenylpropan-2-amine,1,1,2,3,3,3-D 6 ,1- 13 C [9,9,9,1,2,2,4,5,6,7,8-D 11 ,1- 13 C]-amphetamine 1-phenylpropan-2-amine,D 11 ,2- 13 C [9,9,9,1,2,2,4,5,6,7,8-D 11 ,2- 13 C]-amphetamine 1-phenylpropan-2-amine,D 11 ,1- 13 C [9-D,9- 13 C]—(S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid: 5-OHC 6 H 3 C( 13 CDC(NH 2 )COOH)CHNH [9-D,10- 13 C]—(S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid: 5-OHC 6 H 3 C(CD 13 C(NH 2 )COOH)CHNH [6,4,3,1,9-D 5 ,10- 13 C]—(S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid: 5-OHC 6 D 3 C(CD 13 C(NH 2 )COOH)CDNH [6,4,3,1,9-D 5 ,8- 13 C]—(S)-2-amino-3-(5-hydroxy-1H-indol-3-yl)propenoic acid: —OHC 6 D 3 13 C(CDC(NH 2 )COOH)CDNH [3,4,4,5,5-D 5 ,3- 13 C]-2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid: + NH 2 ═C(NH 2 )NHCD 2 CD 2 13 CDC(NH 2 )CO 2 H [3,4,4,5,5-D 5 ,4- 13 C]-2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid: + NH 2 ═C(NH 2 )NHCD 2 13 CD 2 CDC(NH 2 )CO 2 H [3,4,4,5,5-D 5 ,5- 13 C]-2-amino-2-ene-5-(diaminomethylidene amino)pentanoic acid: + NH 2 ═C(NH 2 )NH 13 CD 2 CD 2 CDC(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,2- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid NH 2 C(NH 2 )NCDCD 2 CD 2 13 CD(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,3- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid + NH 2 C(NH 2 )NCDCD 2 13 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,4- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid + NH 2 C(NH 2 )NCD 13 CD 2 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,4- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid + NH 2 C(NH 2 )N 13 CDCD 2 CD 2 CD(NH 2 )CO 2 H [2,3,3,4,4,5-D 6 ,5- 13 C]-2-amino-5-(diaminomethylidene imino)pentanoic acid + NH 2 C(NH 2 )N 13 CDCD 2 CD 2 CD(NH 2 )CO 2 H
[0298] including any metabolite or derivative thereof.
[0299] In another aspect the invention provides a method for diagnosing and evaluating a condition or disease in a subject, said method comprising:
hyperpolarizing a neurochemical agent of the invention comprising at least one isotopically labeled carbon atom directly bonded to at least one deuterium atom; administering to said subject an effective amount of hyperpolarized neurochemical agent; monitoring said hyperpolarized neurochemical agent or any metabolite thereof;
[0303] thereby diagnosing said neurochemical condition or disease.
[0304] The term “monitoring” as used herein is meant to encompass the quantitative and/or qualitative detection and observation of a hyperpolarized neurochemical agent of the invention or its metabolic derivatives administered to said subject. Monitoring may be performed by any non-invasive or invasive imaging method, including, but not-limited to magnetic resonance spectroscopy, magnetic resonance imaging, magnetic resonance spectroscopic imaging, and PET.
[0305] In one embodiment said monitoring is performed by means of magnetic resonance spectroscopy using a magnetic resonance scanner (an MRI scanner). Magnetic resonance signals obtained may be converted by conventional manipulations into 2-, 3- or 4-dimensional data (spatial and temporal) including metabolic, kinetic, diffusion, relaxation, and physiological data.
[0306] In other embodiments, said magnetic resonance spectroscopy is performed using a double tuned 13 C/D RF coil. Due to possible coupling between deuterium nuclei and 13 C-nucleus, the signals 13 C-signals are split, their intensity is diminished and the signal width is broadened. In order to allow visibility of the agent's or its metabolite signals it is sometimes necessary to improve on the line-width of this signal and increase its intensity. This may be achieved by using a double tuned 13 C/ 2 H RF coil that is capable of performing deuterium decoupling during the 13 C acquisition. Various coil design possibilities such as a saddle coil, a birdcage coil, a surface coil, or combinations thereof are suitable for this purpose.
[0307] For example, at 11.8 T, it was shown that the deuterium decoupling led to a 3 fold enhancement in the signal of the carbon-13 at position 2 of [1,1,2,2-D 4 ,2- 13 C]-choline chloride in water. In agreement, the splitting of the signal to a 1:2:3:2:1 multiplet was removed and the overall natural linewidth of this signal (of the split signal envelope) was decreased from about 100 Hz to about 5 Hz. fold.
[0308] Further improvement in the signal intensity may be provided utilizing the 1 H- 13 C NOE effect achieved by proton irradiation in addition to 2 H irradiation, by means of a triple tuned 13 C/ 2 H/ 1 H RF coil that is capable of performing both deuterium and proton decoupling prior to and during the 13 C acquisition. For example, at 11.8 T, proton NOE and decoupling of [1,1,2,2-D 4 ,2- 13 C]-choline was achieved by proton irradiation prior to and during 13 C acquisition. This irradiation led to an increase the signal-to-noise ratio of the 13 C nucleus at position 2 by a factor of two.
[0309] In some embodiments, said subject is administered with consecutive doses of said hyperpolarized neurochemical agent.
[0310] The invention further provides a composition comprising at least one neurochemical agent of the invention. It is noted that said composition may comprise at least one neurochemical agent of the invention in a mixture with pharmaceutically acceptable auxiliaries, and optionally other therapeutic agents. The auxiliaries must be “acceptable” in the sense of being compatible with the other ingredients of the composition and not deleterious to the recipients thereof.
[0311] Compositions administrable to a subject include those suitable for oral, rectal, nasal, topical (including transdermal, buccal, and sublingual), vaginal or parenteral (including subcutaneous, intramuscular, intravenous, and intradermal) administration or administration via an implant. The compositions may be prepared by any method well known in the art of pharmacy. Such methods include the step of bringing in association a neurochemical agent of the invention with any auxiliary agent. The auxiliary agent(s), also named accessory ingredient(s), include those conventional in the art, such as carriers, fillers, binders, diluents, disintegrants, lubricants, colorants, flavoring agents, anti-oxidants, and wetting agents.
[0312] Compositions suitable for oral administration may be presented as discrete dosage units such as pills, tablets, dragees or capsules, or as a powder or granules, or as a solution or suspension. The active ingredient may also be presented as a bolus or paste. The compositions can further be processed into a suppository or enema for rectal administration.
[0313] The invention further includes a composition, as hereinbefore described, in combination with packaging material, including instructions for the use of the composition for a use as hereinbefore described.
[0314] For parenteral administration, suitable compositions include aqueous and non-aqueous sterile injection. The compositions may be presented in unit-dose or multi-dose containers, for example sealed vials and ampoules, and may be stored in a freeze-dried (lyophilized) condition requiring only the addition of sterile liquid carrier, for example water, prior to use. For transdermal administration, e.g. gels, patches or sprays can be contemplated. Compositions or formulations suitable for pulmonary administration e.g. by nasal inhalation include fine dusts or mists which may be generated by means of metered dose pressurized aerosols, nebulizers or insufflators.
[0315] The compounds of the invention may be administered in conjunction with other compounds, including, but not limited to: cholinesterase inhibitors (e.g. rivastigmine), monoamine oxidase inhibitors (e.g. rasagiline), acetylcholine precursors (e.g. choline), dopamine precursor (e.g. L-DOPA), selective serotonin reuptake inhibitors (e.g. fluoxetine), psycostimulants (e.g. methylphenidate), and norepinephrine reuptake inhibitors (e.g. atomoxetine).
[0316] In other embodiments, said diagnosis and evaluation is performed during or after said subject is administered with at least one therapeutic agent.
[0317] In some embodiments said therapeutic agent is selected from the following non-limiting list: cholinesterase inhibitors (e.g. rivastigmine), monoamine oxidase inhibitors (e.g. rasagiline), acetylcholine precursors (e.g. choline), dopamine precursor (e.g. L-DOPA), selective serotonin reuptake inhibitors (e.g. fluoxetine), psycostimulants (e.g. methylphenidate), and norepinephrine reuptake inhibitors (e.g. atomoxetine).
[0318] The invention further provides a kit comprising at least one component containing at least one neurochemical agent of the invention comprising at least one isotopically labeled carbon atom directly bonded to at least one deuterium atom, means for administering said at least one agent and instructions for use.
[0319] In some embodiments, said kit is for use in diagnosing and evaluating a neurochemical condition or disease.
[0320] It is important to note that temporal and spatial distribution of each neurochemical agent of the invention, including its metabolic derivatives, may be quantified by the methods of the invention and may provide markers of a specific brain activity, psychiatric and neurodegenerative diseases or disorders, and therapeutic action and efficacy.
[0321] FIG. 1 depicts the metabolic pathway of the neurochemical agent deuterated-choline to acetylcholine. The carbon-13 nuclei at positions 1 and 2 of the choline molecule can serve as indicators of specific metabolism due to the chemical shift difference of these nuclei in choline and its metabolites. Table 1 shows the major chemical shift differences of 13 C in choline and acetylcholine.
[0000]
TABLE 1
Chemical shift differences of 13 C positions
in choline and acetylcholine.
choline (ppm)
acetylcholine (ppm)
Δδ (ppm)
C 1
56.5
59.2
2.7
C 2
68.3
65.4
2.9
[0322] In Table 2, the carbon-13 (natural abundance) T 1 relaxation times and elongation factors due to two deuteration options possibilities are demonstrated.
[0000]
TABLE 2
Carbon-13 T 1 relaxation times as measured using choline
labeled at specific positions with deuterium (and 13 C at
natural abundance). Ninety five percent confidence intervals are
given for each measurement (in brackets).
T 1 of C1 (sec)
T 1 of C2 (sec)
A
choline Cl −
5.2
4.9
(4.5, 5.9)
(4.4, 5.4)
B
[D 13 ]-choline Br −
32.0
32.9
(28.3, 35.3)
(30.3, 35.3)
C
[1,1,2,2-D 4 ]-choline Cl −
29.1
34.9
(25.1, 33.1)
(26.4, 43.3)
Elongation factor B/A
6.2
6.7
Elongation factor C/A
5.6
7.1
[0323] The data in Table 2 were obtained using a series of inversion recovery studies at 11.8 T which were carried out in order to determine the 13 C T 1 relaxation times of a deuterated choline molecule and of a partially deuterated choline molecule [1,1,2,2-D 4 ]-choline Cr. The T 1 of the trimethyl amine position in the fully deuterated choline molecule was 28 sec, which represented an approximate 8 fold elongation factor compared to the native choline molecule in which the trimethyl amine positions are protonated. An example of such a study on fully deuterated choline is shown in FIG. 2 . Inversion recovery studies were carried out on a 500 MHz scanner (Varian), equipped with a 5 mm double tuned 13 C/ 1 H probe. Carbon-13 signals were detected in these molecules at natural abundance. The number of transitions ranged between 300 to 400 per relaxation delay (r) with a total scanning time of 12 to 67 hours due to a relaxation delay of 130 sec. The data were fitted to the standard inversion recovery equation. The possible effect of concentration on T 1 was investigated in a concentration range of 20 mM to 20M, no significant effect of concentration on T 1 was found in this concentration range. Choline Cl − and [1,1,2,2-D 4 ]-Choline CU were obtained from Sigma-Aldrich (Israel). Choline-D 13 Br − (fully deuterated) was obtained from Cambridge Isotope Laboratories (MA, USA).
[0324] The resulting carbon-13 T 1 relaxation rate increased by 7 to 8 fold (compared to the protonated molecules), reaching a duration of 33 to 35 seconds at the methylene positions. The increase in T 1 obtained for the choline enables their hyperpolarized signals for a longer period of time after the hyperpolarization process. This feature enables the utilization of the choline molecule for neurometabolic studies because it enables visualization of the nuclei that display a large enough chemical shift to enable spectral resolution between substrate and product, in this case between choline and acetylcholine. For metabolism in cancer this feature is also important because it enables spectral resolution between choline and its metabolic products phosphocholine and betaine.
[0325] Indeed the deuteration of choline led to its visibility on hyperpolarized carbon-13 spectroscopy. A single carbon-13 scan of a DNP hyperpolarized D 13 -choline in a 5 mm NMR tube, at 13 C natural abundance showed that all of the three carbon types of the fully deuterated choline are visible with a signal to noise ratio of at least 5:1 in a single scan within 20 sec of the end of the polarization process.
[0326] The T 1 of position 2 in [1,1,2,2-D 4 ,2- 13 C]-choline was further investigated at various magnetic field strengths and temperatures. The liquid state T 1 was measured on a DNP-enhanced liquid state sample at 14.1 T at approx. 37° C. (T 1 =48±2 sec) and at at higher temperatures of between about 40 to about 50° C. (T 1 =56±4 sec).
[0327] In addition, thermal equilibrium T 1 measurement was performed at 9.4 T at 37° C. (T 1 =41 sec). The low field T 1 of [1,1,2,2-D 4 ,2- 13 C]-choline was estimated by placing the enhanced sample in the fringe field of an unshielded 14.1 T magnet (n=2). From this experiment it was concluded that the low field T 1 is long (>40 s) and that the T 1 of the deuterated methylene carbon in choline is less affected by field strength.
[0328] The synthetic routes for achieving a neurochemical agent comprising at least one isotopically labeled carbon bonded to at least one deuterium atom are well known to a skilled artisan in the field of the invention. Non limiting examples of such isotopical labeling (enrichment) of an example neurological agent such as choline include non-hydrogenation dependent (DNP and metal complex) and hydrogenation dependent (PHIP) sensitivity enhancement methods depicted in FIGS. 3A-3C and 4 A- 4 B and 4 D, respectively.
[0329] In FIGS. 3A , 3 B and 3 C the non-hydrogenation dependent (for DNP and metal complex sensitivity enhancement) synthetic process is depicted. In FIGS. 3A and 3B (1-6), choline is synthesized from ethylene glycol labeled with 4 or 6 deuterium nuclei and 1 or 2 carbon-13 nuclei ([D 4 , 13 C]- or [D 4 , 13 C 2 ]- or [D 6 , 13 C]- or [D 6 , 13 C 2 ]-ethylene glycol). Ethylene glycol is reacted with dimethyl amine labeled with D 6 with or without enrichment of 15 N, with or without enrichment of 13 C, under the reaction conditions specified in FIGS. 3A and 3B (120° C. for 3 h). Dimethyl amine hydrochloride is neutralized before use. The following and final step in this reaction is methylation with methyl iodide to form choline. The resulting labeled compounds are depicted. FIG. 3C (1-6) describes the synthesis of choline from 2-bromoethanol labeled with 2 or 4 deuterium nuclei and carbon-13 (e.g. [D 4 ,1- 13 C]- or [D 4 ,2- 13 C]- or [D 4 , 13 C 2 ]-2-bromoethanol) and trimethyl amine (which may be enriched with D 9 or 15 N or 13 C) under anhydrous ether and trimethyl amine excess. In the case trimethyl amine hydrochloride is used in this synthesis, the compound is neutralized before use. These reactions follow protocols which were described in Marsella, J. A., Homogeneously catalyzed synthesis of (3-amino alcohols and vicinal diamines from Ethylene Glycol and 1,2-propanediol. J. Org. Chem. 1987, 52, 467-468; and Walz, D. E.; Fields, M.; Gibbs, J. A., The synthesis of choline and acetylcholine labeled in the ethylene chain with isotopic carbon. J. Am. Chem. Soc. 1951, 73, 2968.
[0330] Condensed trimethylamine (˜8 ml, ˜90 mmol) was reacted with bromoethanol (0.61 ml, 8 mmol) in an acetone/dry ice bath for 1 h and then in an ice bath 1 h. A single product with the 1H and 13 C NMR signal characteristics of choline was obtained. In some embodiments, the synthesis of choline for the purpose of preparing isotopically stabilized product for hyperpolarization, may be achieved by the use of hydrogenation dependant (PHIP) approach relaying on the keto-enol tautomerization of betaine aldehyde as a precursor of choline, as shown in FIG. 3D .
[0331] According to this embodiment, there may be two strategies for the synthesis of such an enol tautomer as a precursor for hyperpolarized choline: 1) hydrogenation of the enol tautomer of betaine aldehyde, which is thermodynamically less stable, by subjecting the equilibrium to conditions that will drive it to the direction of the enol form, and 2) synthesis of a stable enol tautomer of choline where the enol structure is retained by binding of a “protecting” group to the aldehyde's oxygen atom.
[0332] FIG. 4A depicts a general strategy of the first approach. First a choline molecule is oxidized and then a carbon-carbon double bond is hydrogenated. FIG. 4B shows two possibilities for oxidation reactions of choline. The oxidized form of choline exists in a keto-enol equilibrium with the enol form being less abundant. Hydrogenation with para-hydrogen or ortho-deuterium takes place on the less abundant enol form ( FIG. 4A at reactions conditions that favor the reduction of a carbon-carbon double bond versus a carbonyl bond, for example at ambient pressure and temperature and using a Rhodium catalyst such as (COD)(DPPB)Rh(I) BF 4 . The reduction of the enol form drives the equilibrium towards formation of more of the enol form and hydrogentation continues on the enol form. An example of the feasibility of this approach is shown in FIGS. 4B and 4C . First, betaine aldehyde was synthesized. Then, betaine aldehyde was hydrogenated with a hydrogen mixture enriched with para-hydrogen in the presence of a rhodium catalyst to produce hyperpolarized choline signal at approximately 3.6 ppm ( FIG. 4C ).
[0333] Betaine synthesis was carried out according to procedures described by Rhodes, D; Rich, P J; Myers, A C, et al. Determination of betaines by fast-atom-bombardment mass-spectrometry-identification of glycine betaine deficient genotypes of zea-mays. Plant Physiology Volume: 84 Issue: 3 Pages: 781-788 Published: July 1987; and Lehn, J.-M. EP 1 184 359 A1 2002: (dimethylamino)acetaldehyde diethylacetal (2.3 ml, 12.3 mmol, Sigma-Aldrich) was reacted with methyl iodide (0.9 ml, 14.5 mmol) at 70° C. for 5 h. 1 H-NMR showed a single product (A), MS [M + ]: 176.16 m/z. The product of this reaction, (trimethylamino)acetaldehyde diethylacetal iodide (A) underwent Dowex-1-Cl—. 1 H-NMR showed a single product (B), MS [M+]: 176.16 m/z. (0.5 g 2.36 mmol) of B were reacted with 8 ml 10% HCl at 55° C., over night. 1 H-NMR of the product in water showed the hydrate form of betaine aldehyde as a single product. in DMSO a mixture of the aldehyde and hydrate was observed, MS [M-H 2 O + ]: 120.07 (100%), [M+] 102.11 (20%) m/z.
[0334] The second strategy for the synthesis of an enol tautomer as a precursor for hyperpolarized choline involves the synthesis of a stable enol tautomer of choline where the enol structure is retained by binding of a “protecting” group to the aldehyde's oxygen atom. In this way, prior to the hydrogenation reaction, the reactive aldehyde group is protected to avoid interaction with nucleophiles.
[0335] FIG. 4D shows an example for the use of a protecting group incorporated to betaine aldehyde. Such a protecting group is designed to leave the molecule upon hydrogenation of the double bond, resulting in the choline molecule. When the hydrogen used for hydrogenation is enriched with either para-hydrogen or ortho-deuterium, the resulting choline possesses an increased spin order that is then transferred to the adjacent carbon-13.
[0336] Another exemplary neurochemical agent is L-DOPA. FIG. 5 shows the metabolic pathway of L-DOPA to dopamine. Table 3 shows the major 13 C chemical shift differences between similar positions in L-DOPA and dopamine.
[0000]
TABLE 3
The chemical shift differences between similar
carbon positions in L-DOPA and dopamine.
L-DOPA
dopamine
δ/ppm
δ/ppm
Δδ
C1
129.08
132.09
3.01
C2
119.52
119.41
0.11
C3
147.08
147.17
0.09
C4
146.44
145.96
0.48
C5
119.93
119.46
0.47
C6
124.77
124.04
0.73
C7
37.71
34.96
2.75
C8
57.09
43.75
13.34
C9
174.90
—
—
[0337] The chemical shifts shown in Table 3 demonstrate that positions 1, 2, and 3 of L-DOPA and dopamine allow for metabolic resolution between L-DOPA and dopamine.
[0338] Inversion recovery studies were carried out on protonated L-DOPA and dopamine and partially deuterated dopamine a in order to determine the 13 C T 1 relaxation times in these molecules. The inversion recovery studies were carried out on a 500 MHz scanner (Varian), equipped with a 5 mm double tuned 13 C/ 1 H probe. Carbon-13 signals were detected in these molecules at natural abundance. The number of transitions ranged between 300 to 400 per relaxation delay (t) with a total scanning time of 12 to 48 hours. Dopamine HCl and L-DOPA were obtained from Sigma-Aldrich (Israel). [1,1,2,2-D 4 ]-Dopamine HCl, and [D 3 -ring, 2,2-D 2 ]-Dopamine were obtained from Cambridge Isotope Laboratories (MA, USA).
[0339] The results of the inversion recovery studies for carbon positions 1, 2, and 3 in the L-DOPA and dopamine molecule are summarized in Table 4. Despite the comparable elongation factor to the choline molecule, the T 1 values of the methylene positions in dopamine remain below 10 sec and therefore partially deuterated dopamine appears to be unsuitable for use as an injectable hyperpolarized contrast agents in itself.
[0000]
TABLE 4
13 C T 1 relaxation times
T 1 of C 1
T 1 of C 2
T 1 of C 3
(sec)
(sec)
(sec)
A
dopamine HCl
1.1
1.0
6.4
(0.6, 1.3)
(0.2, 2.0)
(4.7, 8.1)
B
[1,1,2,2-D 4 ]-dopamine HCl
8.7
9.3
6.3
(equivalent to 7,7,8,8,-D 4 ]-
(8.2, 9.1)
(8.6, 10.1)
(6.2, 6.4)
dopamine HCl in the current
document)
C
[D 3 ring,2,2-D 2 ]-dopamine
1.0
4.4
5.4
HCl
(0.7, 1.0)
(1.3, 7.4)
(2.2, 8.6)
(equivalent to D 3 ring,7,7-
D 2 ]-dopamine HCl in the
current document)
D
L-DOPA (non deuterated)
2.3
2.3
3.9
(0.7, 4.0)
(0.6, 4.0)
(2.3, 5.3)
Elongation factor B/A
7.9
9.3
1.0
Elongation factor C/A
1.0
4.4
0.8
[0340] T 1 values of additional deuterated compounds showed different T 1 elongation factor and overall T 1 values, For example:
[0000] 1) the compound [2,3,3,4,4,5,5-D 7 ]-arginine: NH 2 C(NH)NHCD 2 CD 2 CD 2 CD(NH 2 )CO 2 H showed a T 1 of carbons at positions 2, 3, 4, and 5 that is not much greater than 8 sec.
2) The compound [D 7 ]-L-tryptophan: C 6 D 4 C(CD 2 -CD(NH 2 )COOH)CH—NH was dissolved in H 2 O and 15% D 2 O (54.5 mM) and showed a T 1 of position 10 that is close to 13 sec at 11.8 T.
BRIEF DESCRIPTION OF THE DRAWINGS
[0341] In order to understand the invention and to see how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:
[0342] FIG. 1 shows the metabolic pathway of the neurological agent choline to acetylcholine.
[0343] FIG. 2 shows the 13 C inversion recovery study of fully deuterated choline.
[0344] FIGS. 3A-3C show a non-hydrogenation dependent (for DNP and metal complex sensitivity enhancement) synthetic process of choline.
[0345] FIG. 3D illustrates the equilibrium between keto-enol tautomers of betaine aldehyde and hydrogenation reaction on the enol tautomer which results in the synthesis of choline.
[0346] FIGS. 4A-4D depicts the general hydrogenation dependant (PHIP) labeling of choline via oxidation of choline to betaine aldehyde ( FIG. 4A ); two possibilities for oxidation reaction of choline ( FIG. 4B ); the result of a PHIP study on betaine aldehyde ( FIG. 4C ) which demonstrates the appearance of a hyperpolarized signal at about 3.8 ppm on a proton spectrum at 11.8 T; and strategies for protecting group incorporation to form a stable enol form of choline ( FIG. 4D ).
[0347] FIG. 5 shows the metabolic pathway of L-DOPA to dopamine.
[0348] FIG. 6 shows the 13 C spectra of the head of a male mouse, 14 weeks old, administered with a dose of 30 mg/kg (200 microliter injected volume) of hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline after treatment with atropine (1 mg/kg) and eserine (0.1 mg/kg), 30 min prior to a hyperpolarized choline injection. The spectra were recorded with a high power pulse (maximal signal intensity achieved with this coil).
[0349] FIG. 7 shows the 13 C spectra of the head of a male mouse, 14 weeks old, administered with at a dose of 30 mg/kg (200 microliter injected volume) of hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline after treatment with atropine (1 mg/kg) and eserine (0.1 mg/kg), 30 min prior to a hyperpolarized choline injection. The spectra were recorded with a low power pulse (⅓ of the maximal signal intensity achieved with this coil).
[0350] FIG. 8 shows the 13 C spectra of the head of a male mouse, 8 weeks old, administered with a dose of about 30 mg/kg (about 2.5 ml injected) of hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline treated with atropine (1 mg/kg) and eserine (0.1 mg/kg), 30 min prior to a hyperpolarized choline injection. The spectra were recorded with a low power pulse (⅙ of the maximal signal intensity achieved with this coil).
[0351] FIG. 9 shows the 13 C spectra of the head of a male mouse, 8 weeks old, administered with a dose of 46 mg/kg (about 2.5 ml injected) of hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline treated with atropine (1 mg/kg) and eserine (0.1 mg/kg), 30 min prior to a hyperpolarized choline injection. The spectra were recorded with a low power pulse (⅙ of the maximal signal intensity achieved with this coil).
[0352] FIG. 10 shows the 13 C spectra of the head of a male mouse, 8 weeks old, administered with a dose of 52 mg/kg (about 2.5 ml injected) of hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline treated with atropine (1 mg/kg), 46 min prior to a hyperpolarized choline injection. The first spectrum was recorded with a low power pulse (⅙ of the maximal signal intensity achieved with this coil, the rest of the spectra were recorded with higher power pulse (maximal signal achieved with this coil).
[0353] FIG. 11 shows the synthesis of [7,8-D 2 ]-L-DOPA with protecting groups (BW-33) by hydrogenation of MADP with D 2
[0354] FIG. 12 shows a process for the removal of protecting groups from BW-33 molecule.
[0355] FIG. 13 shows a reaction with of MADP with D 2 in the presence of a PHIP catalyst.
DETAILED DESCRIPTION OF EMBODIMENTS
[0356] The invention is illustrated by the following Examples in a non-limiting manner:
Example 1
Acetylcholine Synthesis in the Brain
[0357] Optional initial step: The subject is pretreated with atropine prior to choline injection to prevent cholinergic intoxication.
[0358] [1,1,2,2-D 4 ,2- 13 C]-choline is dissolved in 50:50 DMSO:D 2 O containing a trityl radical at 1, or 5, or 10, or 15, or 20, or 25 mM. The mixture is placed in an open top chamber.
[0359] The mixture is polarized by microwaves for at least one hour at a field of 2.5 T at a temperature of 4.2 K (or lower). According to the previously published procedure (Ardenkjaer-Larsen, J. (2001) U.S. Pat. No. 6,278,893).
[0360] When a suitable level of polarization has been reached, the chamber is rapidly removed from the polarizer and, while handled in a magnetic field of no less than 50 mT, the contents are quickly discharged and dissolved in warm saline (40° C., 5 ml).
[0361] The solution containing the polarized [1,1,2,2-D 4 ,2- 13 C]-choline (2, or 3, or 4, 5 ml, or more, the HTNC) is injected to the subject via intravenous catheter that is placed in advance.
[0362] The hyperpolarized solution is followed by 20 ml of saline or another routine wash volume.
[0363] Experiment 1
[0364] Step 1) An anatomic image of the brain is recorded beforehand and the location of the hippocampus is prescribed.
[0365] Step 2) One s, or 2 s, or 3 s, or 4 s, or 5 s, or 6 s, or 10 s, or 15 s, or 20 s, or 40 s, or 60 s after injection, a carbon-13 spectrum is recorded from a 1×1×1 cm 3 (or 0.5×0.5×0.5 cm 3 , or 0.2×0.2×0.2 cm 3 , or 2×2×2 cm 3 ), voxel (single voxel spectroscopy) located at the subject's hippocampus.
[0366] Step 3) The spectrum is Fourier transformed and the level of [1,1,2,2-D 4 ,2- 13 C]-choline and [1,1,2,2-D 4 ,2- 13 C]-acetylcholine in the subject's hippocampus is quantified. Other potential metabolic products of [1,1,2,2-D 4 ,2- 13 C]-choline such as [1,1,2,2-D 4 ,2- 13 C]-betaine, and [1,1,2,2-D 4 ,2- 13 C]-phosphocholine are quantified as well, simultaneously.
[0367] Experiment 2
[0368] Experiment 1 is repeated at a different location in the brain, for example the frontal lobe.
[0369] Experiment 3
[0370] Experiments 1 or 2 performed, with step 2 including a spectroscopic imaging sequence, sampling a slice in the brain at a selected level. The in plane resolution of the spectroscopic image is 0.2 cm, or 0.4 cm, or 0.5 cm, 1 cm, 2 cm, or 3 cm.
[0371] The slice thickness is 0.2 cm, or 0.4 cm, or 0.5 cm, or 1 cm, 2 cm, 5 cm, or 10 cm.
[0372] Alternatively, a multislice spectroscopic imaging sequence can be applied to sample the entire brain.
[0373] Experiment 4
[0374] Experiments 1 or 2 or 3 are performed on a group of 3, 5, 10, or 50, or 100 animals (for example, mice, rats, rabbits, mini-pigs, or pigs).
[0375] The experiment is repeated on the same group of animals (a few days later) or on a different group of animals, this time while the animals receive a drug that is aimed at modifying the acetylcholine level in the brain, for example, a novel or well-known acetylcholine esterase inhibitor therapy.
[0376] The individual and the average rate of choline uptake and acetylcholine synthesis in the normal animal brain are calculated, and drug efficacy is determined.
[0377] Alternatively, the experiment is carried out on the group of animals that have been used to develop an animal model of disease, for example a neurodegenerative disease, for example a one sided lesion to the septo-hippocampal pathway, for example a lesion or transection of the fimbria-formix pathway. By comparing between the animals that serve as animal model of disease and normal healthy animals, or by comparing the lesioned side to the control side in a unilateral disease model, the quality, efficacy, and utility of the animal model is assessed and determined.
[0378] Experiment 5
[0379] Experiments 1 or 2 or 3 or 4 are performed on a group of 3, or 5, or 10, or 50, or 100, or 200, or 500 healthy volunteers who may have no indication of a neurologic or psychiatric disorders and may have no history or current drug addiction or use.
[0380] The individual and the average rate of choline uptake and acetylcholine synthesis in the normal human brain are calculated. The maximal level of synthesized acetylcholine is determined as well. The maximal levels of synthesized betaine and phosphocholine are determined as well.
[0381] The same experiment is performed in a group of patients who are diagnosed with mild cognitive impairment or various degrees of Alzheimer's disease who are not medicated.
[0382] The individual and the average rate of choline uptake and acetylcholine synthesis in the brain within this group of patients as well as the rate of synthesis of betaine and phosphocholine and choline washout rate are calculated. The maximal level of synthesized acetylcholine in these patients is determined as well.
[0383] The same experiment is performed in a group of patients who are receiving a novel drug treatment or an existing acetylcholine esterase inhibitor drug treatment (such as rivastigmine).
[0384] The individual and the average rate of choline uptake and acetylcholine synthesis in the brain within this group of treated patients are calculated.
[0385] By comparison, the drug efficacy in individuals as well as in groups of patients can be determined. Individuals can be monitored routinely at reasonable time durations to confirm continued treatment effectiveness.
[0386] Experiment 6
[0387] Experiments 1 or 2 or 3 or 4 are performed in the same subject or patient, several times trough the day and night, to determine patterns of choline transport and acetylcholine synthesis. The individual's pattern of acetylcholine synthesis and release is used to design an individualized schedule of controlled acetylcholine release from a controlled release device that is implanted in the subject's brain or a controlled release of choline into the brain or circulation.
[0388] Experiment 7
[0389] Experiments 1, or 2, or 3, or 4 are performed in a patient that has been diagnosed with a brain tumor. The level and rate of [1,1,2,2-D 4 ,2- 13 C]-choline transport, [1,1,2,2-D 4 ,2- 13 C]-phosphocholine synthesis, and [1,1,2,2-D 4 ,2- 13 C]-betaine synthesis in the investigated tissue aid in the characterization of the tumor or the malignant potential at the tissue surrounding the tumor, as it is known in the art that choline metabolism is altered in malignant tissues.
[0390] An extension of this experiment is the characterization of tumors in the body, such as tumors in the breast, prostate, and kidney is possible.
Example 2
Dopamine Synthesis in the Brain
[0391] [7,7-D 2 ,8-D,8- 13 C]-L-DOPA (5, or 10, or 15, 20 mg or more) is hyperpolarized and dissolved according to the procedure described in Example 1.
[0392] The subject may be pretreated with a single dose or several doses of aromatic-L-amino-acid decarboxylase inhibitor such as carbidopa or benserazide, or difluoromethyldopa, or α-methyldopa (20 mg, 40 mg, 60 mg, or 80 mg) given orally.
[0393] 1 hour after pretreatment with carbidopa, the hyperpolarized solution (cooled to 37° C. or less), is quickly injected to the subject (preferably in less than 10 sec, or as described in Example 1).
[0394] Experiment 1
[0395] Step 1) Similar to Example 1, Experiment 1, Step 1.
[0396] Step 2) Similarly to Example 1, Experiment 1, Step 2, carbon-13 magnetic resonance spectra are recorded from a single volume element located at a specific location such as the substantia nigra, striatum, basal ganglia, or the thalamus of the subject.
[0397] Step 3) The spectra are Fourier transformed and the levels of [7,7-D 2 ,8-D,8- 13 C]-L-DOPA, [7,7-D 2 ,8-D,8- 13 C]-dopamine, [7,7-D 2 ,8-D,8- 13 C]-homovanillic acid, and [7,7-D 2 ,8-D,8- 13 C]-3-O-methyldopamine and other potential metabolic products of [7,7-D 2 ,8-D,8- 13 C]-L-DOPA, at the specific location, are quantified, simultaneously.
[0398] Experiment 2
[0399] Repeated measurements of the types that are described in Experiment 1, and kinetic analysis as described in Example 1, Experiment 2.
[0400] Experiment 3
[0401] Spectroscopic imaging of the distribution of [7,7-D 2 ,8-D,8- 13 C]-L-DOPA, [7,7-D 2 ,8-D,8- 13 C]-dopamine, and other potential metabolites of [7,7-D 2 ,8-D,8- 13 C]-L-DOPA, as described in Example 1, Experiment 4.
[0402] Experiment 4
[0403] Experiments 1 or 2 or 3 are performed on a group of 3, or 5, or 10, or 50, or 100 animals (for example, rats, rabbits, mini-pigs, pigs).
[0404] The experiment is repeated on the same group of animals (a few days later) or on a different group of animals, this time while the animals receive a drug that is aimed at increasing the dopamine level in the brain, for example, a novel or a well-known monoamine oxidase inhibitor therapy.
[0405] The level of [7,7-D 2 ,8-D,8- 13 C]-dopamine and other [7,7-D 2 ,8-D,8- 13 C]-L-DOPA metabolites in the brain is determined in both groups of animals. The individual and the average rate of [7,7-D 2 ,8-D,8- 13 C]-L-DOPA uptake and [7,7-D 2 ,8-D,8- 13 C]-dopamine synthesis in the naive and treated brain are calculated, and drug efficacy is determined.
[0406] Experiment 5
[0407] Experiments 1 or 2 or 3 are performed on a group of 3, or 5, or 10, or 50, or 100, or 200, or 500 healthy volunteers who may have no indication of a neurologic or psychiatric disorders and may have no history or current drug addiction or use.
[0408] The level of [7,7-D 2 ,8-D,8- 13 C]-dopamine and other [7,7-D 2 ,8-D,8- 13 C]-L-DOPA metabolites in the normal human brain is determined. The individual and the average rate of [7,7-D 2 ,8-D,8- 13 C]-L-DOPA uptake and [7,7-D 2 ,8-D,8- 13 C]-dopamine synthesis in the normal human brain are calculated.
[0409] The same experiment is performed in a group of patients who are diagnosed with Parkinson's disease and who are not medicated.
[0410] The level of [7,7-D 2 ,8-D,8- 13 C]-dopamine and other [7,7-D 2 ,8-D,8- 13 C]-L-DOPA metabolites in the brain of patients with Parkinson's disease is determined. The individual and the average rate of [7,7-D 2 ,8-D,8- 13 C]-L-DOPA uptake and [7,7-D 2 ,8-D,8- 13 C]-dopamine synthesis in the brain within this group of patients are calculated.
[0411] The same experiment is performed in a group of patients who are receiving a novel or well-known monoamine oxidase inhibitor drug treatment (such as rasagiline).
[0412] The level of [7,7-D 2 ,8-D,8- 13 C]-dopamine and other [7,7-D 2 ,8-D,8- 13 C]-L-DOPA metabolites in the treated patients is determined. The individual and the average rate of [7,7-D 2 ,8-D,8- 13 C]-L-DOPA uptake and [7,7-D 2 ,8-D,8- 13 C]-dopamine synthesis in the treated patients are calculated.
[0413] By comparison, the drug efficacy in individuals as well as in groups of patients can be determined. Individuals can be monitored routinely within reasonable time duration to insure drug effectiveness.
[0414] Experiment 6
[0415] Experiments 1 or 2 or 3 are performed in the same subject or patient, several times trough the day and night, to determine patterns of L-DOPA uptake and dopamine synthesis in the individual's brain. The data are used to design a schedule of controlled release of L-DOPA, dopamine, or a drug such as monoamine oxidase inhibitor, from a controlled release device that is implanted in the subject's brain or a controlled release of L-DOPA and carbidopa into the circulation.
[0416] Alternatively, if deep brain stimulation (DBS) is being considered as a therapeutic route, the data are used to aid in determination of the best location for placing DBS electrodes. After placement of DBS electrodes, similar data may be acquired to determine the effects of DBS on dopamine metabolism in other regions in the brain, for example in the substantia nigra.
[0417] Experiment 7
[0418] [7-D,8- 13 C]—(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid or [8- 13 C]-(S)-2-amino-3-(3,4-dihydroxyphenyl)propenoic acid (5, 10, 15, or 20 mg or more) is hydrogenated with a hydrogen gas mixture enriched with parahydrogen or ortho-deuterium in the presence of a hydrogenation catalyst or an asymmetric hydrogenation catalyst. The hydrogenation catalyst is separated from the DOPA product using a filtration column, or molecular size sieve, or phase separation (DOPA is more hydrophilic that most catalysts), within a few seconds. Where both D- and L enantiomers of DOPA are produced, they may be quickly separated (in less than 5 sec). The [7,7-D 2 ,8-D,8- 13 C]-L-DOPA or [7-D,8-D,8- 13 C]-DOPA solution ([D, 13 C]-labeled-L-DOPA) is undergoing magnetic field cycling to transfer the polarization to the 13 C nuclei.
[0419] The subject is pretreated with a single dose or several doses of aromatic-L-amino-acid decarboxylase inhibitor such as carbidopa or benserazide, or difluoromethyldopa, or α-methyldopa (20 mg, 40 mg, 60 mg, or 80 mg) given orally.
[0420] 1 hour after pretreatment with carbidopa, the hyperpolarized [D, 13 C]-labeled-L-DOPA_solution (5 ml, the HTNC) is quickly injected to the subject (preferably in less than 10 sec, or as described in Example 1), via intravenous catheter that is placed in advance. The hyperpolarized solution is followed by 20 ml of saline or another routine wash volume.
[0421] Experiments 1 through 6 in this example (example 2) are performed. The HTNC is the same in both cases; the difference in experiment 7 is that the hyperpolarization step was achieved via hydrogen induced polarization instead of DNP.
Example 3
Dopamine/Acetylcholine Balance in the Brain
[0422] The subject is pretreated with atropine and carbidopa as described in Examples 1 and 2.
[0423] [7,7-D 2 ,8-D,8- 13 C]-L-DOPA (5, 10, 15, 20 mg or more) and [1,1,2,2-D 4 ,2- 13 C]-choline (5, 10, 15, 20 mg or more) are hyperpolarized and dissolved according to the procedure described in Example 1.
[0424] The hyperpolarized solution (cooled to 37° C. or less), is quickly injected to the subject (preferably in less than 10 sec, or as described in Example 1).
[0425] The solution containing the hyperpolarized [7,7-D 2 ,8-D,8- 13 C]-L-DOPA and [1,1,2,2-D 4 ,2- 13 C]-choline (5 ml, the HTNC) is injected to the subject via intravenous catheter that is placed in advance.
[0426] The hyperpolarized solution is followed by 20 ml of saline or another routine wash volume.
[0427] The balance between acetylcholine production and dopamine production and metabolism is quantified in animal models and in the human brain using the experiments that are described above. Specifically, the effects of existing and novel drugs on this balance is investigated and aids in determination of the drug course of action in situ and drug efficacy.
Example 4
In Vivo Carbon-13 Spectroscopy of 1,1,2,2-D 4 ,2- 13 C-Choline
[0428] The compound [1,1,2,2-D 4 ,2- 13 C]-choline was synthesized and showed the following signals on multinuclei NMR spectra: D-NMR: at c.a. 3.3 ppm—a doublet signal (of 2,2-D 2 ), at c.a. 3.9 ppm a singlet signal (of 1,1-D 2 ), at c.a. 4.7 a small signal of natural abundance of HDO in H 2 O. 13 C-NMR: at c.a. 66.8 ppm—a multiplet demonstrating a split signal (of 2- 13 C) due to the close interaction with both 6 deuterons (leading to a split of the signal to five peaks with an intensity ratio of 1:2:3:2:1) and a nitrogen-15 nucleus (leading to a split of the signal to three peaks with a ratio of 1:1:1). 1 H-NMR: at c.a. 3.2 ppm—a singlet signal of the trimethylamine moiety.
[0429] In vivo carbon-13 spectroscopy was carried out following injection of hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline to a mouse (n=2). The spectra showed that hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline, and possibly its metabolites as well, were visible for at least 90 seconds from the end of the polarization process. Further studies in rats (n=3) showed similar results and a visible signal more than 3 minutes after the end of the hyperpolarization process (the dissolution).
[0430] In all of in vitro and in vivo studies, choline was dissolved in 1:1 D 2 O:DMSO-d6 solution, a stable free radical was added prior to freezing, and microwave irradiation was performed at about 94.090 GHz. FIGS. 6 , 7 , 8 , 9 and 10 depict the results of these studies.
[0431] Experiment 1
[0432] A male mouse, 14 weeks old, was treated with atropine (1 mg/kg) and eserine (0.1 mg/kg), 30 min prior to a hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline injection. Hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline was injected at a dose of 30 mg/kg (200 microliter injected volume).
[0433] The bolus injection started approximately 20 seconds after the time of dissolution. The bolus duration was about 20 seconds.
[0434] 13 C spectra of the rat's head were recorded with an 8 mm 13 C surface coil every 5 seconds.
[0435] As shown in FIG. 6 , the first spectrum was recorded 40 seconds after dissolution. The spectra were recorded with a high power pulse (maximal signal intensity achieved with this coil). Exact flip angles are not known due to the inherent B 1 inhomogeneity of a surface coil. The consecutive spectra were processed with exponential multiplication of 30 Hz and phase corrected based on the highest signal (in the first spectrum). Frequency adjustments and zero filling were not applied.
[0436] Experiment 2
[0437] A male mouse, 14 weeks old, was treated with atropine (1 mg/kg) and eserine (0.1 mg/kg), 30 min prior to a hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline injection. Hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline was injected at a dose of 30 mg/kg (200 microliter injected volume).
[0438] The bolus injection started approximately 20 seconds after the time of dissolution. The bolus duration was about 20 seconds.
[0439] 13 C spectra of the rat's head were recorded with an 8 mm 13 C surface coil every 9 seconds.
[0440] As shown in FIG. 7 , the first spectrum was recorded 38 seconds after dissolution. The spectra were recorded with a low power pulse (⅓ of the maximal signal intensity achieved with this coil). Exact flip angles are not known due to the inherent B 1 inhomogeneity of a surface coil. The consecutive spectra were processed with exponential multiplication of 30 Hz and phase corrected based on the highest signal (in the first spectrum). Frequency adjustments and zero filling were not applied.
[0441] Experiment 3
[0442] A male rat, 8 weeks old, was treated with atropine (1 mg/kg) and eserine (0.1 mg/kg), 30 min prior to a hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline injection. Hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline was injected at a dose of about 30 mg/kg (about 2.5 ml injected).
[0443] The bolus injection started 27 seconds after the time of dissolution. The bolus duration was 14 seconds.
[0444] 13 C spectra of the rat's head were recorded with an 8 mm 13 C surface coil every 10 seconds.
[0445] FIG. 8 shows the first spectrum was recorded 55 seconds after dissolution. The spectra were recorded with a low power pulse (⅙ of the maximal signal intensity achieved with this coil). Exact flip angles are not known due to the inherent B 1 inhomogeneity of a surface coil. The consecutive spectra were processed with exponential multiplication of 15 Hz, zero filled to 16384 points, and phase corrected based on the highest signal (in the first spectrum). Frequency adjustments were not applied.
[0446] Experiment 4
[0447] A male rat, 8 weeks old, was treated with atropine (1 mg/kg) and eserine (0.1 mg/kg), 30 min prior to a hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline injection. Hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline was injected at a dose of about 46 mg/kg (about 2.5 ml injected).
[0448] The bolus injection started 22 seconds after the time of dissolution. The bolus duration was 15 seconds.
[0449] 13 C spectrum of the rat's head was recorded with an 8 mm 13 C surface coil every 10 seconds, starting at 44 seconds after dissolution ( FIG. 9 ). The spectra were recorded with a low power pulse (⅙ of the maximal signal intensity achieved with this coil). Exact flip angles are not known due to the inherent B 1 inhomogeneity of a surface coil. The consecutive spectra were processed with exponential multiplication of 60 Hz and phase corrected based on the highest signal (in the second spectrum). Frequency adjustments and zero filling were not applied.
[0450] Experiment 5
[0451] A male rat, 8 weeks old, was treated with atropine (1 mg/kg), 46 min prior to a hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline injection. Hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline was injected at a dose of about 52 mg/kg (about 2.5 ml injected).
[0452] The bolus injection started 30 seconds after the time of dissolution. The bolus duration was 13 seconds.
[0453] 13 C spectrum of the rat's head ( FIG. 10 ) was recorded with a 15 mm 13 C surface coil every 10 seconds, starting at 1 minute and 40 seconds after dissolution. The first spectrum was recorded with a low power pulse (⅙ of the maximal signal intensity achieved with this coil, the rest of the spectra were recorded with higher power pulse (maximal signal achieved with this coil). Exact flip angles are not known due to the inherent B 1 inhomogeneity of a surface coil. The consecutive spectra were processed with exponential multiplication of 15 Hz and phase corrected based on the highest signal (in the second spectrum). Frequency adjustments and zero filling were not applied. In this experiment the signal to noise ratio of the hyperpolarized [1,1,2,2-D 4 ,2- 13 C]-choline in the living rat's head reached a level of about 180:1 almost 2 minutes after the end of the polarization process. This level gradually decayed to about 20:1 ratio, 170 seconds past the end of the polarization process.
Example 5
Hyperpolarizing L-DOPA by Hydrogenation Using Enriched Hydrogen and Synthesis of Deuterated L-DOPA
[0454] The molecule [7,8-D 2 ] L-DOPA was synthesized by hydrogenation of methyl 2-acetamido-3-(3,4-diacetoxyphenyl)-2-propenoate (MADP) with D 2 as described in FIG. 11 . About 200 ml of D 2 were produced by the interaction of 135 mg NaBD 4 with 3 ml D 2 O in the presence of 1% Pt/C for 1 hour and 40 min. MeOH (2.5 ml) was saturated with Ar and combined with 5% Pd/C (11.5 mg) and MADP (97 mg 0.3 mmol), 8 ml of D 2 were consumed by the reaction during 24 h. The protecting groups were removed by acidic reflux as described in FIG. 12 . 46 mg of D 2 -dihydro-MADP (BW-33) were dissolved in 3 ml 3N HCl, 4 h reflux. 36 mg D 2 -L-DOPA for purification was further purified by either Celite filtration or Dowex 50WX4-400 filtration. The D-NMR spectrum of the resulting compound demonstrated the two signals of deuterium at positions 7 and 8 with a 1 ppm difference in chemical shift.
[0455] The MADP molecule was investigated also as a precursor for PHIP reactions to yield hyperpolarized L-DOPA. This was carried out by hydrogenation of MADP with either D 2 or H 2 in the presence of a Rhodium catalyst that is suitable for PHIP reactions, as described in FIG. 13 .
[0456] Experiment 1:
[0457] 25 mg of MADP was reacted with D 2 (about 1 liter) in the presence of 11 mg Rh catalyst in 700 μl CH 3 OH. The deuterium signals at positions 7 and 8 mL-DOPA were identified at approximately 2.05 and 3.15 ppm.
[0458] Experiment 2:
[0459] 25 mg MADP was reacted with H 2 (40 ml) in the presence of 11 mg Rh catalyst in 700 μl CD 3 OD where the last 5 ml injected for PHIP effect. When the reaction was performed with an injection of 5 mL hydrogen mixture enriched with para-hydrogen, a small but distinctive anti-symmetric signal was observed at 3.15 ppm. This signal decayed within less than a minute. These results suggested that indeed the MADP molecule can serve as both a para-hydrogen induced polarization (PHIP) and ortho-deuterium induced polarization (ODIP) precursor for the formation of hyperpolarized L-DOPA. More generally, it is shown that the L-DOPA molecule can be hyperpolarized using a precursor that is comprised of a double bond between positions 7 and 8 and protective groups at the sensitive hydroxy/amine/carboxy groups of the molecule. The protective groups selected here for positions 3, 4, and 8 are expected to hydrolase quickly in the blood, in the case that the hydrogenated MADP is injected to an animal or human subject due to the activity of blood esterase enzymes. The protective group at the amine position can be removed by acidic conditions. Therefore, more generally, the potential utility of the PHIP or OCIP approach for hyperpolarization of L-DOPA is shown using a precursor that is comprised of a double bond between positions 7 and 8 and protective groups that hydrolyze quickly when injected to the blood circulation.
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The invention relates to a neurochemical agent comprising at least one isotopically labeled carbon atom directly bonded to at least one deuterium atom, uses thereof for the manufacture of a composition for diagnosing and evaluating a condition or disease and kits comprising said agent. The invention further encompasses methods for diagnosing and evaluating a condition or disease in a subject utilizing a composition of the invention.
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This application is a continuation-in-part application of Ser. No. 08/835,991, filed on Apr. 11, 1997, now U.S. Pat. No. 5,996,150, This application also claims the benefit of Ser. No. 60/156,345 filed on Mar. 2, 2000.
FIELD OF THE INVENTION
This invention relates to a mobile bed and chair combination for patients in hospitals, nursing homes, or similar health care facilities including the home in which the safe transfer of the patient from a hospital type bed is contemplated by a single healthcare giver.
BACKGROUND OF THE INVENTION
There are various devices known in the art for transporting the disabled from one place to another. The most commonly known is the wheelchair either powered or non-powered. In the hospital and nursing homes, gurneys are used to transfers the patient from one place to another while remaining in a lying or prone position. Often it is necessary to transfer the patient from the hospital bed to a gurney type bed of wheelchair. Studies have shown that upwards to fifty percent of all injuries to either patients or healthcare people have occurred when the patient is being transferred from the bed to a gurney or to a wheelchair. That is, when a patient is transferred from a bed to a wheelchair, the patient must first be raised to a sitting position, rotated so that their feet are over the side of the bed, and then lifted form the bed to the chair. This usually requires three people for a safe transfer, two to lift the patient off the bed, and one to rotate the patient and gently guide him into the chair. Similarly, if the patient is to be transferred from a bed to a gurney, two and sometimes three people are required for a safe transfer, two to lift the patient and one to stabilize the gurney.
Unfortunately, the realities of the healthcare situation in our country and indeed over the world, have stretched the healthcare dollar so thin that many of our provider institutions can no longer provide the necessary personnel to ensure the safe transfer of patients in the above described situations. Instead of the two or three people required to perform the patient transfer, often only one is available. As is often the case, the patient is of a size or weight that is difficult for the healthcare giver to manage by him or herself. The result is either the patient is dropped or the healthcare person sustains a back injury. Such a state of affairs only exacerbates an already strained industry in terms of lost time and money for both the healthcare giver and institution; and the ill will of, or a lawsuit by, the patient should further injury result.
The prior art has attempted to relieve the situation by providing combination wheelchair and bed mechanisms. For example, the patent to Crawford et al, U.S. Pat. No. 5,402,544, discloses a combination chair and gurney which permits one device to operate both as a wheelchair and as a gurney. The object of Crawford et al is to attend to the bodily needs of a disabled person. In Crawford et al, the chair can be converted to a bed and then hand cranked to a height to correspond to a bed height. The mobile bed is then placed adjacent the bed and held stabilized by “elastic bungee cords” connected between the rails of the bed and the Crawford et al device (col. 5 line 25 of Crawford et al). The problem with Crawford et al is that there is still a gap between the two beds, and an uncomfortable obstacle in the form of the rails to negotiate in the patient transfer. Moreover, there is, over time, a very real possibility of the bungee cord breaking with disastrous consequences. Another patent t Ezenwa, U.S. Pat. No. 5,193,633, is designed in particular for paraplegics in a home environment. This patent also shows a chair converting to an adjustable height bed device, and, has a lateral shifting mechanism for use in the wheelchair mode so that the each of reaching over the head by the disabled can be effected. This lateral shifting is stabilized as to the center of gravity by a tilting of the chair toward the center of the wheeled platform. See FIGS. 6 and 7 of Ezenwa. Thus, while this feature is effective for the patient when he reaches high over his head to keep him stabilized, it is counterproductive to the transfer of the patient from the mobile bed to another bed because it presents both a gap between the beds and a raised obstacle therebetween (due to the tilting). This patent like Crawford et al above is seen to require at least two or maybe three people to effectuate a safe transfer of the patient. Another prior art attempt to address the problem of transporting patients from a bed to a convertible wheelchair/bed structure is disclosed by a patent to Jones, U.S. Pat. No. 4,119,342. In this patent, the wheelchair converts to a bed mode of a fixed height (equal to the height of the wheelchair arms). Thus, it is required that the bed in which the patient is lying be lower than this fixed height, so that the bed mode will then hang over the bed by up to seven inches to perform the transfer. This apparatus suffers from three drawbacks. One, the bed must be lower in height than the Jones device because the device is not adjustable; two, assuming the bed is lower, the obstacle created by the thickness of the platform structure (wheelchair arms and pad) would cause a difficult transfer procedure, if not insurmountable if the bed is even one or two inches below the Jones' bed platform; and three, a seven inch overlap has been found by the inventors hereof to be inadequate to ensure a safe patient transfer by one person. This is because in maneuvering the patient onto beds of different heights, there is usually slippage between the bed structures when one person attempts the transfer. Thus, it is seen that, once again, two and probably three people would be required to safely effect a patient transfer in Jones. Other adjustable height wheelchair to bed structures are disclosed by Burke et al, U.S. Pat. No. 5,342,114, and Herbert et al, U.S. Pat. No. 5,179,745. These patented structures, like Crawford et al, above, are only able to be located next to the bed in which the patient is lying. Moreover, these prior art teachings, unlike Crawford et al, have no bungee cords to help hold the two bed structures together. Thus, a minimum of three people are seen needed to transfer a patient from one bed to the other.
SUMMARY OF THE INVENTION
The present invention is directed to a cantilevered mobile bed/chair that, while in its bed mode, is able to overhang a conventional thirty six inch width hospital type bed by up to half its width in cantilevered fashion so that a safe transfer of a patient can be effected, even by a single caregiver. After the transfer, the patient can then be transported by either remaining in the bed mode, or converted into a chair mode for further patient care. The objects of this invention are carried out by a unique lift structure providing cantilever support for a series of three hinged together platforms making up back, seat and foot portions of the chair/bed. The lift structure comprises a telescoping tower which mounts vertically on one side of a rectangular shaped wheeled base. The platforms comprise the patient support for the bed/chair, and are operatively coupled to an E-shaped frame structure that in turn is mounted in cantilever fashion horizontally from the telescoping tower controlled by a screw type jack associated therewith. While a screw jack is provided, it is obvious that other jacks such as hydraulic and scissors may be employed. With this offset tower and cantilever E frame design, the remote side (to the tower of the platforms of the apparatus int eh bed mode are able to overlap a hospital type bed by up to eighteen inches, or half the bed width of a conventional, thirty six inch wide hospital type bed. Thus, when it is desired to transfer a patient from or to a hospital type bed to the apparatus, the jack controlling the telescoping tower operates to raise the platforms above the bed, the apparatus wheeled over to overlap the bed by up to eighteen inches, and then lowered to press into the bed's mattress. Moreover, the platforms comprising the bed are of a thin, highly strong material in which the side edges thereof are beveled or angled downward. This angle down design enables the platforms to further press into the mattress of the hospital type bed, not only ensuing that virtually no movement occurs therebetween, but that a substantially flat profile is presented for the two beds even with a one inch pad on the mobile bed. With such a relatively flat profile, and with the two beds locked in such a tight embrace, it becomes an easy matter for just one caregiver to manage a patient in a transfer procedure.
Although the lift mechanism of the invention can be carried out manually, the best mode comprises an electrically powered lift arrangement. That is, an electric motor is mounted to control a screw jack which is powered by a battery located at the wheeled base of the apparatus. The three platforms forming the head, seat and foot supports are connected by low profile piano hinges. Another electrically driven screw jack is mounted below the seat platform and controls the conversion of the bed into a chair configuration by way of levers and hinges. This second jack, like the first one, is mounted near the tower side of the unit so as to not interfere with the cantilevered overhang portion of the platforms. The chair mode may be under the control of either the caregiver or the patient, and features indefinite adjustment for patient comfort. In the case of immobilized patients, there is an auto seat reposition timer feature associated with the chair mode that periodically readjusts the sitting position to minimize bedsores. The seat platform includes a potty hole for increased patient maintenance. The wheeled base, besides providing support for the tower, accommodates, four, omni-directional wheels that may, in some models, be electrically powered; a hazard-free dry-cell, rechargeable battery and holder therefor; and a battery recharging unit. The back platform has provision for an oxygen bottle, while the foot platform includes an adjustable foot rest. The platforms comprising the bed include VELCRO straps for patient safety. The tower also accommodates an IV holder; combination food tray holder and arm rest that swings into position as needed; and a module for the auto seat reposition timer mentioned above.
Another object of the invention is to provide for a Trendelenburg position bed or where the bed is positioned to have the head lower than the feet. This is accomplished in the bed mode, one of several ways; one, by providing a multi-position gear and locking pin mechanism connected between the tower and E frame, or two, by way of a swing down jack mounted on the E frame. Thus, for example, in the case of the pin and gear arrangement, the pin is pulled and the E frame which is connected to the gear is rotated to be tilted to the desired position, and the pin reinserted to lock the bed in the Trendelenburg position.
A further object of the invention is to allow for portability of the apparatus by keeping the weight to about 160 pounds, yet of sufficient strength to support a load of up to 1500 pounds.
Other objects, features and advantages of the invention will be apparent from the following specification and drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the cantilevered mobile bed/chair apparatus in accordance wit the invention shown in the chair mode;
FIG. 2 is a front view of the apparatus showing the bed mode converting to the chair mode in phantom;
FIG. 3 is a side view of the apparatus showing the cantilevered bed/chair in the bed mode at two different heights;
FIGS. 4A-4D shows a step by step procedure for the safe transfer of a patient from the cantilevered bed/chair apparatus to a hospital type bed;
FIG. 5 shows respectively cut-away side view sections of the adjustable foot rest, and wheel and lock mechanism forming a part of the invention;
FIG. 6 is a partial top view of the three hinged together platforms forming the patient support with the middle seat section showing an oval shaped potty hole;
FIG. 6A is a view of a bed pan useable with the cantilevered bed/chair apparatus;
FIG. 6B is a view of the bed pan in FIG. 6 a in use with the cantilevered bed/chair;
FIGS. 7A-7B show one method of operating the bed/chair apparatus in the Trendelenburg position;
FIG. 8 shows a second method of operating the bed/chair apparatus in the Trendelenburg position;
FIG. 9 shows an embodiment of the invention having a base with three rails positioned about a toilet;
FIG. 10 shows the cantilevered bed/chair having three rails positioned sideways about a toilet;
FIG. 11 shows an embodiment of the cantilevered bed/chair having large wheels attached to the bed frame;
FIG. 12 shows an embodiment of FIG. 11 with the wheels engaged with the ground;
FIG. 13 shows a back view of the embodiment shown in FIG. 11;
FIG. 14 is a rear view of the embodiment of FIG. 12;
FIG. 15A is a side view of a wheelchair apparatus having a lift assist mechanism;
FIG. 15B is a front view of a wheelchair having a lift assist mechanism;
FIG. 16A is a side view of the lift assist mechanism raised;
FIG. 16B is a front view of the lift assist mechanism raised;
FIGS. 17-19 depict a mechanism for raising a patient's knees upward;
FIG. 20 shows the mobile bed apparatus having railings; and
FIGS. 21-24 show an alternative embodiment of a patient leg lift.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Turning to FIG. 1, the overall cantilevered bed/chair apparatus is indicated by 1 . A rectangular base 2 , made from steel or an equivalent material, provides support for four omni-directional wheels 3 , each with a locking mechanism 4 . The wheels, seen in greater detail in a cut-away section view in FIG. 5, are five inches in diameter, and are conventional off-the-shelf items such as No. 3W804 Swivel Stretcher Caster with Central Locking System Stem by Wagner. While not shown in the preferred embodiment, the wheels may be motorized in any well known manner, such as shown by the Ezenwa patent referred to above to convert the apparatus to a powered wheelchair. A tray 2 A nestles within base 2 to provide support for a 12 volt, dry cell battery and battery charger generally indicated at 5 . The battery and charger therefor are conventionally known, such as the “Jump-N-Carry 400” from K & K Jump Start/Chargers, Inc. of Kansas City, Mo. A telescoping tower 6 A- 6 B, made of three and one-half inch square steel for upper section 6 A, and three inch square steel for lower section 6 B, and, designed to lift 2500 pounds, is mounted on one side of rectangular base 2 . Aluminum or other materials may be used instead of steel for the tower without departing from the spirit and scope of the invention herein. The telescoping sections 6 A and 6 B are raised and lowered by way of a jack 8 supported by a block 7 . Jack 8 in the best mode of operation embodiment is a motorized screw jack that is capable of working either by hand or with a motor 9 . The motorized jack is a known 12 volt DC motorized jack, such as “Hi-Torque Acme Power Jack” made by H & H Engineering of Battle Creek, Mich.
Attached to the tower in cantilever fashion, at about mid-way, is an E shaped frame having a back 10 and arms 11 . Two of the arms 11 are located under, and are attached to a seat platform 19 on either side of a potty hole 21 . These arms are made of steel, and are L-shaped in cross section for strength. While L-shaped channel steel is shown, it is apparent that other well known designs for strength, and materials may be employed with equal results. The third arm 11 for the E-shaped frame is located approximately midway along a back platform 18 , and provides operative support therefor when in the bed mode. The back and seat platforms 18 and 19 are hinged together by a piano hinge, shown in detail in FIG. 6 . The seat platform is then connected also by piano hinge to a foot platform 20 . The three platforms are made of ⅜ inch aluminum with beveled down edges, and measures twenty four and one-half inches wide by three feet long for back platform 18 , eighteen inches long for seat platform 19 , and eighteen inches long for foot platform 20 , for a total of six feet in length. The beveled edges of the platforms perform a dual purpose, viz.; for providing rigidity for the platforms, and, for effecting an important aspect of the operation of the apparatus, to be described later with respect to FIGS. 4A-4D. While aluminum is disclosed for the material used in the platforms, it is apparent that other materials may be used including steel, plastic or fibreglass without departing from the spirit and scope of the invention. Arms 11 connected to back 10 of an E shaped frame extend approximately two thirds the width of the platforms, and together with platforms 18 - 19 - 20 , are designed to support a load of 1500 pounds. The three platforms are caused to change position by way of pivoting levers 17 A- 17 B connected to back and foot platforms 18 and 20 by way of anchor blocks 16 A and 16 B respectively. Anchor blocks 16 A- 16 B are connected approximately four inches from the tower side of the platforms. The location of anchor blocks 16 A- 16 B is important because this will leave approximately 18 inches cantilever overhang for the remainder of the platforms that is free of all obstacles. This can be more clearly seen in FIG. 3. A second jack 13 controls the movement of pivoting layers 17 A- 17 B. Jack 13 , like jack 8 , is a screw jack that is mounted to back 10 of the E frame with block 12 , and is controllable, also like jack 8 , either by hand or by a motor 15 supported at 14 . It is apparent that other classes of jacks may be employed, such as hydraulic and scissors without departing from the spirit and scope of the invention.
Attached to back platform 18 is a swing away safety guard rail 22 that encircles the patient for safety, while attached to tower 6 A is a swing away food tray holder and arm rest combination 23 - 24 for patient service. An adjustable foot rest 25 attaches to foot platform 20 in a manner described further down with respect to FIG. 5 . An oxygen tank holder 26 is conveniently attached longitudinally along the tower side and near the top of back platform 18 . An electronic auto seat reposition timer module 27 attaches to the back of tower section 6 A, while an IV holder 36 attaches to the front of tower section 6 A. Time module 27 is an off-the-shelf item such as “Universal Timer, Model UT-1” from Alarm Controls Corp., Deer Park, N.Y. This timer controls the periodic repositioning of the bed/chair apparatus when in the chair mode, so that bed sores of an immobilized patient are minimized. Not shown in order to minimize clutter in the figures, are VELCRO safety straps attachable at various points along platforms 18 - 19 - 20 . For example, the inventors hereof have attached their VELCRO safety straps at the back and foot platforms. It is apparent that such straps may be attached anywhere for optimum patient safety without departing from the spirit and scope of the invention.
OPERATION OF CANTILEVERED MOBILE BED/CHAIR
The operation of the cantilevered bed/chair will be described with reference to FIGS. 2-8. Some of the reference numbers for already identified elements have been omitted in order to keep figure clutter to a minimum. Looking at FIG. 2, the bed/chair apparatus is shown in the bed mode converting to a chair mode seen in phantom lines. It is noted that back platform 18 and foot platform 20 pivot about seat platform 19 which is securely mounted to the E shaped frame. The back and foot platforms move in opposite directions by action of under the seat jack 13 connected to levers 17 A- 17 B (identified in FIG. 1 ). Thus, as the jack extends, the platforms flatten out to form a bed. A chair is formed when the jack contracts. Jack 13 and connecting levers and blocks are all mounted near tower 6 A- 6 B so as to permit maximum cantilever overhang. This is clearly seen in FIG. 3 which shows an eighteen inch overhang for the cantilevered platforms. Also seen in FIG. 3, is a nine inch height for wheeled base 2 and battery/battery charger 5 combination to enable clearance under a typical hospital bed with a lowered guard rail. FIG. 3 depicts the cantilevered bed/chair in the bed mode at two different heights. The height is controlled as jack 8 extends to expand telescoping tower 6 A- 6 B. That is, patient platforms 18 - 19 - 20 , supported by E shaped frame 10 - 11 attached to section 6 A of the telescoping tower, changes height as section 6 B of the telescoping tower remains fixed to base 2 . The bed has a vinyl covered foam pad 28 of about one inch thickness for patient comfort.
FIGS. 4A-4D show the typical patient transfer procedure for the invention. FIG. 4A shows the patient being transferred in gurney fashion to a hospital type bed with the guard rail up. The height of the cantilevered bed is raised, in FIG. 4B, above the hospital type bed by up to eighteen inches as shown in FIG. 4C, and then lowered so as to press into the mattress of the hospital type bed. The pressing in feature of the cantilevered bed is enhanced by the beveled or angled down edges 35 of platforms 18 - 19 - 20 . It has been found that with the beveled edges pressing into the mattress, together with the relatively thin construction of the platforms (⅜ inch thick aluminum), the side profile of the two beds is almost flat even with a one inch foam pad on the cantilevered bed. Moreover, because the beveled edges “bite” into the hospital type bed's mattress, virtually no movement occurs between the two beds, which greatly facilitates the patient transfer procedure, even by one caregiver. Thus, in FIG. 4D, safety rail 22 and food tray holder/arm rest rail 23 / 24 are swung back, and the patient is easily rolled over onto the hospital type bed. Should it be necessary to move a patient from a hospital type bed to the cantilevered bed apparatus, the above described procedure would be reversed.
FIG. 5 shows the adjustable foot rest feature of the invention. Since patients come in many different heights, foot rest 25 attaches to a lower bar 29 B which slides telescopically in box shaped channel 29 A fixed underneath foot platform 20 . Thus, if a patient is taller than average, the foot rest is extended and locked in position to provide appropriate foot support. The foot rest is shown with a twelve inch adjustment. This provides accommodation for patients of up to seven feet in height. It is obvious that greater adjustments may be made with foot rests constructed with larger dimensions for bar 29 B. As noted above in the description of FIG. 1, wheel 3 , also shown in FIG. 5, has a diameter of five inches. This has been found sufficient to accommodate the many different type floor surfaces of most provider institutions.
FIG. 6 shows piano hinges 38 and 39 which, as is well known, have an almost flat profile, yet are extremely strong. These hinges, as mentioned above interconnect platforms 18 , 19 and 20 , and are capable of a long, trouble free useful life. Seat platform 19 has an eight inch by twelve inch elliptical potty hole 21 , useful for increased patient maintenance.
FIG. 6A discloses a bedpan specifically designed for use with the bed/chair of the invention. The bedpan has a flange 40 and receptacle 41 . The cross-sectional shape of the receptacle 41 is substantially identical to the shape of the potty hole 21 . FIG. 6B shows the bedpan in use with the bed/chair. In use, the receptacle 41 extends through the hole 21 and the flange 40 rests upon the platform 19 . The large flat flange provides for comfortable use by the patient. The bedpan is easily installed and removed as necessary.
FIGS. 7 and 8 describe two methods of performing the Trendelenburg position that may be employed in the apparatus herein. This is the position where the head of a patient is made lower than their feet, such as is necessary with some patients suffering from certain heart conditions, or patients in shock. In FIGS. 7A-7B, the Trendelenburg position can be effected with a simple, yet effective swing down bar or jack 32 . The bar is normally in a raised horizontal position next to E shaped frame back 10 . When it is desired to employ its use, bar 32 is swung down in a vertical position in front of and between the front wheels as shown in FIG. 7 A. As the tower is lowered, bar 32 at first makes contact with the floor, and then begins jacking the front half of the apparatus off the floor as shown in FIG. 7B. A second method for effecting the Trendelenburg position is shown in FIG. 8 . This method employs a gear and locking pin arrangement in which a gear 33 is fixed to E shaped frame back 10 , and to tower 6 A by way of a center load bearing or axle. When it is desired to employ the Trendelenburg position, a pin 34 is pulled from a center hole of a series of holes, the platforms tilted to the appropriate position, and the pin reinserted in an off-center hole as shown. Other obvious methods may be employed without departing from the spirit and scope of the inventive apparatus herein. For example, means may be provided for raising the foot platform above the horizontal plane so that the patients legs are raised above their head. Such a means might take the form of a third screw jack connected between a modified lever 17 B and the foot platform, to thereby cause only the foot platform to raise when the third jack is extended.
FIGS. 9 and 10 disclose an embodiment of the bed/chair having a base that can surround a toilet thereby placing the seat platform 19 over the toilet. The base of the bed/chair has three rails forming a U-shape with a wheel 3 at each corner of the base. This differs from the base shown in FIG. 1 in that the rail 2 and battery platform 2 A are deleted. This can be accomplished in two ways. The base can be formed in this manner and the battery 5 can be moved to a different location, such as mounted on one of the remaining rails of the base. Also, the rail 2 and battery platform 2 A can be made to be removable. When it is desired to position the bed/chair about a toilet, the rail and platform would be moved and the bed is so positioned. Afterwards, the rail and battery platform could be reattached.
FIG. 9 shows the bed/chair positioned with the back platform 18 resting against the tank of the toilet. In this manner, the leg platform 20 extends in front of the toilet and the seat platform 19 is positioned over the toilet 42 . In an alternative use of the same device, the bed/chair can be positioned so that the tower 6 A is in front of the toilet and the two sides of the base extend along either side of the toilet. In this manner, the seat platform 19 and potty hole 21 are still positioned over the toilet 42 . Either of these arrangements could be used depending on the ease in maneuvering the bed/chair into position. The result in either position is the same in that the seat platform 19 is positioned over the toilet. The patient can choose either position depending upon what is most convenient.
FIGS. 11-14 disclose a bed/chair that allows forward movement by the patient. In this embodiment, a large wheel 50 , common to the type used as rear wheels in wheel chairs, is connected to the frame. As the bed frame is lowered, the large wheel 50 engages the ground and, as the frame is further lowered, the rear wheels are lifted off the ground. This arrangement is shown in FIG. 12 . Once the rear wheels are lifted off the ground, the patient can roll the bed/chair forward by rolling the wheels 50 . The top of the wheels 50 extend above the seat platform 19 and are easily accessible by the patient.
The rear view of this embodiment is shown in FIG. 13 . In this figure, it is seen that the wheels 50 are connected to a pair of axles 52 , one on each side of the bed/chair. The two axles are connected by a common rod 51 . It is envisioned that quick release wheels 50 are used so that they may be easily attached and detached from the axle 52 . Such wheels are conventionally known in the art.
FIGS. 15A-16B disclose a lift mechanism for a wheelchair. The wheelchair 60 has a seat portion 65 and a back rest portion 65 and pivotable armrests 63 . A series of straps 66 are used to help retain a patient in the chair. The lift assist mechanism consists of a platform 64 lifted by a motor 67 . Any number of conventional means 68 are used to connect the motor 67 with the platform 64 , such as a screw jack or pump jack.
Positioned between the seat 65 and the platform 64 is a spring 70 . The spring 70 has a lifting force of 40-50 pounds. While this force is not sufficient alone to lift a patient, it reduces the amount of weight that is lifted by the motor 67 . Under normal conditions, the patient's weight collapses the spring but during lifting the spring aids the motor in lifting a patient. When lifting of the patient is desired, the armrests 63 are pivoted backwards out of the way. The motor is engaged and the platform 64 is lifted up the rail 68 to a height so that the patient clears the frame of the wheelchair. Once lifted to the height 69 , the patient can be slid laterally onto another chair or bed. Such a device consisting of the seat platform 65 , the lifting platform 64 , the motor 67 , spring 70 and rail 68 can be retrofitted onto an existing wheelchair or any other type of chair.
FIGS. 17-19 show a mechanism for lifting the patient's legs. The device includes a tube 80 attached to the head platform 18 of the bed/chair. Fitting within and attached to the tube 80 is a right angle rod 81 . At the end of the cantilevered section of the rod 81 is a hook 85 . A ring 82 fits onto the hook 85 . Extending from the ring 82 are two flexible cables 83 . A padded rod 84 is connected between the ends of the flexible cables 83 to provide a triangle support.
As shown in FIG. 18, when the bed/chair is in the chair configuration, the padded rod 84 is positioned beneath the knees of the patient 100 . As the head platform 18 is lowered, the tube 80 is moved to a near horizontal position. This results in the right angle rod 81 extending upwardly and the hook 85 positioned above the patient's head. The cables 83 pull the padded rod 84 and therefore the patient's knees upwardly. The tendency for the patient's legs to want to fall back to a horizontal position maintains tension in the flexible cables 83 . In such a position, the patient 100 can be cleaned and any sheets on the bed/chair can be more readily changed.
Other features are envisioned for the cantilevered mobile bed/chair apparatus herein. For example, a means for weighing patients while on the apparatus has been successfully tested. Such a means involves a set of two, six inch strain gauge strips glued to the front and back side of tower section 6 B near base 2 . The strain gauges are connected to a highly sensitive Wheatstone bridge circuit so that any strain on the tower due to a load (such as a patient) on the platforms, translates to a weight on an appropriate scale. Such strain gauges and Wheatstone bridge circuits are known in the art, and may be commercially obtained from e.g., Omega Engineering, Inc. of Stamford, Conn.
The cantilevered mobile bed/chair apparatus disclosed herein weighs only about 160 pounds so as to be portable, and thereby be useful under numerous circumstances and environments. And, despite its many sophisticated features, and its ability to support a load of 1500 pounds, the apparatus herein is designed to be rugged and long lasting.
An embodiment having rails surrounding the seat is shown in FIG. 20 . As can be seen, the head platform of the patient support 18 is provided with a U-shaped rail 22 that extends along each side and the top of the platform. On the far side of the platform, as shown in FIG. 20, the rail 22 is pivotally attached to the head platform 18 . This allows the railing to be moved out of the way during patient transport on and off the patient support. Arm rests 200 are attached to the bottom of the U-shaped rail 22 . The arm rests have pads 203 for the comfort of the patient. More importantly, the arm rests are attached to the rail 22 by a pivoted connection to collar 204 . Collar 204 is slidably maintained on the rail 22 and pivotally connected to the arm rests by pin 205 . As the angle of the head portion 18 relative to the seat portion 19 is changed from the seat to the bed configuration, the collar slides downwardly along the rail. As can be seen, one side is provided with a downwardly depending portion. The collar 204 can slide along the rail until the top of the arm rail 201 is substantially co-linear with the two side portions of the rail 22 .
FIGS. 21-24 disclose an alternative patient leg support. The mechanism itself is shown in FIG. 21 . The mechanism has a first L-shaped member 203 and a main member 206 . A padded member 204 extends from the end of main member 206 . Padded member 204 can rotate to accommodate its changing angle. It is best for the comfort of the patient that the padded platform 204 remain parallel to the seat platform 19 . Since the angle of the main member 206 changes as it is used to raise the patient's legs, it needs to be pivotally connected. The angle of the main member 206 relative to the L-shaped member 203 is accomplished by the pivoting joint 201 . The pivoting joint has an extension 202 for attaching the leg lifting apparatus to the bed, and can be locked to maintain the position of the main member 206 relative to the L-shaped member 203 . The range of motion is shown by arrow 207 and the pivot joint 201 does have a ratchet action.
FIG. 22 shows the patient support in the flat, bed configuration. As can be seen, the main member 206 extends along the side of the platform so that the padded platform 204 is positioned below the patient's knees. In this configuration, the main member 206 is substantially coplanar with the L-shaped member 203 .
The mechanisms as used when the device is in the seat configuration is shown in FIG. 23 . The padded platform 204 remains below the patient's knees, as can be seen, the angle of the padded platform 204 is now different as it is perpendicular to the main member 206 . This maintains the padded platform 204 in the best position for the patient's comfort. Also seen is the angle of the main member 206 relative to the L-shaped member 203 . The L-shaped member 206 is parallel to the head platform 18 whereas the main member 206 is parallel to the seat platform 19 .
If the main member 206 and L-shaped member 203 are locked in the position shown in FIG. 23, the device can be used to lift the patient's legs in an easy manner. If the head platform 18 is lowered until it is substantially coplanar with the seat platform 19 , the seat platform will push against the L-shaped member 203 and the main member 206 will extend upwardly above the patient support. This configuration is shown in FIG. 24 . Throughout the transition, the padded platform 204 can pivot so that it remains in contact with the patient's legs for the patient's comfort. The bottom of the patient's legs now have their weight supported on the platform 204 . In this manner, the patient's legs are lifted and maintained in a raised position.
While this invention has been described in conjunction with a preferred embodiment, it is obvious that modifications and changes may be made by those skilled in the art to which it pertains, without departing from the spirit and scope of this invention, as defined by the claims appended hereto.
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A cantilevered mobile bed/chair apparatus for safely transferring a patient from and to a hospital type bed comprises three hinged together segments forming back, seat and foot platforms operating in conjunction with a four wheeled, rectangular base. The hinged together platforms convert from a fully adjustable chair mode to a bed mode by a first jack located beneath the seat platform. The platforms are raised and lowered by a second jack associated with a telescoping tower attached to an E frame. The telescoping tower is mounted vertically from one side of the rectangular base, and when extended, has a height greater than a hospital bed. The E frame, which supports the platforms, is cantilevered horizontally from the top portion of the telescoping tower, and the height thereof is controlled by the second jack mounted together with the bottom portion of the telescoping tower, to the wheeled base. The side edges of the platforms are beveled or angled downward. When it is desired to transfer a patient from a hospital bed to the bed/chair apparatus, the unit is wheeled over in the bed mode. The lower height is extended by the second jack which enables the platforms to overhang in cantilever fashion the hospital bed by up to eighteen inches, and then lowered so as to press into the mattress of the hospital bed. The angled down edges of the platforms pressing into the mattress results in a tight embrace of the hospital bed, and an almost flat profile for the two beds so that a single caregiver can safely effect the patient transfer. Numerous other features are included for medical and physical maintenance of the patient.
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CROSS-REFERENCES TO RELATED APPLICATIONS
A continuation-in-part of A PORTABLE SYSTEM FOR THE COLLECTION OF URINE (Ser. No. 08/600,641), filed Feb. 13, 1996 and now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to a compact, fully portable processing system for the collection, sterilization, deodorization and eventual disposal of urine. Entrainment by a forced air stream is utilized to convey urine from the user in an arbitrary position--standing, sitting or prone to a suitable collection container.
2. Description of the Prior Art
The collection of urine is a process that has been extensively studied in conjunction with bedridden and incontinent individuals. Bed pans, diapers and/or catherization devices are generally utilized for those confined to beds for reasons of illness and disabilities. All of these practices have their drawbacks in view of suitable comfort and sanitary practices. Bed pan positioning is often difficult and urine collection is often not complete. Diapers are time consuming to attach and are costly. Furthermore, continued usage often leads to skin rashes, chaffing discomfort and potential infections. Catherization devices are most often prescribed for incontinent individuals. However, catherization devices run the risk of infection that can lead to undesirable side effects requiring medications and additional hospitalization confinement.
The prior art describes a variety of devices and processes to facilitate the withdrawal of urine from the body and disposal of the withdrawn urine. U.S. Pat. Nos. 4,270,539, 4,904,248 and 5,053,027 identify a variety of non-invasive devices that are worn and supported either by waist belts or held in place by supporting underwear garments. These devices are dependent on gravity for urine drainage into a collection bag, and therefore do not allow a user position where the urethra is not physically higher than the collection device. A urine aspiration system for the management of urinary incontinence is described in U.S. Pat. No. 4,747,166. Urine is collected in an absorbent pad which is connected to a vacuum source to remove urine from the pad to a collection container. The hydrophobic nature of the pad's cover contacting the body facilitates drying of the body surface in contact with the device within a short time period. The disposable pad must be changed frequently to satisfy sanitary concerns and to maintain the pad's absorptive capacity and sanitary properties.
U.S. Pat. No. 3,757,359 describes a therapeutic bed pan that is situated within the top surface of a mattress. The pan is covered with a perforated cover to permit urine collection within the pan. A vacuum source is activated to drain the bed pan to a collection vessel for eventual disposal.
Vacuum suction devices are described by the prior art. U.S. Pat. No. 2,968,046 discloses a urine receptacle which is emptied by the vacuum from an aspirating water jet. The aspirated stream of urine and air mixes with the water jet and is discharged into a drainpipe. However, the teaching is useful only where a user has access to a plumbed water system with provision for an aspirator system emptying into a drain, and cannot be considered "portable." U.S. Pat. No. 3,114,916 identifies a urinal system containing a cup shaped receptacle, a suction source as separate entities. U.S. Pat. No. 4,360,933 is similar in concept to U.S. Pat. No. 3,114,916; however, the suction source and collection container are described as separate entities that are connected with appropriate plumbing lines within a common housing. U.S. Pat. No. 4,360,933 describes an anti-spill feature that is effective only if the suction source is not active. U.S. Pat. No. 4,531,939 describes a similar system whose suction source is activated by a urine detecting element.
U.S. Pat. Nos. 2,968,046 and 3,114,916, 4,360,933 and 4,531,939 which rely on suction means for urine transport, disclose a variety of receptacle configurations, suction sources and collection containers. The prior art does not disclose a means for minimizing leakage at the body/receptacle interface and the importance of forced air entrainment at the base (lower contact end) of the receptacle. Several of the prior art practices as noted in U.S. Pat. Nos. 4,281,655, 4,631,061, 5,002,541 and 5,195,997 result in urine contacting the body prior to its conveyance to a remote collection container. Means for disengaging the fine urine droplets from a relatively high velocity air flow and removing urine related odors in the effluent air discharged to the surroundings are not addressed. Furthermore, the suction and collection means are not contained within a compact single assembly.
There exists a need for placing an orifice at the lower end of the receptacle in physical contact with the user to admit a wiping entrainment air to remove urine which might otherwise remain against the users or spill. It is functionally important that the ratio of air-to-urine flow be high. This facilitates drying the skin which has been in contact with the urine and more efficiently transports urine to the collection container so that fewer (if any) urine solids or salts are left behind to irritate the skin. A high air-to-urine flow ratio also requires a more efficient means for urine disengagement and demisting such as is taught by this disclosure.
There currently exist limited portable and self-contained urine collection systems for use within the inside of confined automotive interiors. The need for portable and self-contained urine collection hardware for travel usage is particularly desirable in situations where limited rest room facilities or long auto confinements are encountered.
The need for improved urine collection techniques for bedridden or incontinent people takes on an added importance due to an increasing elderly population, a greater dependence on home care and nursing home confinements and all situations where movement away from the bed is burdensome.
What is needed in the art is a compact and self-contained system which facilitates urine collection, sterilization, deodorization and eventual disposal in a sanitary and non-invasive manner for those who are bedridden, immobilized or where rest room facilities are not conveniently available for those confined to automobiles. It is an object of the present invention to satisfy these needs by providing for a leak-free urine collection device which prevents the carryover of fine droplets of urine and removes urine related odors with minimal discomfort regardless of whether the user is in an upright, seated or prone orientation. The teachings of this invention are believed to be a distinct improvement over prior art devices.
SUMMARY OF THE INVENTION
This invention discloses a compact, portable processing system for collecting urine by forced air entrainment. The admission of entrainment air at the lowest point of a receptacle permits efficient and sanitary collection of urine from individuals whether they are situated in an upright, seated or a prone position. A method of collecting urine from a user into a portable and self-contained system consisting of:
a. activating a suction fan or other vacuum device to cause an aspirating flow of ambient air through openings or orifices on the sides of the receptacle with at least one of the openings located at the receptacle's lowest point in close proximity to the user-'s body;
b. contacting the body with the receptacle which provides the necessary suction to seal against the body;
c. entraining urine by an air stream at a high air-to-urine flow ratio to transport the urine to a remote collection container;
d. separating the entrained urine from the air stream utilizing suitable inertial effects; and,
e. collecting the separated urine liquid phase within a suitable container prior to its eventual disposal.
In a second aspect of the present invention, urine mist or droplets can be more effectively eliminated from the entrainment air stream by:
a. discharging the entrained urine into a cyclone element that is situated above the collection container such that the heavier liquid stream is forced to an inside surface which facilitates separation with liquid drainage to the bottom of the container while entrainment air is expelled to the suction source; or
b. impinging the air and urine mixture against an inside surface of the collection container in a direction tangential to the plane of the container's wall to permit resulting centrifugal forces to separate the heavier liquid phase from the entrainment air.
Utilization of the cyclone element which is positioned above the collection container such that the separated urine enters the container at its geometric centroid results in the containment of urine even if the collection system is inadvertently knocked over providing the collected urine is less than one half of the container's capacity.
The receptacle's interfacial surface seal is non-invasive. In the case of the female user, the receptacle is configured to seal about the periphery of the vaginal opening. For male users, it is not required that the receptacle seal against the body, but the male receptacle may be configured to receive a directed urine effluent flow where the urine is entrained and transported to a remote collection container by air flow produced by a vacuum source or fan. On the other hand, for seated or prone male users, it is generally desirable that the receptacle seat against the user's skin. In this case, the seal is accomplished by the slight vacuum produced by the fan and the entrainment air flow which is admitted through one or several openings or orifices in close proximity to the body. A cylindrical or elliptical conical receptacle structure will also function to contain the urine effluent from male users.
A charcoal air filter impregnated with an acid such as phosphoric acid or acid salt such as potassium bisulfate may be placed either downstream of the point where urine is separated from the entraining air flow to remove ammoniacal or other urine odors prior to releasing the separated entrainment air to the surroundings.
The collected urine may be treated by bactericidal/deodorizing chemicals to disinfect and prevent the growth of microbial agents in the collected urine. Such chemical formulations might include but are not limited to citric acid, hydrogen peroxide solutions, potassium and/or sodium bisulfate, potassium persulfate, and sodium hypochlorite. Chemically treated urine can then be transferred to a waste disposal location at the user's convenience.
A pump and spray device may be provided to supply an appropriate flush solution and/or disinfectant rinse to facilitate the removal of urine residuals and contaminants from internal tubing and containment surfaces.
In another aspect of the present invention, an apparatus is provided for the collecting and eventual disposing of urine from the user's body. The basic elements of the portable, self-contained apparatus include:
a. a urine receptacle with a concave elliptical opening with a smooth interface surface at one end and a reduced cylindrical opening at the opposite end such that one or several openings or orifices penetrate the receptacle's wall to accommodate the inflow of entraining air where at least one of the openings is located at the lowest end of the receptacle that contacts the body;
b. a liquid collection container which can serve to separate air and liquid and to contain the liquid; and,
c. a fan or vacuum source to provide the air flow required to entrain and transport the urine from the user to the liquid collection container and to provide the suction needed to form a leak tight interfacial seal with the user's body.
By virtue of the practices of the present invention, methods and apparatus for the collecting and disposing of urine in a sanitary and non-invasive manner are described. The foregoing and other features and advantages of the present invention will become more apparent from the following description.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view looking into the receptacle which collects urine from a female user for transport to the collection container. The receptacle is placed in a position surrounding the urethra. Urine leakage from the subject is prevented by the suction created by a remote fan or other vacuum source connected to the ejection leg of the collection container. Urine is entrained by a high influent air flow entering the receptacle's bottom or lower and side or upper orifices which air flow transports the urine to the liquid collection container. As shown in FIG. 1, the right side of the receptacle cavity is positioned below the receptacle's outlet end.
FIG. 2 is a side view of the urine receiving receptacle noted in FIG. 1.
FIG. 3 shows a perspective and side view of a receptacle configuration for male users while FIGS. 4 and 5 depict a perspective and cross-sectional view of a male/unisex receptacle.
FIG. 6 is a flow typical outline schematic of the urine collection and disposal processing system.
FIGS. 7 and 8 show details of a system liquid/air separation or demisting element where the urine is disengaged from the entraining air flow and allowed to enter the collection container. The configuration where the liquid outlet from separation element is positioned at or close to the geometric centroid of the collection container provides a measure of urine containment against inadvertent tipping of the portable collection system.
FIG. 9 shows an alternative scheme for liquid/air separation where entrained urine and air mixtures are separated by centrifugal forces created by the tangential entry of the high velocity mixed air urine stream impacting the inner wall surface of the collection container.
FIG. 10 shows a schematic of a portable embodiment of the invention configured into a compact envelope. FIG. 10a shows sealing details between the upper and lower portions of this portable unit.
FIGS. 11 and 12 are schematics of a home or hospital embodiment of the invention.
DETAILED DESCRIPTION OF THE INVENTION
The present invention will be described in greater detail with regard to the processing system for the removal and collection of urine from the body. The design of a concave urine collector for receiving the flow of urine is an essential component of the processing system. Common structural design features of the urine collector(s) shown in FIGS. 1-5 which are unique to the present invention and are important for the comfort and convenience of the user are itemized as follows:
(a) The geometry and rigidity of the receptacle: For user comfort and to enable an air-tight seal between the user and the receptacle during use, the collector periphery must be sufficiently rigid that the user's skin is pressed into a conforming contour by the (partial) vacuum in the collector during use, but not so rigid as to be uncomfortable.
(b) The size and location of the entrainment air orifices: At least one or more orifices adjacent the sealing surface where at least one of the orifices is located at the bottom or lowest end of the collector to admit entrainment air to effectively entrain the urine entering the receptacle into a flowing air stream. This entrainment air also serves to dry the skin and prevent an inadvertent spillage when the device is removed. These orifices must be located at- or close to- the periphery of the receptacle within approximately 0-10 mm and preferably 0-4 mm of the user's skin. These orifices must also be of sufficient number and size to enable a aspirating air velocity of approximately 10-30 ft/sec or more adjacent to the skin area encompassed by the receptacle which might otherwise be wet by urine. It should be apparent from the geometric configurations shown in FIGS. 1-5 that the lower air entrainment port at the bottom or lowermost portion of the receptacle is the most important, and preferably the entrainment air port at the bottom or lowermost portion of the receptacle should be the largest and admit the greatest amount of entrainment air.
(c) The line length and diameter leading to the evacuation port: In order to enable the uphill flow of the entrained urine such that the user will not be wet by his own urine regardless of the orientation of the device or of the user's body, an aspirating air velocity of approximately 40 ft/sec or more and a ratio of air-to-urine of approximately 50:1 (by volume) or more is required. Since a maximum urination rate of approximately 40 cc/sec is possible for some persons, the required air flow is about 2 liters/sec or about 4 cfm. A line to the suction source having an I.D. of at least 3/8 inches is desirable but preferably the line to the suction source should have an inside diameter of 1/2-5/8 inches.
The preferred configuration of the collector differs in form for females and males. For females as noted in FIGS. 1 and 2, the collector is shaped with a concave elliptical opening defined by outer rim 4 and sealing surface 6 which contacts the human body. Typically, the concave elliptical opening is 1 inch wide by about 4 inches long. Lower orifice 1 and upper orifice 2 at the lowest and highest ends of the collector, respectively, are located in the periphery of the elliptical collector which enable air at relatively high velocities, preferably about 20 to 50 feet per second to enter the collector. The effluent end 5 of the collector reduces to about 5/8 to 3/4 inches I.D. within a length of approximately 3-4 inches. The elliptical and concave back surface 3 that faces the body is configured to increase in depth from about 1/4-1/2 inches along the collector outer rim 4 adjacent lower orifice 1 to about 1 inch in depth where it intersects the effluent channel 5. The high air velocity associated with the shallow depth at the lower end of the receptacle is effective in entraining a urine liquid stream and drying the skin area which would otherwise be wet with urine.
Typically, the lower orifice 1 which may or may not be circular should have a cross-sectional area of about 1/8 in 2 while the upper orifice 2 has about 1/4 of this area. The air flow, typically ranging from 2 to 15 cubic feet per minute, is effected by a fan located downstream of the urine collection container. The suction from the fan causes the collector's peripheral sealing surface 6 defined upon outer rim 4, typically about 1/8 inch to 1/4 inch wide, to press against the skin to form a seal. By this means, the urine effluent from the body is confined and entrained by air flowing through the receptacle's orifices and into the connecting tube leading to the urine collection container. In practice, an air flow of about 4 ft 3 /min will result in an air velocity of about 75 ft/sec through a 1/8 in 2 receptacle orifice area and a velocity of about 20 ft/sec through a 3/4 inch diameter tube leading to the urine collection container.
In FIG. 3, a typical male receptacle 8 can have a conventional conical shape with an inlet diameter typically from 2 to 3 inches and reduces to an outlet 11 having a diameter of about 5/8 inch. Alternatively, the male receptacle 8 may have an elliptical shape of about 5 inches long by 3 inches wide reducing to an outlet diameter 11 of about 5/8 inches. Lower orifice 9 at the lowest end of the collector rim is about 1/4 inches in diameter while the upper orifice 10 is about 1/8 inches in diameter.
Another male or unisex receptacle 12 is shown in its isometric form and in its cross section in FIGS. 4 and 5. In these Figures, the elongated contour of the inner cone 13 allows efficient recovery of urine emitted from a male member even when it is inserted at an off-angle such that the urine stream is not aimed directly at the orifice 14. Preferably, it is fabricated from a soft hydrophobic plastic or elastomeric material which is not wet by the incoming urine stream. For unisex use, the circular rim defining the inlet region is easily deformed by finger pressure to an ovalized configuration more convenient and comfortable to a female user.
The device, shown in FIGS. 4 and 5, features a multiplicity of orifices 15 along the upper rim of receptacle 12 to admit inlet air to the manifold region 16. During use, the inlet air flows out from the manifold region 16 through the annular orifice 18 and through outlet 17 en route to a central vacuum source. Any urine passing through exhaust orifice 14 is entrained by this airflow and swept along to the central vacuum source where the urine is disengaged and separated from the air flow as discussed previously. Preferably, the total flow area comprised by the multiplicity of orifices 15 in the collector rim is several times greater than the annular flow area 18 defined between the inner and outer funnel shells such that the function of the device is not appreciably impaired if one or even a number of the inlet ports or orifices 15 should be blocked by direct contact with the skin or clothing of the user. However, it is also preferable that the outlet flow area 17 be comparable to the annular flow area 18 so that during use a sufficient vacuum is developed at 16 that any urine which may inadvertently not be aimed directly at orifice 14 will nevertheless be aspirated by an inflow of air past the user's member if there is an imperfect seal between the user's body and the outer rim of the receptacle, or if there is a perfect seal between the user's body and the outer rim of the receptacle, the urine will be aspirated upon withdrawal of the receptacle when the seal is broken. For the female user, it is most desirable that a sweeping air flow be admitted directly to the interior region 13 and 14 through a single large lower orifice 19 at the lowest point of the upper rim of receptacle 12. When utilized by a female user, the secondary air flow through lower orifice 19 dries and aspirates the wetness away from the users skin. To perform this function, lower orifice 19 should be sized such that it will admit about one-half of the total air aspirated through the exhaust port 17 when employed by a female user. It is most efficient if lower orifice 19 contacts the body at the lowest elevation so as to effectively transport urine to the collection chamber.
Visual tests were conducted using a prototype device similar to that shown in the flow schematic illustrated in FIG. 6 with simulated urine stream. The fan assembly generated a static vacuum of about 10 inches of water. A female collector receptacle with a concave elliptical opening of 1 inch wide by 4 inches long was used for the tests. The receptacle featured lower and upper orifices having, respectively, cross-sectional areas of 1/8 in 2 and 1/32 in 2 . These orifices were located at the bottom and top of the receptacle, respectively, to admit an entraining air flow into the system. The air with the entrained urine stream was conveyed through a 3/4 inch diameter flexible transparent tube over a distance of 10 feet to a remote collection container. The simulated urine was composed of 5 wt % sodium chloride and 4 wt % urea dissolved in demineralized water. It should be noted that these salts comprise the major constituents of urine.
It was observed that the simulated urine flow was readily entrained by an air flow of 4 ft 3 /min. The internal velocities through the receptacle and tubing were more than sufficient to transport all of the simulated urine to the collection container. Upon cessation of the simulated urine flow, an effective drying of a simulated body surface in contact with the receptacle was noted.
The urine collection container, configured as shown in FIGS. 6 and 8-11, efficiently separated the liquid urine from the air stream such that liquid was collected in the bottom of the collection container. The effluent air discharged from the top of the collection container was free of entrained liquid. Tests run with a 2 liter urine collection container having a diameter to height ratio of about 1:1 showed an effective separation of an air and a liquid stream with air flows of about 4 ft 3 /min. Injection of the liquid and air mixture in a tangential direction on the upper portion of the container's inner surface, as noted in FIG. 9, was observed to enhance liquid/gas separation.
As noted in the process schematic of FIG. 6, a suction fan which creates the air flows necessary to entrain the urine must be situated downstream of the urine collection container. As a consequence of the fan's operation, the collection container is maintained at a vacuum of 6-10 inches of water during use.
An odor filter may be situated either upstream or downstream of the fan assembly, but it is preferably located upstream of the fan assembly to provide additional protection to the motor and fan against long term fouling from urine contaminants. The odor filter may consist of a high surface area carbon (about 1000 m 2 /gm) impregnated with an acid salt and/or a weak acid to enhance removal of ammoniacal odors from the air flow. Testing has indicated that a contact residence time of about 0.05 to 0.5 seconds with 8-12 mesh activated carbon granules impregnated with a concentration of 10% phosphoric acid effectively removes residual urine odors.
FIG. 7 depicts a typical cyclone separator unit 20 which is integrated with a cap 21 that screws into a collection container 22 shown in FIG. 8. The inlet 23 to the cyclone element 23 receives the entrained urine and air mixture from the receptacle assembly as noted in the process flow schematic of FIG. 6. This mixture enters the cyclone at the upper end of the cylindrical body 24 such that the incoming flow duct is tangential to the surface of wall 24 and is swirled rapidly by the confining geometry. The swirling, which may generate centrifugal forces ranging from 100-1000 gravities depending upon the velocity of the incoming urine/air mixture and the radius of the curvature of the cylindrical body 24, causes the liquid phase to be centrifuged to the outer wall whereupon it drains into the collection container 22. As shown in FIGS. 7 and 8, the separated air stream exhausts through a tubular upper port 25. Upper port 25 typically starts at a vertical plane immediately below the bottom of inlet tube 23 and extends approximately one-quarter of its diameter above the top of cylindrical body 24. Suction is maintained at this station by the action of the fan as shown in the schematic of FIG. 6.
In FIG. 8, a similar cyclone element 20 is also integrated with screw cap 21, but the position of the cyclone is such that the liquid outlet 26 is positioned at the geometric center or centroid of collection container 22. This arrangement achieves an anti-spill configuration; i.e., as long as the collection container 22 is less than one-half filled with liquid, the liquid outlet 26 of the cyclone element will always be above the liquid level whether the assembly should fall on its side, on its end, or even be turned upside down. It will be recognized by one trained in the art that this anti-spill configuration is effective only as long as the collection container 22 is less than half full of liquid and therefore the collection chamber typically should be oversized to approximately twice as great as the maximum intended liquid capacity.
FIG. 9 depicts an alternate configuration for the separation of urine from an entraining air stream. Inlet tube 31 is configured to impart a swirling velocity component to the outflow stream 32 within collection container 30. The swirl serves to separate the gas and liquid phases such that the liquid is centrifuged to the outer wall of collection container 30. Upon reaching the container's wall, the droplets and mist coalesce against the collection chamber wall and descend to the bottom of collection container 30 while the separated air stream flows radially inward and exits through exhaust tube 33 to a region of diminished pressure resulting from the suction source typically through a filter/deodorizing component as shown in FIG. 6.
One embodiment of the urine collection system which is especially convenient for travel or wherever electrical power is available is shown in FIG. 10. In this Figure, the system is completely contained within a "lunch-box" sized container. The container is comprised of top 61 and bottom 62 halves. The bottom half contains a urine collection container 63 over approximately one half of its base area and provides storage volume for the collection hose 64, the male and female urine receptacles 65 and an electrical cable which can be plugged into jack 66 to power the fan 73. Within the bottom half of the container 62, an intermediate partition 67 segregates the urine collection container from the storage volume and restrains it against inadvertent tipping or tumbling within the container assembly.
A cyclone separator element 68 is held by a screw cap 69 at a vertical height such that liquid outlet 70 is at the geometric center of the collection container. This anti-spill design feature is functional as long as the container's liquid volume is less than one-half full. A hermetic sealing configuration between mating edges 71 and 72 (also shown in FIG. 10a) provides anti-spill redundancy and prevents the escape of odoriferous gases.
In the top half of the container, fan 73 is driven by an electric motor 74 which is activated by switch 75. The upper quarter volume containing the fan and motor assembly is partitioned off from the rest of the assembly by baseplate 76 and bulkhead 77. After urine/air separation, it can be seen that the recovered air is admitted from fan inlet region 78 to fan 73 only after passing through a deodorizing/demisting filter 79 into plenum 78 feeding the fan through a hole in bullhead 77. As shown in FIG. 10, the opening in bulkhead 77 is typically adjacent to the fan inlet and concentric with the fan centerline. To reach fan inlet region 78, air which has been separated from the air/urine inflow by cyclone element 68 flows through a deodorizing activated charcoal filter 79. This further suppresses odor and provides a second line of defense against urine escape. During use, the interior volume of the urine collection system is maintained at subambient pressure by the suction of the fan 73. Fan 73 also pumps the clean interior air back up to atmospheric pressure where it exhausts through ports or louvers 80. Typically, it may prove expedient to line the interior wall of the region containing fan 73 and motor 74 adjacent to exhaust ports 80 with an acoustical lining material but it should be apparent to one skilled in the art that this is a user convenience and is not essential to the system's operation.
In the design shown in FIG. 10, a tube fabricated from a flexible inert material such as Tygon™, conducts the incoming urine/air stream to cyclone separation element 68 while accommodating the opening, disassembly and cleaning of the device. The incoming urine and air stream are conveyed through the outer wall of the unit by a fitting 82 which connects to hose elements 64 and 81 on the exterior and interior regions of the urine collection system shown. Finally, a suitable latching mechanism or hinge 83 and latch elements 84 and 85 seal upper 61 and lower 62 halves of the urine collection system.
A home or hospital embodiment of the invention is shown in FIGS. 11 and 12. A urine/air mixture is aspirated through inlet port 91 where it flows directly into a cyclone separator 92 as shown in FIG. 11 or into a swirling jet which impacts the wall of liquid collection container 93 at a shallow angle as shown in FIG. 12. The combination of centrifugal and gravity forces separates gas and liquid phases. The liquid-free effluent gas stream flows up through an acid impregnated activated charcoal filter 94. Filter 94 deodorizes the effluent gas stream by removing ammoniacal contaminants prior to its recompression back to atmospheric pressure by fan element 95. It should be noted that anti-spill configurations are depicted in both FIGS. 11 and 12. The liquid discharge port 96 of cyclone separator 92 in FIG. 11 and the inlet of the gas exhaust tube 97 in FIG. 12 are both located at the geometric center of liquid collection container 93.
In FIGS. 11 and 12, seal ring 98 enables the motor/fan/separator assembly to form a hermetic seal with liquid collection container 93. The two halves of the assembly are closed by a multiplicity of hasps 99 which protect the user against unwelcome odors or from an inadvertent spill. The gas stream exiting from the impregnated charcoal filter 94 is admitted to the center 100 of rotating fan element 95 where it is swirled outward against stator elements 101 which recompresses the effluent air back up to atmospheric pressure. After pressure recovery, the deodorized air stream exits the apparatus through a multiplicity of exhaust ports 102 which may be downstream of an optional acoustic element 103 for noise reduction. As an element of good practice, it should be noted that the motor 104 which drives fan element 95 is desirably self cooled by an air stream which is separate from the primary aspirated air stream, and is drawn in by cooling air fan 105. Optionally, a home or hospital system may be configured with a dedicated trolley or cart 106 to facilitate its transport according to a user's convenience.
As will be apparent to those skilled in the art in the light of the foregoing disclosure, many substitutions, alterations and modifications such as the addition of a liquid sensing device to activate the suction source are possible in the practices of this invention without departing from the spirit or scope thereof.
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This invention relates to a compact, fully portable processing system for collection, sterilization, deodorization and eventual disposal of urine. The system is comprised of several detachable components which include male and female urine receptacles, an electric motor and fan assembly or any other suction source for providing the forced air flow required for urine entrainment; and a liquid collection bottle or reservoir. Optional but desirable features may include a gas/liquid separation or demisting element and a deodorizing filter. The system is self contained and readily disassembled for easy cleaning. It is readily adapted for home, hospital, and automobile usage. This invention has utility wherever rest room facilities are not conveniently available or where individuals are bedridden or immobilized.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention is directed to footwear and, more particularly, to a removable, disposable shoe insert for cushioning and absorbing shock, footwear embodying the same, and a method of making.
[0003] 2. Description of the Related Art
[0004] Footwear on the market today is designed to reduce stress on the feet, legs and body of the wearer while providing comfort and flexibility. Unfortunately over time many materials footwear are made of breakdown and become harder reducing the ability of the footwear to provide shock absorption and comfort properties to the wearer. This holds true for most all types of footwear when standing, walking, running, or performing a work related task. To solve this issue three main components of footwear have been designed to provide comfort, cushion, and shock absorbing properties.
[0005] The outsole of a shoe that comes in contact with the ground can be made of various types of materials. One typical material is a hardened carbon additive rubber outsole that provides durability, reduce wear, and extend the life of the product. Unfortunately if the outsole is made of a highly durable material, such as hardened rubber, its shock absorbing properties are sacrificed, and other parts of the shoe must be designed to provide shock absorption and cushion. In some applications footwear is designed with the outsole as the main component of the shoe, resulting in a hard and ridged shoe. This may be desirable for durability in a work environment, but it reduces the comfort level to the wearer.
[0006] Another component of footwear is the insole, typically a piece designed to provide a barrier between the foot and the materials from which the footwear is manufactured. Typically an insole is made of a comfortable material that is not irritating to the skin. In order to extend the usefulness or improve the comfort of the footwear or both, improvements have been developed where the insole is replaced. Unfortunately the insole piece covers the complete contact area between the foot and the footwear, becoming costly to replace. The insole is not designed for shock absorption properties and is typically of thin design. To add shock absorption properties to the insole can make the insole thicker, thus changing the configuration and properties of the footwear. The relatively thin design of some aftermarket replacement insoles makes them susceptible to replacement in a fraction of the life span of the footwear. This may result in a costly endeavor due to the various sizes and shape of footwear.
[0007] The main component of many types of footwear, including athletic footwear, that is designed to provide shock absorption and cushion is the midsole. Midsoles that are typically made of Ethyl-Vinyl-Acetate, rubber, polyethylene or other materials provide significant shock absorbing and cushioning properties initially, but they can break down after prolonged use. The midsole tends to lose its elasticity and will actually reduce in thickness due to standing or repeated compression from the impact of walking or running. Once these properties are lost, the footwear becomes less effective and obsolete.
[0008] Typically, in the design of footwear the midsole is the focus for providing shock absorbing properties. It is estimated a good running shoe will perform well for 300 miles. At that point the midsole has broken down to a harder and thinner form of the original material and will not provide essential shock absorption. In the case of many average runners, this is less than a year. Other components of the shoe at this point may be in good shape but the midsole component is worn out.
[0009] In some applications, such as work footwear, the product is designed with only an outsole and insole. The foregoing arguments hold true here as well. The outsole could be made of a more durable material, but it would not provide shock absorption or cushion for the wearer. If the outsole is made of more elastic material for better cushioning, its wear properties are sacrificed and the life of the product is short.
[0010] The ideal material providing shock absorbing properties and wear that returns the midsole, outsole, or insole to its original size after repeated use has not yet been invented, and many have been issued trying to solve this problem and extend the useful life of footwear.
[0011] Numerous patents have been issued describing various methods and architectures for providing interchangeable insoles and midsoles. These patents are summarized below.
[0012] U.S. Pat. No. 4,897,936 describes inserts for the forefoot and heel. Inserts are inserted from the insole side and outsole side. Inserts are attached using rings to hold in place. This may prove to be costly for manufacturing and less durable than other options.
[0013] U.S. Pat. No. 5,533,280 describes many interchangeable components with interlocking properties. The many parts and complexity of this arrangement may be costly to manufacture or replace. In addition wear and stability would be major concern.
[0014] U.S. Pat. No. 6,023,857 describes a removable midsole. Disadvantage being the size of the insert taking away from the stability of the shoe, and cost of replacement for different size shoes.
[0015] U.S. Pat. Nos. 6,023,859 and 5,799,417 describe a hinged part of the outsole to allow for a replaceable insert. The outsole requires two hinged mechanisms and locking devices to keep the outsole in place. This may prove to be costly during manufacturing and cumbersome for use.
[0016] U.S. Pat. No. 4,942,677 describes an adjustable insert which may be primarily for medical rehabilitative purposes. This type of design incorporate single or multiple parts of wedge shaped design which may not be desirable under heavy use.
[0017] U.S. Pat. No. 4,624,061 describes two insert components slotted and interconnected one from the inside, the other from the outside of the shoe. Again manufacturing cost may be high and replacement of insert may be complex or prove to be a disadvantage when not interlocking correctly.
[0018] U.S. Pat. No. 6,543,158 describes an insole insert. Insole inserts are generally thin in design and would not provide the amount of shock absorption or comfort as an insert of significant depth. In addition an insole insert is typically manufactured of multiple materials and varying shoe sizes raising the cost of manufacturing. It is possible to standardize the shape, size or single material the heel insert is made of. This allows the insert to be a relatively inexpensive alternative in maintaining footwear characteristics over the life of a shoe.
[0019] U.S. Pat. No. 6,745,499 describes a fluidic cushioning solution to improving shock absorption properties. Providing cushioning by fluid flow is one solution but does not address the problem with materials breaking down over time and repeated use. The manufacturing and overall cost may be a negative for this design. In addition the insert is independent of the forefoot area, reducing complexity of the design.
[0020] U.S. Pat. No. 6,751,891 describes a complex springs and return assembly manufactured into the footwear. Expense of manufacturing would be an issue. The overall footwear may be heavier and noisy. In addition there may be a reduction in performance by the springs over time limiting the life span of the product. A removable insert eliminates the need for long term performance, material return characteristics by being removable. The insert can simply be replaced after it losses its ability to cushion impact which is determined by the wearer or a recommended time period based on wear, weight or size of shoe. The insert improves the shock absorbing properties of the overall shoe by not requiring durability as one of its main traits. No return system is required.
[0021] U.S. Pat. No. 6,754,982 describes multiple cone system with a plate that can be used with any different number of pieces. The plate system adds rigidity, which is an undesirable effect while the cones are providing shock absorption, a desirable effect. With a single insert multiple pieces or additional parts are not required reducing replacement and manufacturing costs.
[0022] U.S. Pat. No. 6,722,058 describes a cartridge that is “U” shaped with multiple pieces. These types of designs and others like it require multiple parts or plates increase manufacturing cost, weight and in some cases create side-to-side stability issues. In addition with multiple components the chance of failure is greater. An insert as described in this patent is a single component that is removable and replaced when the wearer determines the insert has reached its life. The insert can be manufactured out of inexpensive materials allowing the user to replace at their convenience.
BRIEF SUMMARY OF THE INVENTION
[0023] The disclosed embodiments of the present invention are directed to a replaceable insert for footwear, footwear embodying the same, and a method of making. In accordance with one embodiment of the invention, an insert is provided formed of cushioned material sized and shaped to be received in the sole of a shoe, and preferably within the heel, although multiple inserts may be used at multiple locations in the shoe.
[0024] In accordance with another embodiment of the invention, footwear is provided that includes at least one cushioned insert removeably positioned in the outsble of the shoe to provide cushioning to a user and configured for replacement by slideably removing the same from the shoe.
[0025] In accordance with another embodiment of the invention, a method of making footwear with a removable insert is provided, the method including providing footwear with at least one opening in the outsole and a cushioned insert sized and shaped to be slideably received within the opening, and slideably positioning the insert within the opening.
[0026] In accordance with another aspect of the foregoing embodiment, providing the opening in the shoe includes sizing and shaping the opening such that the opening and the insert will have a tight fit, preferably an interference fit.
[0027] In accordance with another embodiment of the invention, a shoe is provided that includes a body having a closed bottom and an opening in a top thereof that communicates with an interior through which a user inserts a foot, the shoe having a toe portion and a heel portion, the bottom of the shoe formed to have at least an outsole, the outsole having a bottom surface that is exposed when the shoe is worn and a top surface, the midsole having a bottom surface that abuts the top surface of the outsole, and a top surface, the bottom having a cavity formed therein that opens through one of the outsole and the midsole; and a plurality of inserts sized and shaped to be received within the cavity through an opening formed in one of the outsole and the midsole, each of the plurality of inserts sized to have a tight fit within the cavity to retain its position in the cavity and yet permit removal by the user for replacement with another of the plurality of inserts.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
[0028] The foregoing and other features and advantages of the present invention will be more readily appreciated as the same become better understood from the following detailed description when taken in conjunction with the accompanying drawings, wherein:
[0029] FIG. 1 is a side view of footwear having a removable insert formed in accordance with the present invention;
[0030] FIG. 2 is a bottom view of the footwear of FIG. 1 ;
[0031] FIG. 3 is an illustration of various geometric configurations of the insert formed in accordance with the present invention; and
[0032] FIG. 4 is a cross-sectional illustration of a shoe with a heel insert formed in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
[0033] FIGS. 1 through 3 illustrate footwear, in this case a shoe 10 having an insole 20 , a midsole 40 , and an outsole 50 . FIG. 1 shows the basic configuration of footwear with an added insert device 30 . Some footwear may not include one component such as the midsole 40 . In those cases the insert would be inserted into the outsole 50 , which would include the area displayed as the midsole 40 .
[0034] The removable insert 30 is shown inserted through the midsole 40 . An alternate design would have the insert 30 inserted through the outsole. In this case, the lower face of the insert 30 would be exposed to the elements. This may require removal or partial removal of the outsole and some type of locking device. The preferred method for simplicity would be insertion through the inside of the shoe 10 . FIG. 2 illustrates a plan view or top view illustrating the interior 60 of the shoe 10 with the insert 30 in place. The insert 30 is located in the midsole 40 , or in some instances the outsole 50 if no or a limited midsole is manufactured into the shoe 10 . The tolerances between the insert and the midsole or outsole are minimal in order to provide a firm placement and retention of the insert into the shoe 10 .
[0035] FIG. 3 illustrates the insert design. The insert 30 can be a cylinder of specific depth and diameter. In different applications it may be better to manufacture the insert in the form of, but not limited to a square 70 , oval or closed “U” shape design, of varying depths. The insert 30 is designed to be made of but not limited to materials such as EVA (Ethyl-Vinyl-Acetate), rubber, polyurethane, materials the midsole, outsole, insole are typically made from. By doing this a piece of footwear can be configured to the user's personal preference or use. An example would be an athletic running shoe that has a midsole 40 made of EVA, the insert 30 could be made of EVA returning the footwear to its original intended shock absorbing parameters each time the insert is replaced. If the insert 30 was made of a softer porous material the advantage of greater shock absorbing and cushioning properties could be obtained without the Worry of repeated use. After a single or limited number of uses the insert could be replaced, returning the footwear to its original improved shock absorbing properties.
[0036] This present invention is not limited to athletic footwear but is applicable to all types of footwear. Examples include, but are not limited to, athletic, casual, dress, and specialty footwear.
[0037] The footwear is manufactured or modified after manufacturing to include a cavity in which the insert is placed. The heel of the footwear provides most of the shock absorbing requirements for the wearer during movement such as walking, running, or while stationary. The preferred location of the cavities in a pair of shoes in which the insert 30 is ideally directly under the impact point of the wearer's heels. This location may be offset but it is most desirable at the point of impact between the heel of the foot and the center of the insert. For example, insert 30 may be a cylindrical insert with a circular diameter in the range of 0.5 inch to 3.0 inches and preferably of 2.0 inches for a size 12 shoe. The size and shape of the insert may vary depending on the size and application of the footwear. The shape and diameter are not limited to a specific dimension or to the cylindrical design but are the most obvious for discussion purposes. Other shapes such as ovals, rectangles, squares, or a closed “U” shape, with the closed flat end of the “U” facing the toe may be more desirable for manufacturing or coverage. The desired goal of the insert 30 is to provide enough area of impact for shock absorption while maintaining the footwear integrity and comfort. If the cavity area is too big, the footwear may not provide the required support or stability. The insert 30 and cavity in the footwear may vary in depth. The cavity depth and vertical dimension of the insert 30 may range from a fraction of an inch from the outside of the outsole 50 to a percentage of that depth. This would be most desirable if the footwear incorporates other shock absorbing devices or materials layered into the footwear. The insert 30 would only seat a percentage of the way between the insole and outside of the outsole as shown in FIG. 4 . The insert 30 may also be made of materials that do not require the use of an insole. In addition the insert 30 may be designed with holes or notched out areas, may be of a unitary design, or it may be layered or formed of adhered segments. An example of varying designs include a single center hole, or a notched out area on one edge that may be desirable for manufacturing, removal, material performance or air transfer. In addition various shapes of this insert 30 may include but are not limited to a cone, bar or strip of specified depth. The advantage of these shapes includes providing variance in the area of coverage for different applications or reduced manufacturing costs.
[0038] By being removable, the insert can be replaced when the material begins to break down and the ability to provide shock-absorbing properties decreases. When to replace this insert 30 is dependent on the wearer. The insert can be replaced after each use or multiple uses over an extended time period. The insert can be constructed of the same material as the midsole or other materials that provide better cushioning and shock absorbing properties but less durable than the midsole or outsole construction. The shoe can provide optimum durability in the initial design of the shoe and increased shock absorbing properties with the disposable insert. In this configuration a shoe can last for a greater period of time than a shoe that is trying to provide both durability and shock absorption, sacrificing one and/or the other providing a mediocre performing shoe.
[0039] Alternative footwear such as work shoes or boots would provide an ideal application for an insert 30 . With some manufactured work footwear the outsole incorporates the midsole into its design. For these applications a removable insert 30 is ideal. The cavity can create an insert 30 area in order to provide better shock absorption and comfort characteristics to an otherwise ridged shoe. The design of some work footwear incorporating a one-piece outsole 50 and midsole 40 is for safety, corrosion resistance, traction and durability, an ideal application. Other applications include but not limited to all types of athletic footwear running, basketball, tennis, cross training, daily footwear casual, business, and specialty footwear.
[0040] For medical reasons the insert 30 materials could be made with highly elastic properties that may not last under repeated use, but would provide the best shock absorption for reduced impact to feet, legs, hips and back. The specific dimension of the insert, for example complete depth from insole to a fraction of an inch to the outside could improve range of motion for the foot. With the insert made of a softer material that compresses easily this would allowing the heel to travel with a greater range of motion relative to the front of the foot. Stretching and recoiling the calf muscle to greater distances.
[0041] As will be readily appreciated from the foregoing, the disclosed embodiments of the present invention provide for a replaceable insert that enables users to replace worn-out support in their footwear. In addition, the insert and shoe design of the present invention enables a user to selectively replace the insert to facilitate a particular activity, such as a high-impact insert for running, a low-impact insert for walking, and a medium impact insert for working conditions. In addition, various environmental factors may be accommodated, such as designing water resistance or water-repellant properties in the insert through the use of materials or architecture. The insert can also be constructed to facilitate breathability between the interior of the shoe and the exterior, such as through the midsole and the outsole to the bottom of the shoe. This can include a pumping-type of action in a one-way or two-way direction to draw air in through the top of the shoe and expel it through the bottom of the shoe as the wearer is walking or running or moving up and down while standing in place.
[0042] More particularly, the disposable insert can be manufactured of a porous or semipermeable material that permits air to pass into and out of the interior of the shoe. This would circulate air in the shoe through repeated compression during movement of the foot. The material that provides circulation for the shoe itself can be manufactured with air passages from the sides, top, or bottom of the shoe or any combination of the foregoing. These passages allow air into and out of the shoe or in only one direction, depending on the design and the incorporation of valves in the insert or the shoe in conjunction with the insert operation. In order to restrict water from entering the shoe, valves or passageways can be designed to restrict water or to channel water away from the interior of the shoe. One design formed in accordance with the present invention; would enable the insert to be rotated about a longitudinal axis to open up air passages when the environment is dry and to rotate in an opposite direction to close air passages between the insert and the shoe to prevent the passage of air and fluid. Thus, passages in the shoe may match up or utilize the insert as a means to control air flow.
[0043] In another embodiment, the insert, which can be disposable, can incorporate a pump mechanism that utilizes valves or channels of different designs and quantities to force air movement in various flow patterns. This would be an actual pump that operates from the pressure of the foot as it moves in the interior of the shoe, and in particular as it exerts pressure on the outsole of the shoe from the interior.
[0044] All of the above U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet, are incorporated herein by reference, in their entirety.
[0045] From the foregoing it will be appreciated that, although specific embodiments of the invention have been described herein for purposes of illustration, various modifications may be made without deviating from the spirit and scope of the invention. Accordingly, the invention is not limited except as by the appended claims.
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A removable, disposable shoe insert that can increase the cushion and shock absorbing properties of a shoe without sacrificing durability or comfort is provided. By using different materials for the insert, the user has the option of when to replace the insert. The insert can be of varying sizes, shapes, hardness, and materials. The insert allows manufactures to make the outsole of more durable materials extending the life of the footwear.
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BACKGROUND OF THE INVENTION
1. Field of the Invention:
The present invention relates a new pigment composition and, more particularly, to a pigment composition useful as a coloring material such as paint, printing ink, or a synthetic resin colorant in which a phosphonic ester compound containing a polyester chain is used as the pigment dispersant or flushing agent.
2. Description of the Prior Art:
In the conventional process for producing paints and printing inks, lecithin, which is one of phospholipids, has been used both as a dispersant for dispersing a pigment into a paint vehicle and printing ink varnish, or as a flushing agent for flushing the aqueous filter cake into an oil vehicle or oil varnish.
Being a natural phospholipid, lecithin is liable to oxidation and rancidity which lead to deterioration and putrefaction. Thus there has been a demand for a dispersant or flushing agent which is stabler and better than lecithin.
In view of the above-mentioned drawbacks of the conventional dispersant or flushing agent and in order to develop a new compound which is compatible with vehicles and varnishes and also with pigments and is useful as a pigment dispersant, the present inventors carried out a series of researches which led to the finding that a phosphoric ester obtained by reacting a polyester having a hydroxyl group with phosphoric acid exhibit outstanding properties and effects required for pigment dispersants. The present invention was completed based on this finding.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to provide a pigment composition composed of a pigment and a dispersant wherein the dispersant is a phosphoric ester compound represented by the formula below. ##STR2## (where one or more than one of the three R's are hydroxyl-terminated polyester residues obtained by self-polycondensation of a hydroxy-carboxylic acid; and one or two of the three R's in case of being remained, are hydrogen atoms, cations, or residues of an alcohol excluding the above-mentioned polyesters.)
DETAILED DESCRIPTION OF THE INVENTION
The dispersant which characterizes the pigment composition of this invention is a specific phosphoric ester compound as defined above.
The phosphoric ester compound used in this invention can be obtained by various methods. According to a preferred method, it is obtained by reacting 1 mole of an ester-forming phosphorus compound with 3 moles, 2 moles, or 1 mole of a hydroxyl-terminated polyester (obtained by self-polycondensation of a hydroxy-carboxylic acid.)
It is also possible to produce the phosphoric ester compound used in this invention by the process is which 1 mole of an ester-forming phosphorus compound is reacted with 1 to 3 moles of hydroxy-carboxylic acid or lower alcohol ester thereof as a monomer and the resulting ester of phosphoric acid and hydroxy-carboxylic acid undergoes chain growth with the same or different hydroxy-carboxylic acid monomer and/or hydroxyl-terminated polyester.
When 1 mole of an ester-forming phosphorus compound is reacted with 3 moles of a hydroxyl-terminated polyester, there is obtained a phosphoric ester compound in which all of the three R's in the above formula are a hydroxyl-terminated polyester residues. Also, when 1 mole of an ester-forming phosphorus compound is reacted with 2 moles or 1 mole of hydroxyl-terminated polyester, there is obtained a phosphoric ester compound in which one or two of the three R's in the above formula are hydroxyl-terminated polyester residues.
Among the ester-forming phosphorus compounds that can be used in this invention are phosphorus oxychloride, phosphorus pentoxide, phosphorus trichloride, phosphoric anhydride, and acetyl phosphate. Perferable among them is phosphorus oxychloride.
The reaction of the above-mentioned ester-forming phosphrous compound with a hydroxyl-terminated polyester should preferably be carried out in an organic solvent which is both inert to the reactants and reaction products and solubilizes them. Examples of such organic solvents include aliphatic saturated hydrocarbons such as octane, petroleum ether, ligroin, mineral spirit, and kerosene; aromatic hydro-carbons such as benzene, toluene, and xylene; halogenated aliphatic hydrocarbons such as trichloroethane and tetrachloroethane; and chlorinated aromatic hydrocarbons such as dichlorobenzene and trichloro-benzene. They have been used for the production of polyesters.
In the case where a halogenated phosphorus compound such as phosphorus oxychloride is used as the ester-forming phosphorus compound, it is desirable to use as a catalyst a tertiary amine such as triethylamine; an organic base such as pyridine, 2, 6-lutidine, and 1,8-diaza-bicyclo-(5.4 0)undecene-7; or an inorganic base such as oxides, hydroxides, carbonates and organic acid salts of alkali metals or alkaline earth metals.
In the case where one or two of the three R's in the above formula are hydrogen atoms or cations (mentioned later), a cation source mentioned later should be added to the reaction mixture to form a salt when the reaction of an ester-forming phosphorus compound with 1 mole or 2 moles of hydroxyl-terminated polyester is substantially complete, or after the hydrolysis is performed as required (in the case where a halogenated phosphorus compound is used as an ester-forming phosphorus compound). The cation source may be added before, during, or after the production of the pigment composition of this invention using the phosphoric ester compound of the above-mentioned formula, which has one or two hydroxyl-terminated polyester residues, with the remaining R's being hydrogen ions.
The molecular weight of the hydroxyl-terminated polyester used in the above-mentioned reaction is not critical. A dimer or a polymer having an average molecular weight lower than 10,000, preferably about 500 to 5,000, can be used.
The hydroxyl-terminated polyester as mentioned above is obtained by self-polycondensation of a hydroxy-carboxylic acid which has both a hydroxyl group and a carboxyl group on the molecule. The preferred hydroxy-carboxylic acids is one which has 4 to 30 carbon atoms. Examples of such hydroxy-carboxylic acid include ricinoleic acid, 12-hydroxy-stearic acid, castor oil fatty acid, hydrogenated castor oil fatty acid δ-hydroxy-valeric acid, ε-hydroxy-caproic acid, p-hydroxyethyloxybenzoic acid, and 2-hydroxynaphthalene-6-carboxylic acid. They may be used individually or in combination with one another.
It is also possible to use, in the same manner a hydroxyl-terminated polyester obtained by esterifying an alcohol with the terminal carboxyl group of a polyester obtained from the above-mentioned hydroxy-carboxylic acid. Examples of the alcohol used for the terminal esterification are alcohols having 1 to 30 carbon atoms, such as methyl alcohol, ethyl alcohol, propyl alcohol, butyl alcohol, hexyl alcohol, octyl alcohol, decyl alcohol, dodecyl alcohol, tridecyl alcohol, hexadecyl alcohol, octadecyl alcohol, tetracosyl alcohol, hexacosyl alcohol, octadecenyl alcohol, cyclohexyl alcohol, and benzyl, alcohol.
The phosphoric ester compound used as a dispersant in this invention is obtained by reacting 3 moles, 2 moles, or 1 mole of the above-mentioned hydroxyl-terminated polyester with 1 mole of the above-mentioned ester-forming phosphorus compound. Where 2 moles or 1 more of the above-mentioned polyester is reacted with 1 mole of the phosphorus compound, one or two R's other than polyester residues in the above-mentioned formula may be groups other than the above-mentioned polyester, such as residues of alcohol compounds, hydrogen atoms, inorganic cations, or organic cations. Examples of the alcohol residues are the residues of the above-mentioned ordinary alcohols, the hydroxy-carboxylic acid above-mentioned as the monomer and hydroxyl ester of the above-mentioned alcohol and the above-mentioned hydroxyl-carboxylic acid.
Examples of inorganic cations include alkaline metals such as sodium and potassium; polyvalent metals such as magnesium, calcium, strontium, barium, manganese, iron, cobalt, nickel, zinc, aluminum, and tin; and ammonium. Examples of organic cations include cations of primary, secondary, and tertiary monoamines and polyamines having 1 to 30 carbon atoms such as methylamine, ethylamine, propylamine, butylamine, hexylamine, octylamine, dodecylamine, octadecylamine, oleylamine, diethylamine, dibutylamine, distearylamine, triethylamine, tributylamine, dimethyloctylamine, dimethyldecylamine, dimethyldodecylamine, dimethyltetradecylamine, dimethylhexadecylamine, dimethyloctadecylamine, dimethyloleylamine, dilaurylmonomethylamine, trioctylamine, dimethylaniline, ethylenediamine, propylene diamine, hexamethylenediamine, and stearylpropylenediamine; quaternary ammoniums such as octadecyl trimethylammonium and dioctadecyl dimethylammonium; and alkanolamines such as ethanolamine, diethanolamine, triethanolamine, dimethylethanolamine, diethylethanolamine, propanolamine, and other alkanolamines obtained by adding ethylene oxide to the above-mentioned higher aliphatic amine. These amines can be used individually or in combination with one another. Where a higher aliphatic amine or ammonium derived from natural oils and fats is used as a raw material, it is possible to use a mixture of amines each differing in carbon number and degree of saturation as such.
The above-mentioned phosphoric ester compound used in this invention comes in different forms according to the substituent group R. The ones defined below are comparatively hydrophobic dispersants adequately soluble in an organic solvent. (1) All of the three R's are residues of hydroxyl-terminated polyester. (2) The three R's are residues of hydroxyl-terminated polyester and residues of other alcohols. (3) One of two of the three R's are cations of a higher amine.
On the other hand, the compound of the above-formula in which one or two of the three R's are cations selected from the alkali metals, ammonium, lower amines, and lower alkanolamines is a comparatively hydrophilic dispersant soluble or dispersible in water or aqueous solutions.
The pigment used in this invention may be any known organic pigment, inorganic pigment, or extender pigment. Examples of organic pigments include phthalocyanine pigments, azo-pigments, condensed azo-pigments, anthraquinone pigments, perinone pigments, perylene pigments, indigo pigments, thioindigo pigment, isindolinone pigment, azomethinazo pigments, dioxadine pigments, quinacridone pigments, aniline black pigments, triphenylmethane pigments, and carbon black. Examples of inorganic pigments include titanium oxide pigments, iron oxide pigments, iron hydroxide pigments, chromium oxide pigments, spinel type calcined pigment, lead chromate pigments, vermilion pigments, Prussian Blue, aluminum powder, and bronze powder. Examples of extender pigments include calcium carbonate, barium sulfate, silicon dioxide, and aluminum hydroxide. These pigments are used in the form of dry fine powder, aqueous filter cake, or aqueous suspension.
The pigment composition of this invention is prepared by compounding 100 parts by weight of the above-mentioned pigment and 1 to 300 parts by weight, preferably 3 to 150 parts by weight, of the above-mentioned phosphoric ester compound. Needless to say, these two components are incorporated with a known proper organic solvent, aqueous or oily paint vehicle, aqueous or oily printing ink varnish, aqueous or oily coating vehicle, thermoplastic resin, thermosetting resin, plasticizer, crosslinking agent, and catalyst. The resulting composition can be used as such as a paint or printing ink. These essential components and optional components can be mixed and dispersed by any known method using a ball mill, sand mill, attritor, continuous horizontal medium dispersing machine, two-roll mill, three-roll mill, pressure kneader, Banbury mixer, or extruder.
In the case where a pigment in the form of an aqueous filter cake or aqueous suspension is used, the pigment composition of this invention can be prepared by the flushing method. According to this method, the pigment is transferred from the aqueous phase to the organic solvent phase by mixing the pigment with the comparatively hydrophobic dispersant among the dispersant used in this invention, alone or, preferably, in the form of a solution in a hydrophobic organic solvent (which may contain a binder for ink or paint).
The pigment composition of this invention may be embodied in the following two forms. (1) A composition containing pigments in high concentrations, which is useful as a coloring agent for printing inks, paints, coating agents, and synthetic resins. In this embodiment, the concentration of pigment is 20 to 95 wt % and the concentration of the dispersant is 1 to 300 wt % pigment weight. (2) A composition useful as a paint which contains a solvent, binder resin, etc. required for paints, printing inks, and coating agents. In this embodiment, the concentration of pigment is 0.1 to 20 wt % and the concentration of the dispersant is 1 to 300wt % for pigment weight.
The paint mentioned above embraces all the known paints containing pigments. Examples include automobile paints, building paints, wood paints, vehicle and machine paints, household paints, plastics paints, precoat metal paints, can paints, ship paints, anticorrosion paints, photocurable paints, electron ray curable paints electrostatic coating power paints, and vinylsol paints.
The printing ink mentioned above embraces all the known printing inks. Examples include letterpress ink, lithographic ink, rotogravure ink, screen ink, newspaper ink, and flexographic ink.
The pigment composition of this invention may be in the form of solid or liquid. In the latter case, the medium is water, a mixture of water and hydrophilic organic solvent, or an organic solvent. Examples of organic solvents include aliphatic, alicyclic, and aromatic hydro-carbons; halogenated hydrocarbons, esters, ketones, glycol ethers, and alcohols. They are not limitative.
The paint vehicle, printing ink varnish, and coating agent vehicle may be any known oily or aqueous binders which are selected according to uses. Examples of the binder include long-oil alkyd resin, medium-oil alkyd resin, short-oil alkyd resin, phenol-modified alkyd resin, styrenated alkyd resin, aminoalkyd resin, oil-free alkyd resin, thermosetting acrylic resin, acryl lacquer resin, acrylpolyol resin, polyester resin, epoxy resin, butylated melamine resin, methylated melamine resin, ureamelamine resin, phenolic resin, rosin-modified phenolic resin, rosin-modified maleic acid resin, phenol-modified maleic acid resin, polyurethane resin, styrene resin, styrene-acrylic resin, styrene-diene copolymer, vinyl chloride copolymer, vinyl-acetate resin, vinyl acetate copolymer, ethylene-vinyl acetate resin, butyral resin, petroleum resin, rosin ester, maleinized rosin ester, drying oil, and boiled oil.
Examples of thermoplastic resins include polyvinyl chloride resin, polystyrene resin, acrylonitrile-styrene resin, acrylic resin, methacrylic-styrene resin, and polyester resin.
Examples of plasticizers include phthalic esters, adipic ester, sebacic esters, polyester plasticizer, and epoxidized soybean oil.
If necessary, the pigment composition of this invention may be used in combination with a known pigment dispersant or flushing agent such as higher aliphatic monoamine, higher aliphatic diamine, and acetate thereof and higher fatty acid salt thereof.
The phosphoric ester compound containing a polyester chain which is used in the present invention is not in danger of deterioration and putrefaction due to oxidation and rancidity, unlike lecithin as a natural phospholipid, which has been conventionally used as a pigment dispersant for paints, printing inks, and plastics colorants. It has good stability and produces an outstanding effect in the surface modification of pigments and the dispersion of pigments in a medium.
The phosphoric ester compound of this invention is readily adsorbed on the pigment surface due to the electronic attraction produced by the phosphoric ester linkage and the ester linkage contained therein and the affinity for mediums produced by the hydrocarbon chain contained therein. This adsorption improves the wettability, dispersibility, and flowability of pigments. In addition, the phosphoric ester compound is useful as a flushing agent for the aqueous filter cake of pigment. It makes the pigment surface lipophilic or hydrophobic, permitting effective flushing of pigments.
The invention is now described in more detail with reference to Referential Examples (production of the phosphoric ester compound) and Working Examples. (In examples, quantities are expressed as parts by weight or percent by weight.)
RENTIAL EXAMPLE 1
(1) Synthesis of hydroxyl-terminated polyester from 12-hydroxy-stearic acid and methylesterification thereof.
Into a four-mouth glass reactor equipped with a stirrer, thermometer, reflux condenser with a moisture distilling tube, and inlet and placed in an oil bath were charged 100 parts of 12-hydroxystearic acid and 100 parts of toluene, followed by stirring for dissolution. After heating, there was added 1.0 part of p-toluenesulfonic acid as a polycondensation catalyst. The reaction liquid was heated to 120° C. to promote the polycondensation of 12-hydroxystearic acid. The progress of the reaction was measured by means of the volume of distilled water and the infrared absorption spectrum of the reaction product after the lapse of 60 minutes, 120 minutes, and 180 minutes. After 200 minutes, the polycondensation reaction was terminated by cooling.
When the reactants were cooled to 63° C., there were added 50 parts of methanol, 100 parts of methyl acetate, and 0.5 parts of p-toluene-sulfonic acid. The reactants were heated to 110° C., with distillation of the solvent, to perform the methylesterification of the terminal carboxyl group of the polyester. When 150 parts of solvent had been distilled away, the reactants were cooled to 63° C. Then 200 parts of methanol were added and the solvent was distilled away by heating to 110° C. The total amount distilled away was 245 parts.
The methylesterification took about 5 hours. After the reaction, 300 parts of water were added to the reaction mixture to extract water-soluble components from the reaction mixture. The oil layer was collected from the separating two layers. For dehydration of the oil phase, 150 parts of toluene and 200 parts of methanol were added, followed by heating to 130° C. with blowing of nitrogen gas. Thus, water and solvents, 345 parts in total, were distilled away.
The reaction product thus obtained was an amber liquid. It was identified a methyl ester of as a self-polycondensation polyester of 12-hydroxystearic acid by the infrared absorption spectrum and gel permeation chromatograph.
It was confirmed by the acid value of the reaction product that the methylesterifiaction of the terminal carboxyl group of the polyester was almost complete. The hydroxyl value of the reaction product was 40.8. This indicates that 1 gram equivalent of the methyl ester of the self-polycondensation polyester of 12-hydroxystearic acid is 1,375 and the average degree of polycondensation is about 5.
(2) Synthesis of phosphoric triester
Into a four-mouth glass reactor equipped with a stirrer, thermometer, dropping funnel, and reflux condenser and placed in a water bath were charged 188.2 parts of the methyl ester of the polyester obtained in the above-mentioned step (1) (1 gram equivalent was 1,375), 188.2 parts of benzene, and 16.6 parts of triethylamine, followed by stirring and dissolution. The dropping funnel was filled with 7.0 parts of phosphorus oxychloride.
The equivalent ratio of the hydroxyl-terminated polyester, phosphorus oxychloride, and triethylamine was 3:3:3.6.
While stirring and cooling the reaction mixture (below 10° C.), phosphorus oxychloride was added dropwise from the dropping funnel over 30 minutes. After addition, the reaction was continued for 2 hours with stirring, followed by cooling.
For the removal of triethylamine (as a dehydrochlorination catalyst) and triethylamine hydrochloride, the reaction mixture was washed with an equal amount of deionized water, half an amount of water acidified with hydrochloric acid, and three times with half an amount of deionized water using a separatory funnel. The washed benzene layer was dried with sodium sulfate and benzene was distilled away under vacuum. Thus there was obtained a brown liquid reaction product.
The reaction product was identified as a phosphoric triester compound of the methyl ester of the self-polycondensation polyester of 12-hydroxy-stearic acid by the infrared absorption spectrum and gel permeation chromatograph. The average molecular weight of the principal component of this compound was 4,200. (Dispersant 1 )
REFERENTIAL EXAMPLES 2 TO 12
Various phosphoric triester compounds were prepared in the same manner as step (2) in Referential Example 1, except that the reactants were replaced by those which are shown in Table 1 below.
TABLE 1______________________________________ Ave.No. Reactants M.W. (I)* (II)**______________________________________2 (Dispersant 2)Methyl ester of poly-12-hydroxy- 880 3 2600stearic acidPhosphorus oxychloride 33 (Dispersant 3)Methyl ester of polyricinolic acid 1430 3 4300Phosphorus oxychloride 34 (Dispersant 4)Butyl ester of poly-12-hydroxy- 920 3 2800stearic acidPhosphorus oxychloride 35 (Dispersant 5)Butyl ester of polyricinolic acid 1470 3 4500Phosphorus oxychloride 36 (Dispersant 6)Dodecyl ester of poly-12-hydroxy- 1310 3 4000stearic acidPhosphorus oxychloride 37 (Dispersant 7)Oleyl ester of polyricinolic acid 1110 3 3400Phosphorus oxychloride 38 (Dispersant 8)Tridecyl ester of poly-12-hydroxy- 1050 3 3200stearic acidPhosphorus oxychloride 39 (Dispersant 9)Oleyl ester of poly-ε-caproic acid 960 3 2900Phosphorus oxychloride 310 (Dispersant 10)Monoalcohol of polyester of azelaic 1100 3 3300acid, hexamethylene glycol, andlauric acid (3:4:1 molar ratio)Phosphorus oxychloride 311 (Dispersant 11)Poly-12-hydroxystearic acid 860 3 2600Phosphorus oxychloride 312 (Dispersant 12)Polyricinolic acid 860 3 2600Phosphorus oxychloride 3______________________________________ *Amount of the reactants (in equivalents) **Average molecular weight of the principal component of the resulting phosphoric triester.
REFERENTIAL EXAMPLE 13
Into a four-mouth glass reactor (the same one as used in step (2) in Referential Example) equipped with a stirrer, thermometer, dropping funnel, and reflux condenser were charged 23.6 parts of phosphorus oxychloride. 147.7 parts of methyl ester of poly-12-hydroxystearic acid having an average molecular weight of 1440 (separately prepared in the same manner as in step (1) in Referential Example 1), which had been mixed with and dissolved in 147.7 parts of benzene and 12.5 parts of triethylamine, was slowly added dropwise at 5° 10° C. over 2 hours. The reaction was carried out at 10° C. for 1 hour. Further, 30.8 parts of the methyl ester of the poly-12-hydroxystearic acid having an average molecular weight of 600 (prepared in the same manner as above), which had been mixed with and dissolved in 30.8 parts of benzene and 6.2 parts of triethylamine, were slowly added dropwise at 10° to 20° C., over 1 hour. The reaction was carried out for 1 hour each at 20° C., 40° C., and 60° C. and for 2 hours at 80° C. with stirring. Finally, the reaction product was cooled.
The molar ratio of polyester (average molecular weight 1440), polyester (average molecular weight 600), phosphorous oxychloride, and triethylamine was 2:1:3:3.6.
The cooled reaction product was washed, purified, dried, concentrated, and desolvated in the same manner as in step (2) of Referential Example 1. Thus there was obtained a brown liquid.
The reaction product was identified as a phosphoric triester of the methyl ester of the poly-12-hydroxystearic acid in the same way as in step (2) of Referential Example 1. The average molecular weight of the principal component of this compund was about 3,500. (Dispersant 13)
REFERENTIAL EXAMPLE 14 TO 19
Various phosphoric triester compounds were prepared in the same manner as in Referential Example 13, except that the reactants were replaced by those which are shown in Table 2 below.
TABLE 2______________________________________ Ave.No. Reactants M.W. (I)* (II)**______________________________________14 (Dispersant 14)Methyl ester of poly-12-hydroxy- 1440 2stearic acidMethyl ester of polyricinolic acid 590 1 3500Phosphorus oxychloride 315 (Dispersant 15)Methyl ester of polyricinolic acid 1430 2Methyl ester of polyricinolic acid 590 1 3500Phosphorus oxychloride 316 (Dispersant 16)Methyl ester of poly-12-hydroxy- 2010 2stearic acidButyl ester of 12-hydroxystearic 1 4400acidPhosphorus oxychloride 317 (Dispersant 17)Methyl ester of polyricinolic acid 2830 1Mixture of dodecyl ester and 2 3900tridecyl esters of ricinolic acidPhosophorus oxychloride 318 (Dispersant 18)Methyl ester of poly-12-hydroxy- 2010 2stearic acidDodecyl alcohol 1 4200Phosphorus oxychloride 319 (Dispersant 19)Methyl ester of polyricinolic acid 2830 1Oleyl alcohol 2 3400Phosphorus oxychloride 3______________________________________ *Amount of the reactants (in equivalents) **Average molecular weight of the principal component of the resulting phosphoric triester.
REFERENTIAL EXAMPLE 20
Synthesis of a phosphoric diester compound:
A four-mouth glass reactor equipped with a stirrer, thermometer, dropping funnel, and reflux condenser and a water bath were provided. The reflux condenser was connected to a safety bottle and a hydrogen chloride gas absorbing bottle which was further connected to a vaccum pump and mercury manometer.
In the reactor was charged 7.0 parts of phosphorus oxychloride. The dropping funnel was filled with 62.8 parts of the methyl ester of the polyester (1 gram equivalent=1,375) obtained in step (1) in Referential Example (1) and 62.8 parts of benzene as a solvent.
With the reactor cooled with iced water, the benzene solution was added dropwise at 5° to 10° C. The reactants were stirred at 10° C. for 1 hour. The reactor was gradually evacuated while increasing the reaction temperature. Hydrogen chloride gas formed by the reaction was absorbed by an aqueous solution of sodium hydroxide filled in the absorbing bottle. The reaction temperature was gradually raised to 40° C. and the reaction system was gradually evacuated to 100 mmHg over 5 hours. When the evolution of hydrogen chloride gas was not noticed any longer, the reaction system was cooled. In this state, the reaction system contains phosphoric (methyl ester of poly-12-hydroxystearic acid) monoester dichloride. The dropping funnel was filled with 62.8 parts of the above-mentioned methyl ester of the polyester, 62.8 parts of benzene, and 4.62 parts of triethylamine, followed by mixing and dissolution. The resulting solution at 10° to 20° C. was added dropwise to the reactor over 60 minutes, followed by stirring for 2 hours. The reaction temperature was raised to 40° C. over 2 hours, and stirring was continued for 2 hours. The reactor was cooled.
The equivalent ratio of the hydroxyl-terminated polyester, phosphorus oxychloride, and triethylamine was 2:3:1.
The reaction liquid was washed with water, a dilute aqueous solution of sodium hydroxide, a dilute aqueous solution of hydrochloric acid, and water, for the dechlorination (hydrolysis) of the phosphoric ester chloride and removal of chloride and the removal of triethylamine hydrochloride. The washed benzene layer was dried with sodium sulfate, and benzene was distilled away under reduced pressure. Thus there was obtained a brown liquid reaction product.
It was confirmed by infrared absorption spectrum and gel permeation chromatograph that the reaction product is composed mainly of a phosphoric diester compound of the methyl ester of the self-polycondensation polyester of 12-hydroxystearic acid. (Dispersant 20)
The average molecular weight of the principal component was 2,500 to 2,800.
REFERENTIAL EXAMPLE 21 TO 30
Various phosphoric diester compounds were prepared in the same manner as in Referential Example 20, except that the reactants were replaced by those which are shown in Table 3 below.
TABLE 3______________________________________ Ave.No. Reactants M.W. (I)* (II)**______________________________________21 (Dispersant 21)Methyl ester of poly-12-hydroxy- 800 2 1600stearic acid to 1800Phosphorus oxychloride 322 (Dispersant 22)Methyl ester of polyricinolic acid 1430 2 2600 to 2900Phosphorus oxychloride 323 (Dispersant 23)Butyl ester of poly-12-hydroxy- 920 2 1700stearic acid to 1900Phosphorus oxychloride 324 (Dispersant 24)Butyl ester of polyricinolic acid 1470 2 2700 to 3000Phosphorus oxychloride 325 (Dispersant 25)Dodecyl ester of poly-12-hydroxy- 1050 2 1900stearic acid to 2100Phosphorus oxychloride 326 (Dispersant 26)Oleyl ester of polyricinolic acid 1110 2 2200 to 2200Phosphorus oxychloride 327 (Dispersant 27)Benzyl ester of poly-12-hydroxy- 1236 2 2200stearic acid to 2500Phosphorus oxychloride 328 (Dispersant 28)Oleyl ester of poly-ε-caproic acid 950 2 1800 to 2000Phosphorus oxychloride 329 (Dispersant 29)Poly-12-hydroxystearic acid 860 2 1600 to 1800Phosphorus oxychloride 330 (Dispersant 30)Polyricinolic acid 860 2 1600 to 1800Phosphorus oxychloride 3______________________________________ *Amount of the reactants (in equivalents) **Average molecular weight of the principal component of the resulting phosphoric diester.
REFERENTIAL EXAMPLE 31
Into the same four-mouth glass reactor as used in Referential Example 21, which was equipped with a stirrer, thermometer, dropping funnel, evacuating system, and hydrogen chloride gas absorber, was charged 7.0 parts of phosphorus oxychloride.
The dropping funnel was filled with 65.8 parts of the methyl ester of poly-12-hydroxystearic acid (average molecular weight=1,440) prepared in the same manner as in step (1) of Referential Example 1, and 65.8 parts of benzene as a solvent. The reaction was carried out in the same manner as in Referential Example 21 to give phosphoric (methyl ester of poly-12-hydroxystearic acid) monoester dichloride. Then, 27.4 parts of the methyl ester of poly-12-hydroxystearic acid (average molecular weight=600) prepared in the same manner as in step (1) of Referential Example 1 was mixed with and dissolved in 27.4 parts of benzene and 4.62 parts of triethylamine. The reaction was carried out in the same manner of in Referential Example 21.
The equivalent ratio of the polyester (average molecular weight=1,440, the polyester (average molecular weight=600), phosphorous oxychloride, and triethylamine was 1:1:3:1.
After cooling, the reaction liquid underwent dechlorination (hydrolysis), washing, purification, drying, concentration, and desolvation in the same manner as in Referential Example 21. Thus there was obtained a brown liquid reaction product.
It was confirmed by infrared absorption spectrum and gel permeation chromatograph that the reaction product is composed mainly of a phosphoric diester of the methyl ester of poly-12-hydroxystearic acid. (Dispersant 31)
The average molecular weight of the principal component was about 1,900 to 2,100.
REFERENTIAL EXAMPLES 32 TO 39
Various phosphoric diester and monoester compounds were pripared in the same manner as in Referential Example 31, except that the reactants were replaced by those which are shown in Table 4 below.
TABLE 4______________________________________ Ave.No. Reactants M.W. (I)* (II)**______________________________________32 (Dispersant 32)Methyl ester of poly-12-hydroxy- 1440 1stearic acidMethyl ester of polyricinolic acid 590 1 1900 to 2100Phosphorus oxychloride 333 (Dispersant 33)Methyl ester of polyricinolic acid 1430 1Methyl ester of polyricinolic acid 590 1 1900 to 2100Phosphorus oxychloride 334 (Dispersant 34)Methyl ester of poly-12-hydroxy- 2010 1 1600stearic acid to 1800Butyl ester of 12-hydroxystearic 1acidPhosphorus oxychloride 335 (Dispersant 35)Methyl ester of polyricinolic acid 1430 1Butyl ester of ricinolic acid 1 1600 to 1800Phosphorus oxychloride 336 (Dispersant 36)Methyl ester of poly-12-hydroxy- 1375 1stearic acidDodecyl alcohol 1 1400 to 1600Phosphorus oxychloride 337 (Dispersant 37)Methyl ester of polyricinolic acid 1430 1Oleyl alcohol 1 1500 to 1700Phosphorus oxychloride 338 (Dispersant 38)Methyl ester of poly-12-hydroxy- 1375 1 1400stearic acid to 1500Phosphorus oxychloride 339 (Dispersant 39)Methyl ester of polyricinolic acid 1430 1 1400 to 1500Phosphorus oxychloride 3______________________________________ *Amount of the reactants (in equivalents) **Average molecular weight of the principal component of the resulting phosphoric diester of monoester.
EXAMPLE 1
Into a flusher were charged 238 parts of an aqueous filter cake (pigment content=42%) of copper phthalocyanine blue pigment (C. I. pigment Blue 15-3). To the flusher were further added 20 parts of Dispersant 1 (obtained in Referential Example 1) dissolved in 58.5 parts of a petroleum ink solvent. Flushing was carried out by mixing in the usual way. As compared with the conventional flushing agent, the dispersant in this example more readily freed water from the cake and transferred the copper phthalocyanine blue pigment to the oily dispersant phase.
After complete removal of water, there was obtained a flushed color containing copper phthalocyanine blue pigment. This flushed color was made into an offset litho ink according to the following formulation.
______________________________________Flushed color (pigment = 56%) 34.8 partsLitho varnish 63.0 parts5% cobalt drier 0.2 parts8% manganese drier 1.0 partsInk solvent 1.0 partsTotal 100.0 parts______________________________________
The litho varnish is formulated as follows:
______________________________________Rosin-modified phenolic resin 35.0 partsDrying oil 25.0 partsDrying oil-modified isophthalic acid alkyd 10.0 partsInk solvent 29.5 partsAluminum chelator 0.5 partsTotal 100.0 parts______________________________________
The ink thus prepared was used offset printing on uncoated printing paper. There was obtained a printed matter of bright cyan color.
A flushed color was prepared in the same manner as above from an aqueous filter cake (pigment content=27%) of disazo yellow pigment (C.I. pigment yellow 12) and an aqueous filter cake (pigment content=25%) of brilliant carmine 6B pigment (C.I pigment red 57-1). The flushed color was made into a yellow and a magenta offset litho ink.
A flushed color was prepared in the same manner as above from an aqueous filter cake of lake red C pigment (C.I. pigment red 53-1), and the flushed color made into a bronze red offset litho ink. A flushed color was also prepared from aqueous filter cake of copper phthalocyanine green pigment (C.I. pigment green 7), and the flushed color was made into a green offset litho ink.
The dispersant readily freed water in the flushing operation and readily transferred the pigment to the oil phase. In addition, the flushed color was easily made into inks and the resulting inks gave a printed matter of bright color in offset litho printing.
When tested as mentioned above, Dispersants 2 to 19 also produced the same effect as Dispersant 1.
EXAMPLE 2
Using Dispersant 1 obtained in Referential Example 1, carbon black was mixed with and dispersed into varnish on a three-roll mill according to the following formulation.
______________________________________Carbon black pigment 20 partsDispersant 1 6 partsOffset litho ink varnish 69 partsTotal 95 parts______________________________________
The resulting carbon black dispersion was made into a carbon black ink by uniform mixing according to the following formulation.
______________________________________Carbon black dispersion 95.0 parts5% cobalt drier 0.2 parts8% manganese drier 1.0 partsInk solvent 3.8 partsTotal 100.0 parts______________________________________
The ink thus prepared was used for offset printing to give a printed matter of high balckness. When tested as mentioned above, Dispersants 2 to 19 also produced the same effect as Dispersant 1.
The yellow ink, red ink, blue ink, and black ink prepared in this example were used as a four-color process ink for offset litho printing to give a bright beautiful multicolor printed matter.
EXAMPLE 3
A blue quick drying enamel (air drying type) for metallic materials (e.g., machines and vehicles) was produced according to the following formulation.
______________________________________Flushed color (pigment = 56%) of copper 9.6 partsphthalocyanine blue obtained in Example 1Rutile titanium white 2.0 partsFast drying styrenized alkyd resin 72.6 partsXylene 6.6 partsMineral spirit 8.8 parts6% cobalt naphthenate 0.3 partsAntiskinning agent 0.1 partsTotal 100.0 parts______________________________________
The resulting enamel provided bright beautiful coatings.
Flushed colors were prepared in the same manner as in Example 1 from an aqueous filter cake of disazo yellow pigment (C.I. pigment yellow 14), fast yellow pigment (formed by coupling acetoacetanilide by diazotizing 4-aminophthalimide), watchung red pigment (C. I. pigment red 48), and carmine FB pigment (C. I. pigment rod 3). The flushed colors were made into paints of varied colors according to the above-mentioned formulation. The paints gave bright beautiful coated plates.
EXAMPLE 4
A dispersion of copper phthalocyanine blue (C.I. pigment blue 15-3) in a xylene-butanol mixed solvent was prepared by dispersing the pigment using a continuous horizontal medium dispersing machine according to the following formulation.
______________________________________Copper phthalocyanine blue pigment 10 parts(dried and pulverized)Dispersant 1 obtained in Referential Example 1 2 partsXylene 13 partsButanol 5 partsTotal 30 parts______________________________________
The resulting dispersion was made into an acrylic lacquer enamel for automobiles according to the following formulation.
______________________________________Solvent dispersion 3.0 partsRutile titanium white 14.0 partsThermoplastic acrylic resin 70.0 partsToluene 6.8 partsXylene 3.2 partsButanol 2.2 partsCellosolve 0.8 partsTotal 100.0 parts______________________________________
The resulting enamel provided bright beautiful coatings.
When tested as mentioned above, Dispersants 2 to 19 also produced the same effect as Dispersant 1.
EXAMPLE 5
Into a flusher were charged 238 parts of an aqueous filter cake (pigment content=42%) of copper phthalocyanine blue pigment (C.I. pigment blue 15-3) and 60 parts of the amine salt of Dispersant 20 dissolved in 40 parts of a petroleum ink solvent. (The amine salt was prepared by neutralizing the phosphoric acid radical of Dispersant 20 with about one equivalent of rosin amine.) Flushing was performed in the usual way. As compared with known flushing agents, the amine salt of Dispersant 20 more readily freed water from the filter cake and more readily transferred the copper phthalocyanine blue pigment to the oily dispersant phase.
After the complete removal of water, there was obtained a flushed color containing copper phthalocyanine blue pigment. The resulting flushed color was made into an offset litho printing ink according to the following formulation.
______________________________________Flushed color (pigment content = 50%) 38.0 partsOffset litho ink varnish 60.0 parts5% cobalt drier 0.2 parts8% manganese drier 1.0 partsInk solvent 0.8 partsTotal 100.0 parts______________________________________
The litho varnish was formulated as follows:
______________________________________Rosin-modified phenolic resin 35.0 partsDrying oil 25.0 partsDrying oil-modified isophthalic acid alkyd 10.0 partsInk solvent 29.5 partsAluminum chelator 0.5 partsTotal 100.0 parts______________________________________
The ink thus prepared was used for offset printing on uncoated printing paper. There was obtained a printed matter of bright cyan color.
A flushed color was prepared in the same manner as above from an aqueous filter cake (pigment content=27%) of disazo yellow pigment (C.I. pigment yellow 12) and an aqueous filter cake (pigment content=25%) of brilliant carmine 6B pigment (C.I. pigment red 57-1). The flushed color was made into a yellow and a magenta offset litho ink.
A flushed color was prepared in the same manner as above rom an aqueous filter cake of lake red C pigment (C.I. pigment red 53-1), and the flushed color was made into a bronze red offset litho ink. A flushed color was also prepared from an aqueous filter cake of copper phthalocyanine green pigment (C.I. pigment green 7), and the flushed color was made into a green offset litho ink.
The dispersant readily freed watrer in the flushing operation and readily transferred the pigment to the oil phase. In addition, the flushed color was easily made into inks and the resulting inka gave a printed matter of bright in offset litho printing.
When tested as mentioned above, Dispersants 21 to 39 also produced the same effect as Dispersant 20.
The same superior effect as mentioned above was produced when the dispersant was neutralized with coconut amine, beef tallow propylene diamine, or hydroxides of calcium, strontium, or aluminum, in place of rosin amine.
EXAMPLE 6
Using Dispersant 20 obtained in Referential Example 20, carbon black was mixed with and dispersed into varnish on a three-roll mill according to the following formulation.
______________________________________Carbon black pigment 20 partsBeef tallow propylene diamine salt of 6 partsDispersant 20Offset litho ink varnish 69 partsTotal 95 parts______________________________________
The resulting carbon black dispersion was made into a carbon black ink by uniform mixing according to the following formulation.
______________________________________Carbon black dispersion 95.0 parts5% cobalt drier 0.2 parts8% manganese drier 1.0 partsInk solvent 3.8 partsTotal 100.0 parts______________________________________
The ink thus prepared was used for offset printing to give a printed matter of high blackness. When tested as mentioned above, Dispersants 21 to 39 also produced the same effect as Dispersant 20.
The same superior effect as mentioned above was produced when the dispersant was neutralized with rosin amine, coconut amine, coconut propylene diamine, or hydroxide of calcium, strontium, or aluminum in place of beef tallow propylene diamine.
The yellow ink, red ink, blue ink, and black ink prepared in this example were used as a four-color process ink for offset litho printing to give a bright beautiful multicolor printed matter.
EXAMPLE 7
A blue quick drying enamel (air drying type) for metallic materials (e.g., machines and vehicles) was produced according to the following formulation.
______________________________________Flushed color (pigment = 50%) of copper 10.8 partsphthalocyanine blue obtained in Example 5Rutile titanium white 2.0 partsFast drying styrenized alkyd resin 72.6 partsXylene 6.6 partsMineral spirit 7.6 parts6% cobalt naphthenate 0.3 partsAntiskinning agent 0.1 partsTotal 100.0 parts______________________________________
The resulting enamel provided bright beautiful coatings.
Flushed colors were prepared in the same manner as in Example 5 from an aqueous filter cake of disazo yellow pigment (C.I. pigment yellow 14), fast yellow pigment (formed by coupling acetoacetanilide by diazotizing 4-aminophthalimide), watching red pigment (C.I. pigment red 48), and carmine FB pigment (C.I. pigment red 3). The flushed colors were made into paints of varied colors according to the above-mentioned formulation. The paints gave bright beautiful coate plates.
EXAMPLE 8
A dispersion of copper phthalocyanine blue (C.I. pigment blue 15-3) in a xylene-butanol mixed solvent was prepared by dispersing the pigment using a continuous horizontal medium dispersing machine according to the following formulation.
______________________________________Copper phthalocyanine blue pigment 10 parts(dried and pulverized)Salt of Dispersant 20 obtained in Referential 2 partsExample 20 (neutralized with about oneequivalent of triethylamine)Xylene 13 partsButanol 5 partsTotal 30 parts______________________________________
The resulting dispersion was made into an acrylic lacquer enamel for automobiles according to the following formulation.
______________________________________Solvent dispersion above-mentioned 3.0 partsRutile titanium white 14.0 partsThermoplastic acrylic resin 70.0 partsToluene 6.8 partsXylene 3.2 partsButanol 2.2 partsCellosolve 0.8 partsTotal 100.0 parts______________________________________
The resulting enamel provided bright beautiful coatings.
When tested as mentioned above. Dispersants 21 to 39 also produced the same effect as Dispersant 20.
The same superior effect as mentioned above was produced when the dispersant was neutralized with rosin amine, coconut amine, beef tallow propylene diamine, coconut propylene diamine, or hydroxide of calcium, strontium, or aluminum, in place of triethylamine.
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There is provided a new pigment composition composed of a pigment and a dispersant wherein the dispersant is a phosphoric ester compound represented by the formula below. ##STR1## (where one or more than one of the three R's are hydroxyl-terminated polyester residues obtained by self-polycondensation of a hydroxy-carboxylic acid; and one or two of the three R's, in case of being remained, are hydrogen atoms, cations, or residues of an alcohol excluding the above-mentioned polyesters.)
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BACKGROUND OF THE INVENTION
The invention relates to a die casting mold part of a die casting mold, having at least one first component comprising a pressure zone, at least one second component and at least one heat exchange chamber which is formed by the components and through which a fluid can flow, for controlling the temperature of the pressure zone, the first component having a heat transfer surface which belongs to at least one wall of the heat exchange chamber and is thermally associated with the pressure zone. The invention furthermore relates to a die casting device.
Such die casting molds are used, for example, for die casting devices for die casting. Die casting is preferably used for the casting of metals, in particular nonferrous metals or special materials. In die casting, the molten casting material, i.e. the melt, is pressed under high pressure with a relatively large speed into a casting mold—also referred to as a mold insert. Melt flow rates of from 20 to 160 m/s and short shot times of from 10 to 100 ms for introduction are achieved in this case. The casting mold, or die casting mold, consists for example of metal, preferably a hot working steel. For die casting, distinction may be made between the hot chamber method and the cold chamber method. In the former, the die casting device and a furnace for keeping the melt hot form a unit. The casting apparatus, which delivers the melt to the casting mold, lies in the melt; in each casting process, a particular volume of the melt is pressed into the casting mold. In the cold chamber method, conversely, the die casting device and the furnace for keeping the melt hot are arranged separately. Only the amount required for the respective casting is dosed into a casting chamber and introduced from there into the casting mold.
The die casting mold consists of at least one die casting mold part, which comprises the first component and the second component. The first component comprises a cavity which constitutes the heat exchange chamber. The cavity, or heat exchange chamber, is closed by means of the second component, which is formed in the shape of a plate, so as to keep a fluid used for cooling the die casting mold part in the heat exchange chamber. The fluid can therefore only be introduced into the heat exchange chamber through an inlet, or an inlet valve, and discharged from the heat exchange chamber through an outlet, or an outlet valve.
The first component comprises the pressure zone, to which pressure is applied by the melt when carrying out the casting process. In this case, the pressure zone is part of a wall of the heat exchange chamber. Preferably, the heat transfer surface which is thermally associated with the pressure zone belongs to the same wall. This means that heat can be transferred between the pressure zone and the heat transfer surface, and the pressure zone is consequently associated in terms of heat transfer with the heat transfer surface. The second component is preferably provided lying away from the pressure zone.
A similar structure is known, for example, from DE 35 02 895 A1. In the case of the die casting mold described in DE 35 02 895 A1, however, the problem arises that reliable and uniform temperature control of the pressure zone is not achievable. For this reason, cooling of the die casting mold part must be dimensioned in such a way that reliable cooling is provided and, at the same time, the cooling of a die-cast component to be produced is not compromised by excessively rapid and/or nonuniform cooling. The constraints of sufficient cooling of the die casting mold part and maximally uniform cooling of the die-cast component lead to comparatively low cycle times in the production of the die-cast component, so as to achieve good durability of the die-cast component in this manner. This, however, means that only a comparatively small number of die-cast components can be produced per unit time.
In relation to this, it is an object of the invention to provide a die casting mold part which does not present the disadvantages mentioned in the introduction, but simultaneously permits a good cooling characteristic and a high throughput (die-cast components per unit time).
SUMMARY OF THE INVENTION
The foregoing object is achieved according to the invention by a die casting mold part. In this case, the second component comprises at least one fluid guide projection extending into the heat exchange chamber and/or a fluid guide recess which is open in the direction of the first component, the fluid guide recess forming at least one part of the heat exchange chamber and/or the fluid guide projection and/or the fluid guide recess forming a flow contour surface, in particular adapted to the profile of the heat transfer surface, of the second component. Thus, the second component is firstly intended to comprise the fluid guide projection or the fluid guide recess. Both the fluid guide projection and the fluid guide recess face in the direction of the first component. This means that the fluid guide projection extends into the heat exchange chamber and the fluid guide recess is formed to be open in the direction of the first component. The fluid guide recess is in this case intended to form at least one part of the heat exchange chamber, so that fluid which is used for controlling the temperature of the pressure zone, or the heat transfer surface, can flow through the fluid guide recess.
By introducing the fluid, adjusted to a particular temperature, into the heat exchange chamber, the temperature of the pressure zone can be adjusted at least approximately in a controlling and/or regulating manner. To this end at least one temperature sensor, with which the temperature of the pressure zone can be determined at least approximately, may be provided on or in the die casting mold part. On the basis of this determined temperature, the temperature and/or throughput (volume or mass per unit time) of the fluid can subsequently be selected, or adjusted. The fluid flows through the heat exchange chamber while flowing over the heat transfer surface. Because the latter is associated thermally, or in terms of heat transfer, with the pressure zone, temperature control of the pressure zone is thereby carried out.
Usually, the temperature of the fluid is in this case much lower than the temperature of the pressure zone, or of the die casting mold part, so that the die-cast component to be produced cools, and can be removed from the die casting device, as rapidly as possible. In contrast to the die casting mold parts known from the prior art, in this case the heat exchange chamber is accordingly formed at least partially in the second component, which permits improved application of the fluid to the heat transfer surface and consequently an improved cooling characteristic, i.e. more rapid cooling of the die casting mold part.
As an alternative or in addition, the fluid guide projection and/or the fluid guide recess form the flow contour surface. The latter is provided on the second component. A flow contour surface is in this case intended to mean a non-planar surface contour. With the contouring of the second component provided in this way, the flow of the fluid onto the heat transfer surface can be improved, or the fluid can be applied in a controlled way to regions of the heat transfer surface. The better cooling characteristic, i.e. the more rapid cooling, can also be achieved in this way. Preferably, the flow contour surface is in this case intended to be adapted to the profile of the heat transfer surface. For example, the flow contour surface and the heat transfer surface may extend parallel to one another at least locally. In this way, the fluid is guided in such a way that the fluid can be applied in a controlled way to regions of the heat transfer surface.
For example, this is provided for regions of the heat transfer surface which correspond to regions of the pressure zone which are thermally loaded particularly heavily. As an alternative, merely the heat transfer surface, or the heat transfer surface and the second component, may also have contouring. Preferably, the heat transfer surface and/or the second component are contoured in such a way that maximally uniform cooling of the die-cast component to be produced is achieved. In this way, stresses in the material of the die-cast component are avoided and a high stability is thus achieved.
At this point, it should expressly be mentioned that the die casting mold part may be used both for the hot chamber method and for the cold chamber method, and for arbitrary material compositions of the melt.
According to a refinement of the invention, the fluid guide recess forms the heat exchange chamber at least for the most part, and in particular completely. It may accordingly be provided that, besides the fluid guide recess, a further recess is present, for example in the first component, which forms the heat exchange chamber together with the fluid guide recess. In this case, however, the volume of the fluid guide recess is intended to be greater than the volume of the further recess. It is particularly advantageous for the heat exchange chamber to be formed exclusively by the fluid guide recess, i.e. no further recess is provided.
According to a preferred refinement, the fluid guide recess is formed in the manner of a trough in the second component. The fluid guide recess is accordingly a recess which is enclosed by the second component in such a way that an opening is merely provided so that the fluid guide recess is open in the direction of the first component. In particular, the fluid guide recess is intended to be at least laterally delimited by the second component. In such an embodiment, for example, a third component connected or connectable to the second component—for example by means of a screw connection—may form the bottom of the fluid guide recess.
According to another configuration of the invention, the first component is formed in the manner of a lid or flatly. In this case, “in the manner of a lid” is intended to mean a configuration of the first component in which—as seen in cross section—it extends further toward the second component in its edge regions than in a central region. This may, for example, be achieved by curvature of the first component or by providing an edge web. As an alternative, however, the first component may also be formed flatly, in which case it has a planar profile as seen in cross section and a distance from the second component is thus essentially constant.
According to a refinement of the invention, a recess of the first component at least locally forms the heat exchange chamber. Such an embodiment has already been indicated above. The heat exchange chamber may be formed fully by the recess of the first component, in which case the fluid guide projection of the second component extends into the recess. As an alternative, both the recess of the first component and the fluid guide recess of the second component may be provided, and together form the heat exchange chamber. Preferably, the volume of the fluid guide recess is in this case greater than that of the recess.
According to an advantageous refinement, the flow contour surface comprises at least one convex and/or concave region jointly formed by the fluid guide projection and/or the fluid guide recess. The flow contour surface may in principle be arbitrarily shaped. Preferably, however, it comprises convexly or concavely formed regions in which the flow contour surface extends continuously, i.e. has no jumps or shoulders. If a plurality of convex and/or concave regions are provided, then the transition between these preferably extends continuously. By the continuous flow contour surface, the heat exchange chamber can be configured favorably in terms of flow, i.e. the fluid flowing through it can experience a comparatively low flow resistance. Furthermore, the occurrence of vortices and/or backward flows is reduced, so that reliable flow of the fluid over the heat transfer surface is provided.
The convex or concave regions may in this case be at least jointly formed by the fluid guide projection and/or the fluid guide recess. This accordingly means that the fluid guide projection or the fluid guide recess at least locally comprises a convexly and/or concavely extending surface. The fluid guide projection or the fluid guide recess may thus also be used as so-called turbulators, so as to increase the heat transfer from the heat transfer surface to the fluid.
According to another configuration of the invention, the contour of the heat transfer surface at least locally is approximated to an in particular three-dimensional contour of the pressure zone or corresponds thereto. This may, for example, be achieved by a uniform wall thickness of the wall which is associated with both the pressure zone and the heat transfer surface on respectively opposite sides. As an alternative, however, by means of a corresponding selection of the wall thickness, a desired thermal conduction rate therein may be achieved, or adjusted in a controlled way for particular regions. For example, it may be provided that the wall thickness of the wall decreases in the flow direction of the fluid, since the fluid is heated while flowing through and its cooling effect on the heat transfer surface or the pressure zone therefore decreases. In order to compensate for this, it may be necessary to increase the thermal conductivity of the wall, which is usually achievable by a smaller wall thickness.
In a preferred configuration, the flow contour surface extends with respect to the heat transfer surface in such a way that there is at least zonally an approximately consistently large flow cross section for the fluid through the flow path of the fluid lying in the heat exchange chamber. Accordingly, the flow contour surface at least locally extends substantially parallel to the heat transfer surface. The consistently large flow cross section for the fluid is thus achieved. Such a configuration has the advantage of reducing the occurrence of vortices and/or backward flows, which preferentially occur in regions in which the flow cross section for the fluid changes too greatly, or too rapidly.
According to a refinement of the invention, the heat exchange chamber is fluidically connected to at least one fluid connection, formed in particular as a fluid line. In order to supply fluid to the heat exchange chamber and/or discharge fluid therefrom, the fluid connection to which the heat exchange chamber is fluidically connected is provided. Preferably, two fluid connections are associated with the heat exchange chamber, in which case the fluid can be supplied to the heat exchange chamber through one of the fluid connections and discharged from the heat exchange chamber through the other. The fluid connections may in this case be formed at least locally as a fluid line—for example formed in a similar way to a pipeline.
According to an advantageous configuration of the invention, the fluid line is at least locally provided in the first component and/or the second component. The fluid line accordingly extends partially through the first and/or second components. For example, the fluid line is provided as a bore and accordingly forms a fluid supply bore or a fluid discharge bore. If a plurality of fluid connections, or fluid lines, open into the heat exchange chamber, then they are preferably arranged significantly separated from one another, in particular when fluid is supplied to the heat exchange chamber by means of one of the fluid connections and fluid is removed by means of the other fluid connection. In this case, an arrangement of the openings of fluid connections or fluid lines on the heat exchanger on—as seen in the flow direction—opposite sides thereof is preferred.
According to another configuration of the invention, the first component or the second component comprises a compartment into which the second component or the first component can be inserted at least locally, in particular fully. Besides inserting the first or second component into the compartment, the former is preferably engaged by the other respective component in such a way that it is fixed at least in the lateral direction, i.e. no slipping of the one component relative to the other component is possible in this direction. In order to support the one component in the vertical direction, a bearing surface may be provided on the other component in the region of the compartment. This bearing surface is preferably formed as a bearing web which extends around further regions of the compartment in an outer region of the compartment. The bearing surface may in this case cooperate with a mating surface of the one component in order to achieve a sealing effect between the one component and the other.
According to a refinement of the invention, the pressure zone of the first component delimits at least a part of a casting mold for a die-cast component, of a casting delivery region and/or of a casting inlet. The casting mold is provided in order to form the die-cast component. During the casting process, the melt is thus introduced into it and the die-cast component is subsequently removed from it. The die casting mold essentially replicates at least one region of the die-cast component in negative. The pressure zone is then provided in order to delimit the casting mold at least locally. The melt is accordingly applied directly to the pressure zone when the casting process is being carried out, so that the latter is exposed to both high temperatures and strong temperature changes. As an alternative or in addition, it is of course also possible to provide that the pressure zone of the first component delimits the casting delivery region or the casting inlet. The latter is often also referred to as a casting die or as a mating die.
According to a preferred refinement, a pressure region of the second component jointly delimits the casting mold, the casting delivery region and/or the casting inlet. Besides the pressure zone of the first component, the pressure region of the second component is thus also provided adjacent to the casting mold, so that the pressure zone and the pressure region together delimit the casting mold at least locally. It is thus possible to provide that the melt is applied to both the first component and the second component during the casting process. As an alternative or in addition, it is likewise possible to provide that the pressure region of the second component delimits the casting delivery region or the casting inlet.
According to an advantageous configuration of the invention, the heat exchange chamber is adapted in its shape to the profile of at least one flow channel associated with the casting mold, the casting delivery region and/or the casting inlet. The shape is therefore adapted in particular to the circumferential contour of the pressure zone, in which particularly good or uniform cooling is intended to be achieved. The heat exchange chamber may for example comprise, in the region of the heat transfer surface, at least one convexity which is thermally associated with the flow channel or the corresponding region of the casting mold, of the casting delivery region and/or of the casting inlet. This applies particularly in plan view, so that from this perspective there may for example be a coast-like profile having at least one convexity or concavity. In this way, an outstanding cooling effect, or cooling characteristic, can also be achieved in the region of the flow channel.
According to a refinement of the invention, the first component is releasably connected to the second component, in particular by means of a screw connection. It is provided that the first component is formed separately from the second component. The at least two components are subsequently assembled to form the die casting mold part while being releasably connected to one another, so that the heat exchange chamber is formed. The releasable connection may in principle be produced arbitrarily. A screw connection having at least one screw or a threaded bolt is, however, preferred.
According to a refinement of the invention, the first and/or the second component comprises at least one sensor compartment for a temperature sensor. The temperature sensor is used to determine the temperature of the first or second component, at least approximately. With the aid of the determined temperature, temperature control of the fluid, or adjustment of a fluid throughput, can be carried out in a controlling and/or regulating manner. Preferably, the sensor compartment is arranged in such a way that the temperature sensor can at least approximately record the temperature of the pressure zone or of the pressure region of the first or second component, respectively.
According to another configuration of the invention, a seal sealing the heat exchange chamber is provided between the first component and the second component. In order to prevent unintended emergence of the fluid from the heat exchange chamber, the seal is associated therewith. The seal may, for example, be configured as an O-ring and essentially engage the heat exchange chamber in the circumferential direction. Replacement of the fluid contained in the heat exchange chamber is of course still possible by means of the fluid connection, or the fluid line.
The invention furthermore relates to a die casting device having at least one die casting mold part, in particular according to the embodiments above, the die casting mold part being part of a die casting mold and having at least one first component comprising a pressure zone, at least one second component and at least one heat exchange chamber which is formed by the components and through which a fluid can flow, for controlling the temperature of the pressure zone, the first component having a heat transfer surface which belongs to at least one wall of the heat exchange chamber and is thermally associated with the pressure zone. In this case, the second component comprises at least one fluid guide projection extending into the heat exchange chamber and/or a fluid guide recess which is open in the direction of the first component, the fluid guide recess forming at least one part of the heat exchange chamber and/or the fluid guide projection and/or the fluid guide recess forming a flow contour surface, in particular adapted to the profile of the heat transfer surface, of the second component. The die casting device is for example a die casting machine, and is accordingly formed in order to produce die-cast components. Besides further generally known elements, it comprises at least one die casting mold part, which is formed or refined according to the embodiments above.
According to an advantageous configuration of the invention, at least one die casting mold respectively forms a casting mold unit, a casting delivery unit and/or a casting inlet unit of the die casting device, the casting mold unit comprising a casting mold, the casting delivery unit comprising a casting delivery region and the casting inlet unit comprising a casting inlet. In this case, the casting mold, the casting delivery region and the casting inlet are respectively delimited at least locally by the pressure zones of the first components of the die casting mold part of the die casting mold. In the casting mold unit, the casting mold is provided, into which the melt is introduced and from which the die-cast component can subsequently be removed. The melt is supplied via the casting delivery unit and/or the casting inlet. Usually, the casting mold unit and the casting delivery unit consist of at least two die casting mold parts, while the casting inlet unit comprises merely one die casting mold part.
According to a refinement of the invention, the casting mold, the casting delivery region and/or the casting inlet are fluidically connected to one another in order for a casting material to flow through. The fluid, or molten, casting material is also referred to as a melt. As already established above, the casting material is supplied to the casting mold via the casting delivery region or the casting inlet. Accordingly, there must be fluidic connection between the casting mold and the casting delivery region, or the casting inlet. The casting mold, the casting delivery region and the casting inlet therefore constitute casting regions through which the melt, or the casting material, can flow.
According to a refinement of the invention, the heat exchange chambers of the casting mold unit, of the casting delivery unit and/or of the casting inlet unit are fluidically connected to one another in order for the fluid to flow through in particular by means of at least one passage or at least one line. Both the casting mold unit and the casting delivery unit, as well as the casting inlet unit, may respectively consist of a die casting mold which, in its turn, comprises at least two die casting mold parts. The casting mold unit, and the casting delivery unit or the casting inlet unit, therefore respectively comprise at least one heat exchange chamber. These heat exchange chambers are intended to be connected to one another in such a way that the fluid can flow through them in common.
In this way, for example, it may be provided that the heat exchange chamber of the casting mold unit comprises a fluid supply connection for supplying the fluid and the casting inlet unit comprises a fluid outlet connection for removing the fluid from the die casting device. The fluid supplied through the fluid supply connection accordingly flows first through the casting mold unit, and subsequently through the casting delivery unit and then through the casting inlet unit, and then emerges from the die casting device through the fluid outlet connection. As an alternative, it is of course possible to provide that the heat exchange chambers of the casting mold unit, of the casting delivery unit and/or of the casting inlet unit respectively comprise mutually separate fluid connections.
Lastly, it is provided that the heat exchange chambers of the casting mold unit, of the casting delivery unit and/or of the casting inlet unit are connected to at least one common fluid connection. In this way, as already mentioned above, it is possible to supply the fluid simultaneously both to the casting mold unit and to the casting delivery unit, as well as to the casting inlet unit, without having to provide separate respective fluid connections. In this way, the construction outlay for the die casting device, or the respective die casting mold part, can be reduced.
Likewise, the casting mold unit, casting delivery unit and casting inlet unit may be regulated or driven individually.
BRIEF DESCRIPTION OF THE DRAWINGS
The invention will be explained in more detail below with the aid of the exemplary embodiments represented in the drawing, without the invention being restricted.
FIG. 1 shows an exploded representation of a die casting device having a casting mold unit, a casting delivery unit and a casting inlet unit, these respectively comprising a die casting mold consisting of two die casting mold parts,
FIG. 2 shows a lateral sectional representation of the die casting device,
FIG. 3 shows one of the die casting mold parts of the casting mold unit, the die casting mold part comprising a first component and a second component, in a view which shows a vertical section of the die casting mold part,
FIG. 4 shows the first component of the die casting mold part according to FIG. 3 ,
FIG. 5 shows the second component of the die casting mold part according to FIG. 3 ,
FIG. 6 shows one of the die casting mold parts of the casting delivery unit, having a first component and a second component, in a view which shows a vertical section of the die casting mold part,
FIG. 7 shows the first component of the die casting mold part according to FIG. 6 ,
FIG. 8 shows the second component of the die casting mold part according to FIG. 6 ,
FIG. 9 shows the second component of the die casting mold part in a view which shows a horizontal section in a plane in which fluid lines of the second component extend,
FIG. 10 shows a die casting mold part of the casting inlet unit, having a first component and a second component,
FIG. 11 shows the die casting mold part of the casting inlet unit in a sectional view which shows a horizontal section,
FIG. 12 shows a view of the first component of the die casting mold part known from FIGS. 10 and 11 from below, a heat exchange chamber formed in the first component being open,
FIG. 13 shows the die casting mold part of the casting inlet unit in a view from below, the heat exchange chamber of the first component being closed by means of the second component,
FIG. 14 shows a view of the die casting mold parts of a casting mold unit, casting delivery unit and casting inlet unit, only the second component of the die casting mold part respectively being represented for the casting mold unit and the casting delivery unit, and
FIG. 15 shows the die casting device known from FIG. 14 , the first component of the casting mold unit and of the casting delivery unit being inserted into the respectively associated second component, and/or vice versa.
DETAILED DESCRIPTION
FIG. 1 shows a die casting device 1 , for example a die casting machine or a part thereof. The die casting device 1 is used for producing one or more die-cast components (not represented). It comprises a casting mold unit 2 , a casting delivery unit 3 and a casting inlet unit 4 . The casting mold unit 2 consists of a first die casting mold 5 , the casting delivery unit 3 consists of a second die casting mold 6 and the casting inlet unit 4 consists of a third die casting mold 7 . The first die casting mold 5 is composed of two die casting mold parts 8 and 9 and the second die casting mold is composed of die casting mold parts 10 and 11 . The third die casting mold 7 consists of a die casting mold part 12 . The die casting mold part 8 comprises a first component 13 and a second component 14 . In a similar way to this, first components 15 , 17 , 19 and 21 and second components 16 , 18 , 20 and 22 are associated with the die casting mold parts 9 to 12 .
The die casting mold parts 8 and 9 of the casting mold unit 2 will first be discussed in more detail below. The casting mold unit 2 comprises a casting mold 23 , which is present at least locally between pressure zones 24 and 25 of the first components 13 and 15 . The casting mold 23 essentially has a cavity having a shape which replicates a negative of a die-cast component to be produced. In a casting process carried out with the die casting device 1 , casting material, or melt, is accordingly introduced into the casting mold 23 between the pressure zones 24 and 25 and, after cooling and solidification of the melt, the die-cast component is removed from the casting mold 23 . To this end, the die casting mold part 8 and/or the die casting mold part 9 can be moved in the vertical direction away from the other respective die casting mold part 9 or 8 . To this end, a corresponding movement device is accordingly provided.
Essentially, the die casting mold parts 8 and 9 are constructed similarly, so that only the die casting mold part 8 will be discussed initially and only the differences from the die casting mold part 9 will be indicated. The second component 14 of the die casting mold part 8 comprises a fluid guide recess 26 , which completely forms a heat exchange chamber 27 of the die casting mold part 8 . The first component 13 is for this reason formed flatly, or in the shape of a plate, and is arranged on the second component 14 in such a way that it closes the heat exchange chamber 27 , or the fluid guide recess 26 . The fluid guide recess 26 is in this case formed in the manner of a trough in the second component 14 . This means that the second component 14 closes the fluid guide recess 26 with the exception of the opening 28 facing in the direction of the first component 13 .
In order to receive the first component 13 , the second component 14 comprises a compartment 29 which is formed in such a way that the second component 14 can fully receive the first component 13 . The pressure zone 24 of the first component 13 in this case lies essentially on a plane having sealing surfaces 30 , which cooperate with corresponding sealing surfaces (not represented here) of the die casting mold part 9 , in order to seal the casting mold 23 from an environment of the die casting device 1 during the casting process. In the compartment 29 , a bearing surface 31 is provided which is formed as a circumferential bearing web and is used to support the first component 13 in the compartment 29 .
Two fluid inlet connections 32 and two fluid outlet connections 33 open into the heat exchange chamber 27 , only one of the latter being visible. The fluid inlet connections 32 and the fluid outlet connections 33 engage as fluid inlet lines and fluid outlet lines, respectively, through the walls delimiting the heat exchange chamber 27 , in order to allow the heat exchange chamber 27 to be supplied with a fluid. In this case, the fluid may be supplied through the fluid inlet connections 32 to the heat exchange chamber 27 and discharged through the fluid outlet connections 33 . The association represented here is to be interpreted as purely exemplary. Thus, the fluid inlet connections 32 and the fluid outlet connections 33 may respectively be interchanged so that the fluid can flow through the heat exchange chamber 27 in different directions. Arranged opposite the pressure zone 24 , there is a heat transfer surface 34 over which the fluid present in the heat exchange chamber 27 flows. The heat transfer surface 34 in this case belongs to a wall of the heat exchange chamber 27 , preferably the same wall as the pressure zone 24 .
The die casting mold part 9 arranged directly opposite the die casting mold part 8 differs from the first essentially in that the first component 15 in this case has a recess 35 which at least locally jointly forms a heat exchange chamber 36 of the die casting mold part 9 . Furthermore, the second component 16 of the die casting mold part 9 has merely one fluid inlet connection 37 .
The comments made above for the die casting mold parts 8 and 9 can essentially be applied to the die casting mold parts 10 and 11 . Nevertheless, the latter will be discussed briefly below. The die casting mold parts 10 and 11 are a component of the casting delivery unit 3 , in which a casting delivery region 38 exists, or is delimited by the first components 17 and 19 . The casting delivery region 38 is in this case present in flow channels 39 (here indicated merely for the first component 17 ) incorporated into the first components 17 and 19 . In the flow channels 39 , there is also a pressure zone 40 of the casting delivery unit 3 .
Opposite the pressure zone 40 , a heat transfer surface 41 is provided on the first component 17 . If the first component 17 is arranged in a compartment 42 provided therefor in the second component 18 , the heat transfer surface 41 together with the second component 18 delimits a heat exchange chamber 43 of the die casting mold part 10 . In the recess 42 , a bearing surface 44 is provided which is formed as a circumferential bearing web. The recess 42 is in this case formed in such a way that the second component 18 can fully receive the first component 17 , so that sealing surfaces 45 of the first component 17 lie flush with sealing surfaces 46 of the second component 18 and cooperate with sealing surfaces (not represented here) of the first component 19 and of the second component 20 in order to seal the casting delivery region 38 from an environment of the die casting device 1 .
In the second component 18 , at least one fluid inlet connection 47 and one fluid outlet connection 48 are provided, which open into the heat exchange chamber 43 . The heat exchange chamber 43 is also formed as a fluid guide recess 49 in this case.
The die casting mold part 11 provided directly opposite the die casting mold part 10 is constructed in a similar way thereto. To this extent, the comments made for the die casting mold part 10 are readily applicable to the die casting mold part 11 and vice versa. FIG. 1 shows that the first component 19 of the die casting mold part 11 comprises a recess 50 . If the first component 19 is arranged in the second component 20 , then this recess 50 serves to jointly form a heat exchange chamber 51 . In a similar way to the second component 18 of the die casting mold part 10 , the second component 20 respectively comprises a fluid inlet connection 52 and a fluid outlet connection 53 .
FIG. 1 furthermore shows the casting inlet unit 4 having the third die casting mold 7 . Associated with the casting inlet unit 4 , there is a cooling ring 54 which comprises a heat exchange chamber 55 that can be closed by a closure plate 56 . The cooling ring 24 in this case comprises a central opening 57 , into which a casting material extension 58 of the first component 21 of the die casting mold part 12 engages. On the casting material extension 58 , a flow channel is formed as a casting inlet 59 which also extends over further regions of the first component 21 as far as the casting delivery unit 3 . Molten casting material (melt) can flow along this casting inlet 59 in order to enter the casting mold unit 2 through the casting delivery unit 3 . In the flow channel 59 , there is to this extent likewise a pressure zone 60 . The latter lies, relative to a wall of the first component 21 , opposite a heat transfer surface 61 (which cannot be seen here). This heat transfer surface 61 is present in a heat exchange chamber 62 , which is formed by a recess 63 of the first component 21 .
The heat exchange chamber 62 is open in the direction of the second component 22 . The second component 22 is in this case used to close the heat exchange chamber 62 , or the recess 63 . The second component 22 comprises a fluid guide projection 64 , which extends into the heat exchange chamber 62 . The fluid guide projection 64 forms a flow contour surface 65 of the second component 22 . The flow contour surface 65 is in this case a non-planar surface contour and comprises a concave region 66 . The concave region 66 is in this case jointly formed by the fluid guide projection 64 . Both a fluid inlet connection 67 and a fluid outlet connection 68 are connected to the heat exchange chamber 62 of the die casting mold part 12 . This, however, cannot be seen in FIG. 1 .
The die casting device 1 represented in FIG. 1 is used for producing die-cast components from a casting material, which is present in the form of the melt. In order to produce the die-cast component, the die casting mold parts 8 and 10 and the die casting mold parts 9 and 11 are moved toward one another so that the casting mold 23 , or the casting delivery region 38 , are sealed. The pressurized melt is subsequently supplied through the opening 57 to the casting inlet unit 4 , then runs along the casting inlet 59 in the direction of the casting delivery unit 3 and flows into its casting delivery region 38 , or the flow channels 39 . The flow channels 39 ensure distribution of the flow of melt, so that the melt can be supplied to the casting mold 23 at different positions as seen in the lateral direction. Melt is supplied to the casting delivery unit 4 until the casting mold 23 is filled.
The melt is subsequently cooled, to which end fluid is introduced into the heat exchange chambers 27 , 36 , 43 , 51 , 55 and 62 . The temperature of the fluid, or its mass flow rate, is selected in such a way that there is an optimal cooling characteristic of the die-cast component. To this end, in particular, it is necessary to cool the latter as uniformly as possible, in order to ensure sufficiently high stability of the die-cast component. A further aim is maximally rapid cooling, in order to achieve a high throughput of the die-cast components and therefore lower production costs.
After solidification, or cooling, of the melt, the die casting mold parts 8 and 10 and the die casting mold parts 9 and 11 are respectively moved away from one another, so that the casting mold 23 and the casting delivery region 38 are released. Likewise, the cooling ring 54 is removed from the casting inlet unit 4 . Subsequently, the produced die-cast component can be removed, together with the sprue remaining in the casting delivery region 38 and the casting material remaining in the region of the casting inlet unit 4 , from the die casting device 1 . In the scope of finishing work, the sprue is removed from the die-cast component and preferably re-melted.
FIG. 2 shows a sectional view of the die casting device 1 , an arrangement of the die casting mold parts 8 to 12 which exists during the casting process being shown. The die casting mold parts 8 and 9 and the die casting mold parts 10 and 11 thus lie closely next to one another. It is clear that the casting mold 23 is delimited not merely by the pressure zone 24 of the die casting mold part 8 and a pressure zone (not denoted in detail) of the die casting mold part 9 , but that the second components 14 and 16 each comprise a pressure region 69 and 70 , respectively, which jointly define the casting mold 23 . In this case, the pressure region 69 ends essentially flatly with the pressure zone 24 and the pressure region 70 with the pressure zone 25 of the first component 15 of the die casting mold part 9 . It can again be seen that the first components 13 and 15 are respectively received fully in the second components 14 and 16 , to which end the compartment 29 is provided in the case of the die casting mold part 8 .
It can furthermore be seen that the components 13 and 14 , 15 and 16 , 17 and 18 , as well as 19 and 20 , are respectively held together by means of a screw connection 71 . Each screw connection 71 in this case comprises at least one screw 72 . It can also be seen that a sensor compartment 73 , in which a temperature sensor (not represented here) can be arranged, is respectively provided in the second components 14 and 16 . By means of this temperature sensor, the temperature of the second components 14 and 16 , or at least approximately the temperature of the pressure zones 24 and 25 , can be determined. On the basis of this determined temperature, the temperature of the fluid or its mass flow rate is subsequently adjusted in a controlling and/or regulating manner. In this way, the melt present in the die casting device 1 can be cooled rapidly and in a controlled way to a particular temperature. Between the components 13 and 14 , 15 and 16 , 17 and 18 , 19 and 20 as well as 21 and 22 , a seal 74 is respectively provided which encloses the entire respectively associated heat exchange chamber 27 , 36 , 43 , 51 or 62 . A high fluid pressure can therefore respectively be applied in the heat exchange chambers 27 , 36 , 43 , 51 and 62 , without the fluid being able to escape unintentionally therefrom.
FIG. 2 again makes it clear that the heat exchange chamber 27 of the die casting mold part 8 may be formed merely by the fluid guide recess 26 of the second component 14 . Conversely, the heat exchange chambers 36 , 43 are respectively formed jointly by the recesses 35 and 50 of the first components 15 and 19 as well as a recess 75 of the first component 17 . It is clear, however, that the die casting mold parts 8 , 9 , 10 and 11 are essentially constructed similarly, while the die casting mold part 12 has a structurally different construction. In the latter, as already described above, the fluid guide projection 24 extends into the heat exchange chamber 62 which is formed by the recess 63 in the first component 21 . In this case, it is furthermore provided that the contour of the heat transfer surface 61 is at least locally adapted to the contour of the pressure zone 60 . The flow contour surface partially extends with respect to the heat transfer surface 61 in such a way that an approximately consistently large flow cross section for the fluid is formed at least zonally.
FIG. 3 shows the die casting mold part 8 in a sectional representation. In this case, unlike the die casting mold part 8 represented in FIG. 2 , the heat exchange chamber 27 is formed together both by the fluid guide recess 26 of the second component 14 and by a recess 76 of the first component 13 . The recess 76 and the fluid guide recess 26 are accordingly in flow connection with one another, in order to form the heat exchange chamber 27 . In this case, they have the same dimensions in the lateral direction, so that side walls of the fluid guide recess 26 and of the recess 76 lie flush with one another. A casting mold compartment 77 can likewise be seen, which is delimited by the pressure zone 24 and the pressure zone 69 . In order to carry out the casting process, the die casting mold part 9 is at least locally received in this casting mold compartment 77 in order to form the casting mold 23 .
In order to make it possible to fill the casting mold 23 , a feed 78 is formed in the second component 14 . Via this feed 78 , a flow connection can be established to the flow channels 39 , or in the casting delivery region 38 of the casting delivery unit 3 . The feed 78 is present even when the sealing surface 30 cooperates with a corresponding sealing surface of the die casting mold part 9 in such a way that the casting mold 23 is sealed from an environment of the die casting device 1 .
FIG. 4 shows the first component 13 . In this case, it is clear that the recess 76 is present in the manner of a trough therein.
FIG. 5 shows the second component 14 . It can be seen that the fluid guide recess 26 has smaller dimensions in the lateral direction than the compartment 29 , in order to form the bearing surface 31 . In FIGS. 4 and 5 , bores 79 can be seen which are provided in order to receive the screws 72 . It is accordingly clear that six screws 72 are provided in order to fasten the first component 13 on the second component 14 .
FIG. 6 shows a sectional view of the die casting mold part 10 , with its first component 17 and the second component 18 . The die casting mold part 10 is formed in the known way. In this regard, reference is made to the embodiments above.
FIG. 7 shows the first component 17 of the die casting mold 10 in a view from below. It is therefore clear that the first component 17 comprises the recess 75 . In this case, this recess 75 comprises tongues 80 , which essentially extend below the flow channels 39 in order to sufficiently cool the pressure zone 40 located therein, by virtue of the fact that the heat transfer surface 41 is also present in this region and fluid can flow over it. Each of the tongues 80 accordingly corresponds to one of the flow channels 39 .
FIG. 8 shows the second component 18 of the die casting mold part 10 . The first component 17 described above is in this case formed as an insertion component for the compartment 42 . It is clear that, in the case of the die casting mold part 10 of the casting delivery unit 3 , the second component 18 comprises a region of the flow channels 39 , and thus forms them together with the first component 17 . The embodiment shown here corresponds to that already known, so that in turn reference is made to the embodiments above.
FIG. 9 shows a sectional view of the second component 18 . In addition to that described above, it is clear that the fluid inlet connection 47 and the fluid outlet connection 48 are respectively formed as a fluid inlet line and a fluid outlet line. Here again, reference should be made to the embodiments above.
FIG. 10 shows the casting inlet unit 4 , consisting of the first component 21 and the second component 22 . The first component 21 comprises the casting material extension 58 , in which the casting inlet 59 and the pressure zone 60 are locally present. Both, however, continue in a bottom region of the first component 21 in the direction of the casting delivery unit 3 .
FIG. 11 shows a sectional view of the casting inlet unit 4 , consisting of the first component 21 and the second component 22 . In order to clarify the structure of the casting inlet unit 4 , a flow 81 of the melt is represented. This is present in the region of the pressure zone 60 . In relation to the wall associated with the pressure region 60 , the heat transfer surface 61 lies opposite thereto. The latter delimits the heat exchange chamber 62 , which corresponds with the fluid inlet connection 67 and the fluid outlet connection 68 . Fluid flowing in through the fluid inlet connection 67 therefore flows through the heat exchange chamber 62 as far as the fluid outlet connection 68 . In this case, the heat transfer surface 61 and therefore also the pressure zone 60 are cooled by the fluid.
It will be indicated here that there is also one of the seals 74 between the first component 21 and the second component 22 . The fluid inlet connection 67 is formed in such a way that fluid flowing out of it into the heat exchange chamber 62 first encounters a deviating region 82 , which is formed by the wall of the first component 21 at the highest point of the heat exchange chamber 62 . The deviating region 82 causes deviation of the fluid, so that the latter flows in the direction of the fluid outlet connection 68 .
FIG. 11 makes it clear that the flow contour surface 65 of the second component extends with respect to the heat transfer surface 61 in such a way that there is an essentially constant flow cross section for the fluid. To this end, the flow contour surface 65 extends at least locally parallel to the heat transfer surface 61 . The second component 22 is arranged on the first component 21 in such a way that it closes the heat exchange chamber 62 . To this end, the heat exchange chamber 62 is provided with an opening on the opposite side of the first component 21 from the pressure zone 60 , and the second component 22 is arranged for closure thereof in this opening.
FIG. 12 shows a view of the first component 21 from below. Because the second component 22 is not represented, a view through the opening into the heat exchange chamber 62 is possible. It is clear that the first component 21 in this case provides a bearing surface 83 for the second component 22 . The seal 74 , which is arranged between the first component 21 and the second component 22 in order to seal the heat exchange chamber 62 , is also present in the bearing surface 83 .
Besides the bores 79 which are arranged for establishing the screw connection 71 between the components 21 and 22 , FIG. 12 also shows a further sensor compartment 73 . A temperature sensor may be arranged therein in order to determine the temperature of the first component 21 , or of the casting inlet unit 4 , at least approximately.
It can also be seen in FIG. 12 that the heat transfer surface 61 has a three-dimensional contour. In this case, the profile of the heat transfer surface 61 , which is shown as being concave in FIG. 11 , is present merely in a vertical section surface (starting from the line 84 ). In the lateral direction, which lies perpendicularly to the section plane, there may be a profile of the heat transfer surface 61 differing from this concave profile. The heat transfer surface 61 is in this case preferably contoured in such a way that maximally uniform cooling of the melt takes place owing to the fluid located in the heat exchange chamber 62 . In principle, however, the heat transfer surface 61 may be configured arbitrarily and, for example, also formed in such a way as to ensure the simplest possible producibility of the first component 21 .
FIG. 13 shows a view of the first component 21 from below, the opening of the heat exchange chamber 62 (which cannot be seen here) being closed by the second component 22 . A compartment 85 , which the first component 21 comprises for the second component 22 , may be fully filled by the second component 22 , although it does not have to be. In the example represented, the second component 22 comprises indentations in the region of a part of the bores 79 , so that the compartment 85 is not fully filled by the second component 22 . It is, however, advantageous for the compartment 85 to be configured in principle in such a way that the second component 22 is fully received in the compartment 85 at least in the vertical direction. This means that a depth of the compartment 85 essentially corresponds to a wall thickness of the second component 22 in the region of the bearing surface 83 , so that the components 21 and 22 form an essentially planar surface with their bottom surfaces.
FIG. 14 shows a view of the die casting device 1 , only the second component 14 and the second component 18 being represented together with the casting inlet unit 4 . Here, it is again clear that the casting inlet 59 of the casting inlet unit 4 is in flow connection with a region of the flow channels 39 which is formed by the second component 18 . The same applies for flow channels 39 lying opposite in the flow direction and the feed 78 of the second component 14 . The components 14 and 18 represented, and the casting inlet unit 4 , correspond essentially to the known embodiments, so that in this regard reference is made to the embodiments above.
FIG. 15 shows the arrangement known from FIG. 14 , the first component 13 now being inserted into the second component 14 and the first component 17 into the second component 18 . The die casting mold parts 8 and 10 are thus essentially complete. There is therefore a flow connection between the casting inlet unit 4 , or the casting inlet 59 , and the casting mold 23 , because the components 17 and 18 together form the flow channels 39 and thus establish a connection between the casting inlet 59 and the feed 78 , and consequently to the casting mold 23 . Here again, reference should be made to the embodiments above for a more detailed description of the individual elements.
It should again be pointed out that at least the die casting mold parts 8 , 9 , 10 and 11 are respectively constructed similarly, so that the properties respectively established above for these elements are for the most part applicable to every other of these elements.
With the die casting device 1 proposed here, or the die casting mold parts 8 to 12 , it is possible to achieve good flow through the heat exchange chambers 27 , 36 , 43 , 51 and 62 , and therefore high heat exchange, or good cooling, of the casting mold 23 , of the casting delivery region 38 and of the casting inlet 59 . In this way, the solidification time of the die-cast component to be produced can be reduced and, at the same time, homogeneous cooling thereof can be achieved. In the regions to be called, there is accordingly an essentially homogeneous temperature pattern at any time. Particularly in the region of the casting mold 23 , an FEM method is used for the configuration of the die casting mold parts 8 and 9 .
The fluid used for the cooling may be either gaseous or liquid. By expedient configuration of the heat exchange chambers 27 , 36 , 51 , 55 and 62 , the effectiveness of the temperature control, or cooling, can be increased. To this end, for example, fluid guide projections in the sense of the die casting mold part 12 , which extend into the respective heat exchange chamber 27 , 36 , 43 , 51 or 55 , are also provided in the die casting mold parts 8 , 9 , 10 and 11 . Such fluid guide projections to this extent serve as turbulators, in order to generate turbulence and therefore increase the heat transfer.
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The invention relates to a die cast part ( 8, 9, 10, 11, 12 ) of a die casting mold ( 5, 6, 7 ), having at least one first component ( 13, 15, 17, 19, 21 ) comprising a pressure zone ( 24, 25, 40, 60 ), at least one second component ( 14, 16, 18, 20, 22 ) and at least one heat exchange chamber ( 27, 36, 43, 51, 55, 62 ) permeated by a fluid and formed by the components ( 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 ) for controlling the temperature of the pressure zone ( 24, 25, 40, 60 ), wherein the first component ( 13, 15, 17, 19, 21 ) comprises a heat transfer surface ( 34, 41, 61 ) integral to at least one wall of the heat exchange chamber ( 27, 36, 43, 51, 55, 62 ) and thermally associated with the pressure zone ( 24, 25, 40, 60 ). The second component ( 14, 16, 18, 20, 22 ) comprises at least one fluid guiding protrusion ( 64 ) protruding into the heat transfer chamber ( 27, 36, 43, 51, 55, 62 ) and/or a fluid guiding recess ( 26, 49 ) open toward the first component ( 13, 15, 17, 19, 21 ), wherein the fluid guiding recess ( 26, 49 ) forms at least one portion of the heat exchange chamber ( 27, 36, 43, 51, 55, 62 ) and/or the fluid guiding protrusion ( 64 ) and/or the fluid guiding recess ( 24, 49 ) form or forms a flow contour surface ( 65 ) of the second component ( 14, 16, 18, 20, 22 ) in particular adapted to the curve of the heat transfer surface ( 34, 41, 61 ). The invention further relates to a die casting device ( 1 ).
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FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of 5,6-dihydro-4-(S)-ethylamino)-6-(S)methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide hydrochloride commonly known as Dorzolamide Hydrochloride. This compound is described in U.S. Pat. No. 4,797,413 as an agent to reduce intraoccular pressure by inhibiting carbonic anhydrase enzyme.
BACKGROUND OF THE INVENTION
A process for the preparation of Dorzolamide Hydrochloride and its derivatives is known. U.S. Pat. No. 5,688,968 describes preparation of Dorzolamide HCl starting from chiral 5,6-dihydro-4-(S)-hydroxy-6-(S)-methyl-4H-thiopyran-7,7-dioxide, as depicted in scheme 1:
The process described in EP 0 296 879 (equivalent of U.S. Pat. No. 4,797,413) is of particular relevance. EP 0 296 879 describes the synthesis of Dorzolamide Hydrochloride starting from thiophene-2-thiol as depicted in scheme 2 and 3
The process described in EP 0,296,879 (scheme 2) has the following disadvantages: (a) The starting material Thiophene-2-thiol is unstable and undergoes oxidation to form disulfide, leading to lower yield of viii; (b) the yield of sulfonamide (xii) from sulphonic acid (x) is very poor (35%) and requires use of 18-crown-6 ether, which is expensive; (c) oxidation of alcohol (xiii) to sulfone is carried out using oxone which is expensive and hazardous; and separation of cis/trans isomer is done by column chromatography which is industrially inconvenient.
OBJECTIVE OF THE INVENTION
The object of present invention is to provide an improved process for commercial manufacture of 5,6-dihydro-4-(S)-(ethylamino)-6-(S)methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide hydrochloride commonly known as Dorzolamide Hydrochloride starting from stable 2-bromo thiophene.
Another object of the invention is to provide an improved process for Dorzolamide hydrochloride preparation, which is less time consuming involving fewer steps and increases the product efficiency.
Another object of the invention is to provide a process for Dorzolamide hydrochloride manufacture, which avoids use of expensive catalyst.
Another object of the invention is to provide a process for Dorzolamide hydrochloride manufacture, which avoids the use of expensive reagents.
Another object of the invention is to provide a process for Dorzolamide hydrochloride manufacture, which is industrially feasible.
SUMMARY OF THE INVENTION
Accordingly, the present invention provides a process for preparing 5,6-dihydro-4-(S)-(ethylamino)-6-(S)methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide hydrochloride of formula (I),
the process comprising
(a) react compound of formula II wherein X is halo, with magnesium metal and treating the generated Grignard reagent in a solvent in situ with sulfur, triethyl amine hydrochloride, crotonic acid and suitable base to obtain compound of formula III,
(b) reacting compound of formula III with a chlorinating agent to obtain a acid chloride, followed by subjecting the acid chloride to cyclisation in the presence of a Lewis acid to obtain a compound of formula IV;
(c) reacting compound of formula IV with a mixture of chlorosulphonic acid and a chlorinating agent to form a sulphonylchloride of formula XX, extracting the sulphonylchloride in a chlorinated solvent, washing with water, drying and evaporating the chlorinated solvent to obtain compound of formula V;
(d) reducing compound of formula V to obtain compound of formula VI;
(e) oxidising compound of formula VI to obtain compound of formula VII;
(f) subjecting compound of formula VII to a Ritter reaction to obtain compound of formula VIII
(g) reducing compound of formula VIII to obtain compound of formula IX
(h) converting compound of formula IX to acid addition salt thereof of formula XXI and recrystallizing enriched salt from the solvent and then converting salt of formula XXI to compound of formula X
(i) resolving compound of formula X into compound of formula I.
In one embodiment of the invention, in step (a), the organic solvent is selected from the group consisting of ethers, cyclic ethers and aromatic hydrocarbon.
In another embodiment of the invention, the organic solvent used in step (a) is tetrahydrofuran.
In yet another embodiment of the invention, step (a) is carried out in the presence of a base selected from the group consisting of organic alkylamine and pyridine.
In a further embodiment of the invention, the base is trialkyl amine.
In a preferred embodiment the base is triethyl amine.
In another embodiment of the invention, in compound of formula II, X is a halo selected from the group consisting of Cl, Br and I.
In another embodiment of the invention, step (a) is carried out at a temperature in the range of 0° C. to 70° C.
In another embodiment of the invention, in step (b), the organic solvent is an aprotic non-polar solvent.
In another embodiment of the invention, the aprotic non-polar solvent used is a chlorinated solvent such as MDC.
In another embodiment of the invention, the Lewis acid is selected from the group consisting of AlCl 3 , ZnCl 2 and SnCl 4 and more preferably SnCl 4 .
In another embodiment of the invention, sulfonyl chloride of formula XX is dissolved in an organic solvent selected from the group consisting of ether and ketone.
In a further embodiment of the invention, the organic solvent is tetrahydrofuran.
In another embodiment of the invention, the sulfonyl chloride of formula XX is dissolved in an organic sovlent and then treated with ammonia followed by chlorination with a chlorinating agent selected from the group consisting of POCl 3 , PCl 5 , PCl 3 , SOCl 3 and more preferably SOCl 2 and in the presence of a chlorination solvent selected from the group consisting of CHCl 3 , MDC, and EDC, preferably MDC.
In another embodiment of the invention, in step (d) reduction is effected using sodium borohydride in the presence of a solvent and at a temperature in the range of 0° C. to 40° C.
In a further embodiment of the invention, the solvent is a lower aliphatic alcohol and more preferably methanol.
In another embodiment of the invention, in step (e) compound of formula VI is oxidised with sodium perborate in presence of acetic acid at 20° C. to 70° C.
In another embodiment of the invention, in step (f) the Ritter reaction of compound of formula VII is effected in a strong acid with acetonitrile at 10° C. to 40° C.
In a further embodiment of the invention, the strong acid is selected from the group consist of sulfuric acid and a mixture of concentrated sulfuric acid and forming sulfuric acid.
In another embodiment of the invention, in step (g), reduction is effected using borane dimethylsulfide complex in an organic solvent selected from ether and cyclic ether.
In a further embodiment of the invention, the organic solvent used in step (g) is tetrahydrofuran.
In another embodiment of the invention, in step (h), the organic solvent is selected from the group consisting of a ketone, an ester, a dipolar aprotic solvent, lower aliphatic alcohol, aliphatic hydrocarbon and aromatic hydrocarbon.
In a further embodiment of the invention, the ester is ethyl acetate.
In a further embodiment of the invention, the acid used for salt formation in step (h) is a mineral acid selected from the group consisting of HCl, H 2 SO 4 , HNO 3 , and HBr more preferably HCl dissolved in a lower aliphatic alcohol.
In a further embodiment of the invention, the acid used for salt formation in step (h) is ethanolic HCl.
In another embodiment of the invention, the organic solvent used for recrystallization is selected from the group consisting of a ketone, an ester, a dipolar aprotic solvent, lower aliphatic alcohol, aliphatic hydrocarbon or aromatic hydrocarbon, preferably an ester, lower aliphatic alcohol or mixture thereof, more preferably ethyl acetate, ethanol or mixture thereof.
In a further embodiment of the invention, the compound of formula X is rsolved using di-p-toluyl-L-tartarate and di-p-toluyl-D-tartarate.
DETAILED DESCRIPTION OF THE INVENTION
The invention provides a process for preparing 5,6-dihydro-4-(S)-(ethylamino)-6-(S)methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide hydrochloride of formula (I), comprising of nine steps, as depicted in scheme 4 below:
Step I:
Preparation of compound of formula III by reacting compound of formula II with magnesium metal followed by treatment of thus generated Grignard reagent in a solvent in situ with sulfur, triethyl amine hydrochloride, crotonic acid and suitable base at 0° C. to 70° C. as shown in scheme 5,
X of formula II is a halo —Cl, —Br, —I preferably —Br.
The organic solvents are ethers, cyclic ethers and aromatic hydrocarbon but preferably cyclic ethers and sore preferably THF. The base is an organic alkylamine or pyridine, preferably trialkyl amine and more preferably triethyl amine.
Step II:
Preparation of compound of formula IV by reacting compound of formula III with chlorinating agent followed by cyclisation of acid chloride of formula XIX generated in-situ in presence of Lewis acid in a solvent at 0° C. to 40° C. as shown in scheme 6.
The organic solvents are aprotic non-polar solvents, preferably chlorinated solvents and more preferably MDC. Lewis acids are AlCl 3 , ZnCl 2 , SnCl 4 and more preferably SnCl 4 .
Step III:
Preparation of compound of formula V by reacting compound of formula IV with mixture of chlorosulphonic acid and chlorinating agent at −10° C. to 10° C., extracting thus formed sulphonylchloride of formula XX in a chlorinated solvent, washing with water, drying and evaporating the chlorinated solvent. Dissolving the sulfonyl chloride of formula XX in suitable organic solvents followed by treatment with ammonia as shown in scheme 7
The chlorination agent is selected from POCl 3 , PCl 5 , PCl 3 , SOCl 2 and more preferably SOCl 2 . Chlorination solvents are preferably selected from CHCl 3 , MDC, and EDC, more preferably MDC. The organic solvent for dissolving sulfonyl chloride is an ether or a ketone, preferably other and more preferably THF.
Step IV:
Preparation of compound of formula VI by reducing compound of formula V with sodium borohydride in presence of solvent at 0° C. to 40° C. as shown in scheme 8.
The organic solvent is lower aliphatic alcohol and more preferably methanol.
Step V:
Preparation of compound of formula VII by oxidizing compound of formula VI with sodium perborate in presence of acetic acid at 20° C. to 70° C. as shown in scheme 9.
Step VI:
Preparation of compound of formula VIII by Ritter reaction of compound of formula VII in strong acid with acetonitrile at 10° C. to 40° C. as shown in scheme 10.
The strong acids are concentrated sulfuric acid or mixture of concentrated sulfuric acid and filming sulfuric acid.
Step VII:
Preparation of compound of formula IX by reducing compound of formula VIII with borane dimethylsulfide complex in organic solvents. As shown in scheme 11
The organic solvents are ethers, cyclic ethers, preferably cyclic ethers and more preferably THF.
Step VIII:
Preparation of compound of formula X by converting the compound of formula IX to its acid addition salt in a solvent followed by recrystallisation of the enriched salt from an organic solvent or a mixture of solvents as shown in scheme 12. The organic solvent is a ketone, an ester, a dipolar aprotic solvent, lower aliphatic alcohol aliphatic hydrocarbon or aromatic hydrocarbon, preferably an ester and more preferably ethyl acetate. The acid used for salt formation is a mineral acid like HCl, H 2 SO 4 , HNO 3 , HBr more preferably HCl dissolved in lower aliphatic alcohol preferably ethanol. The acid used for salt formation is most preferably ethanolic HCl. The organic solvent for recrystallization is a ketone, an ester, a dipolar aprotic solvent, lower aliphatic alcohol, aliphatic hydrocarbon or aromatic hydrocarbon, preferably an ester, lower aliphatic alcohol or mixture thereof, more preferably ethyl acetate, ethanol or mixture thereof.
Step IX:
Preparation of compound of formula I by resolution of compound of formula X using di-p-toluyl-L-tartarate and di-p-toluyl-D-tartarate.
The process of manufacturing Dorzolamide hydrochloride by the present invention comprises use of 2-bromo thiophene as a stating material avoiding use of unstable thiophene-2-thiol. The process of the said invention requires less number of steps since sulfonamide of formula IV is prepared directly from compound of formula III avoiding isolation of sulfonic acid X. This eliminates the use of an expensive catalyst. The process of invention uses cheap, commercially available sodium perborate as an oxidizing agent, thus making the process more economical. The process of the said invention makes use of hydrochloride salt formation as a means to separate cis:trans isomer thus avoiding industrially cumbersome column chromatography.
EXPERIMENTAL
Example 1
Preparation of (RS) 3-(2-mercaptothiophene)butanioc acid(III)
To a mechanical stirred mite of magnesium turnings (20 gm, 0.833 moles) in THF (700 ml), crystal of iodine and 2-bromo thiophene (II) (5.0 gm 0.0305 mole) were added to initiate reaction. Once reaction was initiated, 2-bromo thiophene (95 gm 0.58 mole) was added to maintain reflux which was then continued for 2 hrs then cooled to 45° C. Sulfur (19.66 gm, 0.614 mole) was then added maintaining temp. below 50° C. and stirring continued for 2 hrs. Triethyl amine hydrochloride (84 gm, 0.611 mole) was then added at 45° C. and stirring continued for 1 hrs. A mixture of triethyl amine (80 gm, 0.79 mole) and crotonic acid (63 gm, 0.733 mole) in THF (200 ml) was then added at 45° C. The mixture was refluxed for 18 to 20 hrs. pH was adjusted to 2 to 2.5 by 6 N HCl at 0° to 15° C. The compound of formula (III) was extracted with MDC and concentrated to dryness to gave title compound (123 gm, 100%).
1 H NMR (CDCl3) δ 1.35 (d, 3H, J=6.9 Hz, CH 3 ) 2.48 (dd, 1H, J=8.0 J=16.1 Hz,CH 2 ) 2.77 (dd, 1H, J=6.4 J=16.1 Hz, CH 2 ) 3.36–3.42 (m, 1H,CH) 7.03 (dd, 1H, J=3.4 J=5.3 Hz, 3-H) 7.20 (dd, 1H, J=1.2 J=3.4 Hz, 4-H) 7.43 (dd, 1H, J=1.2 Hz, J=5.3 Hz, 2-H)
Example 2
Preparation of 5,6 dihydro-4H-6-methylthieno[2,3-b]thiopyran-4-one (IV)
To a solution of product from example 1 (123 gm 0.609 mole) in MDC (1845 m) and DMF (10 ml) thionyl chloride (54.35 ml, 0.73 mole) was added dropwise and mixture stirred at reflux temperature of 37 to 40° C. for 2 hrs. The mixture was cooled to −10° C. and a solution of SnCl 4 (39.12 ml, 0.33 moles) in MDC was added dropwise maintaining temperature below 0° C. The reaction was stirred at 0° C. for 1 hr, and water (500 ml) was then added dropwise while maintaining temperature below 10° C. The layers were separated. The aqueous phase was extracted with MDC and organic layers were washed with water followed by saturated bicarbonate solution, finally with brine. MDC layer was then stirred with silica gel (100 gm), filtered and washed by MDC. Organic layer was dried with anhydrous sodium sulphate. Finally organic layer was concentrated completely to get title compound (91 gm, 81.1%)
1 H NMR (CDCl3) δ 1.48 (d, 3H, J=6.9 Hz, CH 3 ) 2.69 (dd, 1H, J=11.4 J=16.8 Hz, CH 2 ) 2.88 (dd,1H, J=3.2 J=16.8 Hz, CH 2 ) 3.80 (t,1H, CH) 7.01 (d,1H, J=5.5 Hz, 3-H)7.46 (d, 1H, J=5.5 Hz, 2-H)
Example 3
Preparation of 5,6 dihydro-4H-6-methylthieno[2,3-b]thiopyran-4-one-2-sulfonamide (V)
To stirred solution of chlorosulphonic acid (196.9 ml, 2.96 mole), thionyl chloride (71.67 ml, 0.987 mole) was added slowly at temperature 0° C. to 10° C. The mixture was stirred at a temperature of 30° C. to 32° C. for 3 hrs and then cooled to 0° C. Compound prepared in Example 2 (91 gm, 0.494 Mole) was slowly added at temperature of 0° C. to 5° C. The mixture was then stirred at temperature of 0 to 5° C. for 1 hr and the temperature then raised to 25 to 30° C. and maintained for 5 to 10 hrs. MDC (1000 ml) was then added and the reaction mass was quenched using 700 gm of ice below temperature of 20° C. The lower organic layer was separated. The aqueous layer was extracted with MDC and mixed to main organic layer which is washed with chilled water. The organic layer was concentrated to get a sticky mass (130 gm) which was then dissolved in THF (100 ml), to which was added to (150 ml) chilled liquor ammonia. This was stirred for 2 hrs and ice water (2000 ml) added. This was further stirred for 3 hrs and filtered and washed with water, and dried to get title compound (V) (65 gin 50%).
1 H NMR (DMSO d-6) δ 1.51 (d, 3H, J=6.9 Hz, CH 3 ) 2.70 (dd, 1H, J=11.4 J=16.8 Hz, CH 2 ) 2.93 (dd, 1H, J=3.2 J=16.8 Hz,CH 2 ) 3.80–4.0 (bm, 1H, CH) 4.62–4.80 (bm, 1H, CH) 7.32 (bs, 2H, NH 2 ) 7.84 (d, 1H, J=5.5 Hz, 3-H)
Example 4
Preparation of 5,6 dihydro-4H-4-hydroxy-6-methylthieno[2,3-b]thiopyran-2-sulfonamide (VI)
To a suspension of product from example 3 (65 gm, 0.247 mole) in methanol (455 ml) sodium borohydride (7.03 gm, 0.185 mole) was added and the resulting mixture stirred for 2 hrs at 25 to 30° C. Methanol was concentrated from reaction mixture to get a sticky mass. Water (1000 ml) was added to the sticky mass and the mixture stirred for 0.5 hrs and the pH adjusted to 6.5 to 7.0 by acetic acid. Stirring was then done 1 hrs at 20 to 25° C. The product obtained was filtered and washed with water. The cake was sucked to remove as much water as possible, and dried to get title compound (64.4 gm, 99%).
Example 5
Preparation of 5,6 dihydro-4H-4-hydroxy-6-methylthieno[2,3-b]thiopyran-2-sulfonamide-7,7 dioxide (VII)
To a suspension of product from example 4 (64.4 gm, 0.242 mole) in Acetic acid (320 ml) sodium perborate (83.48 gm, 0.545 mole) was added and resulting mixture stirred for 1 hr at 25 to 30° C., then heated to attain temperature 60 to 65° C. and maintained for 3 hrs. Acetic acid was concentrated from reaction mixture to get a sticky mass, which was dissolved in water (400 ml). Product was extracted with ethyl acetate. Organic layer was concentrated to keep inside volume 100 ml and then cooled to 0 to 5° C. and stirred for 2 hrs. The product was filtered and washed with chilled ethyl acetate. The cake was sucked to remove as much ethyl acetate as possible, and dried to get title compound (55 gm, 76.27%).
1 H NMR (DMSO d-6) δ 1.49 (d,3H,CH 3 ) 2.42 (m,2H, CH 2 ) 3.55 (m,1H, 6-H) 4.60–4.90 (m,1H, 4-H) 7.51 (bs,2H, NH 2 ) 7.69 (bs,1H, 3-H)
Example 6
Preparation of 5,6 dihydro-4H-4-acetylamino-6-methylthieno[2,3-b]thiopyran-2-sulfonamide-7,7 dioxide (VIII)
A solution of product from example 5 (55 gm, 0.185 mole) in acetonitrile (715 ml) was cooled to 0 to 5° C. and sulfuric acid (167.5 ml, 3.144 mole) added dropwise maintaining temperature 0 to 5° C. The temperature was allowed to rise to 25 to 30° C. The mixture was stirred for 25 to 27 hrs. The reaction mixture was added to mixture of water and ethyl acetate below 5° C. and pH of reaction mixture was adjusted to 7.5 by 50% solution of sodium hydroxide. The sodium sulphate salt was filtered and washed with ethyl acetate. The organic layer was separated. Aqueous layer was extracted with ethyl acetate. The organic layer was concentrated to get sticky mass as title compound (VII) (50 gm. 91.6%).
1 H NMR (DMSO d-6) δ 1.47(d, 3H, CH 3 ) 1.96 & 2.01 (s,3H each, COCH 3 ) 2.30–2.60 (m,2H, CH 2 ) 3.70–3.85 (m,1H, CH) 5.20–5.30 (m,1H, CH) 7.44 & 7.88 (s, 2H, NH 2 ) 7.59 (s, 1H, 3-H)
Example 7
Preparation of 5,6 dihydro-4H-4-ethylamino-6-methylthieno[2,3-b]thiopyran-2-sulfonamide-7,7 dioxide (IX)
To a solution of borane dimethyl sulfide complex (52.59 ml, 0.546 mole) and THF 108 ml) product from example 6 (50 gm, 0.148 mole) in THF (80 mole) was added at 0 to 5° C. The temperature was allowed to rise 25 to 30° C. and mixture stirred for 10 hrs. The reaction mite was added to 1 N sulfuric acid (190 ml) at 0 to 5° C. and stirred for 1 hr. pH was adjusted to 7 with 50% sodium hydroxide solution, and stirred for 1 hr and then product extracted with ethyl acetate. Ethyl acetate layer was concentrated to get sticky mass as title compound (IX) (39.5 gm, 82.41%).
Example 8
Preparation of Trans 5,6 dihydro-4H-4-ethylamino-6-methylthieno[2,3-b]thiopyran-2-sulfonamide-7,7 dioxide (X)
A solution of product from example 7 (39.5 gm, 0.132 mole) in ethyl acetate (426 ml) was cooled to 0 to 5° C. and ethanolic HCl (20 ml) was added and stirred for 3 hrs at 0 to 5° C. The product was precipitated out, filtered and washed with chilled ethyl acetate. The cake was sucked to remove as much ethyl acetate as possible, and dried to get compound (21 gm) The product was suspended into ethyl acetate (210 ml), refluxed for 1 hr, then cooled to 10° C. The product was filtered and washed with chilled ethyl acetate. The cake was sucked to remove as much ethyl acetate as possible, and dried to hydrochloride salt of title compound (18 gm). The salt was then treated with saturated solution of sodium bicarbonate and mixture extracted with ethyl acetate. The organic extract were dried, filtered and concentrated to dryness to yield title compound (X) (15 gm, 37.98%).
Example 9
Preparation of 5,6 dihydro-4H-4-(S)-ethylamino-6-(S)-methylthieno[2,3-b]thiopyran-2-sulfonamide-7,7 dioxide Hydrochloride (I)
A mixture of compound from example 8 (15 gm0.0462 mole) and di-p-toluyl-D-tartaric acid monohydrate (4.55 gm, 0.01125 mole) in n-propanol (1600 ml) was heated to boiling and hot solution filtered through a filter-aid pad with a layer of charcoal. The filtrate was concentrated by boiling to a volume of about (400 ml) and then allowed to crystallize. After standing overnight the crystals were filtered off and material recrystallized twice more from n-propanol (400 ml) to yield a 2:1 salt of free base to acid. Combined mother liquors from this recrystallization were saved for stage B. The salt was then treated with a saturated solution of sodium bicarbonate and mid extracted with ethyl acetate. The organic extract were dried, filtered and concentrated to dryness to yield (3.2 gm) of freebase. The hydrochloride salt was prepared from 5,6 N HCl ethanol and crystallized from methanol-isopropanol to yield (2.83 gm) of (+) isomer, SOR 8.23 (C 0.9 methanol) M.P. 283–285° C. The combine mother liquor was treated with saturated solution of sodium bicarbonate and mixture extracted with ethyl acetate. The organic exacts were dried, filtered and concentrated to dryness. The residue was treated with di-p-toluyl-L-tartaric acid monohydrate (4.55 gm, 0.01125 mole) in n-propanol (1600 ml) and the isomer separated by the process described previously to give title compound (I) (3.75 gm, 22.48%) SOR=−8.34 (C 1, Methanol) M.P. 283 to 285° C.
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The present invention relates to an improved process for the preparation of 5,6-dihydro-4-(S)-(ethylamino)-6-(S)methyl-4H-thieno[2,3b]thiopyran-2-sulphonamide-7,7-dioxide hydrochloride of formula (I) commonly known as Dorzolamide Hydrochloride useful as an agent to reduce intraoccular pressure by inhibiting carbonic anhydrase enzyme
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation of application Ser. No. 13/218,734 filed on Aug. 26, 2011. This application also claims priority of Provisional Patent Application Ser. No. 61/377,655 filed on Aug. 27, 2010.
FIELD
[0002] This disclosure relates to a shield for a pacifier or other structure that is to be placed in the mouth of an infant.
BACKGROUND
[0003] Once an infant begins to turn his head with neck extension, suckling becomes an active oral pattern with large up and down and forward/back movements of the jaw; and rhythmic forward/back movement of a cupped tongue. The newborn's respiratory function is characterized by obligatory nasal breathing because of the close approximation of the tongue to the soft palate and posterior pharyngeal wall, which can obstruct oral airway patency.
[0004] The perioral region is richly supplied with neural mechanoreceptors capable of inducing the tissue changes associated with movements of the lower face (Barlow 1991).
[0005] Human lip muscles display excitatory reflex responses. Particular attention is directed to the obicularis oris, buccinators muscles, mentalis muscles and underlying bone as being supportive resting areas of the pacifier shield.
[0006] Oral shields are commonly used in applications such as pacifiers, teethers, feeding devices and sippy cups. Shield designs (Panicci, U.S. Pat. No. 4,403,613 and Uehara, U.S. Pat. No. 6,767,357) disclose the lower part of the shield slightly curving away from the face. The Panicci design is not sufficiently offset to allow for free forward posturing of the mandible. Additionally, Panicci does not recognize the need to be supportive only on upper arch, and is not designed based on available anthropometrics. Panicci (in contradiction to the present invention) will intensify the sensory and motor components against the lower lip and contribute a retrusive stimulation and force against the mandible and other areas below the upper arch and intermaxillary space. This reflex will actually cause more restriction of the upper airway.
[0007] The relative magnitudes of lip-muscle reflex components are known to vary in a systematic manner with the stimulation of the lip muscle and site of stimulation.
[0008] Current designs of pacifier baglets (to be differentiated from the pacifier shield) claim benefits to orthodontic development, particularly of the maxillary arch. These designs are often paired with different oral shields for corresponding size or marketing purposes. Beyond these claims of orthodontic benefits, pacifiers have also been shown to reduce the incidence of SIDS (Sudden Infant Death Syndrome). The mechanism of this protection is believed to be in the maintenance of a patent oral airway during infant sleeping in a supine position and pacifier sucking. It has been hypothesized that the association of pacifier use with reduced risk of Sudden Infant Death may be mediated by forward movement of the mandible and tongue. Pacifier use helps to open the upper airway and further to move the mandible forward when an infant is sucking on a pacifier (Tonkin S L, Lui D, McIntosh C G, Rowley S, Knight D B, Gann A L, Effect of Pacifier Use on Mandibular Position in Preterm Infants, Acta Paediatr, 2007, October; 96(10):1433-6. Epub 2007 Aug. 20). Retroposition of mandibles have been considered an additional risk factor for sudden infant death. (Rees K, Facial Structure in the sudden infant death syndrome: case control study, BMJ 1998 317:179-180) Forward posturing of the mandible may therefore increase the efficiency of the oral airway. Further Tonkin found that there was significant forward movement of the mandible when premature infants were sucking on a pacifier, and be proposed that the common pathologic mechanism of SIDS was airway occlusion by backward displacement of the tongue and mandible (Tonkin St et al., Positional upper airways narrowing and an apparent life threatening event, NZ Med J. 2002 115:193-4; Tonkin S., Sudden Infant Death Syndrome: Hypothesis of Causation, Pediatrics 1975; 55:650-661).
[0009] Further, treatment of airway obstruction by mandibular advancement and distraction osteogenesis, used to eliminate mandibular retrognathia and malposition of the tongue, is also used as a surgical solution for airway obstruction in some cases (Bouchard C., Management of Obstructive Sleep Apnea: Role of Distraction Osteogenesis, Oral Maxillofacial Surg ClinN Am 21(20090459-475)).
[0010] The design of the pacifier shield has largely been based on safety testing/requirements, ease of manufacturing, skin health and moisture retention under shield, handle grip, sized generally “to fit” at different ages, esthetics and marketability. The approximation of the shield against the face, and particularly against the perioral region, can have a restrictive effect on the posturing of the lower jaw during sucking. The retrusive pressure of the shield'against the lower perioral region may play an unreported, but significant role in reclueing the beneficial effect that infant pacifier sucking has on the airway of the infant. The shield may in fact, discourage a more forward mandibular posture during sucking of the baglet as the shield is pulled back tight against the inferior perioral area, more specifically the anterior mandibular alveolus, erupting mandibular incisors and mandibular symphysis. This inward suck force creates a strong posteriorly-directed pressure of the shield against the mandible.
SUMMARY
[0011] Reproducible standardized biomarkers of the face of infants are available in the literature Cephalometric radiology, anthropometry, stereo-photometry and most recently apical CT have been used on cohorts of infants of differing ages, sex, inter-racial differences and nationalities. Examples are—Waitzman A. A. et al, Craniofacial Skeletal Measurements based on Computed Tomography: Part II Normal Values and Growth Trends, Cleft Palate-Craniofacial J March 1992 29(2): 118-128; or White J et al., Three Dimensional Facial Characteristics of Caucasian infants without clefts and correlation with Body measurements, Cleft palate-Craniofacial 41((6)2004:593-602; or Yamanda T et al Three Dimensional Analysis of Facial Morphology in Normal Japanese Children, CP-Cranio-facial J 39(5) 2002; 517-526. These previously published data allow for development of shield dimensions for different cohorts which then can result in the inventive shield being marketed to populations of different ages, in varying demouraphies, and/or with varying facial features.
[0012] The principle of designing a shield based on available standardized biomarkers of the face, as applied in the current inventive shield, can focus on the following non-limiting biomarkers that most closely describe the key perimeter values and contact points for a shield.
[0013] Using normal transverse lip length data (male and female combined) within the first year of life, the period in which the American Academy of Pediatrics recommends pacifier use:
[0000]
1 month
Mean (1.08″) Range (0.98″-1.26″). Normal lip position.
1 year
Mean (1.28″) Range (1.14″-1.50″). Normal lip position.
[0014] Extended lip measurements were extrapolated to be approximately 0.5″ greater when using data from older children, extrapolated to infants.
[0015] Further analysis of Nasion-Stmion Distance minus Nose length distances provides the deminsions under the nose (point sub-Nasale) to the lower lip and chin projection (the most posterior point along the symphysis menti, inferior to the infradentale point and superior to the mental protuberance):
[0000]
1 month
Mean (1.58″-0.88″ = 0.70″)
1 year
Mean (1.76″-1.02″ = 0.74″)
[0016] Further continuing the example, we considered the Bigonial Diameter (the greatest distance between the lateral gonial angles of the mandible):
[0000]
1 month
Mean (2.85″) Range (2.72″-3.07″).
1 year
Mean (3.06″) Range (2.92″-3.27″).
[0017] Note: all illustrative data taken from Young J W; Selected Facial Measurements of Children for Oxygen-Mask Design Report #AM 66-9; Office of Aviation Medicine Federal Aviation Agency, April 1966.
[0018] Using this cohort data were are able to design a better fitting shield for nose breathing, a better fitting shield—both fitting the face and allowing for more forward mandible position.
[0019] This disclosure features a shield for a pacifier, teether, feeding device, sippy cup or the like, wherein the shield carries a structure that is adapted to be inserted into the mouth of a young child. The shield comprises a body defining an opening at which the structure is carried and an inner surface surrounding this opening and encompassing the perioral areas surrounding the lips. The body defines a superior portion superior to the opening and an inferior portion inferior to the opening, and defines a lateral axis passing laterally through the opening. The superior portion is generally concave laterally on both sides Of the vertical midline, to define an inner surface that closely conforms to the upper lip and perioral areas. At least the part of the inferior portion close to and on either side of the vertical midline is offset outward away from the face compared to the inner surface of the superior portion that is close to and on either side of the vertical midline, to allow the mandible to move anteriorly without being inhibited by the shield.
[0020] The most lateral parts of the inferior portion of the body may curve back towards the perioral area. The body may define a generally butterfly, round or heart shape from side-to-side. The inferior portion may be angled away from the face. The inner surface of the superior portion may define a curved planar area. At least most of the inferior portion may be offset from the superior portion. The superior and inferior portions may be angled away from the mid-portion to create a convex dome shape. The inferior portion may be offset and angled sufficiently so as to provide room between the shield and face to allow a feeding tube to be placed into the mouth without causing the superior portion of the shield to be thrust into the upper lip. The shield may be supported by contact with the maxillary arch.
[0021] The shield may be generally symmetric about both the lateral and vertical midlines so that it can be oriented with the superior portion above or below the opening. The shield may define offset pockets that span the vertical centerline at the peripheries of both the superior and inferior portions, to allow room for the mental protuberance to be able to move forward during use. The shield may further comprise a plurality of support pads that are in contact with the user's cheek infra-orbitally and in the maxillary perioral area. The shield may comprise at least four support pads symmetrically arranged about both the vertical and lateral midlines.
[0022] The shield may be dimensioned based on a user cohort derived from one or more of photographic, cephalometric, anthropometric, stereo-photometric and apical CT data. The shield may be constructed and arranged to allow forward movement of the mandible during sucking. The shield may be constructed and arranged to allow downward movement of the mandible during sucking. The shield may be constructed and arranged to allow for maxillary lip support, infra-orbital cheek support, infra nasal support and intermaxillary freeway space support.
[0023] Featured in another embodiment is a shield for a pacifier, teether, feeding device, sippy cup or the like, wherein the shield carries a structure that is adapted to be inserted into the mouth of a young child, the shield comprising a body defining a generally butterfly, round or heart shape from side-to-side, and an opening at which the structure is carried. There is an inner surface surrounding this opening and encompassing the perioral areas surrounding the lips, the body defining a superior portion superior to the opening and an inferior portion inferior to the opening, and defining a lateral axis passing laterally through the opening, wherein the superior portion is generally concave laterally on both sides of the vertical midline, to define an inner surface that closely conforms to the upper lip and perioral areas, wherein the inner surface of the superior portion defines a curved planar area, wherein at least the part of the inferior portion close to and on either side of the vertical midline is offset outward away from the face compared to the inner surface of the superior portion that is close to and on either side of the vertical midline, to allow the mandible to move anteriorly without being inhibited by the shield, and wherein the most lateral parts of the inferior portion of the body curve back towards the perioral area, and at least most of the inferior portion is offset from the superior portion.
[0024] Featured in yet another embodiment is a shield for a pacifier, teether, feeding device, sippy cup or the like, wherein the shield carries a structure that is adapted to be inserted into the mouth of a young child, the shield comprising a body defining a generally butterfly, round or heart shape from side-to-side, and an opening at which the structure is carried. There is an inner surface surrounding this opening and encompassing the perioral areas surrounding the lips, the body defining a superior portion superior to the opening and an inferior portion inferior to the opening, and defining a lateral axis passing laterally through the opening, wherein the superior portion is generally concave laterally on both sides of the vertical midline, to define an inner surface that closely conforms to the upper lip and perioral areas, wherein at least the part of the inferior portion close to and on either side of the vertical midline is offset outward away from the face compared to the inner surface of the superior portion that is close to and on either side of the vertical midline, to allow the mandible to move anteriorly without being inhibited by the shield, wherein the most lateral parts of the inferior portion of the body curve back towards the perioral area, wherein the shield is generally symmetric about both the lateral and vertical midlines so that it can be oriented with the superior portion above or below the opening, and wherein the shield defines offset pockets that span the vertical centerline at the peripheries of both the superior and inferior portions, to allow room for the mental protuberance to be able to move forward during use.
BRIEF DESCRIPTION OF THE DRAWINGS
[0025] Illustrative, non-limiting embodiments are shown in the drawings, in which:
[0026] FIGS. 1A-1C illustrate a first embodiment of the shield;
[0027] FIGS. 2A-2C illustrate a second embodiment of the shield;
[0028] FIGS. 3A-3B illustrate a third embodiment of the shield;
[0029] FIGS. 4A-4C illustrate a forth embodiment of the shield;
[0030] FIG. 4D illustrates a fifth embodiment of the shield; and
[0031] FIGS. 5A-5B illustrate a sixth embodiment of the shield.
DETAILED DESCRIPTION OF EMBODIMENTS
[0032] The present invention encourages the perioral forces, created by the shield against the face, to be stabilized against the upper perioral area (maxillary arch, lip, cheek and intermaxillary arch space), with lighter forces (or no force) against the lower perioral area (mandibular arch). The shield can be used in any application, for example as part of pacifiers, teethers, feeding devices/utensils and sippy cups, which include a structure (such as a nipple or baglet) that goes into the infant's mouth.
[0033] Part, most of, or all of, the inside surface of the lower or inferior portion (typically the lower half) of the shield is offset from the inside surface of the upper or superior portion of the shield. This moves the inferior portion away from the face. The offset part of the shield is typically offset in the range of about 2 mm to about 10 mm, and more preferably from 2-8 mm, from the upper or superior portion of the shield. The lower offset portion of the shield may also be angled away from the vertical, and away from the face, at more than 0 degrees and up to about 20 degrees. The variation of the degree of angulation of the offset, when angulation is present, will be in part determined by the angle of the bulb or oral device (teether, nipple, spout etc.) which extends from the shield. A greater angle may be used with less of an offset to allow the lower part of the shield to be sufficiently spaced from the face. Similarly, a greater offset may be combined with no angle or a lesser angle.
[0034] The shield design takes on different levels of significance when used with different bulb designs. For example, so called cherry shaped and reverse orthodontic shaped bulbs have straight necks (shafts) and will push, slide, and seat (thereby ‘angle’ upward) into the palate during sucking, and cause greater tipping of the lower part of the shield against the chin than a bulb with a so called orthodontic design which itself is angulated from the neck (shaft) of the bulb, and will thus result in less shield tipping. Thus, greater offset may be needed in a shield for a reverse design in order to prevent the shield from contacting the lower perioral area during use.
[0035] The shield, by stabilizing forces against the upper lip, maxillary arch, cheeks and intermaxillary freeway space, may also have an added benefit of discouraging protrusion of the maxillary front teeth.
Description of Offset:
[0036] The offset could be presented in a number of manners. A number of embodiments that accomplish an offset are described below and shown in the drawings.
Embodiment 1
FIG. 1 .
[0037] FIGS. 1A-1C , show a shield 10 with a conventional pacifier shield “butterfly” shape that is curved inward laterally at a 20 degree angle from its horizontal centerline 30 . The 20 degree inward lateral angle can vary; 20 degrees was chosen as a median value. The angle can range from about 10 degrees to about 30 degrees. FIG. 1A is a view of shield 10 from the outside 40 that does not touch the face, showing nipple opening 18 and seating flange 19 . FIG. 1B is a top view, and FIG. 1C a side view. Dimensions are in mm. Note that this design is sized for a 9 month+ infant. Smaller overall dimensions (scaled down) would be used for shields designed for 0 month, 0-3 months, and other ranges as desired, using the dimensional data and ranges set forth above and otherwise available in literature. Shield 10 comprises unitary molded plastic body 12 that defines top edge 14 , lower edge 16 , outer surface 40 , inner surface 39 , central opening 18 (for insertion and seating of a nipple) and openings to provide for passage of air, such as opening 20 . The butterfly curvature is such that axes 34 and 36 that emanate from medial bisecting plane 38 and bisect the lateral edges 35 and 37 lie at about a 20 degree angle to plane 32 that is orthogonal to plane 38 . Additionally, the inferior (below the nipple) portion 42 is extruded outward (away from the face) (i.e., offset) 2 mm-10 mm (in this example 8.5 mm) from main plane 41 of the superior portion 29 that contacts the infant's face, i.e., the inside surface of the inferior portion 42 at the lowermost extent of the inner face (i.e., point 43 ) is spaced 8.5 mm from plane 41 that contacts the face.
Embodiment 2
FIG. 2 .
[0038] FIGS. 2A-2C are outside, top and inside axonometric views, respectively, of second shield embodiment 50 . The footprint of shield 50 is the same at approximately 60 mm wide by 40 mm height, designed for a 12 month+ infant, but the initial contact with the infant only comes from the corner of the lips and extends just above the upper lip, essentially at the protruding plane bounded by edges 52 - 55 . This plane defines the innermost surface of the shield, and the areas above and below the plane are offset from the plane. The construction prevents the shield from entering the infant's mouth, but allows the lower part of the shield (below the plane bounded by edges 52 - 55 ) to remain away from the infant's face. This design could also be described as two shields in one—a small shield that covers from the corner of the lips up to upper edge 57 and a secondary shield that extends from the plane to lower edge 59 that serves to prevent the shield from being swallowed or inhaled by the infant. This design contains the same curvature inward, 20 degrees, but also shows the same offsets of about 2-10 mm.
Embodiment 3
FIG. 3
[0039] FIGS. 3A-3B are inside and bottom views, respectively, of shield 80 with a conventional pacifier shield “butterfly” shape that is curved inward laterally at a nominal 20 degree angle from centerline, similar to the shield shown in FIG. 1 . FIG. 3A is a view of shield from the inside that touches the face, while FIG. 3B is a bottom view. Opening 82 is for the bulb or other structure that goes into the infant's mouth, and is bisected by horizontal axis 83 . Above axis 83 is superior portion 91 and below is inferior portion 95 . The offset begins at contour line 93 and extends to lowermost inside location 88 . The upper extent of inside surface 89 is location 86 . Surface 89 is generally concave toward the face to generally follow the contour of the face, thus lateral edges 90 and 92 are located more posteriorly than is the inner part of bulb-receiving opening 82 . Air openings 84 , 85 and 87 are identified, for context. Inferior portion 95 is sloped away from the face, i.e., offset, to lower contour 101 . What differentiates this design from the FIG. 1 design is that the outer parts of inferior portion 95 , which end at edges 90 and 92 , curve toward the face similar to the curving of superior portion 91 , such that lateral inferior inside surface portions 103 and 105 are closer to the face than is central lower location 88 . The offset on this design thus creates more of a “pocket” offset located in portion 95 and generally between openings 85 and 87 , as visible in FIG. 3B . The pocket provides room for the chin/lower mandible to move unobstructed into when the mandible is in the forward or downward position.
Embodiment 4
FIG. 4
[0040] FIGS. 4A-4C are front and back views, and a central vertical cross-section, respectively, of a reversible shield 120 ; i.e., a shield that is symmetric about lateral plane 122 so that either “upper” or “lower” edges 142 and 146 can be located just below the nose. Thus, both portion 126 and portion 128 can be the superior or inferior portion. Inside surface 150 is shown in FIG. 4A . This shield is for the reversible or cherry baglet (pacifier nipple) design. This shield allows for the chin/mandible to move forward or downward without requiring a top/bottom orientation. The key elements to this shield design are that the outer wings 130 , 132 of the shield (generally located laterally of axes “A” and “B,” respectively,) are designed to firmly contact or “mount” to anatomical structures of the face that are stationary throughout the suck cycle (e.g., the cheeks), and still allow for outward and downward mandibular movement with little or no contact with the shield. Recessed pockets 140 and 144 are hounded by beginning contours 141 and 145 and end contours 142 and 146 , respectively. Pockets 140 and 144 are located centrally, above and below nipple-receiving opening 124 , and end approximately at vertical axes “A” and “B,” outside of which are located wings 130 and 132 . Back side recesses 170 and 171 create annular seat 172 against which the nipple (not shown) is seated. A cap (not shown) would also typically cover the back side of the shield to help conceal/anchor the pacifier baglet, as is known in the art.
Embodiment 5
FIG. 4 D
[0041] FIG. 4D is another embodiment of the reversible shield 120 a, which is very similar in design to shield 120 , but with the addition of four support pads 181 - 184 . Using Cranio-facial data (Waitzman et al, and Young J W., supra) these pads are placed nominally 40 mm apart (20 mm off of center of pacifier 190 to center of pads 191 , 192 , designed for a 12 month+ infant) on the superior 126 and inferior 128 inside surface 150 of the shield and function as mini “bumpers.” The pads could be placed as close as 25 mm apart (center of pad to center of pad) for younger/smaller infants and as much as 42 mm apart for larger children. Vertical spacing from central axis 122 to axes 193 and 194 is about 15 mm, and can range from about 20 mm for older infants to as little as 10 mm for premature infants. The shape of the pads are preferably circular or elliptical, but can take other shapes as well. Shown is a circular embodiment at 7 mm diameter. Minimum diameter may be as low as 5 mm, and spaced approximately 10 mm offset from center in the superior/inferior direction (which is the same as from axis 122 to axes 193 / 194 ). These features may extend out of the shield nominally at 2 mm, +2 mm or −1 mm. Transverse dimensions, although they may vary according to age, sex, nationality and other demographics, would cause the bumpers to contact the infra orbital cheek area and underlying maxillary bone. The pads thus help to anchor the superior portion. The inferior pads lateral placement, however, is too wide to contact the curving mandibular symphysis.
[0042] Likewise, when reversed (superior to inferiorly rotated), the same contacts or non contacts with the perioral areas will also apply to this inventive shield design. Other designs and dimensions are obvious to one skilled in the field.
Embodiment 6
FIG. 5
[0043] FIGS. 5A and 58 are front and side views, respectively, of another embodiment of shield 210 . Shield 210 accomplishes the offset of inferior portion 218 from superior portion 216 (located below and above lateral midline 214 , respectively), via angling outward alone, without any planar offset. The angle is typically but not necessarily nominally 20 degrees, to create the “chin pocket” discussed above.
[0044] Polycarbonate, polycarbonate frame with silicone overmold, other thermoplastics, urethanes or thermoplastic elastomers that will serve as a rigid barrier (90A durometer or higher), polypropylene, and polyethylene are all acceptable materials. The shield may be comprised of sections of softer durometer material, but will contain a rigid section as a frame to pass safety testing/guidelines.
[0045] Other embodiments will occur to those skilled in the field and are within the scope of the claims.
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A shield for a pacifier, teether, feeding device, sippy cup or the like. The shield carries a structure that is adapted to be inserted into the mouth of a young child. There is, a body defining an opening at which the structure is carried and an inner surface surrounding this opening and encompassing the perioral areas surrounding the lips. The body demes a superior portion superior to the opening and an inferior portion inferior to the opening, and defines a lateral axis passing laterally through the opening. The superior portion is generally concave laterally on both sides of the vertical midline, to define an inner surface that closely conforms to the upper lip and perioral areas. At least the part of the inferior portion close to and on either side of the vertical midline is offset outward away from the face compared to the inner surface of the superior portion that is close to and on either side of the vertical midline, to allow the mandible to move anteriorly without being inhibited by the shield.
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SUMMARY OF THE INVENTION
The present invention concerns odorant and flavorant compositions which contain tetrahydro-α-pyrones of the formula ##STR2## wherein R represents an alkyl group having from three to eight carbon atoms. The alkyl group may be straight-chain or branched.
The compounds of formula I may exist as stereoisomers due, inter alia, to the methyl substituent at the 5-position of the tetrahydro-α-pyrone ring. It has emerged that one stereoisomer (the cis- or trans-isomer) of a stereoisomeric pair of formula I may have different organoleptic properties when compared with the other stereoisomer. Formula I is intended to embrace, inter alia, these stereoisomeric forms and their mixtures.
Certain compounds of formula I are known per se, but their organoleptic properties have never been described. The 5-methyl-6-pentyl-tetrahydro-α-pyrone (alternate nomenclature: 4-methyl-5-decanolide or 5-methyl-6-pentyl-tetrahydro-α-pyran-(2H)-2-one), I', the compound of formula I wherein R represents pentyl, is a novel compound. Due to the particular organoleptic properties possessed by 5-methyl-6-pentyl-tetrahydro-α-pyrone both the mixture of isomers I' and the cis-isomer of the formula ##STR3## and the trans-isomer of the formula ##STR4## are preferred compounds of formula I. The cis-isomer I'a has a very pleasant and surprising room-filling odor which on the one hand is reminiscent of certain aspects of the smell of the flower of the tuberose (Polianthes tuberosa) and gardenia varieties and on the other hand is reminiscent of caramel, condensed milk and coconut, especially coconut milk. The trans-isomer exhibits similar olfactory characteristics, though somewhat less pronounced; the weaker characteristics are compensated by side aspects. The invention therefore also concerns 5-methyl-6-pentyl-tetrahydro-α-pyrone, I', and a process for its manufacture.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
The process in accordance with the invention for the manufacture of the 5-methyl-6-pentyl-tetrahydro-α-pyrone comprises subjecting 2-pentyl-3-methyl-cyclopentan-1-one to a Bayer-Villiger oxidation in accordance with Scheme I. ##STR5##
A peracid, for example peracetic acid, trifluoroperacetic acid, perbenzoic acid or monoperphthalic acid, preferably peracetic acid, is used as the oxidizing agent. The reaction is conveniently effected in an inert organic diluent such as methylene chloride, dichloroethane, toluene, xylene, etc. at temperatures between -30° C. and +50° C., preferably in the temperature range of 20° C. to 35° C.
As the starting material there can be used pure cis- or trans-2-pentyl-3-methyl-cyclopentan-1-one, which leads predominantly to cis- or, respectively, trans-5-methyl-6-pentyl-tetrahydro-α-pyrone. A convenient method uses a cis/trans mixture of 2-pentyl-3-methyl-cyclopentan-1-one since a cis/trans mixture can be readily obtained by hydrogenation in a manner known per se of 2-pentyl-3-methyl-2-cyclopenten-1-one (dihydrojasmone) a known perfumery product of the formula ##STR6##
The cis-2-pentyl-3-methyl-cyclopentan-1-one is the primary product of the hydrogenation. Depending on the reaction conditions (solvent, temperature, catalyst etc.) there is formed from the cis-isomer more or less of the corresponding trans compound.
Where a cis/trans mixture of the 5-methyl-6-pentyl-tetrahydro-α-pyrone (compound of formula I) is obtained, this can be separated into the pure cis- and trans-isomers according to methods known per se, for example by chromatographic or distillative procedures.
The yield of olfactorily good material is high for both the hydrogenation and oxidation reaction steps, normally above 75%.
The compound I' (the cis-isomer I'a, the trans-isomer I'b as well as their mixtures) in accordance with the invention and the remaining compounds of formula I are distinguished in general by fragrance notes which are reminiscent of certain aspects of the fragrance of flowers of the tuberose and gardenia varieties, condensed milk, caramel and coconut and also are reminiscent of those of tropical fruits.
With regard to their aforementioned valuable olfactory properties the compounds I are suitable as odorants and/or flavorants, especially in combination with the extensive range of natural and synthetic odorants or flavorants available today for the creation of perfume and flavoring compositions which can be used in all conventional fields of application. Examples of the numerous known odorant ingredients of natural or synthetic origin, whereby the range of the natural raw materials can embrace not only readily-volatile but also moderately-volatile and difficultly-volatile components and that of the synthetics can embrace representatives from numerous classes of substances, are:
Natural products, such as tree moss absolute, basil oil, tropical fruit oils (such as bergamot oil, mandarine oil, etc.), mastix absolute, myrtle oil, palmarosa oil, patchouli oil petitgrain oil, wormwood oil, lavender oil, rose oil, jasmine oil, ylang-ylang oil, sandalwood oil,
alcohols, such as farnesol, geraniol, linalool, nerol, phenylethyl alcohol, rhodinol, cinnamic alcohol, cis-3-hexenol, menthol, α-terpineol,
aldehydes, such as citral, α-hexylcinnamaldehyde, hydroxycitronellal, Lilial® (Givaudan) (p-tert.butyl-a-methyl-dihydrocinnamaldehyde), methylnonylacetaldehyde, phenylacetaldehyde, anisaldehyde, vanillin,
ketones, such as allyl ionone, α-ionone, β-ionone, isoraldeine (isomethyl-α-ionone), verbenone, nootkatone, geranylacetone,
esters, such as allyl phenoxyacetate, benzyl salicylate, cinnamyl propionate, citronellyl acetate, decyl acetate, dimethylbenzylcarbinyl acetate, ethyl acetoacetate, ethyl acetylacetate, cis-3-hexenyl isobutyrate, linalyl acetate, methyl dihydrojasmonate, styrallyl acetate, vetiveryl acetate, benzyl acetate, cis-3-hexenyl salicylate, geranyl acetate, etc.
lactones, such as γ-undecalactone, δ-decalactone, pentadecan-15-olide,
various components often used in perfumery, such as indole, p-menthane-8-thiol-3-one, methyleugenol, eugenol, anethol.
The ordorant compositions produced using compounds I, especially those having a flowery, flowery-spicy, flowery-fruity and flowery-oriental direction, captivate especially by their originality.
When used as odorants the compounds of formula I (or their mixtures) can be employed in wide limits which in compositions can range, for example, from about 0.1 (detergents) to about 30 weight percent (alcoholic solutions) without these values being, however, limiting values, since the experienced perfumer can also achieve effects with even lower concentrations or can synthesize novel complexes with even higher amounts. The preferred concentrations range between about 0.5 and about 10 weight percent. The compositions produced with the compounds I can be used for all kinds of perfumed consumer goods (eau de cologne, toilet water, extracts, lotions, creams, shampoos, soaps, salves, powders, toothpastes, mouth washes, deodorants, detergents, fabric conditioners, tobacco, etc.).
The compounds can accordingly be used for the production of compositions and--as the above compilation shows--using a wide range of known odorants or odorant mixtures. In the production of such compositions the known odorants or odorant mixtures enumerated above can be used according to methods known to the perfumer such as e.g. from W. A. Poucher, Perfumes, Cosmetics and Soaps 2, 7th Edition, Chapman and Hall, London 1974.
As flavorants the compounds I can be used, for example, for the production or improvement, intensification, enhancement or modification of fruit flavors, e.g. mango, passion fruit, peach and coconut. As fields of use for these flavors there come into consideration, for example, foodstuffs (yoghurt, confectionary, desserts, especially desserts based on caramel, etc.), semi-luxury consumables (tea, coffee, tobacco, etc.) and drinks (lemonade etc.).
The pronounced flavor qualities of the compounds I enable them to be used as flavorants in low concentrations. A suitable dosage embraces the range of 0.01 to 100 ppm, preferably of 0.1 to 10 ppm, in the finished product, i.e. the flavored foodstuff, semi-luxury consumable or drink.
The compounds can be mixed with the ingredients used for flavoring compositions or added to such flavorings in the usual manner. Under the flavorings used in accordance with the invention there are to be understood flavoring compositions which can be diluted or distributed in edible materials in a manner known per se. They contain, for example, about 0.01-30, especially 0.1-10, wt. % of flavorant(s) of formula I. They can be converted according to methods known per se into the usual forms of use such as solutions, pastes or powders. The products can be spray-dried, vacuum-dried or lyophilized.
The known flavoring substances which are conveniently used in the production of such flavorings are either already referred to in the above compilation or can be taken readily from the literature such as e.g. J. Merory, Food Flavorings, Composition, Manufacture and Use, Second Edition, The Avi Publishing Company, Inc., Westport, Conn. 1968, or G. Fenaroli, Fenaroli's Handbook of Flavor Ingredients, Second Edition, Volume 2, CRC Press, Inc. Cleveland, Ohio, 1975.
For the production of such usual forms of use there come into consideration, for example, the following carrier materials, thickeners, flavor improvers, spices and auxiliary ingredients, etc.:
Gum arabic, tragacanth, salts or brewers' yeast, alginates, carrageen or similar absorbents; maltol, spice oleoresins, smoke flavors; cloves, diacetyl, sodium citrate; monosodium glutamate, disodium inosine-5'-monophosphate (IMP), disodium guanosine-5-phosphate (GMP); or special flavoring substances, water, ethanol, propylene glycol, glycerine, etc.
Having regard to their superior olfactory properties the compounds of formula I are preferably used in luxury perfumes and in cosmetic compositions.
The following Examples illustrate the invention.
I. MANUFACTURE OF THE COMPOUNDS OF FORMULAS I', I'A AND I'B
Example 1
Commercially available 2-pentyl-3-methyl-2-cyclopenten-1-one (dihydrojasmone) (78.0 g, 0.47 mol) is dissolved in 90 ml of pure ethanol, treated with 0.50 g of 10% palladium on active charcoal and subsequently hydrogenated at normal pressure and room temperature while stirring intensively until saturated (hydrogen consumption: 12.0 l in 2 hours). The reaction solution is freed from the catalyst by filtration and subsequently concentrated under reduced pressure. Distillation of the crude product (76.0 g) over a distillation column gives 68.0 g of material of b.p. 0 .12 67°-68° C., which contains in a yield of above 98% cis-2-pentyl-3-methyl-cyclopentan-1-one (IIa) and trans-2-pentyl-3-methyl-cyclopentan-1-one (IIb) in the ratio of 3:2.
The above mixture of IIa and IIb (42.6 g, 0.25 mol) is dissolved in 200 ml of methylene chloride, treated with 34.0 g of anhydrous sodium acetate and subsequently treated with 62.5 g of peracetic acid (40%) in the course of 30 minutes while stirring well and cooling with ice. Subsequently, the ice-cooling is removed and the reaction solution is held in a temperature range of 25°-30° C. by occasional cooling with water at 15° C.
After 1.5 hours an exothermic reaction can no longer be ascertained and analysis by gas chromatography shows the desired conversion of above 95%. The reaction solution is now washed three times with water, three times with sodium sulphite solution (10%) and twice with sodium chloride solution, and the organic phase is dried with anhydrous sodium sulphate and subsequently concentrated under reduced pressure.
Distillation of the thus-obtained crude lactone (41.9 g) over a distillation column gives 35.9 g (78%) of olfactorily good product of b.p. 0 .05 82°-83° C. consisting of above 97% of cis-5-methyl-6-pentyl-tetrahydro-α-pyrone (cis-4-methyl-5-decanolide, I'a) and trans-5-methyl-6-pentyl-tetrahydro-α-pyrone (trans-4-methyl-5-decanolide, I'b) in the ratio of about 3:2.
The isomers I'a and I'b, characterized hereinafter by their spectral data, are obtained by separating the above-described mixture with the aid of gas chromatography. Isomer I'a shows a somewhat longer retention time than isomer I'b on conventional gas chromatography columns.
cis-5-Methyl-6-pentyl-tetrahydro-α-pyrone (I'a):Infrared spectrum: 1735, 1238, 1200, 1140, 1095, 1069, 1054, 993, 908 cm -1 ; 1 H-NMR (400 MHz, CDCl 3 ): 0.90 (t,J˜7, --CH 3 ), 0.96 (d,J˜7, H 3 C-C(4), 1.25-1.60 (m, together 6H), 1.62-1.72 (m,2H), 1.95-2.10 (m,3H), 2.53 (dxd, J˜7, 2H--C(2), 4.28 (m, H--C(5) ppm;mass spectrum (m/e): (M + , 0.2), 128(3), 113(23), 99(3), 95(1), 85(15), 84(39), 69(5), 67.5(5), 57(10), 56(100), 55(24), 43(26), 41(22).
trans-5-Methyl-6-pentyl-tetrahydro-α-pyrone (I'b):Infrared spectrum: 1735, 1248, 1200, 1118, 1098, 1080, 1032, 2020 cm -1 ; 1 H-NMR (400 MHz, CDCl 3 ): 0.90 (t,J˜7, --CH 3 ), 1.00 (d,J˜7, H 3 C--C(4), 1.22-1.64 (m, together 8H), 1.66-1.78 (m,2H), 1.86-1.94 (m,1H), 2.42-2.51 (m, H a --C(2), 2.58-2.65 [m, H b --C(2)], 3.93 [m, H--C(5)] ppm;mass spectrum (m/e): 184 (M + , 0.2), 128(4), 114(10), 113(100), 99(3), 95(2), 85(27), 84(44), 69(8), 67(8), 57(14), 56(100), 55(34), 43(29), 41(26).
In an analogous manner there are obtained:
cis/trans-4-methyl-5-nonanolide, odor: after coconut, celery,
cis/trans-4-methyl-5-undecanolide, odor: sweet, fruity.
II. FORMULATION EXAMPLES
Example 2
Perfume composition in the direction of ylang-ylang containing cis- and trans-5-methyl-6-pentyl-tetrahydro-α-pyrone.
______________________________________ Parts by weight______________________________________Linalool 150Benzyl acetate 130Benzyl salicylate 100Cinnamyl acetate 80Geranyl acetate 80Benzyl benzoate 80Methyl benzoate 78Geraniol 75Cinnamic alcohol 60Thibetolide 30cis-3-Hexenyl salicylate 30Hydroxycitronellal 20Eugenol 20cis-3-Hexenyl benzoate 20Methyl jasmonate 10β-Ionone 5cis-3-Hexenol 1cis-3-Hexenyl acetate 1 970______________________________________
The addition of 30 parts by weight of the cis/trans mixture I'a/I'b (3:2) brings about a very pleasant rounding-off of this perfume composition. The bottom note in the direction "ylang-ylang" is enriched by aspects reminiscent of frangipani flowers (Plumeria acutifolia) and tuberose. These positive effects can still be established clearly even after 24 hours.
Example 3
Herb tea composition usable for flavors and for perfume creations (compositions):
______________________________________ Parts by weight______________________________________Linalool 210Anethol 120Phenylethyl alcohol 120Terpineol 60Citronellol 60Geranylacetone 60cis-3-Hexenyl benzoate 60Anisaldehyde 45Phenylacetaldehyde 30Eugenol 30Menthol 30Estragol 15Verbenone 15β-Ionone 9Citral 6Methyl jasmonate 3cis-3-Hexenol 1Dipropylene glycol 96 970______________________________________
The addition of 30 parts by weight of the cis/trans mixture I'a/I'b (3:2) confers more warmth and naturalness to this composition. A note, which can be associated with freshly dried alpen herbs, comes into play very advantageously.
Example 4
Flavor with "milky character":
______________________________________ Parts by weight a b______________________________________Acetoin 25 25Vanillin 20 20Maltol 10 10Diacetyl 10 10Ethyl lactate 10 10δ-Decalactone 10 10Caproic acid 7 7Ethyl butyrate 4 4Caprylic acid 1 1cis- and trans-1'a/1'b -- 10Propylene glycol 903 893 1000 1000______________________________________
After dilution in sugar syrup solution (20 g of flavor a or b per 100 l of sugar syrup 10° Bx) the two flavors a and b are compared for taste.
Flavor b is clearly preferred by a panel of test persons, since the desired notes reminiscent of cream and condensed milk come into play strongly.
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The invention concerns odorant and flavorant compositions which contain one or more compounds of the formula ##STR1## wherein R represents an alkyl group having from three to eight carbon atoms. The invention also concerns 5-methyl-6-pentyl-tetrahydro-α-pyrone (compound of formula I in which R represents pentyl) in the form of its cis-isomer, its trans-isomer or its cis/trans isomer mixture, and a process for its manufacture by a Bayer-Villiger oxidation of 2-pentyl-3-methyl-cyclopentan-1-one. As fields of use for these compounds there come into consideration, for example, perfume and flavoring compositions, foodstuffs, semi-luxury consumables and drinks.
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FIELD AND BACKGROUND OF THE INVENTION
The present invention relates to a fruit juice dispenser or the like having a receiving device for a concentrate container provided with a spigot hose, the dispensers having a hose pump driven by an electric motor with a squeezing means which extends into a hose receiving chamber and can be displaced in the direction of conveyance, and having an electromagnetically controlled water feed device arranged between the hose pump and spigot opening.
In one fruit juice dispenser which is today on the market, a collapsible container in which fruit juice concentrate is contained is received in a receiving device developed as cooling compartment which is cooled by a cooling unit. The concentrate can be removed from the concentrate container by a spigot hose which is arranged on the bottom of the container and the end of which is connected to a spigot valve. In such a fruit juice dispenser the spigot valve is adapted to be connected to a water feed device which dilutes the concentrate with water before it emerges from the spigot opening.
The fruit juice concentrate is pumped or fed in dosed amount from the container through the spigot hose by means of a pump. In the known fruit juice dispenser, a hose pump is used which prevents direct contact between the fruit juice concentrate and the pump. The hose pump consists of a rotating pump disk on the edge of which squeezing means are arranged which can move away inward against spring force, in this case in the form of squeeze rollers, said means pressing the hose, placed against the rear wall around the disk, in such a manner that constrictions are produced in the hose, these constrictions being moved along by the rotation in the direction of conveyance. By this peristalsis, which is produced by a stripping-out movement, a volume transport up to the spigot opening is assured.
Such a pump has the disadvantage, on the one hand, of excessive wear and, on the other hand, of taking up a relatively large amount of space. The wear is due essentially to the strong stripping-out action of the rollers. This furthermore results in a creeping and thus to a tensioning of the spigot hose which lead to its flattening. The places of connection must therefore be made very stable in order to counteract the possible risk of tearing. Furthermore, as a result of the arcuate deflection of the spigot hose around the pump disk, which is approximately of palm size, an unnecessary excess length of the pump hose results. The said relatively large amount of space required is due to the swinging away movement of the bow-shaped rear wall near the housing. Handling is also inconvenient, since work must be done on the front surface of the apparatus. There are scarcely sufficient gripping possibilities.
SUMMARY OF THE INVENTION
The object of the present invention, therefore, is so to develop a fruit juice dispenser of this type that, despite its compactness, the greatest possible dependability in operation is achieved.
By virtue of the invention, there is provided a fruit juice dispenser of this type in which the hose pump is so compact that several hose pumps can also be arranged closely alongside of each other. Furthermore, due to the fact that rotating squeezing elements are dispensed with, the dependability of operation is increased. This is achieved by a linear path of the spigot hose from the concentrate container to the place of the spigot and by a plate-block squeezing contour which operates transverse thereto as hose pump, the spigot hose being held against said contour by means of the spring-loaded rear wall of a flap which can be opened towards the front in order to insert the spigot hose. The spigot hose now extends directly, in maximum short length, from the fruit-juice supply to the spigot opening. This saves material and permits the peristaltic action to take place over a shorter path and without any stretching tension on the body of the hose.
Therefore, the above-mentioned stripping-out action does not take place here, since the plate-block squeezing contour which operates transverse to the linear course of the hose produces only correspondingly transversely directed indentations in the hose body. This takes place with much less wear and thus more gently than would be possible by squeeze rollers of the aforementioned pump disk. Furthermore, better conditions are also present for the attachment and removal of the hose, since this is done via a flap which can be opened towards the front. Therefore, handling is effected directed frontally and not in the plane of the front wall of the fruit juice dispenser.
In order to produce an effective constricting and to compensate for possible hose tolerances, the rear wall of the hose receiving chamber is under spring action, as mentioned. It presses the hose substantially "floatingly" against the squeezing contour. An exact positioning as well as an attachment of the hose which assures the linear course is obtained by openings on the hose-chamber side for the passage or insertion of the spigot hose. Such openings may be arranged on the flap. In a preferred further development of the invention, the pump housing wall has openings on the hose receiving chamber side, said openings forming the bearing for the plate-block eccentric shaft for the removing of the plate block, including the eccentric shaft, from the pump housing. This is useful, in particular, for the cleaning of the hose pump.
By this further development, a user-friendly disassembling of the hose pump is also made possible. The eccentric shaft is preferably clipped to the hose-receiving-chamber-side openings forming the bearings. In order furthermore to assure a sufficient width of action of the plate block, the further development is such that the width of the end surface of the plates corresponds to a multiple of the diameter of the hose hole. This end surface is preferably somewhat larger than the width of the hose when the body of the hose is pressed flat. A stress-free dosing, which nevertheless is precisely defined on both ends by constrictions, is present when the squeezing contour corresponds to half the length of the wave. What is meant is the extending into and out of a line formed by the linearly extending hose. A further advantageous measure is furthermore achieved by a flow control device for the feeding of the water such that a given open period of the solenoid valve of the water-feed device corresponds to a given amount of water admitted.
In this connection, it is advantageous for the flow-control device to be developed as a signal impeller which is turned by the flowing water and the signals from which serve to control the drive voltage of the hose-pump electric motor. Control which is independent of the water pressure present can be obtained with such a signal impeller device. As signal, there can be used, for instance a small magnet seated on the impeller vane and the recurring approach of which, i.e. the resultant speed of rotation of the impeller, is converted by a pulse receiver.
BRIEF DESCRIPTION OF THE DRAWINGS
With the above and other advantages in view, the present invention will become more clearly understood in connection with the detailed description of a preferred embodiment, when considered with the accompanying drawings of which:
Embodiments of the invention will be explained in further detail with reference to the drawings, in which:
FIG. 1 is a view of a fruit juice dispenser having two separate concentrate containers and hose pumps, shown substantially diagrammatically;
FIG. 2 is a sectional view through a hose pump of a first embodiment;
FIG. 3 is a perspective view of a housing having a clippable plate block in accordance with a second embodiment;
FIG. 4 is an individual showing of a plate;
FIG. 5 shows the hose pump, partially broken away in order to show the wavy line of the plate block; and
FIG. 6 is a section through the lower portion of the hose pump, showing the flow control device.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
FIG. 1 shows a fruit juice dispenser 1 having a receiving chamber 2 for two concentrate containers 3 which consist of a multi-layer plastic-foil material and which are closed and collapsible, except for an outlet opening 4, in order to prevent microbial contamination. The outlet opening adjoins a spigot hose 5 which extends into a spigot valve 6. The spigot hose extends linearly vertically between concentrate container 3, or its outlet opening 4, and the spigot point formed by the spigot valve 6. Between the spigot valve 6 and the opening 4, the spigot hose lies in a hose pump 7 which doses and conveys the discharge of the concentrate. The spigot valve 6 can be opened or closed by turning the spigot spout 6". The closed position is intended basically for the replacement or transportation of the container 3.
Behind the hose pump 7 and adjacent the spigot valve 6 the fruit juice dispenser 1 has a water-feed device 8 by which water is added to the concentrate conducted through the spigot hose 5 so that the diluted fruit juice, which is now drinkable, can be removed from the spigot opening 6' of the spigot valve 6.
In the case of the hose pump 7 shown in FIGS. 2 and 5, the concentrate is conducted, by means of a squeezing contour W extending in direction of conveyance, through the spigot hose 5 into the spigot valve 6, which is open in the position of rotation shown therein (downward) of the spigot spout 6" having the spigot opening 6'. The spigot valve 6 is placed on the water-feed device 8, the water-feed device being adapted to be opened and closed by a solenoid valve 9. The water flowing through the water-feed device 9 is maintained at a constant rate of flow by a flow-control device 27 shown in FIG. 6, so that a given period of opening of the solenoid vale 9 corresponds to a given amount of water discharged by the water feed device 8.
Within the hose pump 7, the spigot hose 5 lies within a hose-receiving chamber 15 which is limited on one side by the plates 11 which are arranged in wave shape and form the squeezing contour W, and on the other side by a rear wall 13 which is under spring action. The corresponding compression springs can be noted from FIGS. 2 and 4 and are designated 14. The rear wall 13 is associated with an opening flap 16 which can be opened in forward direction in order to insert the spigot hose 5 into the hose receiving chamber 15. For this purpose, the opening flap 16 is hinged around a vertical axis on the pump housing 7'.
The plates 11 which are movable back and forth transversely and therefore crosswise to the direction of conveyance in the direction of the hose receiving chamber 15, i.e. to the linear direction of extension of the spigot hose 5, have, in their center, a slot 17 (see FIG. 4), extending transverse to the said direction of movement, into which slot a helically developed eccentric shaft 12 engages. The eccentric shaft 12 passes through all plates 11 of the plate block 18 and in this way impresses on the plate-block end 18' extending into the hose-receiving chamber 15 the wave shape developing the squeezing contour W shaped in accordance with the helical shape of the eccentric shaft 12. The squeezing contour W corresponds, in accordance with FIG. 5, to at least a half of the length of a wave of a wavy line which alternately intersects the geometric line of extent. The eccentricity of the eccentric shaft 12, and thus the maximum transverse stroke of a plate 11, corresponds approximately to the diameter of the hose. In this way, a dependable constriction 5' of the spigot hose 5 by the squeeze contour W is assured, particularly as the width of the end surface of the equally wide plates 11 corresponds to a multiple of the outside diameter of the spigot hose 5 of round cross section and also produces the constriction 5' with the body of the hose pressed flat.
Upon the rotation of the eccentric shaft 12 around its axis, the plates 11, which are stacked one above the other, carry out a phase-shifted movement back and forth in such a manner that the constriction of the spigot hose 5--forming the peristalsis--moves in the direction of conveyance.
The ratio of concentrate to water fed can be adjusted by the speed of conveyance of the hose pump 7 corresponding to the speed of rotation of the eccentric shaft 12. Upon actuation of a release lever 19, for instance by a cup which is held below the spigot opening 6', both the water feed and the hose pump 7 are placed in operation.
The spigot hose 5 is securely positioned lying behind the flap 16 in the hose-receiving chamber 15 in the said linear extent on the pump housing 7'. This is achieved by openings 15 on the side of the hose chamber. Such openings 15' are located on the feed side of the spigot hose 5 on the top of the pump housing 7' and also on the bottom side thereof, in front of the place of attachment of the spigot hose 5 to the spigot valve 6. They can be niches adapted to the cross section of the spigot hose 5. Such niches may suitably extend from the inside of the opening flap 16. The rear wall which is under spring load is then aligned with the bottom of the niche in the direction of the hose chamber 15. The rear wall can have a suitable receiving groove for the spigot hose.
FIG. 3 shows a second embodiment of the invention. Within a pump housing 7' there is a plate block 18 consisting of a plurality of plates 11 stacked one above the other, the eccentric shaft 12 in this case also being inserted through the slots in the plates 11o At the end, the eccentric shaft 12 has a gear 20 which is driven by a drive gear 21 operated by an electric motor (not shown). The electric motor preferably forms a preassembly unit together with the hose pump 7. The plate block 18 can be removed together with the eccentric shaft 12 from the pump housing 7' of shaft shape. For this purpose, the housing wall 22 has openings 23 which continue up to an eccentric shaft bearing 24. In this connection, the openings 23 are associated with opposites ends of the pump housing. In the embodiment shown, the openings 23 debouch on the side of the hose receiving chamber in the direction of the end 18' of the plate block. The eccentric shaft 12 is clipped in its bearing 24 by the opening 23. For this purpose, the opening has a narrowing 25 at which the opening is smaller than the diameter of the eccentric shaft at its bearing point. In this way, a simple attaching of the eccentric shaft 12 in the pump housing 7' is assured. By the overcoming of the detent force, the plate block 18 can be pulled out of the housing 7', together with the eccentric shaft 12, and cleaned. Since when the opening flap 16 is closed (not shown in FIG. 3) the end 18' of the plate block is acted on by force--not least of all because of the spring-actuated rear wall 13 and the elasticity of the hose 5--the axial attachment can be developed very weak. The constriction 25 need therefore be only slightly narrower than the bearing diameter of the eccentric shaft 12. Dependable tooth engagement between the gears 20 and 21 is then assured by the action of the force.
The helical eccentric shaft 12 consists in both embodiments of circular disks 26 which are arranged staggered one above the other, their thickness corresponding to the thickness of the plates 11. Due to the uniform angular shift from step to step the eccentric shaft 12 is thus imparted a helical shape. The eccentric shaft 12 has at least one complete revolution so that assurance is had that in every position of rotation a squeezing contour W is formed, this squeezing contour W effecting a sealing constricting 5' of the spigot hose 5.
As is more specifically shown in FIG. 5, the physical axis of the eccentric shaft 12 which at the same time forms the journal pins passes through all the said circular disks 26.
FIG. 6 shows the flow-control device 27 associated with the hose pump 7. This device is seated in the bottom portion of the hose pump 7. The flow-control device 27 controls, by valve control, the feed of water for the concentrate. This takes place in the manner that a given period of opening of the solenoid valve 9 of the water-feed device 8 corresponds to a given amount of water admitted. For this purpose, it has a transmitter device. This is a signal impeller 28 inserted in the flow stream. Its signal is used to control the drive voltage of the electric motor of the hose pump. The motor is a dc motor.
The signal impeller 28 bears a small magnet 29 on one of its vanes which turn within the flow stream. A pulse receiver 30 arranged in the housing section of the flow-control device 27 records the approach-produced pulses and converts them into the adjusted speed of operation of the electric motor of the hose pump 7.
Regardless of the water pressure, the same mixing quality of concentrate to water is thus obtained at all times. By means of a connecting channel 31, the impeller chamber 32 is in communication with a chamber 32 of the solenoid valve 9 via which the water-feed device 8 is fed.
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A fruit juice dispenser or the like has a receiving device (1) for a concentrate container (3), and is equipped with a spigot hose (5), having a hose pump (7) which is driven by an electric motor. A squeezing device extends into a hose-receiving chamber (15), and is displaceable in direction of conveyance. An electromagnetically controlled water-feed device (8) is arranged between the hose pump (7) and the spigot opening. To obtain the greatest possible reliability in operation with a compact arrangement, there is provided a linear course of the spigot hose (5) from the concentrate container (3) to the spigot valve (6). The pump includes a plate-block squeezing contour (W) against which contour the spigot hose (5) is held by means of a spring-actuated rear wall (13) of a flap (16) which can be opened in forward direction for the insertion of the spigot hose (5).
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TECHNICAL FIELD
This invention relates to the preparation of polyalkylene polyamines.
BACKGROUND OF PRIOR ART
One of the early techniques for preparing linear polyalkylene polyamine compounds, such as diethylenetriamine and triethylene tetramine and higher homologues, has been to react an alkyl halide with an amine such as ammonia, ethylenediamine and the like at elevated temperatures and pressures. Generally, high yields of cyclic polyethylene polyamines, e.g. piperazine, triethylenediamine as well as other cyclic amines were produced. Another problem in the process was that hydrohalide salts of ammonia or hydrogen chloride were produced by the reaction, and thus expensive corrosion resistant equipment was required. U.S. Pat. No. 3,751,474 is representative.
More recently a series of patents disclosed the preparation of linear polyalkylene polyamine compounds by reacting a diol or an alkanolamine compound with an alkylenediamine compound under preselected process conditions to produce linear alkylene polyamines.
These include:
U.S. Pat. No. 3,714,259, which shows preparing linear poly(ethylene)amines by contacting ethanolamine with an ethylendiamine compound in the presence of hydrogen and hydrogenation catalyst. An example of a hydrogenation catalyst is nickel containing copper and chromium components;
U.S. Pat. No. 4,036,881, which shows the preparation of polyalkylene polyamines by reacting an alkanolamine with an alkylene amine compound in the presence of a phosphorous-containing substance selected from the group consisting of acidic metal phosphates, phosphoric acid compounds and hydrides and phosphate esters; and
U.S. Pat. No. 4,044,053, which is somewhat similar to the '881 patent except that the alkylene amine compound is present in an excess amount and a diol is used in place of the alkanolamine.
SUMMARY OF THE INVENTION
It has been found that non-cyclic or linear polyalkylene polyamines are produced in high yield directly by reacting an alkylene amine compound and an alkanolamine in the presence of a catalytically effective amount of a salt of a substance containing nitrogen or sulfur, or the corresponding acid at temperatures of from 250°-350° C. under a pressure sufficient to maintain the mixture in liquid phase.
DETAILED DESCRIPTION OF THE INVENTION
Briefly, the invention relates to a process for synthesizing predominantly non-cyclic polyalkylene polyamines, and preferably predominantly linear polyethylene polyamines such as diethylenetriamine and higher homologues. In the process an alkylene amine having two primary amino groups, and preferably an unbranched alkylene moiety such as ethylene diamine, is reacted with an alkanolamine having a primary or secondary hydroxy moiety and a primary amine group. Preferably, the alkanolamine has an unbranched alkylene moiety.
The alkylene amine reactants that can be used in practicing the process are represented by the general formula: ##STR1## where R is a hydrogen or a lower alkyl (C 1-4 ) radical, X is a number from 2 to about 6, and Y is a number from 1 to about 4. Examples of alkylene diamine compounds suited for the reaction include 1,3-propylenediamine, diethylenetriamine, triethylenetetramine and ethylenediamine which is the preferred alkylene diamine composition.
The alkanolamine compounds which are used in practicing the process include those represented by the formula: ##STR2## wherein R is hydrogen or a lower alkyl C 1-4 radical; X is a number from 2 to about 6; and Y is a number from 0 to 3. Examples of alkanolamine compounds that can be used are ethanolamine, isomeric propanolamines, N-(2-aminoethyl) piperazine and ethanolamine.
The polyalkylene amines that are produced by the reaction of an alkylenediamine and an alkanolamine or diol then are represented by the formula: ##STR3## wherein R is hydrogen or a lower alkyl (C 1-4 ) radical; X is a number from 2 to about 6; and Y is a number from 2 to about 6. Examples of linear polyalkylene polyamines that are produced include tributylenetetramine, diethylenetriamine, triethylenetetramine and tetraethylenepentamine.
The catalysts which are suited for practicing the process described herein are the metal salts of nitrogen and sulfur-containing compounds and their corresponding acids. With respect to nitrogen-containing substances, the salts are of nitrates and the corresponding acids typically inorganic nitrates. Virtually any metal salt of the nitrate can be used, and these generally include Group 1, 2, 3a, 4, 6b-8b metals and include hydrogen, ammonium ion, lithium, sodium, potassium, beryllium, magnesium, chromium, manganese, iron, cobalt, zinc, aluminum, antimony, bismuth, tin, ammonium ion and boron. Hydrogen and the ammonium ion are deemed Group 1 metals for purposes of this invention. Nitrites, when used, are converted to nitrates and, for purposes herein, are deemed nitrates.
With respect to the catalytic substance containing sulfur, such compounds include sulfates and the corresponding acid. With respect to the sulfates, typically inorganic sulfates, the metals specified with respect to the nitrogen-containing substances are also suited and these include the ammonium ion and hydrogen.
The above-mentioned nitrogen and sulfur-containing substances are not intended to be exhaustive of those which may be employed as a catalyst material. However, as might be expected, it is preferred to use those which are more reactive and provide for substantial conversion with high selectivity to the product. Specific examples of catalytic materials which are effective at low levels include nitric acid, beryllium nitrate, boron nitrate, iron nitrate, aluminum nitrate, bismuth nitrate, sulfuric acid, beryllium sulfate, iron sulfate, ammonium sulfate, boron sulfate, and aluminum sulfate.
The quantity of nitrogen and sulfur-containing substance is somewhat empirical and can vary widely depending upon the reactivity of the catalyst and the reactivity of the reactants present. Usually, though, the amount used to provide a catalytic effect ranges from about 0.01 to 20% mole percent based upon the amount of the alkylenediamine compound present in the reaction mixture, and preferably in an amount of from about 0.5 to 8 mole percent based on the amount of alkylenediamine compound. Within these ranges though, the level of catalyst again is somewhat empirical and is adjusted depending on the product state desired. It has been found that as the reactivity of the catalyst increases and conversion increases, selectivity is reduced. In those instances where there is substantial catalytic activity, then, the quantity of catalyst is reduced to increase selectivity with a concomitant reduction in conversion.
In the preparation of linear polyalkylene polyamines, and preferably the linear polyethylene polyamines, the reaction is maintained at a temperature of from about 225° to about 350° C., and preferably from about 275° to 300° C. The pressure utilized for carrying out the reaction is that sufficient to maintain the reaction in essentially liquid phase which normally ranges from about 800 to 2500 psig. When utilizing these temperatures and pressures, the reaction is allowed to proceed until a desired conversion is obtained or reaction is complete. Normally the reaction is carried out within about 1 to 2 hours.
It is important in carrying out the process that the proportion of alkylenediamine compound to alkanolamine compound, be in a stoichiometric excess, e.g. to 10:1, to result in highest selectivity to linear product. When the alkylene diamine compound approaches a 1:1 molar ratio, on a weight basis with the alkanolamine, or falls below that level then the alkanolamine may have a tendency to form the cyclic amine compositions. Generally, the mole ratio of alkylenediamine compound to alkanolamine compound is from about 0.3 to 5, and preferably about 0.5 to 2:1.
Recovery of the linear polyalkylene polyamines from the reaction mixture can be accomplished by conventional techniques, these techniques generally involving a distillation reaction. Often a small amount of a salt, such as the one used as the catalytic material, is added to the polyalkylene polyamine separation purification as described in U.S. Pat. No. 3,755,447.
The following examples illustrate the nature of the process described herein that are not intended to limit the scope of the invention.
EXAMPLES 1-9
A series of runs 1-8 were made to produce linear polyethylene polyamines by the reaction of ethylenediamine and ethanolamine in a mole ratio of 1:2 in the presence of nitrogen-containing catalysts. The reaction was carried out in a 2 milliliter shaker reactor at a pressure of 1,000 psig and a temperature of 300° C. Each reaction was carried out for about two hours. At the completion of the reaction, the contents were cooled and the reaction mixture analyzed by gas-liquid chromotography.
Run 9 attempted to duplicate the art as taught by U.S. Pat. No. 4,036,881, which used boron phosphate as the catalyst. This was used for comparative purposes.
Tables 1 and 2 show results in terms of the amount of polyamines produced by the reaction. Conversion and selectivity are specified. As noted, the catalytic component was varied and the amount varied on the basis of weight mole percent of the alkylenediamine.
TABLE 1__________________________________________________________________________POLYETHYLENE AMINES FROM ETHYLENEDIAMINE AND ETHANOLAMINE.sup.a Level Mole Temp. AE- AE- AE-Run Catalyst % °C. PIP TEDA DETA AEP TAEA TETA BAEP PEEDA TETA TEPA BAEP PEEDA__________________________________________________________________________1 nitric 5.0 300 -- 0.27 9.04 4.28 0.30 1.78 3.95 1.69 24.53 -- 2.37 -- acid2 lithium 5.0 300 -- 0.23 7.07 5.42 0.92 3.06 6.42 4.16 20.36 -- 1.49 -- nitrate3 beryllium 5.0 300 4.69 0.06 5.02 2.80 0.38 1.78 2.40 1.04 20.38 0.20 4.58 -- nitrate4 boron 2.5 300 8.19 0.94 4.35 4.62 0.29 0.54 1.61 1.44 14.06 -- 6.53 -- nitrate5 iron 2.5 300 4.75 0.27 3.30 3.02 0.49 1.09 2.58 1.30 20.23 -- 4.72 -- nitrate6 alumi- 2.5 300 4.62 0.66 4.96 4.10 1.10 2.61 3.14 2.55 23.17 -- 5.32 -- num nitrate7 bismuth 2.5 300 -- 0.36 5.51 3.55 0.19 1.75 3.67 2.05 34.14 -- 4.07 -- nitrate8 ammo- 4.8 300 2.90 -- 0.51 2.86 -- 1.05 1.10 0.69 -- 1.09 0.20 -- nium nitrate__________________________________________________________________________ .sup.a All numbers refer to weight percent of individual components in th product mixture on a feedstockfree basis. PIP--Piperazine TEDA--Triethylene diamine DETA--Diethylenetriamine AEP--Aminoethylpiperazine TAEA--Tris(aminoethyl)amine TETA--Triethylenetetramine BAEP--N,N.sup.1Bis(aminoethyl)piperazine PEEDA--N(Piperazinoethyl)ethylenediamine AETETA--N(Aminoethyl)triethylenetetramine TEPA--Tetraethylenepentamine AEBAEP--N(2-(2-aminoethylamino)-N.sup.1(2-aminoethyl)piperazine AEPEEDA--N(2-Piperazinoethyl)diethylenetriamine
TABLE 2______________________________________COMPARISON OF NITROGEN AND PHOSPHOROUSCATALYSTS Conver-Example Catalyst Level.sup.a sion.sup.b Selectivity.sup.c______________________________________1 Nitric Acid 5.0 37.2 73.92 Lithium Nitrate 5.0 26.2 63.93 Beryllium Nitrate 5.0 63.2 64.14 Boron Nitrate 2.5 75.0 45.25 Iron Nitrate 2.5 71.2 60.26 Aluminum Nitrate 2.5 74.5 61.87 Bismuth Nitrate 2.5 52.0 75.28 Ammonium Nitrate 4.8 55.1 25.19 Boron Phosphate 5.0 94.9 31.0______________________________________ .sup.a Mole percent of catalyst included, based on total amine feed. .sup.b Weight percent of ethylenediamine and ethanolamine consumed in the reaction. .sup.c Weight percent of noncyclic polyethylene amine products formed based on total reaction product.
Tables 1 and 2 show that the nitrogen containing catalysts were effective in producing a variety of linear polyalkylene polyamines. Iron, aluminum, lithium and bismuth nitrates gave good yields of polyalkylene polyamines with good conversion. As compared to the prior art catalyst, boron phosphate, selectivity was better in almost every case, ammonium nitrate being less effective. Although conversions were not as high as with boron phosphate conversions were good.
EXAMPLES 10-13
A series of runs 10-13 and similar to the previous examples were made to produce linear polyethylene polyamines by the reaction of ethylenediamine and ethanolamine except that a mole ratio of 1:1, a lower catalyst level and a pressure of 1200 psig was used. At the completion of the reaction, the contents were cooled and the reaction mixture analyzed by gas-liquid chromatography.
Run 14 corresponds to Example 9, which provides a comparison with the nitrates only using 2.5 mole percent boron phosphate.
Tables 3 and 4 show results in terms of the amount of polyamines produced by the reaction.
TABLE 3__________________________________________________________________________POLYETHYLENE AMINES FROM ETHYLENEDIAMINE AND ETHANOLAMINE.sup.a level mole Temp. AE- AE- AE-Run Catalyst % °C. PIP TEDA DETA AEP TAEA TETA BAEP PEEDA TETA TEPA BAEP PEEDA__________________________________________________________________________10 iron 2.5 300 0.40 0.15 5.91 1.36 0.50 2.86 0.80 -- -- -- -- -- nitrate11 alumi- 2.5 300 2.52 -- 4.28 1.66 0.36 1.26 0.25 0.51 -- -- 0.13 -- num nitrate12 bismuth 2.5 300 2.22 -- 0.08 0.08 0.42 1.82 0.12 0.46 -- -- -- -- nitrate13 beryllium 5.0 300 1.76 -- 2.43 1.42 0.43 0.79 0.55 1.42 0.11 0.11 0.03 -- nitrate__________________________________________________________________________ .sup.a All numbers refer to weight percent of individual components in th product mixture on a feedstockfree basis. PIP--Piperazine TEDA--Triethylene diamine DETA--Diethylenetriamine AEP--Aminoethylpiperazine TAEA--Tris(aminoethyl)amine TETA--Triethylenetetramine BAEP--N,N.sup.1Bis(aminoethyl)piperazine PEEDA--N(Piperazinoethyl)ethylenediamine AETETA--N(Aminoethyl)triethylenetetramine TEPA--Tetraethylenepentamine AEBAEP--N(2-(2-aminoethylamino)-N.sup.1(2-aminoethyl)piperazine AEPEEDA--N(2-Piperazinoethyl)diethylenetriamine
TABLE 4______________________________________Comparison of Nitrogen andPhosphorous CatalystsExample Catalyst Level.sup.a Conversion.sup.b Selectivity.sup.c______________________________________10 Iron Nitrate 2.5 39.8 77.211 Aluminum Nitrate 2.5 60.3 53.812 Bismuth Nitrate 2.5 49.4 43.713 Beryllium Nitrate 5.0 69.5 45.714 Boron Phosphate 2.5 76.9 45.0______________________________________ .sup.a Mole percent of catalyst included, based on total amine feed. .sup.b Weight percent of ethylenediamine and ethanolamine consumed in thi reaction. .sup.c Weight percent of noncyclic polyethylene amine products formed based on total reaction product.
Again, the tables show that the nitrate salts provided good yields of polyethylene polyamines, as compared to the prior art boron phosphate. As compared to the results in Tables 1 and 2, it can be seen that conversion decreased slightly for the same catalyst and that selectivity also decreased slightly. Selectivity would be expected to decrease as compared to the runs in Examples 1-8 since the ethanolamine concentration is higher and it can react with itself to form cyclics.
EXAMPLES 15-22
A series of runs similar to the previous examples were made to produce linear polyethylene polyamines except that a mole ratio of ethylenediamine and ethanolamine of 1:2, sulphur-containing catalysts at various levels, and a pressure of 1,000 psig was used. Each reaction was carried out for about two hours. At the completion of the reaction, the contents were cooled and the reaction mixture analyzed by gas-liquid chromatography.
Example 23 provides a comparison with boron phosphate at low levels.
Tables 5 and 6 show results in terms of the amount of polyamines produced by the reaction.
TABLE 5__________________________________________________________________________POLYETHYLENE AMINES FROM ETHYLENEDIAMINE AND ETHANOLAMINE.sup.a level mole Temp. AE- AE- AE-Run Catalyst % °C. PIP TEDA DETA AEP TAEA TETA BAEP PEEDA TETA TEPA BAEP PEEDA__________________________________________________________________________15 sulfuric 1.67 300 -- 1.35 17.80 13.56 1.63 5.17 3.75 3.50 5.38 0.19 2.31 0.47 acid16 ammo- 1.75 300 5.36 0.92 4.91 5.21 0.18 1.54 2.36 3.04 7.85 1.59 4.89 1.86 nium sulfate17 alumi- 0.45 300 6.56 0.61 8.37 6.84 0.39 2.03 3.66 2.79 4.97 0.39 5.28 0.63 num sulfate18 boron 0.62 300 0.10 1.49 27.30 5.63 0.64 5.31 2.50 2.55 5.51 2.80 3.87 0.79 sulfate19 boron 2.50 300 0.09 0.07 3.74 3.06 -- 0.47 1.15 1.11 3.97 -- 1.32 -- sulfate20 ammo- 0.60 300 5.26 -- 11.69 8.72 -- 3.61 1.61 2.00 0.46 -- 1.48 -- nium sulfate21 iron 2.50 300 -- 0.29 7.15 8.20 0.16 0.38 2.39 1.63 4.40 -- 3.60 -- sulfate22 beryllium 5.0 300 5.76 0.96 10.31 6.95 0.37 1.66 1.70 1.48 4.60 -- 1.96 0.20 sulfate__________________________________________________________________________ .sup.a All numbers refer to weight percent of individual components in th product mixture on a feedstockfree basis. PIP--Piperazine TEDA--triethylene diamine DETA--Diethylenetriamine AEP--Aminoethylpiperazine TAEA--Tris(aminoethyl)amine TETA--Triethylenetetramine BAEP--N,N.sup.1Bis(aminoethyl)piperazine PEEDA--N(Piperazinoethyl)ethylenediamine AETETA--N(Aminoethyl)triethylenetetramine TEPA--Tetraethylenepentamine AEBAEP--N(2-(2-aminoethylamino)-N.sup.1(2-aminoethyl)piperazine AEPEEDA--N(2-Piperazinoethyl)diethylenetriamine
TABLE 6______________________________________Comparison of Sulfate and Phosphate CatalystsExample Catalyst Level.sup.a Conversion.sup.b Selectivity.sup.c______________________________________15 Sulfuric 1.67 42.9 54.8 Acid16 Ammonium 1.75 66.1 40.5 Sulfate17 Aluminum 0.45 25.5 36.618 Boron 0.62 40.3 71.0 Sulfate19 Boron 2.50 55.9 54.6 Sulfate20 Ammonium 0.60 51.9 45.3 Sulfate21 Iron 2.50 31.4 63.4 Sulfate22 Beryllium 5.00 46.0 47.1 Sulfate23 Boron 0.80 50.9 66.0 Phosphate 9 Boron 5.00 94.9 31.0 Phosphate______________________________________ .sup.a Mole percent of catalyst included, based on total amine feed. .sup.b Weight percent of ethylenediamine and ethanolamine consumed in the reaction .sup.c Weight percent of noncyclic polyethylene amine products formed.
The results in Tables 5 and 6 clearly show that sulfur containing catalysts including sulfuric acid are effective for producing linear polyethylamine polyamines from the reaction of ethylene diamine and ethanolamine. Boron sulfate gave extremely high selectivity at a low level, e.g. 0.62 mole percent ethylenediamine. Surprisingly, with the sulfate catalyst higher concentration of catalyst resulted in substantially reduced selectivity with only modest improvements in conversion, see boron sulfate. Boron phosphate, on the other hand, experienced a doubling in conversion while selectivity dropped in half.
EXAMPLES 24-29
A series of runs similar to Examples 15-22 were made except that a mole ratio of diamine to alkanolamine of 1:1 was used in the presence of sulfur-containing catalysts.
Tables 7 and 8 show results in terms of the amount of polyamines produced by the reaction. Conversion and selectivity are specified.
TABLE 7__________________________________________________________________________POLYETHYLENE AMINES FROM ETHYLENEDIAMINE AND ETHANOLAMINE.sup.a level mole Temp. AE- AE- AE-Run Catalyst % °C. PIP TEDA DETA AEP TAEA TETA BAEP PEEDA TETA TEPA BAEP PEEDA__________________________________________________________________________24 boron 1.25 300 64.75 -- 14.33 5.32 -- 0.61 2.32 -- -- -- -- -- sulfate25 boron 2.50 300 7.14 0.08 2.38 10.17 -- 0.19 4.00 5.89 3.88 1.46 4.53 0.26 sulfate26 ammo- 0.60 300 4.43 -- 16.75 1.63 0.93 3.38 2.43 0.67 -- -- -- 0.71 nium sulfate27 ammo- 1.75 300 4.15 -- 5.91 1.02 -- -- 0.31 0.72 0.64 -- -- -- nium sulfate28 boron 0.625 300 -- 0.66 9.69 1.70 -- 0.81 1.35 0.54 5.48 -- 1.24 -- sulfate29 sulfuric 1.67 300 -- 0.84 9.15 1.82 0.21 1.02 1.26 0.75 4.22 -- 1.91 -- acid__________________________________________________________________________ .sup.a All numbers refer to weight percent of individual components in th product mixture on a feedstockfree basis. PIP--Piperazine TEDA--triethylene diamine DETA--Diethylenetriamine AEP--Aminoethylpiperazine TAEA--Tris(aminoethyl)amine TETA--Triethylenetetramine BAEP--N,N.sup.1Bis(aminoethyl)piperazine PEEDA--N(Piperazinoethyl)ethylenediamine AETETA--N(Aminoethyl)triethylenetetramine TEPA--Tetraethylenepentamine AEBAEP--N(2-(2-aminoethylamino)-N.sup.1(2-aminoethyl)piperazine AEPEEDA--N(2-Piperazinoethyl)diethylenetriamine
TABLE 8______________________________________Comparison of Sulfate and Phosphate CatalystsExample Catalyst Level.sup.a Conversion.sup.b Selectivity.sup.c______________________________________24 Boron 1.25 26.3 17.1 Sulfate25 Boron 2.50 84.5 19.1 Sulfate26 Ammonium 0.60 46.1 31.4 Sulfate27 Ammonium 1.75 39.0 51.4 Sulfate28 Boron 0.625 25.9 74.5 Sulfate29 Sulfuric 1.67 34.5 68.9 Acid14 Boron 2.50 76.9 45.0 Phosphate23 Boron 0.8 50.9 66.0 Phosphate______________________________________ .sup.a Mole percent of catalyst included, based on total amine feed. .sup.b Weight percent of ethylenediamine and ethanolamine consumed in the reaction .sup.c Weight percent of noncyclic polyethylene amine products formed.
These results show that generally selectivity to polyethylene polyamines increased as compared to Tables 5 and 6. This would be expected from the earlier work where selectivity is increased where the concentration of diamine vis-a-vis the ethanolamine increased. Conversions were slightly lower.
EXAMPLES 30-34
A series of runs similar to Runs 15-22 were made except that a mole ratio of 2:1 and a pressure of 1,500 psig was used.
Runs 35 and 36 provide a comparison with boron phosphate.
Tables 9 and 10 show results in terms of the amount of polyamines produced by the reaction.
TABLE 9__________________________________________________________________________POLYETHYLENE AMINES FROM ETHYLENEDIAMINE AND ETHANOLAMINE.sup.a level mole Temp. AE- AE- AE-Run Catalyst % °C. PIP TEDA DETA AEP TAEA TETA BAEP PEEDA TETA TEPA BAEP PEEDA__________________________________________________________________________30 boron 2.50 300 5.58 0.06 10.49 5.78 0.46 0.72 2.34 2.93 1.07 -- 0.48 -- sulfate31 boron 1.25 300 3.08 -- 10.85 1.26 -- -- 1.02 0.61 -- -- -- -- sulfate32 boron 0.625 300 -- 0.34 4.18 0.53 -- -- 0.78 0.10 1.19 -- -- -- sulfate33 ammo- 1.75 300 5.96 -- 9.79 1.68 -- -- 1.35 0.84 -- -- -- -- nium sulfate34 sulfuric 1.67 300 10.58 0.19 8.53 1.08 0.10 1.32 0.87 0.41 0.87 -- -- -- acid__________________________________________________________________________ .sup.a All numbers refer to weight percent of individual components in th product mixture on a feedstockfree basis. PIP--Piperazine TEDA--triethylene diamine DETA--Diethylenetriamine AEP--Aminoethylpiperazine TAEA--Tris(aminoethyl)amine TETA--Triethylenetetramine BAEP--N,N.sup.1Bis(aminoethyl)piperazine PEEDA--N(Piperazinoethyl)ethylenediamine AETETA--N(Aminoethyl)triethylenetetramine TEPA--Tetraethylenepentamine AEBAEP--N(2-(2-aminoethylamino)-N.sup.1(2-aminoethyl)piperazine AEPEEDA--N(2-Piperazinoethyl)diethylenetriamine
TABLE 10______________________________________Comparison of Sulfate and Phosphate CatalystsExample Catalyst Level.sup.a Conversion.sup.b Selectivity.sup.c______________________________________30 boron 2.50 45.7 42.6 Sulfate31 Boron 1.25 34.4 64.5 Sulfate32 Boron 0.625 32.0 75.4 Sulfate33 Ammonium 1.75 21.4 49.9 Sulfate34 Sulfuric 1.67 41.5 45.2 Acid35 Boron 0.80 52.3 62.0 Phosphate36 Boron 5.00 66.2 43.0 Phosphate______________________________________ .sup.a Mole percent of catalyst included, based on total amine feed. .sup.b Weight percent of ethylenediamine and ethanolamine consumed in the reaction .sup.c Weight percent of noncyclic polyethylene amine products formed.
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A process for selectively preparing predominantly non-cyclic polyalkylene polyamine compounds are disclosed wherein an alkylene polyamine compound is contacted with a hydroxy compound in the presence of a catalytically effective amount of a salt of a nitrogen or sulfur containing substance or the corresponding acid at a temperature of from 250° to 300° C. under a pressure sufficient to maintain the reaction mixture essentially in liquid phase. The polyalkylene polyamine thus formed is recovered from the reaction mixture.
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[0001] The present application claims the benefit of U.S. Provisional Patent Application No. 62/167,818, filed May 28, 2015, incorporated by reference in its entirety herein.
BACKGROUND
[0002] Aspects of the present invention relate to entanglement prevention in brush assemblies in autonomous robotic vacuums.
[0003] Autonomous robotic vacuums often work in rooms on a schedule, when the user is not present. As such a vacuum traverses an environment, the vacuum picks up dirt, dust, lint, hair, and other debris and collects it in an onboard bin. In environments where substantial amounts of hair fall on the ground, brushes on board an autonomous robotic vacuum pick up the hair. Such pick up is known to cause clogging of the brush assembly, and in particular the hub on which the brush(es) is/are mounted, potentially preventing the brush(es) from rotating, and thus keeping the vacuum from operating properly. As such vacuums tend to be battery operated, the battery can run down before the vacuum finishes traversing the environment. Alternatively, if the vacuum keeps moving with the clogged brush assembly, proper cleaning cannot occur.
[0004] When the user returns, s/he may not know that there has been an entanglement. In that situation, the user may simply recharge the vacuum and set it again to operate when the user is away. However, the vacuum will not clean, because the entanglement still is there. As a result, the user will come home and find that the vacuum has not performed its intended tasks.
[0005] If the user examines the vacuum, s/he may see the entanglement. The user then has to remove the entanglement manually. However, in some circumstances the user may not see the entanglement, around the hub, very clearly. Also, even if the user does see the entanglement, it may not be easy to remove. Over time, the buildup of hair and debris could cause fatal damage to the robotic vacuum.
[0006] It would be desirable to provide an approach which avoids entanglement in the first instance.
SUMMARY OF THE INVENTION
[0007] In view of the foregoing, it is an object of the present invention to provide an apparatus which draws or leads hair and other potential entanglement debris away from the hub of a brush assembly as the brush rotates during vacuuming, thus avoiding or reducing entanglement and attendant problems, and obviating or reducing the need for manual removal of the entanglement.
[0008] In one aspect, an effect of the entanglement prevention apparatus is to enable the brush to be closer to the hub, enabling the brush to clean more effectively.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] FIG. 1 is an exploded view of an entanglement prevention apparatus in accordance with one aspect of the invention.
[0010] FIG. 2 is another exploded view of an entanglement prevention apparatus in accordance with one aspect of the invention.
[0011] FIG. 3 is another view of an entanglement prevention apparatus, as related to a brush assembly, in accordance with one aspect of the invention.
[0012] FIG. 4 is yet another view of an entanglement prevention apparatus, as related to a brush assembly, in accordance with one aspect of the invention.
[0013] FIG. 5 is an exploded view of an entanglement prevention apparatus, as related to a brush assembly, in accordance with one aspect of the invention.
[0014] FIG. 6 is another exploded view of an entanglement prevention apparatus, as related to a brush assembly, in accordance with one aspect of the invention.
[0015] FIG. 7 is yet another exploded view of an entanglement prevention apparatus, as related to a brush assembly, in accordance with one aspect of the invention.
DETAILED DESCRIPTION
[0016] As now will be described in detail with respect to one or more embodiments, in one aspect the invention provides an apparatus which attaches to a vacuum brush, enabling the brush to rotate freely. The apparatus has a profile which draws hair and other entanglement debris away from a hub of the brush assembly, or prevents it from reaching the hub, thus enabling the brush/brush assembly to continue to rotate freely.
[0017] In one aspect of the invention, any number of autonomous robotic vacuums which operate with a brush assembly may employ the entanglement prevention apparatus described herein. One example of a robotic device which has vacuuming as one of its functions is described in U.S. Pat. No. 7,555,363, commonly assigned with the present application. The contents of this patent are incorporated herein by reference.
[0018] Looking at FIG. 1 , an entanglement prevention apparatus 100 is constituted by a first endpiece 110 and a second endpiece 160 . In an embodiment, the endpieces 110 and 160 may be snapfit or otherwise attached to each other. Between the two endpieces 110 , 160 sits an insert 120 which is shaped to fit closely with endpiece 110 ; a bar 130 providing support to insert 120 ; a washer 140 ; and a bushing 150 . In an embodiment, bar 130 and washer 140 may be press fit or otherwise attached to insert 120 . In an embodiment, bushing 150 may be press fit or otherwise attached to second endpiece 160 . The overall assembly of apparatus 100 is such that, when attached to a brush assembly as will be discussed in more detail herein, the insert 120 , with bar 130 and washer 140 , spins freely within the apparatus.
[0019] Each of the components of apparatus 100 now will be discussed in more detail. In an embodiment, first endpiece 110 may be generally circular in cross section, except for a tongue-shaped extension 112 which in some circumstances can facilitate holding the structure fast to a brush housing assembly. In an embodiment, the endpiece 110 may be made of plastic. Other materials which facilitate snap fitting or other attachment to second endpiece 160 also are possible.
[0020] Endpiece 110 has a first side 114 and a second, opposite side 116 . Sides 114 and 116 are sized to accommodate insert 120 , as now will be discussed.
[0021] In an embodiment, insert 120 has a generally circular portion 122 and an extension 124 which is shaped to engage with the above-mentioned brush assembly. In an embodiment, extension 124 may have raised portions 126 which facilitate firmer engagement with the brush assembly. Circular portion 122 has a first surface, facing extension 124 , with a first radius, and a second surface, on an opposite of the first surface, having a second, larger radius. In an embodiment, the progression from the first radius to the second radius is smooth and generally continuous. As a result, the circular portion 122 has a profile which variously may be known to ordinarily skilled artisans as a bevel, a chamfer, a taper, a slanted or angled surface, or a truncated cone. Each of these terms can have meanings which are synonymous or which are slightly different from each other. In the description herein, for convenience, the shape will be referred to as a bevel. However, this term should be understood to be shorthand for any of the several terms just mentioned, with corresponding definitions being applicable. Thus, for example, in the context of the present disclosure, something that is referred to as a chamfer will be understood also to be a bevel, a taper, a slanged or angled surface, or a truncated cone. Calling a structure one of these names does not prevent it from being known under one of the other names.
[0022] The bevel profile of circular portion 122 fits in a complementary fashion with a corresponding concave profile of side 116 of endpiece 110 . The fitting is such that, when endpieces 110 and 160 are mated (snap fit) to each other, insert 120 rotates freely within the assembly comprising endpieces 110 and 160 . Also, the profile of side 114 complements the shape of circular portion 122 . Side 114 ′s profile, the smaller part of the bevel profile, faces the brush assembly, as will be seen. Elements 130 , 140 , and 150 , which will be discussed in more detail below, facilitate the free rotation of insert 120 .
[0023] Bar 130 , which in an embodiment is metal, fits in an opening in insert 120 . Bar 130 may be force fit into insert 120 , or otherwise may be firmly attached or adhered to insert 120 . In an embodiment, washer 140 may have an opening corresponding to that of a diameter of bar 130 , and may facilitate rotation of bar 130 within insert 120 .
[0024] Bushing 150 , which in an embodiment also is metal, has a flanged portion 152 and a cylindrical portion 154 . Cylindrical portion 154 may fit into an opening in second endpiece 160 . This fit may be a force fit or a press fit, or other kind of attachment or adherence that puts bushing securely in the second endpiece 160 . An end of bar 130 may slide into an opening in bushing 150 . The metal to metal contact between bar 130 and bushing 150 reduces friction, and enables the bar 130 to rotate freely within the bushing 150 . Alternatively, for example, bushing 150 may be made of nylon, plastic, or other material which produces relatively little friction when in contact with bar 130 . As another alternative, bearings may replace bushing 150 . As yet another alternative, bar 130 may be made of a material other than metal. However, where torqueing of extension 124 in insert 120 potentially is an issue, having the bar 130 be made of more rigid material can be desirable.
[0025] Second endpiece 160 may be made of a material which facilitates a press fit or a snap fit with first endpiece 110 . On a side opposite the side of endpiece 160 into which bushing 150 fits, there may be extensions, 162 , 164 which facilitate attachment of apparatus 100 into a larger structure, such as an underside of a vacuum, which in an embodiment is an autonomous robotic vacuum.
[0026] FIG. 2 shows an exploded view of apparatus 100 in an opposite direction or orientation, so that certain portions of elements 110 - 160 are more visible. In particular, side 116 of first endpiece 110 is more visible, as is the surface on that side which complements the upper surface of circular portion 122 . Cylindrical mating surface 118 also is visible. The lip on that mating surface surrounds circular portion 122 as that portion nests within first endpiece 110 .
[0027] FIG. 2 shows a hole in the middle of insert 120 , into which bar 130 fits. In an embodiment, washer 140 seats in the underside of insert 120 , and is attached so that bar 130 is secure within extension 124 of insert 120 . As with the previous embodiment, washer 140 may facilitate rotation of bar 130 within insert 120 . The other side of second endpiece 160 also is more visible in FIG. 2 , with extensions 162 , 164 more visible.
[0028] FIG. 3 shows a brush assembly 300 which includes brush 310 , apparatus 100 , and end cap 350 . In an embodiment, brush 310 includes bristled portions 320 and non-bristled portions 330 , for cleaning of different types of surfaces, different types of debris, and the like. In an embodiment, bristled portions 320 and/or non-bristled portions 330 are attached in serpentine fashion in brush 310 . Such a configuration may facilitate collection of gathered debris for direction toward a dustbin within the robotic vacuum. FIG. 3 shows an embodiment in which these portions 320 , 330 are attached in a double serpentine configuration. Such a configuration also can facilitate guidance of debris toward a dustbin or other receptacle on board a robotic vacuum such as may be seen in U.S. Pat. No. 7,555,363.
[0029] In FIG. 3 , apparatus 100 is attached to brush 310 as part of the overall brush assembly 300 . In an embodiment, extension 124 of insert 120 of apparatus 100 fits into an opening (not seen in this figure, but visible in FIGS. 5 and 7 , for example) at the center of the brush assembly 300 . In an embodiment, end cap 350 is attached to brush 310 on an opposite side from apparatus 100 . End cap 350 may be configured to attach to motive structure, for example, in an autonomous robotic vacuum or other cleaning apparatus, so as to facilitate rotation of the brush assembly 300 by motive force. Such attachment may require a different configuration for end cap 350 than for apparatus 100 . In an embodiment, end cap 350 may have the same structure, configuration, and operation as apparatus 100 . In an embodiment, rotation of the brush may come through attachment, either directly or via some kind of gearing arrangement, to motive wheels, again as may be seen in U.S. Pat. No. 7,555,363.
[0030] FIG. 4 shows a side view of brush assembly 300 , making it easier to see end cap 350 as juxtaposed with apparatus 100 . The double serpentine configuration of bristled and non-bristled portions 320 , 330 in an embodiment also is more apparent.
[0031] FIG. 5 shows an exploded view of apparatus 100 as it fits into brush assembly 300 . As alluded to earlier, extension 124 of insert 120 fits through first endpiece 110 into an opening (unnumbered) in brush 310 so as to attach firmly within the opening, through press fit, force fit, or other manner of adherence, while enabling the subassembly comprising insert 120 , bar 130 , and washer 140 to continue to rotate freely through bushing 150 , thus enabling free rotation of brush assembly 300 at that end. The extensions on the side of second endpiece 160 may facilitate attachment of that assembly within an autonomous robotic vacuum. Such attachment will not impede free rotation of the insert 120 within apparatus 100 , however. The brush assembly opening into which extension 124 fits is central to the brush assembly.
[0032] FIG. 6 shows a different, side view of what FIG. 5 shows, including an exploded view of apparatus 100 , to show how parts 110 - 160 come together and go into brush assembly 300 .
[0033] FIG. 7 shows yet a different view of brush assembly 300 , with an assembled version of apparatus 100 and insert 120 juxtaposed with an opening in brush assembly 300 .
[0034] It has been discovered that the bevel shape of first endpiece 110 , into which insert 120 fits, tends to effectively guide hair and other potential entanglement debris away from the hub in which brush assembly 300 is mounted, or prevent such debris from reaching the hub in the first place. As a result, debris will not wrap around any portion of the bushing or bearing mechanism, potentially fouling it. Hair or fibers have difficulty going from a smaller diameter to a larger diameter along the bevel as the assembly rotates. The bevel creates a barrier to keep fiber or hair from impinging on the bushing or bearing, preventing clogging. The effect of this structure is to enable the brush 310 to be positioned more closely to the hub on which brush assembly 300 is mounted, enabling a longer brush which can clean more surface during a pass of the robotic device. As a result, the brush 310 can clean more effectively within the overall robotic vacuum structure (actually, closer to the outer edges of that structure), in part because of the brush proximity to the hub.
[0035] What has been described here is a brush assembly for use in an autonomous robotic device with various capabilities. The robotic device's autonomy is in contrast to a remote control operation of the device. Autonomy enables the robotic device to operate without supervision or external influence, for example, to clean the environment, or zones within the environment in which the robot is operating. The entanglement prevention feature described herein works well with an autonomous robotic device which may operate, for example, on a schedule when the owner/user/operator is unavailable (for example, in the case of a home robotic vacuum, away from home). Entanglement prevention means that, for example, while the owner/user/operator is unavailable, the autonomous robotic device may operate with lessened risk of non-functionality, or battery drain, or the like because of fouling or other impeding of rotation of the brush assembly.
[0036] The brush assembly, of which the entanglement prevention apparatus described herein is a part, may be part of a home robotic vacuum, but also may be configured as a cartridge which a user may select from among several types of cleaning cartridges or modules (e.g. waxers, dusters, buffers, mops, or other types of cleaners). That is, an autonomous robotic device employing a brush assembly with the entanglement prevention apparatus described herein may be configured to receive different kinds of cleaning cartridges or modules, so as to perform as a floor cleaning product which performs different types of cleaning, not just vacuuming. A non-limiting example of such a cartridge configuration again may be seen in U.S. Pat. No. 7,555,363.
[0037] Although the invention has been described in language specific to structural features and/or methodological steps, it is to be understood that the invention is not to be limited to the specific features or steps disclosed. Rather, the specific features and steps are disclosed as preferred forms of implementing the invention, which is to be defined by the claims.
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An apparatus draws or leads hair and other potential entanglement debris away from the hub of a brush assembly in a vacuum as the brush rotates during vacuuming, thus avoiding or reducing entanglement and attendant problems, and obviating or reducing the need for manual removal of the entanglement. The apparatus has a profile which draws hair and other entanglement debris away from a hub of the brush assembly, or prevents it from reaching the hub, thus enabling the brush/brush assembly to continue to rotate freely. In one implementation, the apparatus attaches to a vacuum brush in an autonomous robotic vacuum.
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CROSS REFERENCE TO RELATED APPLICATION
The present application is a continuation of U.S. application Ser. No. 10/729,004 filed on Dec. 8, 2003, now U.S. Pat. No. 6,971,734 which is a Continuation of U.S. application Ser. No. 10/102,700 filed on Mar. 22, 2002, now U.S. Pat. No. 6,692,113, the entire contents of which are herein incorporated by reference.
CO-PENDING APPLICATIONS
Various methods, systems and apparatus relating to the present invention are disclosed in the following co-pending patents and/or applications filed by the applicant or assignee of the present invention:
U.S. Pat. No. 6,428,133, U.S. Pat. No. 6,526,658, U.S. Pat. No. 6,795.215, U.S. Pat. No. 7,154,638.
The disclosures of these co-pending applications are incorporated herein by reference.
BACKGROUND OF THE INVENTION
The following invention relates to a printhead module assembly for a printer.
More particularly, though not exclusively, the invention relates to a printhead module assembly for an A4 pagewidth drop on demand printer capable of printing up to 1600 dpi photographic quality at up to 160 pages per minute.
The overall design of a printer in which the printhead module assembly can be utilized revolves around the use of replaceable printhead modules in an array approximately 8½ inches (21 cm) long. An advantage of such a system is the ability to easily remove and replace any defective modules in a printhead array. This would eliminate having to scrap an entire printhead if only one chip is defective.
A printhead module in such a printer can be comprised of a “Memjet” chip, being a chip having mounted thereon a vast number of thermo-actuators in micro-mechanics and micro-electromechanical systems (MEMS). Such actuators might be those as disclosed in U.S. Pat. No. 6,044,646 to the present applicant, however, might be other MEMS print chips.
In a typical embodiment, eleven “Memjet” tiles can butt together in a metal channel to form a complete 8½ inch printhead assembly.
The printhead, being the environment within which the printhead module assemblies of the present invention are to be situated, might typically have six ink chambers and be capable of printing four color process (CMYK) as well as infrared ink and fixative. An air pump would supply filtered air through a seventh chamber to the printhead, which could be used to keep foreign particles away from its ink nozzles.
Each printhead module receives ink via an elastomeric extrusion that transfers the ink. Typically, the printhead assembly is suitable for printing A4 paper without the need for scanning movement of the printhead across the paper width.
The printheads themselves are modular, so printhead arrays can be configured to form printheads of arbitrary width.
Additionally, a second printhead assembly can be mounted on the opposite side of a paper feed path to enable double-sided high-speed printing.
OBJECTS OF THE INVENTION
It is an object of the present invention to provide an improved printhead module assembly.
It is another object of the invention to provide a printhead assembly having improved modules therein.
SUMMARY OF THE INVENTION
According to a first aspect of the invention, there is provided a printhead assembly which comprises
an elongate support structure; and
at least one elongate printhead module positioned on the support structure, along a length of the support structure, the, or each, printhead module comprising
an elongate elastomeric feed member that is positioned on the support structure, the feed member defining a number of longitudinally extending flow passages that are connectable to at least an ink supply, and a plurality of outlet holes in a surface of the feed member in fluid communication with the flow passages; an ink distribution assembly that is positioned on the feed member, the ink distribution assembly defining a mounting formation to permit a printhead chip to be mounted on the ink delivery assembly, a plurality of ink inlets that are in fluid communication with the outlet holes of the feed member, a plurality of exit holes and tortuous ink flow paths from each ink inlet to a number of respective exit holes; and a printhead chip that is mounted on the ink distribution assembly so that the ink can be fed from the exit holes to the printhead chip.
A number of elongate printhead modules may be mounted, end-to-end, on the support structure.
Each feed member may be an extruded member having a generally rectangular cross section, with the ink flow paths extending from one end of the feed member to an opposite end. Each printhead module may include two closures that are engageable with respective ends of the feed member. The feed member may define a number of inlet openings in the surface of the ink feed member. Each inlet opening may be in fluid communication with a respective flow path to permit at least ink to be delivered to the flow paths.
A delivery structure may be mounted on each ink feed member. Each delivery structure may define a number of inlet conduits in fluid communication with respective delivery outlets. The delivery structure may be engageable with the feed member such that each delivery outlet is in fluid communication with a respective ink flow path, via one of the inlet openings of the feed member.
The delivery structure may include a connecting plate and a plurality of connectors that are arranged on the connecting plate. Each connector may define a respective delivery outlet and may be engageable with a respective conduit. The connectors may be configured to engage the feed member at respective inlet openings.
Each printhead module may include an end cap assembly which includes a fastening plate, one of the closures and the connecting plate. The closure may be interposed between and pivotally mounted to the connecting plate and the fastening plate. The connecting plate may be fastenable to the fastening plate so that an end portion of the feed member is sandwiched between the connecting and fastening plates.
The outlet holes and the inlet holes of each ink feed member may be the product of a laser ablation process carried out on the surface of the ink feed member.
According to a second aspect of the invention, there is provided a printhead module for a printhead assembly incorporating a plurality of said modules positioned substantially across a pagewidth in a drop on demand ink jet printer, comprising:
an upper micro-molding locating a print chip having a plurality of ink jet nozzles, the upper micro-molding having ink channels delivering ink to said print chip,
a lower micro-molding having inlets through which ink is received from a source of ink, and
a mid-package film adhered between said upper and lower micro-moldings and having holes through which ink passes from the lower micro-molding to the upper micro-molding.
Preferably the mid-package film is made of an inert polymer.
Preferably the holes of the mid-package film are laser ablated.
Preferably the mid-package film has an adhesive layer on opposed faces thereof, providing adhesion between the upper micro-molding, the mid-package film and the lower micro-molding.
Preferably the upper micro-molding has an alignment pin passing through an aperture in the mid-package film and received within a recess in the lower micro-molding, the pin serving to align the upper micro-molding, the mid-package film and the lower micro-molding when they are bonded together.
Preferably the inlets of the lower micro-molding are formed on an underside thereof.
Preferably six said inlets are provided for individual inks.
Preferably the lower micro-molding also includes an air inlet.
Preferably the air inlet includes a slot extending across the lower micro-molding.
Preferably the upper micro-molding includes exit holes corresponding to inlets on a backing layer of the print chip.
Preferably the backing layer is made of silicon.
Preferably the printhead module further comprises an elastomeric pad on an edge of the lower micro-molding.
Preferably the upper and lower micro-moldings are made of Liquid Crystal Polymer (LCP).
Preferably an upper surface of the upper micro-molding has a series of alternating air inlets and outlets cooperative with a capping device to redirect a flow of air through the upper micro-molding.
Preferably each printhead module has an elastomeric pad on an edge of its lower micro-molding, the elastomeric pads bearing against an inner surface of the channel to positively locate the printhead modules within the channel.
As used herein, the term “ink” is intended to mean any fluid which flows through the printhead to be delivered to print media. The fluid may be one of many different colored inks, infra-red ink, a fixative or the like.
BRIEF DESCRIPTION OF THE DRAWINGS
A preferred form of the present invention will now be described by way of example with reference to the accompanying drawings wherein:
FIG. 1 is a schematic overall view of a printhead;
FIG. 2 is a schematic exploded view of the printhead of FIG. 1 ;
FIG. 3 is a schematic exploded view of an ink jet module;
FIG. 3 a is a schematic exploded inverted illustration of the ink jet module of FIG. 3 ;
FIG. 4 is a schematic illustration of an assembled ink jet module;
FIG. 5 is a schematic inverted illustration of the module of FIG. 4 ;
FIG. 6 is a schematic close-up illustration of the module of FIG. 4 ;
FIG. 7 is a schematic illustration of a chip sub-assembly;
FIG. 8 a is a schematic side elevational view of the printhead of FIG. 1 ;
FIG. 8 b is a schematic plan view of the printhead of FIG. 8 a;
FIG. 8 c is a schematic side view (other side) of the printhead of FIG. 8 a;
FIG. 8 d is a schematic inverted plan view of the printhead of FIG. 8 b;
FIG. 9 is a schematic cross-sectional end elevational view of the printhead of FIG. 1 ;
FIG. 10 is a schematic illustration of the printhead of FIG. 1 in an uncapped configuration;
FIG. 11 is a schematic illustration of the printhead of FIG. 10 in a capped configuration;
FIG. 12 a is a schematic illustration of a capping device;
FIG. 12 b is a schematic illustration of the capping device of FIG. 12 a , viewed from a different angle;
FIG. 13 is a schematic illustration showing the loading of an ink jet module into a printhead;
FIG. 14 is a schematic end elevational view of the printhead illustrating the printhead module loading method;
FIG. 15 is a schematic cut-away illustration of the printhead assembly of FIG. 1 ;
FIG. 16 is a schematic close-up illustration of a portion of the printhead of FIG. 15 showing greater detail in the area of the “Memjet” chip;
FIG. 17 is a schematic illustration of the end portion of a metal channel and a printhead location molding;
FIG. 18 a is a schematic illustration of an end portion of an elastomeric ink delivery extrusion and a molded end cap; and
FIG. 18 b is a schematic illustration of the end cap of FIG. 18 a in an out-folded configuration.
DETAILED DESCRIPTION OF THE INVENTION
In FIG. 1 of the accompanying drawings there is schematically depicted an overall view of a printhead assembly. FIG. 2 shows the core components of the assembly in an exploded configuration. The printhead assembly 10 of the preferred embodiment comprises eleven printhead modules 11 situated along a metal “Invar” channel 16 . At the heart of each printhead module 11 is a “Memjet” chip 23 ( FIG. 3 ). The particular chip chosen in the preferred embodiment being a six-color configuration.
The “Memjet” printhead modules 11 are comprised of the “Memjet” chip 23 , a fine pitch flex PCB 26 and two micro-moldings 28 and 34 sandwiching a mid-package film 35 . Each module 11 forms a sealed unit with independent ink chambers 63 ( FIG. 9 ) which feed the chip 23 . The modules 11 plug directly onto a flexible elastomeric extrusion 15 which carries air, ink and fixitive. The upper surface of the extrusion 15 has repeated patterns of holes 21 which align with ink inlets 32 ( FIG. 3 a ) on the underside of each module 11 . The extrusion 15 is bonded onto a flex PCB (flexible printed circuit board).
The fine pitch flex PCB 26 wraps down the side of each printhead module 11 and makes contact with the flex PCB 17 ( FIG. 9 ). The flex PCB 17 carries two busbars 19 (positive) and 20 (negative) for powering each module 11 , as well as all data connections. The flex PCB 17 is bonded onto the continuous metal “Invar” channel 16 . The metal channel 16 serves to hold the modules 11 in place and is designed to have a similar coefficient of thermal expansion to that of silicon used in the modules.
A capping device 12 is used to cover the “Memjet” chips 23 when not in use. The capping device is typically made of spring steel with an onsert molded elastomeric pad 47 ( FIG. 12 a ). The pad 47 serves to duct air into the “Memjet” chip 23 when uncapped and cut off air and cover a nozzle guard 24 ( FIG. 9 ) when capped. The capping device 12 is actuated by a camshaft 13 that typically rotates throughout 180°.
The overall thickness of the “Memjet” chip is typically 0.6 mm which includes a 150-micron inlet backing layer 27 and a nozzle guard 24 of 150-micron thickness. These elements are assembled at the wafer scale.
The nozzle guard 24 allows filtered air into an 80-micron cavity 64 ( FIG. 16 ) above the “Memjet” ink nozzles 62 . The pressurized air flows through microdroplet holes 45 in the nozzle guard 24 (with the ink during a printing operation) and serves to protect the delicate “Memjet” nozzles 62 by repelling foreign particles.
A silicon chip backing layer 27 ducts ink from the printhead module packaging directly into the rows of “Memjet” nozzles 62 . The “Memjet” chip 23 is wire bonded 25 from bond pads on the chip at 116 positions to the fine pitch flex PCB 26 . The wire bonds are on a 120-micron pitch and are cut as they are bonded onto the fine pitch flex PCB pads ( FIG. 3 ). The fine pitch flex PCB 26 carries data and power from the flex PCB 17 via a series of gold contact pads 69 along the edge of the flex PCB.
The wire bonding operation between chip and fine pitch flex PCB 26 may be done remotely, before transporting, placing and adhering the chip assembly into the printhead module assembly. Alternatively, the “Memjet” chips 23 can be adhered into the upper micro-molding 28 first and then the fine pitch flex PCB 26 can be adhered into place. The wire bonding operation could then take place in situ, with no danger of distorting the moldings 28 and 34 . The upper micro-molding 28 can be made of a Liquid Crystal Polymer (LCP) blend. Since the crystal structure of the upper micro-molding 28 is minute, the heat distortion temperature (180° C.–260° C.), the continuous usage temperature (200° C.–240° C. and soldering heat durability (260° C. for 10 seconds to 310° C. for 10 seconds) are high, regardless of the relatively low melting point.
Each printhead module 11 includes an upper micro-molding 28 and a lower micro-molding 34 separated by a mid-package film layer 35 shown in FIG. 3 .
The mid-package film layer 35 can be an inert polymer such as polyimide, which has good chemical resistance and dimensional stability. The mid-package film layer 35 can have laser ablated holes 65 and can comprise a double-sided adhesive (ie. an adhesive layer on both faces) providing adhesion between the upper micro-molding, the mid-package film layer and the lower micro-molding.
The upper micro-molding 28 has a pair of alignment pins 29 passing through corresponding apertures in the mid-package film layer 35 to be received within corresponding recesses 66 in the lower micro-molding 34 . This serves to align the components when they are bonded together. Once bonded together, the upper and lower micro-moldings form a tortuous ink and air path in the complete “Memjet” printhead module 11 .
There are annular ink inlets 32 in the underside of the lower micro-molding 34 . In a preferred embodiment, there are six such inlets 32 for various inks (black, yellow, magenta, cyan, fixitive and infrared). There is also provided an air inlet slot 67 . The air inlet slot 67 extends across the lower micro-molding 34 to a secondary inlet which expels air through an exhaust hole 33 , through an aligned hole 68 in fine pitch flex PCB 26 . This serves to repel the print media from the printhead during printing. The ink inlets 32 continue in the undersurface of the upper micro-molding 28 as does a path from the air inlet slot 67 . The ink inlets lead to 200 micron exit holes also indicated at 32 in FIG. 3 . These holes correspond to the inlets on the silicon backing layer 27 of the “Memjet” chip 23 .
There is a pair of elastomeric pads 36 on an edge of the lower micro-molding 34 . These serve to take up tolerance and positively located the printhead modules 11 into the metal channel 16 when the modules are micro-placed during assembly.
A preferred material for the “Memjet” micro-moldings is a LCP. This has suitable flow characteristics for the fine detail in the moldings and has a relatively low coefficient of thermal expansion.
Robot picker details are included in the upper micro-molding 28 to enable accurate placement of the printhead modules 11 during assembly.
The upper surface of the upper micro-molding 28 as shown in FIG. 3 has a series of alternating air inlets and outlets 31 . These act in conjunction with the capping device 12 and are either sealed off or grouped into air inlet/outlet chambers, depending upon the position of the capping device 12 . They connect air diverted from the inlet slot 67 to the chip 23 depending upon whether the unit is capped or uncapped.
A capper cam detail 40 including a ramp for the capping device is shown at two locations in the upper surface of the upper micro-molding 28 . This facilitates a desirable movement of the capping device 12 to cap or uncap the chip and the air chambers. That is, as the capping device is caused to move laterally across the print chip during a capping or uncapping operation, the ramp of the capper cam detail 40 serves to elastically distort and capping device as it is moved by operation of the camshaft 13 so as to prevent scraping of the device against the nozzle guard 24 .
The “Memjet” chip assembly 23 is picked and bonded into the upper micro-molding 28 on the printhead module 11 . The fine pitch flex PCB 26 is bonded and wrapped around the side of the assembled printhead module 11 as shown in FIG. 4 . After this initial bonding operation, the chip 23 has more sealant or adhesive 46 applied to its long edges. This serves to “pot” the bond wires 25 ( FIG. 6 ), seal the “Memjet” chip 23 to the molding 28 and form a sealed gallery into which filtered air can flow and exhaust through the nozzle guard 24 .
The flex PCB 17 carries all data and power connections from the main PCB (not shown) to each “Memjet” printhead module 11 . The flex PCB 17 has a series of gold plated, domed contacts 69 ( FIG. 2 ) which interface with contact pads 41 , 42 and 43 on the fine pitch flex PCB 26 of each “Memjet” printhead module 11 .
Two copper busbar strips 19 and 20 , typically of 200 micron thickness, are jigged and soldered into place on the flex PCB 17 . The busbars 19 and 20 connect to a flex termination which also carries data The flex PCB 17 is approximately 340 mm in length and is formed from a 14 mm wide strip. It is bonded into the metal channel 16 during assembly and exits from one end of the printhead assembly only.
The metal U-channel 16 into which the main components are place is of a special alloy called “Invar 36”. It is a 36% nickel iron alloy possessing a coefficient of thermal expansion of 1/10 th that of carbon steel at temperatures up to 400° F. The Invar is annealed for optimal dimensional stability.
Additionally, the Invar is nickel plated to a 0.056% thickness of the wall section. This helps to further match it to the coefficient of thermal expansion of silicon which is 2×10 −6 per ° C.
The Invar channel 16 functions to capture the “Memjet” printhead modules 11 in a precise alignment relative to each other and to impart enough force on the modules 11 so as to form a seal between the ink inlets 32 on each printhead module and the outlet holes 21 that are laser ablated into the elastomeric ink delivery extrusion 15 .
The similar coefficient of thermal expansion of the Invar channel to the silicon chips allows similar relative movement during temperature changes. The elastomeric pads 36 on one side of each printhead module 11 serve to “lubricate” them within the channel 16 to take up any further lateral coefficient of thermal expansion tolerances without losing alignment. The Invar channel is a cold rolled, annealed and nickel plated strip. Apart from two bends that are required in its formation, the channel has two square cut-outs 80 at each end. These mate with snap fittings 81 on the printhead location moldings 14 ( FIG. 17 ).
The elastomeric ink delivery extrusion 15 is a non-hydrophobic, precision component. Its function is to transport ink and air to the “Memjet” printhead modules 11 . The extrusion is bonded onto the top of the flex PCB 17 during assembly and it has two types of molded end caps. One of these end caps is shown at 70 in FIG. 18 a.
A series of patterned holes 21 are present on the upper surface of the extrusion 15 . These are laser ablated into the upper surface. To this end, a mask is made and placed on the surface of the extrusion, which then has focused laser light applied to it. The holes 21 are evaporated from the upper surface, but the laser does not cut into the lower surface of extrusion 15 due to the focal length of the laser light.
Eleven repeated patterns of the laser ablated holes 21 form the ink and air outlets 21 of the extrusion 15 . These interface with the annular ring inlets 32 on the underside of the “Memjet” printhead module lower micro-molding 34 . A different pattern of larger holes (not shown but concealed beneath the upper plate 71 of end cap 70 in FIG. 18 a ) is ablated into one end of the extrusion 15 . These mate with apertures 75 having annular ribs formed in the same way as those on the underside of each lower micro-molding 34 described earlier. Ink and air delivery hoses 78 are connected to respective connectors 76 that extend from the upper plate 71 . Due to the inherent flexibility of the extrusion 15 , it can contort into many ink connection mounting configurations without restricting ink and air flow. The molded end cap 70 has a spine 73 from which the upper and lower plates are integrally hinged. The spine 73 includes a row of plugs 74 that are received within the ends of the respective flow passages of the extrusion 15 .
The other end of the extrusion 15 is capped with simple plugs which block the channels in a similar way as the plugs 74 on spine 17 .
The end cap 70 clamps onto the ink extrusion 15 by way of snap engagement tabs 77 . Once assembled with the delivery hoses 78 , ink and air can be received from ink reservoirs and an air pump, possibly with filtration means. The end cap 70 can be connected to either end of the extrusion, ie. at either end of the printhead.
The plugs 74 are pushed into the channels of the extrusion 15 and the plates 71 and 72 are folded over. The snap engagement tabs 77 clamp the molding and prevent it from slipping off the extrusion. As the plates are snapped together, they form a sealed collar arrangement around the end of the extrusion. Instead of providing individual hoses 78 pushed onto the connectors 76 , the molding 70 might interface directly with an ink cartridge. A sealing pin arrangement can also be applied to this molding 70 . For example, a perforated, hollow metal pin with an elastomeric collar can be fitted to the top of the inlet connectors 76 . This would allow the inlets to automatically seal with an ink cartridge when the cartridge is inserted. The air inlet and hose might be smaller than the other inlets in order to avoid accidental charging of the airways with ink.
The capping device 12 for the “Memjet” printhead would typically be formed of stainless spring steel. An elastomeric seal or onsert molding 47 is attached to the capping device as shown in FIGS. 12 a and 12 b . The metal part from which the capping device is made is punched as a blank and then inserted into an injection molding tool ready for the elastomeric onsert to be shot onto its underside. Small holes 79 ( FIG. 13 b ) are present on the upper surface of the metal capping device 12 and can be formed as burst holes. They serve to key the onsert molding 47 to the metal. After the molding 47 is applied, the blank is inserted into a press tool, where additional bending operations and forming of integral springs 48 takes place.
The elastomeric onsert molding 47 has a series of rectangular recesses or air chambers 56 . These create chambers when uncapped. The chambers 56 are positioned over the air inlet and exhaust holes 30 of the upper micro-molding 28 in the “Memjet” printhead module 11 . These allow the air to flow from one inlet to the next outlet. When the capping device 12 is moved forward to the “home” capped position as depicted in FIG. 11 , these airways 32 are sealed off with a blank section of the onsert molding 47 cutting off airflow to the “Memjet” chip 23 . This prevents the filtered air from drying out and therefore blocking the delicate “Memjet” nozzles.
Another function of the onsert molding 47 is to cover and clamp against the nozzle guard 24 on the “Memjet” chip 23 . This protects against drying out, but primarily keeps foreign particles such as paper dust from entering the chip and damaging the nozzles. The chip is only exposed during a printing operation, when filtered air is also exiting along with the ink drops through the nozzle guard 24 . This positive air pressure repels foreign particles during the printing process and the capping device protects the chip in times of inactivity.
The integral springs 48 bias the capping device 12 away from the side of the metal channel 16 . The capping device 12 applies a compressive force to the top of the printhead module 11 and the underside of the metal channel 16 . The lateral capping motion of the capping device 12 is governed by an eccentric camshaft 13 mounted against the side of the capping device. It pushes the device 12 against the metal channel 16 . During this movement, the bosses 57 beneath the upper surface of the capping device 12 ride over the respective ramps 40 formed in the upper micro-molding 28 . This action flexes the capping device and raises its top surface to raise the onsert molding 47 as it is moved laterally into position onto the top of the nozzle guard 24 .
The camshaft 13 , which is reversible, is held in position by two printhead location moldings 14 . The camshaft 11 can have a flat surface built in one end or be otherwise provided with a spline or keyway to accept gear 22 or another type of motion controller.
The “Memjet” chip and printhead module are assembled as follows: 1. The “Memjet” chip 23 is dry tested in flight by a pick and place robot, which also dices the wafer and transports individual chips to a fine pitch flex PCB bonding area. 2. When accepted, the “Memjet” chip 23 is placed 530 microns apart from the fine pitch flex PCB 26 and has wire bonds 25 applied between the bond pads on the chip and the conductive pads on the fine pitch flex PCB. This constitutes the “Memjet” chip assembly. 3. An alternative to step 2 is to apply adhesive to the internal walls of the chip cavity in the upper micro-molding 28 of the printhead module and bond the chip into place first. The fine pitch flex PCB 26 can then be applied to the upper surface of the micro-molding and wrapped over the side. Wire bonds 25 are then applied between the bond pads on the chip and the fine pitch flex PCB. 4. The “Memjet” chip assembly is vacuum transported to a bonding area where the printhead modules are stored. 5. Adhesive is applied to the lower internal walls of the chip cavity and to the area where the fine pitch flex PCB is going to be located in the upper micro-molding of the printhead module. 6. The chip assembly (and fine pitch flex PCB) are bonded into place. The fine pitch flex PCB is carefully wrapped around the side of the upper micro-molding so as not to strain the wire bonds. This may be considered as a two step gluing operation if it is deemed that the fine pitch flex PCB might stress the wire bonds. A line of adhesive running parallel to the chip can be applied at the same time as the internal chip cavity walls are coated. This allows the chip assembly and fine pitch flex PCB to be seated into the chip cavity and the fine pitch flex PCB allowed to bond to the micro-molding without additional stress. After curing, a secondary gluing operation could apply adhesive to the short side wall of the upper micro-molding in the fine pitch flex PCB area. This allows the fine pitch flex PCB to be wrapped around the micro-molding and secured, while still being firmly bonded in place along on the top edge under the wire bonds. 7. In the final bonding operation, the upper part of the nozzle guard is adhered to the upper micro-molding, forming a sealed air chamber. Adhesive is also applied to the opposite long edge of the “Memjet” chip, where the bond wires become ‘potted’ during the process. 8. The modules are ‘wet’ tested with pure water to ensure reliable performance and then dried out. 9. The modules are transported to a clean storage area, prior to inclusion into a printhead assembly, or packaged as individual units. This completes the assembly of the “Memjet” printhead module assembly. 10. The metal Invar channel 16 is picked and placed in a jig. 11. The flex PCB 17 is picked and primed with adhesive on the busbar side, positioned and bonded into place on the floor and one side of the metal channel. 12. The flexible ink extrusion 15 is picked and has adhesive applied to the underside. It is then positioned and bonded into place on top of the flex PCB 17 . One of the printhead location end caps is also fitted to the extrusion exit end. This constitutes the channel assembly. The laser ablation process is as follows: 13. The channel assembly is transported to an eximir laser ablation area. 14. The assembly is put into a jig, the extrusion positioned, masked and laser ablated. This forms the ink holes in the upper surface. 15. The ink extrusion 15 has the ink and air connector molding 70 applied. Pressurized air or pure water is flushed through the extrusion to clear any debris. 16. The end cap molding 70 is applied to the extrusion 15 . It is then dried with hot air. 17. The channel assembly is transported to the printhead module area for immediate module assembly. Alternatively, a thin film can be applied over the ablated holes and the channel assembly can be stored until required. The printhead module to channel is assembled as follows: 18. The channel assembly is picked, placed and clamped into place in a transverse stage in the printhead assembly area. 19. As shown in FIG. 14 , a robot tool 58 grips the sides of the metal channel and pivots at pivot point against the underside face to effectively flex the channel apart by 200 to 300 microns. The forces applied are shown generally as force vectors F in FIG. 14 . This allows the first “Memjet” printhead module to be robot picked and placed (relative to the first contact pads on the flex PCB 17 and ink extrusion holes) into the channel assembly. 20. The tool 58 is relaxed, the printhead module captured by the resilience of the Invar channel and the transverse stage moves the assembly forward by 19.81 mm. 21. The tool 58 grips the sides of the channel again and flexes it apart ready for the next printhead module. 22. A second printhead module 11 is picked and placed into the channel 50 microns from the previous module. 23. An adjustment actuator arm locates the end of the second printhead module. The arm is guided by the optical alignment of fiducials on each strip. As the adjustment arm pushes the printhead module over, the gap between the fiducials is closed until they reach an exact pitch of 19.812 mm. 24. The tool 58 is relaxed and the adjustment arm is removed, securing the second printhead module in place. 25. This process is repeated until the channel assembly has been fully loaded with printhead modules. The unit is removed from the transverse stage and transported to the capping assembly area. Alternatively, a thin film can be applied over the nozzle guards of the printhead modules to act as a cap and the unit can be stored as required. The capping device is assembled as follows: 26. The printhead assembly is transported to a capping area. The capping device 12 is picked, flexed apart slightly and pushed over the first module 11 and the metal channel 16 in the printhead assembly. It automatically seats itself into the assembly by virtue of the bosses 57 in the steel locating in the recesses 83 in the upper micro-molding in which a respective ramp 40 is located. 27. Subsequent capping devices are applied to all the printhead modules. 28. When completed, the camshaft 13 is seated into the printhead location molding 14 of the assembly. It has the second printhead location molding seated onto the free end and this molding is snapped over the end of the metal channel, holding the camshaft and capping devices captive. 29. A molded gear 22 or other motion control device can be added to either end of the camshaft 13 at this point. 30. The capping assembly is mechanically tested. Print charging is as follows: 31. The printhead assembly 10 is moved to the testing area. Inks are applied through the “Memjet” modular printhead under pressure. Air is expelled through the “Memjet” nozzles during priming. When charged, the printhead can be electrically connected and tested. 32. Electrical connections are made and tested as follows: 33. Power and data connections are made to the PCB. Final testing can commence, and when passed, the “Memjet” modular printhead is capped and has a plastic sealing film applied over the underside that protects the printhead until product installation.
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A printhead assembly for a pagewidth inkjet printer includes an elongate support structure. A plurality of elongate printhead modules is positioned, end to end, in the support structure. Each printhead module includes a feed member that defines a number of longitudinally extending flow passages in fluid communication with respective flow passages of adjacent feed members and a number of ink outlet holes in fluid communication with each of the flow passages. A lower micro-molding is mounted on the feed member. The lower micro-molding includes a number of inlets in fluid communication with respective ink outlet holes and a number of exit holes in fluid communication with respective inlets. An upper micro-molding is mounted on the lower micro-molding and defines a recess and a number of ink passages in fluid communication with respective exit holes and terminating at the recess. A printhead chip is positioned in the recess to receive ink from the ink passages. A mid-package layer is interposed between the upper and lower micro-moldings and has adhesive to provide adhesion between the upper and lower micro-moldings.
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BACKGROUND OF THE INVENTION
The present invention relates to improvements in or relating to propellers, now more generally referred to as "impellers", of the type designed for producing a turbulent motion within a gaseous, liquid or other medium, or a medium having a more or less pronounced consistency, in order to effect in such medium the stirring of a mixture, an aeration, a mixing or dispersive action. However, this enumeration should not be construed as limiting the scope of the present invention.
As a rule, the problem to be solved in the technical field concerned is to produce in a closed or open vessel or the like a stirring or turbulent action distributed throughout the vessel in which the impeller is mounted and the medium is to be processed, with the minimum power consumption.
The various research efforts performed up to now with a view to solve this problem have been directed principally to the study of the vessel shapes and also of the impeller blade profiles, with correlative attempts to reduce through the use of suitable techniques the sometimes high cost of the vessel and blades.
Prior researches made by the Applicant proved that substantial power savings could be made when preparing a mixture by using an impeller having the best possible "pumping" (or "blowing") characteristics.
Pumping, which is the fluid flow output passing through the impeller determines the creation, in the medium receiving the impeller, of movements causing both the transport of particles constituting the medium and a distortion of the particles. This distortion, due to differential speeds, is due to the turbulent energy (W T ) created by the impeller, and the transport proper is due to the displacement energy (W D ) also created by the impeller.
The level of turbulent energy required for producing a predetermined effect is actually subordinate to this desired effect. Thus, for instance, it is easy to mix two miscible liquids, but on the other hand it is difficult to create particles of gradually decreasing magnitude in one phase dispersed in another phase.
Generally, the permissible energy savings are achieved by not exceeding the strict minimum amount of turbulent energy W T which is necessary for obtaining the desired result.
Having thus ascertained the importance of the flow output per unit of power consumption of the impeller, the Applicant directed his search more particularly towards the fluid flow patterns in the mixer vessel. This study eventually proved that a number of advantageous properties could be obtained by improving the knowledge of these flow patterns. As a rule, these improved properties led to a substantial reduction in the power consumption required for obtaining a given local effect through a better distribution of the active areas in the mixing volume, in general.
Observing the phenomena produced in a mixing vessel due to the operation of a conventional propeller proves that, in contrast to what occurs in a indefinite medium (the term "indefinite medium" denotes a liquid area not influenced by solid walls, for example in the case of a ship propeller churning sea water, in opposition to a closed vessel in which the dimensions of the vessel are small in relation to the dimensions of the impeller so that certain reflexion effects occur due to the presence of the walls) wherein the propeller jet is cylindrical, a characteristic outflaring of the jet a is produced, this jet thus assuming the shape of a more or less open cone having an apex angle α (see FIG. 1 of the attached drawings). This outflaring effect is subordinate to the proximity of the lateral walls and also to the viscosity of the fluid filling the vessel c. The more or less outflared configuration of the jet under given geometrical properties of the vessel and fluid viscosities may constitute an advantage, but in most instances it constitutes an inconvenience, inasmuch as the jet energy is considerably diluted therein and the local effects at points remote from the impeller may drop below a critical limit. Thus, the apex angle α of the cone formed by the blowing impeller may attain 120° in water if ratio d/D of the impeller diameter to the vessel diameter is 0.7 and the jet bursts out either in the bottom of the said vessel or against its vertical side wall, according to the distance from the impeller to the bottom.
Moreover, the slower the dissipation of the jet energy, the greater the distance attained by the fluid to which energy is impressed by the impeller, the dissipation being due not only to the peripheral friction forces increasing with the external surface and therefore with the outflaring, but also to the internal turbulent effects. These effects depend on the continuity of the impeller profile characteristics.
SUMMARY OF THE INVENTION
In actual practice, it is therefore very important to have the possibility, in a vessel of a given configuration of creating from the onset a conical or cylindrical jet shape of predetermined geometry and turbulence, and this constitutes the essential object of the invention.
This object is achieved according to this invention by so shaping the impeller blades that the axial effect of these blades is completed by a centrifugal or centripetal effect obtained by preserving an optimum pumping efficiency, i.e. by limiting to a minimum value the energy dissipated in the form of turbulence.
Moreover, the use of auxiliary profiles according to this invention enhances the axial or centrifugal or centripetal effect and creates in addition localized turbulences of predetermined amplitude.
BRIEF DESCRIPTION OF THE DRAWINGS
Other objects, features and advantages of the present invention will be apparent from the following detailed description, taken with the accompanying drawings, wherein:
FIG. 1 is a schematic view of an impeller within a vessel;
FIGS. 1a, 1b and 1c are schematic views of portions of impeller blades illustrating the forces involved during rotation thereof;
FIG. 1d is a perspective view of an impeller according to the invention;
FIGS. 2 and 3 are perspective views of the formation of impeller blades by rolling and pressing, respectively;
FIGS. 2a and 3a are end views of the arrangements of FIGS. 2 and 3, respectively;
FIGS. 4 through 6 are perspective schematic views illustrating various impeller blade configurations;
FIGS. 7 and 8 are perspective views of compound configurations of impeller blades;
FIGS. 9 and 10 are a perspective view and an end view, respectively, of an impeller blade having one type of an auxiliary flap; and
FIGS. 11 through 13 are schematic views of further auxiliary flap configurations.
DETAILED DESCRIPTION OF THE INVENTION
The present invention is based on the to be discussed presently theoretical principles, the understanding of which will be facilitated by the following definitions.
Lift coefficient -- (See FIG. 1a)
When a propeller or impeller is rotating in a viscous fluid, a section of a blade of the impeller, having an area (S), located at the radius (R) reacts on the fluid with a force having two components, i.e. the lift force (L) which is perpendicular to the direction of the velocity (W) of the section relative to the fluid flow, and the drag force (D) parallel to (W). In hydrodynamics it is well known that (L) and (D) can be written as:
L=1/2d.sub.m C.sub.L S W.sup.2
D=1/2d.sub.m C.sub.D S W.sup.2
wherein:
d m is the fluid density;
C l is the lift coefficient;
C d is the drag coefficient; and
W 2 =V 2 +(ωR) 2 , with
V=axial velocity through the propeller, and
ω=angular velocity of the propeller.
In FIG. 1b is indicated the angle of incidence (I) between the velocity (W) and the axis (p) for which L is equal to zero. The values of (I) and (C L ) are correlated for this profile as:
I=10 C.sub.L
up to now, and particularly for marine type propellers, when designing the propeller the coefficient C L was chosen approximately constant. Such propellers give a very weak radial movement in an infinite volume.
It has been found that if I is chosen to increase continuously from the rotational axis to the tip, a centrifugal component of velocity appears, and the angle (α) of the blowing cone increases.
Conversely, when I is chosen to decrease from the rotational axis up to the tip, a centripetal component appears, and angle (α) decreases for given conditions.
This angle α is determined by the construction of the impeller blade, and the construction may be as follows.
The sheet metal member or plate from which the blade element e is to be made is formed to have a substantially trapezoidal contour. The major base e 1 of this blank is used as the blade portion located near the shaft or axis. Therefore, this portion operates at a relatively low speed but has a strong incidence in the fluid and a relatively great cross-sectional area. For opposite reasons, the minor base e 2 of the trapezium is adapted to constitute the external portion of the blade. The ratio of the major base to the minor base is selected according to the area preferred for the maximum flow intensity.
The plate thus cut is shaped either by rolling as illustrated in FIGS. 2 and 2a, or in a press, as illustrated in FIGS. 3 and 3a of the drawings, in order to impart a cylindrical or tapered configuration thereto, or a compound shape by combining cylindrical, conical and/or flat portions.
The variation in the lift coefficient C L is obtained by varying both the angle of incidence of the fluid (medium) on the average chord of the profile, and the relative sag i.e. the ratio CD/AB as indicated in FIG. 1c.
The most advantageous positions for mixing operations are as a rule and according to this invention those wherein the section AB of FIG. 1c is either circular or elliptical with a relative sag i.e. ratio CD/AB, between 2% and 12%, and blade incidence angles i.e. angle (I), between 3° and 10°, whereby C L values of from 0.7 to 1.6 for a-10-degree incidence and a 12% relative are obtained.
According to this invention and to a typical embodiment thereof, in which the blades are obtained by cylindrical circular rolling between the rollers d of FIG. 2, in a first case illustrated in FIG. 4 the minor base e 2 is engaged first into the nip formed by rollers d or similarly between the V-sectioned bending tools 4, 4a of a bending press of FIG. 3.
Thus, the angle β formed between the roller generatrix and the center line M 1 M 2 of blade e is directed as shown by the arrow in FIG. 4, and will be referred to as a positive angle.
Therefore, the incidence of the blade section chord decreases as the distance from the rotational axis f increases, and the lift coefficient C L increases accordingly. Therefore, this blade has a centripetal corrective component with respect to the fluid jet, which tends to reduce the blowing cone angle of the impeller, the term "blowing" having the same meaning as "pumping" but being employed more particularly when the impeller pumps the fluid downwardly.
Conversely, when as in the case illustrated in FIG. 6 the major base of the trapezium is engaged first, β will be "negative", and the blade chord incidence will increase from the axis of rotation of the impeller to the outer periphery thereof, so that the C L and the blade correction will be centrifugal, thus resulting in an increase or opening of the blowing cone angle.
By way of example, when the ratio d/D of the impeller diameter to the vessel diameter approximates 0.5 with a 1-centipoise viscosity and a given value (approximating 20°) of the positive angle β, movable blades producing a purely axial flow are obtained, the blowing volume having in this case a cylindrical pattern.
When, as illustrated in FIG. 5, β is zero, the conical flow is characteristic and the angle α of FIG. 1 has a value close to 45° under the same conditions.
Another exemplary embodiment is illustrated in FIGS. 7 and 8. In this case the blade has been given a compound cylindrical -plano-conical shape. In FIGS. 7 and 8, the area 1 is cylindrical as in the preceding example.
The area 2 is flat, either tangent to the preceding cylindrical area 1 (FIG. 7) or bent along this tangent (FIG. 8). The next area 3 is cylindrical in FIG. 7 and corresponds to a definitely centrifugal helix. Area 3 is tapered in FIG. 8 which is clearly centripetal.
In this case the corrective effect is due to the fact that the sag and the incidence, and therefore also the C L thereof, increase from the axis to the outer periphery of the blade in the case illustrated in FIG. 7, and decrease in the case of FIG. 8.
Auxiliary flaps may also be added to the improved impellers of this invention without departing from the basic principles of the invention. These auxiliary flaps consist of profiles designed and calculated with a view to obtain a well-defined and desired result. They are constructed like the main blades from plate blanks and are roller-shaped or pressed. If desired, they can be disposed to constitute either extensions or projections on the lower and/or upper surfaces of the main blades.
These auxiliary flaps may serve the purpose of either simply enhancing an axial or centrifugal or centripetal effect, or developing an eddy area of predetermined intensity and location.
FIGS. 9 to 13 of the attached drawings illustrate diagrammatically by way of example, not of limitation, several embodiments of these auxiliary flaps.
In FIG. 9 the flaps are similar to the ailerons currently added to aircraft wings for modifying the lift thereof.
In the case of FIGS. 9 and 10, the flap i is secured for instance to the lower surface of the blade e and its axis intersects that of the blade e so as to produce a centripetal action. Flap i could as well constitute an extension of blade e.
In FIG. 11, the desired effect is centrifugal. The flap j is secured to the outer tip of the blade, it has a vertical cylindrical circular configuration, it projects from both the lower and upper surfaces of the blade, and its total height corresponds to the chord of the main blade, at 0.7 of its radius. The desired result may be inverted, for example by using a concave flap instead of a convex flap, as seen by an observer standing at the impeller axis. Finally, FIG. 12 illustrates a particularly simple embodiment in which the main blade e consists of a possibly flat member to which flat or curved elements k disposed or bent in one direction are secured in one section, the next section comprising similar elements k 1 but disposed in the opposite direction.
If the total lift of the elements bent in one direction is equal to the lift of the elements bent in the opposite direction, and if the lengths of each section are relatively moderate, the whole of the complmentary energy absorbed by these elements is converted into turbulence. Of course, the bent elements may be located either along the trailing edge as shown or along the leading edge, or possibly along both edges simultaneously.
A specific arrangement illustrated in FIG. 13 comprises the use of only two sets of elements m, m 1 bent in opposite directions. If the total lift thus obtained is zero, then equal flows, i.e. a central flow and a peripheral flow, are obtained.
This specific arrangement is particularly advantageous when non-newtonian fluids are to be mixed together, for, in contrast to all other impellers, the assembly illustrated in FIG. 13 and described hereinabove occupies the entire cross-sectional area of the mixing vessel, whereby the peripheral dead area possibly resulting from the existence of a mixed fluid shearing threshold is eliminated.
Of course, this invention should not be construed as being strictly limited by the specific embodiments described, illustrated and suggested herein, since various modifications and variations may be made thereto without departing from the basic principles of the invention as set forth in the appended claims.
|
An impeller for producing a stirring action within a fluid medium contained in a vessel includes blades, each blade being shaped to produce a variation in the lift coefficient of the impeller from the rotational axis thereof to the blade tip, in order to provide a centrifugal or centripetal component, as case may be, of the outflaring or reduction imparted to the impeller blowing cone.
| 1 |
FIELD OF THE DISCLOSURE
[0001] This disclosure relates to viscoelastic damping materials and constructions which may demonstrate low temperature performance and adhesion and which may be used in making vibration damping composites.
SUMMARY OF THE DISCLOSURE
[0002] Briefly, the present disclosure provides a viscoelastic damping material comprising: a) a copolymer of: i) at least one monomer according to formula I:
[0000] CH 2 ═CHR 1 —COOR 2 [I]
[0000] wherein R 1 is H, CH 3 or CH 2 CH 3 and R 2 is a branched alkyl group containing 12 to 32 carbon atoms, and ii) at least one second mononomer; and b) at least one adhesion-enhancing material. In some embodiments, the adhesion-enhancing material is one of: inorganic nanoparticles, core-shell rubber particles, polybutene materials, or polyisobutene materials. Typically R 2 is a branched alkyl group containing 15 to 22 carbon atoms. Typically R 1 is H or CH 3 . Typically second mononomers are acrylic acid, methacrylic acid, ethacrylic acid, acrylic esters, methacrylic esters or ethacrylic esters esters. The viscoelastic damping material may additionally comprise a plasticizer.
[0003] In another aspect, the present disclosure provides a viscoelastic damping material comprising a copolymer of: i) at least one monomer according to formula I:
[0000] CH 2 ═CHR 1 —COOR 2 [I]
[0000] wherein R 1 is H, CH 3 or CH 2 CH 3 and R 2 is a branched alkyl group containing 12 to 32 carbon atoms, and ii) a monofunctional silicone (meth)acrylate oligomer. Typically R 2 is a branched alkyl group containing 15 to 22 carbon atoms. Typically R 1 is H or CH 3 . The viscoelastic damping material may additionally comprise a plasticizer.
[0004] In another aspect, the present disclosure provides a viscoelastic construction comprising: a) at least one viscoelestic layer comprising a polymer or copolymer of at least one monomer according to formula I:
[0000] CH 2 ═CHR 1 —COOR 2 [I]
[0000] wherein R 1 is H, CH 3 or CH 2 CH 3 and R 2 is a branched alkyl group containing 12 to 32 carbon atoms; bound to b) at least one PSA layer comprising a pressure sensitive adhesive. In some embodiments, the viscoelestic layer is bound to at least two layers comprising a pressure sensitive adhesive. Typically R 2 is a branched alkyl group containing 15 to 22 carbon atoms. Typically R 1 is H or CH 3 . In some embodiments, the viscoelestic layer comprises copolymer which is a copolymer of at least one second mononomer selected from acrylic acid, methacrylic acid, ethacrylic acid, acrylic esters, methacrylic esters, or ethacrylic esters. In some embodiments, the PSA layer comprises an acrylic pressure sensitive adhesive. In some embodiments, the PSA layer comprises an acrylic pressure sensitive adhesive which is a copolymer of acrylic acid.
[0005] In another aspect, the present disclosure provides a viscoelastic construction comprising: a) discrete particles of a polymer or copolymer of at least one monomer according to formula I:
[0000] CH 2 ═CHR 1 —COOR 2 [I]
[0000] wherein R 1 is H, CH 3 or CH 2 CH 3 and R 2 is a branched alkyl group containing 12 to 32 carbon atoms; dispersed in b) a PSA layer comprising a pressure sensitive adhesive. In some embodiments, the PSA layer comprises an acrylic pressure sensitive adhesive. In some embodiments, the PSA layer comprises an acrylic pressure sensitive adhesive which is a copolymer of acrylic acid.
[0006] In another aspect, the present disclosure provides a vibration damping composite comprising a viscoelastic damping material or a vibration damping composite of the present disclosure adhered to at least one substrate. In some embodiments, the material or construction is adhered to at least two substrates. In some embodiments, at least one substrate is a metal substrate.
DETAILED DESCRIPTION
[0007] The present disclosure provides material sets and constructions that demonstrate a pressure sensitive adhesive (PSA) that offers both vibration damping performance at very low temperatures and high frequencies as well as substantial adhesive performance and durability when used with a variety of substrates over a wide range of temperatures. The combination of both low temperature damping and adhesive performance attained using a single material set or construction represents a significant technical challenge in the field of visco-elastic damping materials. In some embodiments of the present disclosure, this is achieved through the use of specialty acrylic materials, specific additives, multi-layer construction, or combinations of the above.
[0008] The present disclosure provides material sets and constructions that demonstrate a pressure sensitive adhesive that offers both vibration damping performance at very low temperatures and high frequencies as well as substantial adhesive performance and durability when used with a variety of substrates over a wide range of temperatures. In some embodiments, materials or constructions according to the present disclosure exhibit high tan delta, as measured by Dynamic Mechanical Analysis (DMA) at −55° C. and 10 Hz as described in the examples below. In some embodiments, materials or constructions according to the present disclosure exhibit tan delta (as measured by Dynamic Mechanical Analysis (DMA) at −55° C. and 10 Hz as described in the examples below) of greater than 0.5, in some embodiments greater than 0.8, in some embodiments greater than 1.0, in some embodiments greater than 1.2, and in some embodiments greater than 1.4. In some embodiments, materials or constructions according to the present disclosure exhibit high peel adhesion, as measured as described in the examples below. In some embodiments, materials or constructions according to the present disclosure exhibit peel adhesion (as measured as described in the examples below) of greater than 10 N/dm, in some embodiments greater than 20 N/dm, in some embodiments greater than 30 N/dm, in some embodiments greater than 40 N/dm, in some embodiments greater than 50 N/dm, and in some embodiments greater than 60 N/dm. In some embodiments, materials or constructions according to the present simultaneously achieve high tan delta, at one or more of the levels described above, and high peel strength, at one or more of the levels described above.
[0009] In some embodiments, viscoelastic damping materials according to the present disclosure include long alkyl chain acrylate copolymers which are copolymers of monomers including one or more long alkyl chain acrylate monomers. The long alkyl chain acrylate monomers are typically acrylic acid, methacrylic acid or ethacrylic acid esters but typically acrylic acid esters. In some embodiments, the side chain of the long alkyl chain contains 12 to 32 carbon atoms (C12-C32), in some embodiments at least 15 carbon atoms, in some embodiments at least 16 carbon atoms, in some embodiments 22 or fewer carbon atoms, in some embodiments 20 or fewer carbon atoms, in some embodiments 18 or fewer carbon atoms, and in some embodiments 16-18 carbon atoms. Typically, the long alkyl chain has at least one branch point to limit crystallinity in the formed polymer that may inhibit damping performance. Long chain alkyl acrylates with no branch points may be used in concentrations low enough to limit crystallinity of the formed polymer at application temperatures. In some embodiments, additional comonomers are selected from acrylic acid, methacrylic acid or ethacrylic acid, but typically acrylic acid. In some embodiments, additional comonomers are selected from acrylic, methacrylic or ethacrylic esters, but typically acrylic esters.
[0010] In some embodiments, the long alkyl chain acrylate copolymers comprise additional comonomers or additives that join in the polymerization reaction, which imparting adhesive properties. Such comonomers may include polyethylene glycol diacrylates.
[0011] In some embodiments, the long alkyl chain acrylate copolymers comprise additional comonomers or additives that join in the polymerization reaction, which can help to impart greater adhesive properties through modulation of the rheological properties of the viscoelastic damping copolymer, or through the addition of functional groups. Such comonomers may include but are not limited to (meth)acrylic acid, hydroxyethyl (meth)acrylate, dimethylaminoethyl (meth)acrylate, monofunctional silicone (meth)acrylates, and isobornyl (meth)acrylate.
[0012] In some embodiments, the viscoelastic damping copolymer may be crosslinked to improve the durability and adhesion properties of the material. Such crosslinking agents can include but are not limited to photoactivated crosslinkers such as benzophenones, or 2,4-bis(trichloromethyl)-6-(4-methoxyphenyl)-triazine. Crosslinking agents can also include copolymerizable multifunctional acrylates such as polyethylene glycol diacrylate or hexanediol diacrylate as examples.
[0013] In some embodiments the viscoelastic damping copolymer may be polymerized through all known polymerization methods including thermally activated or photoinitiated polymerization. Such photopolymerization processes can include for example common photoinitiators such as diphenyl (2,4,6-trimethylbenzoyl)-phosphine oxide.
[0014] In some embodiments, viscoelastic damping materials according to the present disclosure include long alkyl chain acrylate copolymers and additional adhesion-enhancing materials which impart adhesive properties. Such additional adhesion-enhancing materials may include polybutenes, silicones, or polyisobutenes. Such additional adhesion-enhancing materials may also be particulate materials. Such particulate adhesion-enhancing materials may include fumed silica, core-shell rubber particles, or isostearyl acrylate microspheres.
[0015] In some embodiments, long alkyl chain acrylate copolymers according to the present disclosure form a part of a multilayer viscoelastic construction. In some embodiments, the long alkyl chain acrylate copolymers according to the present disclosure form a viscoelastic damping layer of a two-layer viscoelastic construction, the second, attached layer being a layer of more highly adhesive material over a broader temperature range. In some embodiments, the long alkyl chain acrylate copolymers according to the present disclosure form a viscoelastic damping core layer of a multilayer viscoelastic construction, sandwiched between two layers of more highly adhesive material. In some embodiments, the long alkyl chain acrylate copolymers according to the present disclosure form a layer of a multilayer viscoelastic construction which additionally comprises at least one layer of more highly adhesive material. In some embodiments, the long alkyl chain acrylate copolymers according to the present disclosure form an interior layer of a multilayer viscoelastic construction which additionally comprises at least two layers of more highly adhesive material. In some embodiments, the more highly adhesive material is an acrylic PSA material.
[0016] In some embodiments, a two-layer viscoelastic construction comprises a viscoelastic layer attached to a second layer which is a layer of more highly adhesive material. In some embodiments, the two-layer viscoelastic construction is made by lamination of a viscoelastic layer to an adhesive layer. In some embodiments, the two-layer viscoelastic construction is made by application of an adhesive tape to a viscoelastic layer. In some embodiments, the two-layer viscoelastic construction is made by application of an adhesive in liquid or aerosolized form to a viscoelastic damping layer to provide greater adhesion to the damping layer. In some embodiments, the two-layer viscoelastic construction is made by application of an adhesive in paste form to a viscoelastic layer. In some embodiments, a two-layer viscoelastic construction is provided in the form of a roll, sheet, or pre-cut article. In some embodiments, a two-layer viscoelastic construction is made shortly prior to use by application of an adhesive to a viscoelastic layer. In some embodiments, a two-layer viscoelastic construction is made in situ by application of an adhesive to a substrate followed by application of a viscoelastic layer to the adhesive.
[0017] In some embodiments, the multilayer viscoelastic construction comprises a viscoelastic layer sandwiched between two layers of more highly adhesive material. In some embodiments, the multilayer viscoelastic construction is made by lamination of a viscoelastic layer to at least one adhesive layer. In some embodiments, the multilayer viscoelastic construction is made by application of an adhesive tape to at least one side of a viscoelastic layer. In some embodiments, the multilayer viscoelastic construction is made by application of an adhesive in liquid form to at least one side of a viscoelastic layer. In some embodiments, the multilayer viscoelastic construction is made by application of an adhesive in paste form to at least one side of a viscoelastic layer. In some embodiments, a multilayer viscoelastic construction is provided in the form of a roll, sheet, or pre-cut article. In some embodiments, a multilayer viscoelastic construction is made shortly prior to use by application of an adhesive to a viscoelastic layer. In some embodiments, a multilayer viscoelastic construction is made in situ by application of an adhesive to a substrate followed by application of a viscoelastic layer to the adhesive, followed by application to the viscoelastic layer of additional adhesive or an additional adhesive-bearing substrate. In some embodiments, the multilayer construction is made in-situ by application of the viscoelastic damping composition in liquid form between two adhesive layers followed by a subsequent cure of the damping layer to form the viscoelastic damping copolymer.
[0018] The materials or constructions according to this disclosure may be useful for aerospace applications in which maximum damping performance of high frequency vibration energy is required at very low temperatures, in combination with good adhesion properties.
[0019] Objects and advantages of this disclosure are further illustrated by the following examples, but the particular materials and amounts thereof recited in these examples, as well as other conditions and details, should not be construed to unduly limit this disclosure.
EXAMPLES
[0020] Unless otherwise noted, all reagents were obtained or are available from Sigma-Aldrich Company, St. Louis, Mo., or may be synthesized by known methods. Unless otherwise reported, all ratios are by weight percent.
[0000] The following abbreviations are used to describe the examples:
° F.: degrees Fahrenheit ° C.: degrees Centigrade cm: centimeters g/cm 3 : grams per cubic centimeter Kg: kilograms Kg/m 3 : kilograms per cubic meter mil: 10 −3 inches mJ/cm 2 : milliJoules per square centimeter ml: milliliters
[0030] mm: millimeters
μm: micrometers N/dm: Newtons per decimeter pcf: pounds per cubic foot pph: parts per hundred
Test Methods
Peel Adhesion Test (PAT)
[0035] The force required to peel the test material from a substrate at an angle of 180 degrees was measured according to ASTM D 3330/D 3330M-04. Using a rubber roller, the adhesive sample was manually laminated onto a primed 2 mil (50.8 μm) polyester film, obtained under the trade designation “HOSTAPHAN 3SAB” from Mitsubishi Plastics, Inc., Greer, S.C., and allowed to dwell for 24 hours at 23° C./50% relative humidity. A 0.5×6 inches (1.27×12.7 cm) section was cut from the laminated film and taped to either a 0.10 inch (2.54 mm) or 0.20 inch (5.08 mm) thick, Shore A 70, 320 Kg/m 3 polyether-polyurethane foam, or a grade 2024 aluminum test coupon, obtained from Aerotech Alloys, Inc., Temecula, Calif. The tape was then manually adhered onto the test coupon using a 2 Kg rubber roller and conditioned for 24 hours at 23° C./50% relative humidity. The peel adhesive force was then determined using a tensile force tester, model “SP-2000”, obtained Imass Inc., Accord, Massachusetts, at a platen speed of 12 in./min (0.305 m/min.). Three tape samples were tested per example or comparative, and the average value reported in N/dm. Also reported are the failure modes, abbreviated as follows:
A: Adhesive tape cleanly delaminated from the substrate 2B: Two-bond failure, wherein the adhesive tape delaminated from the carrier backing C: Cohesive failure, wherein the adhesive layer ruptured, leaving material on both the backing and the substrate.
Dynamic Mechanical Analysis (DMA)
[0039] Dynamic Mechanical Analysis (DMA) was determined using a parallel plate rheometer, model “AR2000” obtained from TA Instruments, New Castle, Del. Approximately 0.5 grams of visco-elastic sample was centered between the two 8 mm diameter, aluminum parallel plates of the rheometer and compressed until the edges of the sample were uniform with the edges of the plates. The temperature of the parallel plates and rheometer shafts was then raised to 40° C. and held for 5 minutes. The parallel plates were then oscillated at a frequency of 10 Hz and a constant strain of 0.4% whilst the temperature was ramped down to −80° C. at a rate of 5° C./min. Storage modulus (G′), and tan delta were then determined.
Glass Transition Temperature (Tg)
[0040] Tan delta, the ratio of G″/G′, was plotted against temperature. Tg is taken as the temperature at maximum tan delta curve.
Damping Loss Factor (DLF)
[0041] A composite material was prepared for Damping Loss Factor as follows. A nominally 6 by 48 inch by 7 mil (15.24 by 121.92 cm by 0.178 mm) strip of aluminum was cleaned with a 50% aqueous solution of isopropyl alcohol and wiped dry. A primer, type “LORD 7701”, obtained from Lord Corporation, Cary, N.C., was applied to a nominally 6 by 48 by 0.1 inch (15.24 by 121.92 cm by 2.54 mm) strip of 20 pcf (0.32 g/cm 3 ) white foraminous micro cellular high density polyurethane foam. The adhesive tape was applied to the aluminum strip, nipped together to ensure wet out, then applied to the primed surface of the high density urethane. A 5 mil (127 μm) adhesive transfer tape, obtained under the trade designation “VHB 9469PC” obtained from 3M Company, St. Paul, Minn., was then applied on the opposite side of the urethane strip. The resulting composite material cut into 2 by 24 inch (5.08 by 60.96 cm) samples and applied to a 3×40 inch×0.062 mil (7.62×101.4 cm×1.58 mm) aluminum beam.
[0042] The beam was suspended by its first nodal points, and the center of the beam mechanically coupled to an electromagnetic shaker model “V203” from Brüel & Kjaer North America, Inc., Norcross, Ga., via an inline force transducer, model “208M63” from PCB Piezotronics, Inc., Depew, New York, in a thermally controlled chamber at temperatures of −10° C., −20° C. and −30° C. On the opposite side of the beam to the inline force transducer was mounted an accelerometer, model “353B16 ICP”, also from Piezotronics, Inc. A broad band signal was sent to the electromagnetic shaker and the force the shaker excerpted on the beam was measured, as was the resulting acceleration of the beam. The frequency response function (FRF) was calculated from the cross spectrum of the measured acceleration and force, and from the magnitude of the FRF, peak amplitudes were used to identify the modal frequencies. The half power bandwidth around each modal frequency was also identified as the span of frequencies between the −3 dB amplitude points above and below the modal frequency. The ratio of the half power bandwidth to modal frequency was calculated and reported as the Damping Loss Factor.
Materials
[0043] Abbreviations for the reagents used in the examples are as follows:
A-75: A benzoyl peroxide, obtained under the trade designation “LUPEROX A75” from Arkema, Inc. Philadelphia, Pa. AA: Acrylic acid, obtained from Sigma-Aldrich Company, St. Louis, Mo. BDDA: 1,4-butanediol diacrylate, obtained under the trade designation “SR213” from Sartomer, USA, LLC, Exton, Pa. DMAEMA: N,N-dimethylaminoethylmethacrylate, obtained from Sigma-Aldrich Company. E-920: A methacrylate-butadiene-styrene copolymer, obtained under the trade designation “CLEARSTRENGTH E-920” from Arkema, Inc., King of Prussia, Pa. F-85E: Ester of hydrogenated rosin, obtained under the trade designation “FORAL 85-E” from Eastman Chemical Company, Kingsport, Tenn. HDDA: 1,6-hexanediol diacrylate, obtained under the trade designation “SR238B” from Sartomer, USA, LLC. I-651: 2,2-Dimethoxy-1,2-diphenylethan-1-one, obtained under the trade designation “IRGACURE 651” from BASF Schweiz AG, Basel, Switzerland. IOA: Isooctyl acrylate, obtained under the trade designation “SR440” from Sartomer, USA, LLC. IOTMS: Isooctyltrimethoxysilane, obtained from Gelest, Inc., Morrisville, Pa. ISF-16: 2-hexyldecanol, obtained under the trade designation “ISOFOL 16” from Sasol North America, Inc., Houston, Tex. ISF-18: 2-hexyldodecanol, obtained under the trade designation “ISOFOL 18” from Sasol North America, Inc. ISF-24: 2-decyltetradecanol, obtained under the trade designation “ISOFOL 24” from Sasol North America, Inc. KB-1: 2,2-dimethoxy-1,2-di(phenyl)ethanone, obtained under the trade designation “ESACURE KB1” from Lamberti USA, Inc., Conshohocken, Pa. L-26M50: A 50% solution of tert-butyl peroxy-2-ethylhexanoate in mineral spirits, obtained under the trade designation “LUPEROX 26M50” from Arkema Inc. MTMS: Methyltrimethoxysilane, obtained from Gelest, Inc. N2326: A 16.4% colloidal silica dispersion, obtained under the trade designation “NALCO 2326” from Nalco Company, Naperville, Ill. PB-100: Polyisobutene having a molecular weight of 250,000 obtained under the trade designation “OPPANOL B-100” from BASF Corporation, Freeport, Tex. PB-910: Polybutene, having a molecular weight of 910, obtained under the trade designation “INDOPOL H-100” from Ineos Oligomers, League City, Tex. PB-1000: Polyisobutene having a molecular weight of 1,000 obtained under the trade designation “GLISSOPAL R-1000” from BASF Corporation. PB-1900: Polybutene having a molecular weight of 2,500 obtained under the trade designation “INDOPOL H-1900” from BASF Corporation. PEGDA: Polyethylene glycol (600) diacrylate, obtained under the trade designation “SR610” from Sartomer, USA, LLC. R-100: A random butadiene-styrene copolymer, obtained under the trade designation “RICON 100” from Sartomer, USA, LLC. R-972: A hydrophobic fumed silica, obtained under the trade designation “AEROSIL R-972” from Evonik Degussa Corporation, Parsippany, New Jersey. RC-902: A radiation curable silicone, obtained under the trade designation “TEGO RC-902” from Evonik Degussa Corporation. S-1001: Styrene Ethylene Propylene Block Copolymer, obtained under the trade designation “SEPTON 1001” from Kuraray Co. Ltd., Tokyo, Japan. SAMV: Ammonium lauryl sulfate, obtained under the trade designation “STEPANOL AMV” from Stepan Company, Northfield, Illinois. T-10: Clear silicone release liner, obtained under the trade designation “CLEARSIL T-10” from Solutia, Inc. St. Louis, Mo. T-50: Clear silicone release liner, obtained under the trade designation “CLEARSIL T-50” from Solutia, Inc. T-145A: Silicone resin, obtained under the trade designation “TOSPEARL 145A” from Momentive Performance Materials Holdings, LLC, Columbus Ohio. TMT: 2,4-bis(trichloromethyl)-6-(4-methoxyphenyl)-triazine. TPO: Diphenyl (2,4,6-trimethylbenzoyl)-phosphine oxide, obtained under the trade designation “DAROCUR TPO” from BASF Schweiz AG. 467-MP: A 2 mil. (50.8 μm) adhesive transfer tape having a paper liner, obtained under the trade designation “ADHESIVE TRANSFER TAPE 467 MP” from 3M Company. 467-MPF: A 2 mil. (50.8 μm) adhesive transfer tape having a film liner, obtained under the trade designation “ADHESIVE TRANSFER TAPE 467 MPF” from 3M Company
Non-commercial materials described in the examples were synthesized as follows:
HEDA: 2-hexa-1-decyl acrylate. 100 grams of 2-hexyl-1-decanol, 45.97 grams triethylamine and 350 grams of methylene chloride were added to a 1 liter flask and cooled to 5° C. using an ice bath. 41.1 grams acryloyl chloride was slowly added, dropwise over one hour, while mechanically stirring the mixture. After 10 hours the mixture was filtered and then concentrated under vacuum at 25° C. The remaining resultant oil was diluted with ethyl acetate and washed with 1.0 Molar hydrochloric acid, followed by 1.0 Molar sodium hydroxide solution, then a saturated sodium chloride solution. The organic layer was then concentrated under vacuum at 25° C. The crude oil was mixed with an equal amount of hexane and passed through a column of neutral alumina to remove colored impurities, after which the alumina was eluted with hexane. The collected filtrate was concentrated under vacuum at 25° C., resulting in a colorless oil of 2-hexa-1-decyl acrylate. ISA: An isostearyl acrylate. 197.17 grams ISF-18, 78.12 grams triethylamine and 700 grams of methylene chloride were added to a 2 liter flask and cooled to 5° C. using an ice bath. 69.86 grams acryloyl chloride was slowly added, dropwise over one hour, while mechanically stirring the mixture. After 10 hours the mixture was filtered and then concentrated under vacuum at 25° C. The remaining resultant oil was diluted with ethyl acetate and washed with 1.0 Molar hydrochloric acid, followed by 1.0 Molar sodium hydroxide solution, then a saturated sodium chloride solution. The organic layer was then concentrated under vacuum at 25° C. The crude oil was mixed with an equal amount of hexane and passed through a column of neutral alumina to remove colored impurities, after which the alumina was eluted with hexane. The collected filtrate was concentrated under vacuum at 25° C., resulting in a colorless oil of 100% isostearyl acrylate. ISA-MS: Isostearyl acrylate microspheres. Mixture A was prepared by adding 180 grams ISA, 0.58 grams A-75 and 1.8 grams BDDA to a 500 ml glass jar and mixed in a roller mill until dissolved. Mixture B was prepared by adding to a 1 liter glass beaker, 420 grams distilled water, 7.2 grams SAMV and 1.8 grams BDDA, and dispersing until homogeneous using a high shear mixer, model “OMNI-MIXER” from OCI Instruments, Waterbury, Conn. Mixture A was then added to the glass beaker and high shear mixing continued for approximately 2 minutes until very small droplets of about 3 microns diameter were formed. The product was then transferred to a 1 liter glass reactor equipped with a mechanical stirrer. The reactor was filled with nitrogen gas, heated to 65° C., and held at this temperature, with continuous stirring, for 24 hours, after which it was cooled to 23° C. The resulting suspension was filtered through a cheese cloth to remove agglomerates and coagulated using 500 mls isopropanol. The coagulum was then dried in an oven at 45° C. for approximately 16 hours.
Single-Layer Constructions
Sample 1
[0081] A 25 dram (92.4 mls) glass jar was charged with 19.6 grams HEDA, 0.4 grams AA and 0.008 grams I-651. The monomer mixture was stirred for 30 minutes at 21° C., purged with nitrogen for 5 minutes, and then exposed to low intensity ultraviolet light, type “BLACK RAY XX-15BLB” obtained from Fisher Scientific, Inc., Pittsburgh, Pa., until a coatable pre-adhesive polymeric syrup was formed. An additional 0.032 grams I-651 and 0.03 grams PEGDA were blended into the polymeric syrup using a high speed mixer, model “DAC 150 FV” obtained from FlackTek, Inc., Landrum, S.C. The polymeric syrup was then coated between silicone release liners T-10 and T-50 at an approximate thickness of 8 mils (203.2 μm) and cured by means of UV-A light at 2,000 mJ/cm 2 .
Samples 2-6
[0082] The procedure generally described in Sample 1 was repeated, according to the quantities of acrylate monomers listed in Table 1. Physical characteristics of the resultant cured adhesive coatings are listed in Table 2.
[0000]
TABLE 1
Composition
Additives
(as pph of
% Acrylate
Acrylate)
Sample
HEDA
IOA
ISA
AA
I-651
PEGDA
1
98.0
0
0
2.0
0.20
0.23
2
93.5
0
0
6.5
0.20
0.23
3
0
0
98.0
2.0
0.20
0.23
4
100.0
0
0
0
0.20
0.23
5
0
0
100.0
0
0.20
0.23
6
0
93.5
0
6.5
0.20
0.23
[0000]
TABLE 2
Adhesion To
Adhesion To
Polyurethane
Aluminum
Peel
Peel
Adhesive
Fail-
Adhesive
Fail-
Storage
Tan
Sam-
Force
ure
Force
ure
Modulus
Delta
ple
(N/dm)
Mode
(N/dm)
Mode
@ −55° C.
@ −55° C.
1
26
A
21
A
3.3 × 10 6
0.96
2
21
A
48
A
2.0 × 10 7
0.72
3
24
A
15
A
1.3 × 10 7
1.09
4
3
C
3
C
1.1 × 10 6
1.50
5
10
A
4
A
3.5 × 10 6
1.36
6
25
A
64
A
3.1 × 10 8
0.10
Sample 7
[0083] A 25 dram (92.4 mls) glass jar was charged with 19.6 grams HEDA, 0.4 grams AA and 0.008 grams I-651. The monomer mixture was stirred for 30 minutes at 21° C., purged with nitrogen for 5 minutes, and exposed to the low intensity ultraviolet light until a coatable pre-adhesive polymeric syrup was formed. An additional 0.032 grams I-651, 0.046 grams PEGDA and 2.0 grams R-972 were subsequently blended into the polymeric syrup using the high speed mixer. The polymeric syrup was then coated between silicone release liners at an approximate thickness of 8 mils (203.2 μm) and cured by means of UV-A light at 2000 mJ/cm 2 .
Samples 8-33
[0084] The procedure generally described in Sample 7 was repeated, wherein various amounts of fumed silica, plasticizer, polybutenes, polyisobutenes, silicones, core-shell rubber particles and isostearyl acrylate microspheres, were blended into the pre-adhesive polymeric syrup according to the quantities listed in Table 3. Physical characteristics of the resultant cured adhesive coatings are listed in Table 4.
[0000]
TABLE 3
Composition
% Acrylate
Additives (as pph of Acrylate)
Sample
HEDA
AA
ISA
R-972
PEGDA
TMT
ISF-24
PB-910
PB-1000
PB-1900
7
99.0
1.0
0
10.0
0.23
0
0
0
0
0
8
98.0
2.0
0
7.0
0.23
0
0
0
0
0
9
98.0
2.0
0
10.0
0.23
0
0
0
0
0
10
98.0
2.0
0
13.0
0.23
0
0
0
0
0
11
0
2.0
98.0
7.0
0.23
0
0
0
0
0
12
0
2.0
98.0
10.0
0.23
0
0
0
0
0
13
93.5
5.0
0
10.0
0.23
0
0
0
0
0
14
98.0
2.0
0
10.0
0.23
0
4.0
0
0
0
15
98.0
2.0
0
10.0
0.23
0
5.0
0
0
0
16
98.0
2.0
0
0
0.20
0
0
0
5.0
0
17
98.0
2.0
0
5.0
0.20
0
0
0
5.0
0
18
98.0
2.0
0
5.0
0.20
0
0
0
10.0
0
19
98.0
2.0
0
5.0
0.20
0
0
5.0
0
0
20
98.0
2.0
0
5.0
0.20
0
0
0
0
5.0
21
98.0
2.0
0
5.0
0
0.15
0
0
15.0
0
22
98.0
2.0
0
5.0
0.20
0
0
0
5.0
0
Composition
% Acrylate
Additives (as pph of Acrylate)
Sample
HEDA
AA
IOA
ISA-MS
PEGDA
TMT
T-145A
RC-902
HDDA
E-920
23
0
6.5
93.5
0
0
0
5.0
0
0
0
24
0
6.5
93.5
0
0
0
10.0
0
0
0
25
93.5
6.5
0
0
0
0
5.0
0
0
0
26
98.0
2.0
0
0
0
0
0
10.0
0.08
0
27
98.0
2.0
0
0
0.20
0
0
0
0
10.0
28
98.0
2.0
0
0
0
0.15
0
0
0
5.0
29
0
6.5
93.5
5.0
0.23
0
0
0
0
0
30
0
6.5
93.5
10.0
0.23
0
0
0
0
0
31
93.5
6.5
0
10.0
0.23
0
0
0
0
0
Composition
% Acrylate
Additives (as pph of Acrylate)
Sample
HEDA
AA
IOA
PEGDA
HDDA
PB-100
S-1001
D-TPO
32
100.0
0
0
0
0.1
6.0
0
0.3
33
100.0
0
0
0
0.1
0
10.0
0.3
[0000]
TABLE 4
Adhesion To
Adhesion To
Polyurethane
Aluminum
Peel
Peel
Adhesion
Fail-
Adhesion
Fail-
Storage
Tan
Sam-
Force
ure
Force
ure
Modulus
Delta
ple
(N/dm)
Mode
(N/dm)
Mode
@ −55° C.
@ −55° C.
7
2
A
1
A
1.4 × 10 6
1.67
8
22
A
35
A
1.2 × 10 7
0.96
9
26
A
27
A
4.0 × 10 7
0.92
10
23
A
24
A
3.6 × 10 7
0.89
11
153
C
120
C
1.8 × 10 7
1.04
12
55
2B
77
2B
1.3 × 10 7
1.01
13
24
A
47
2B
2.9 × 10 7
0.64
14
96
C
92
C
2.6 × 10 7
0.97
15
76
C
69
C
1.8 × 10 6
0.95
16
26
A
22
A
1.5 × 10 6
1.15
17
85
A
88
2B
7.7 × 10 6
1.13
18
77
C
79
C
1.1 × 10 7
1.22
19
57
A
39
A
8.1 × 10 6
1.15
20
55
A
39
A
1.4 × 10 7
1.08
21
54
A
48
A
8.4 × 10 6
1.30
22
125
C
56
A
9.1 × 10 6
1.04
23
16
A
37
A
3.5 × 10 8
0.58
24
18
A
36
A
3.8 × 10 8
1.26
25
20
A
22
A
3.0 × 10 7
0.70
26
1
A
0
A
1.3 × 10 6
1.16
27
16
A
12
A
7.2 × 10 6
1.01
28
15
A
16
A
1.4 × 10 7
1.06
29
31
A
77
A
2.7 × 10 6
1.10
30
28
A
97
A
3.2 × 10 6
1.10
31
26
A
68
A
5.2 × 10 5
0.86
32
5
A
4
A
4.8 × 10 6
1.35
33
2
A
3
A
7.7 × 10 6
1.18
Visco-Elastic Core VEC-1
[0085] A 25 dram (92.4 mls) glass jar was charged with 19.8 grams HEDA, 0.2 grams DMAEMA and 0.008 grams I-651. The monomer mixture was stirred for 30 minutes at 21° C., purged with nitrogen for 5 minutes, and exposed to the low intensity ultraviolet light until a coatable pre-adhesive polymeric syrup was formed. An additional 0.032 grams I-651 and 0.03 grams TMT were subsequently blended into the polymeric syrup using the high speed mixer. The polymeric syrup was then coated between silicone release liners T-10 and T-50 at an approximate thickness of 8 mils (203.2 μm) and cured by means of UV-A light at 2,000 mJ/cm 2 .
Visco-Elastic Cores VEC-2-VEC-10
[0086] The procedure generally described in VEC-1 was repeated, according to the compositions listed in Table 5. With respect to VEC-6, the nominal thickness was 16 mils (406.4 μm). Physical characteristics of the visco-elastic cores are listed in Table 6.
[0000]
TABLE 5
Composition
Additives
Visco-Elastic
% Acrylate
(as pph of Acrylate)
Core
HEDA
ISA
IOA
DMAEMA
TMT
PEGDA
VEC-1
99.0
0
0
1.0
0.15
0
VEC-2
98.0
0
0
2.0
0.15
0
VEC-3
96.0
0
0
4.0
0.15
0
VEC-4
0
96.0
0
4.0
0
0.23
VEC-5
0
0
96.0
4.0
0
0.23
VEC-6
0
96.0
0
4.0
0.15
0
VEC-7
0
90.0
10.0
0
0.15
0
VEC-8
0
100.0
0
0
0.15
0
VEC-9
0
0
100.0
0
0.15
0
VEC-10
0
75.0
25.0
0
0.15
0
[0000]
TABLE 6
Core Thickness
Storage Modulus
Tan Delta
Visco-Elastic Core
mils (μm)
@ −55° C.
@ −55° C.
VEC-1
8 (203.2)
2.4 × 10 6
1.33
VEC-2
8 (203.2)
3.2 × 10 6
1.32
VEC-3
8 (203.2)
5.1 × 10 6
1.32
VEC-4
8 (203.2)
6.0 × 10 6
1.36
VEC-5
8 (203.2)
2.6 × 10 8
0.13
VEC-6
16 (406.4)
5.9 × 10 6
1.37
VEC-7
8 (203.2)
1.0 × 10 7
1.35
VEC-8
8 (203.2)
1.1 × 10 7
1.34
VEC-9
8 (203.2)
2.6 × 10 8
0.14
VEC-10
8 (203.2)
1.6 × 10 7
1.26
Multi-Layer Constructions
Adhesive Skin SKN-1
[0087] A one quart (946 mls.) glass jar was charged with 372 grams IOA, 28 grams AA and 0.16 grams I-651. The monomer mixture was stirred for 30 minutes at 21° C., purged with nitrogen for 5 minutes, and exposed to the low intensity (0.3 mW/cm 2 ) ultraviolet light until a coatable pre-adhesive polymeric syrup was formed. An additional 0.64 grams I-651 and 0.6 grams TMT were subsequently blended into the polymeric syrup using the high speed mixer. The polymeric syrup was then coated between silicone release liners T-10 and T-50 at an approximate thickness of 1 to 2 mils (25.4-50.8 μm) and cured by means of UV-A light at 1,500 mJ/cm 2 .
Adhesive Skins SKN-2-SKN-4
[0088] The procedure generally described in SKN-1 was repeated, according to the monomer and tackifier compositions listed in Table 7.
[0000]
TABLE 7
Composition
Additives
(as pph of
Adhesive
% Acrylate
Acrylate)
Skin
IOA
AA
TMT
F-85E
SKN-1
93.0
7.0
0.15
0
SKN-2
95.0
5.0
0.15
0
SKN-3
93.0
7.0
0.15
20.0
SKN-4
90.0
10.0
0.10
0
Sample 34
[0089] Adhesive skin SKN-1 was laid on a clean 12 by 48 by 0.5-inch (30.5 by 121.9 by 1.27 cm) glass plate and the upper silicone release liner removed. One of the silicone release liners was removed from a sample of visco-elastic core VEC-3, and the exposed surface of the core laid over the exposed adhesive skin of SKN-1. The core and skin were then laminated together by manually applying a hand roller over the release liner of the visco-elastic core. The release liner covering the visco-elastic core removed, as was a release liner of another sample of adhesive skin SKN-1. The skin was then laminated onto the exposed core by means of the hand roller, resulting in a SKN-1:VEC-3:SKN-1 laminate. The laminate was then allowed to dwell for 24 hours at 50% RH and 70° F. (21.1° C.) before testing.
Samples 35-42
[0090] The procedure generally described in Sample 34 was repeated, according to the adhesive skin and visco-elastic core constructions listed in Table 8. With respect to Sample 42, the adhesive skin is represented by adhesive transfer tape 467-MP/467-MPF. Physical characteristics of the resultant multi-layer constructions are also presented in Table 8.
Sample 43
[0091] A one quart jar glass jar was charged with 405 grams ISA, 45 grams IOA and 0.18 grams I-651, corresponding to the composition “VEC-7” of Table 5. The monomer mixture was stirred for 30 minutes at 21° C., purged with nitrogen for 5 minutes, and exposed to the low intensity ultraviolet light until a coatable pre-adhesive polymeric syrup was formed. An additional 0.72 grams I-651 and 0.675 grams TMT were subsequently blended into the polymeric syrup using the high speed mixer. The polymeric syrup was then coated between layers of adhesive transfer tapes 467-MP and 467-MPF, at an approximate thickness of 8 mils (203.2 μm), and cured by means of UV-A light exposure through the 467-MPF side at 2,000 mJ/cm 2 .
Samples 44-46
[0092] The procedure generally described in Sample 43 was repeated, according to the compositions for VEC-8, VEC-9 and VEC-10, respectively, listed in Table 5. Physical characteristics of the visco-elastic cores and of the resultant multi-layer constructions are listed in Table 7 and Table 8, respectively.
[0000]
TABLE 8
Adhesion To
Adhesion To
Polyurethane
Aluminum
Visco-
Adhesion
Adhesion
Adhesive
Elastic
Peel Force
Failure
Peel Force
Failure
Sample
Skin
Core
(N/dm)
Mode
(N/dm)
Mode
34
SKN-1
VEC-3
92
A
77
A
35
SKN-2
VEC-3
39
A
59
A
36
SKN-1
VEC-2
46
A
59
A
37
SKN-1
VEC-1
44
A
59
A
38
SKN-3
VEC-3
55
A
83
A
39
SKN-4
VEC-3
81
A
83
A
40
SKN-4
VEC-4
88
2B
77
2B
41
SKN-4
VEC-6
68
A
63
A
42
467-
VEC-5
70
A
112
A
MP/MPF
43
467-
VEC-7
45
2B
39
2B
MP/MPF
44
467-
VEC-8
37
C
39
C
MP/MPF
45
467-
VEC-9
47
A
49
A
MP/MPF
46
467-
VEC-10
53
C
51
C
MP/MPF
Damping Performance
[0093] DLF values were determined for selected adhesive samples according to the test method described above. Results are listed in Table 9.
[0000]
TABLE 9
Number
Sam-
of
Loss Factor @ −10° C.
Loss Factor @ −20° C.
ple
Layers
120 Hz
400 Hz
800 Hz
120 Hz
400 Hz
800 Hz
2
1
0.21
0.23
0.21
0.13
0.16
0.17
15
1
0.18
0.21
0.21
0.12
0.14
0.15
39
3
0.27
ND
ND
0.23
0.27
ND
40
3
0.27
0.26
ND
0.24
ND
ND
41
3
0.23
0.16
0.12
0.30
0.28
ND
42
3
0.17
0.20
0.21
0.07
0.07
0.08
43
3
0.26
0.20
0.17
0.27
0.16
0.18
ND = Not detectable
[0094] Various modifications and alterations of this disclosure will become apparent to those skilled in the art without departing from the scope and principles of this disclosure, and it should be understood that this disclosure is not to be unduly limited to the illustrative embodiments set forth hereinabove.
|
This disclosure relates to viscoelastic damping materials and constructions which may demonstrate low temperature performance and adhesion and which may be used in making vibration damping composites. Viscoelastic damping materials and constructions may include polymers or copolymers of monomers according to formula I: CH 2 ═CHR 1 —COOR 2 [I] wherein R 1 is H, CH 3 or CH 2 CH 3 and R 2 is a branched alkyl group containing 12 to 32 carbon atoms.
| 2 |
TECHNICAL FIELD
The present invention relates to a method and device for encapsulating, individually or collectively, structures carried by a substrate. It also relates to an encapsulation mould for such a method or device, and a method for producing such a mould.
The field of the invention is more particularly, but not limitatively, that of the encapsulation of microsystems on a glass or silicon substrate.
STATE OF THE PRIOR ART
In all fields, the packaging stage represents the final stage in the manufacturing of a product. The packaging of microelectromechanical systems (MEMS or “Micro Electro Mechanical Systems”) is complex, as MEMS comprise mechanical parts, generally deformable or mobile, that are very sensitive to liquids and in general to their environment.
In many cases, microsystems must be protected from the external environment in a cavity sealed against moisture and gases so as to limit their aging and increase their reliability.
The creation of this cavity allowing the encapsulation of the microsystem is also called “Packaging”. The packaging stage has now become as important as the production method for microsystems.
In the 1980s, a novel approach was developed: wafer-level encapsulation (or WLP for “Wafer-Level Packaging”) allows for collective and simultaneous encapsulation of all microsystems present on a carrier substrate.
The ultimate purpose of encapsulating MEMS in a cavity is to protect them from the environment outside the cavity and to ensure the stability and reliability of their performance. In order to achieve this purpose, the encapsulation must generally provide some or all of the following functions:
mechanical protection of the MEMS against the scratches, impacts and vibrations that may occur during their testing, handling, transportation or use; chemical protection of the MEMS against corrosion, contamination and moisture by means of the stability and inertia of the environment inside the cavity; a passage for connections (generally electrical connections) between the microsystems and the environment outside the cavity; thermal management of the devices, i.e. particularly heat protection.
A drawback of the existing methods of encapsulation is that they are very complex and cumbersome to implement. In particular, each encapsulation generally requires the production of a mould that must be completely dissolved during encapsulation.
The purpose of the present invention is to provide a method and a device for encapsulation that is simpler and/or more efficient than those of the state of the art.
DISCLOSURE OF THE INVENTION
This objective is achieved with a method for encapsulating at least one structure carried by a carrier substrate, comprising:
applying onto the carrier substrate, at least one cap carried by a mould, the mould comprising an adhesion layer, each cap being in contact with the adhesion layer, then bonding the at least one cap onto the carrier substrate, then separating the mould and the at least one cap,
characterized in that the adhesion layer is produced from a fluorinated polymer, and therefore comprises the fluorinated polymer.
By fluorinated polymer is meant, throughout this document, a polymer containing fluorine atoms. According to the invention, the fluorinated polymer preferably comprises at least one carbonated chain and along this chain several links of the C—F type between a carbon atom C and a fluorine atom F, as is the case in a fluorocarbon polymer. The fluorinated polymer preferably, but not limitatively, comprises Teflon. The fluorinated polymer preferably comprises a fluorocarbon polymer such as:
Teflon of the PTFE type, also called polytetrafluoroethylene, Teflon of the FEP-type, also called fluorinated ethylene propylene, Teflon of the PFA-type, also called perfluoroalkoxy, PVDF, also called polyvinylidene fluoride, ETFE, also called modified ethylene and tetrafluoroethylene copolymer, and ECTFE, also called ethylene chlorotrifluoroethylene.
In a first embodiment of the encapsulation method according to the invention, it is possible to separate the mould and the at least one cap mechanically, by pulling the mould from the at least one cap. The mould preferably comprises a mould substrate in contact with the adhesion layer, and the break-away force required to separate the mould substrate and the adhesion layer is preferably greater than the break-away force required to separate the adhesion layer and the at least one cap.
In a second embodiment of the encapsulation method according to the invention, the mould can be separated from the at least one cap chemically, by dissolving the adhesion layer. It is possible for example to dissolve the adhesion layer in an acid bath or in a solvent bath, for example in a nitric acid bath.
In the encapsulation method according to the invention, the at least one cap is preferably bonded to the carrier substrate using a polymer seal or eutectic seal situated between the at least one cap and the carrier substrate, or using a thermocompression weld. When applying the at least one cap, the seal can be structured at the level of at least one passage for a connection linked to the at least one structure. Moreover, the at least one cap can be perforated, and can comprise one or more holes of various shapes and sizes. These holes are particularly useful in the case where the cap encapsulates an optical structure such as a light detector or an acoustic structure such as a microphone.
The mould preferably includes silicon atoms. Thus, the mould can adhere to the fluorinated polymer due to its silicon atom content, in particular via Si—C bonds between silicon atoms of the mould and carbon atoms of the fluorocarbon polymer.
Each cap can comprise a metallic layer in contact with the fluorinated polymer.
The invention also relates to an encapsulated structure obtained by the encapsulation method according to the invention.
According to yet another aspect of the invention, a device is proposed for the encapsulation of at least one structure carried by a carrier substrate, implementing a method according to the invention and comprising:
a mould comprising an adhesion layer and carrying at least one cap such that each cap is in contact with the adhesion layer, means for applying, onto the carrier substrate, the at least one cap carried by the mould, means for bonding onto the carrier substrate the at least one cap applied onto the carrier substrate, means for separating the mould and the at least one cap bonded to the carrier substrate,
characterized in that the adhesion layer comprises a fluorinated polymer.
The fluorinated polymer preferably comprises a fluorocarbon polymer, and more particularly preferably polytetrafluoroethylene.
In a first embodiment of the device according to the invention, the separation means can comprise means for mechanically separating the mould and the at least one cap, arranged in order to pull the mould from the at least one cap. The mould can then comprise a mould substrate in contact with the adhesion layer, and the break-away force required in order to separate the mould substrate and the adhesion layer is preferably greater than the break-away force required in order to separate the adhesion layer and the at least one cap.
In a second embodiment of the device according to the invention, the separation means can comprise means for chemically separating the mould and the at least one cap, arranged in order to dissolve the adhesion layer. The chemical separation means can for example comprise an acid bath or a solvent bath, in particular a nitric acid bath.
The bonding means can comprise means for welding a polymer seal or a eutectic seal located between the at least one cap and the carrier substrate, or thermocompression welding means. The seal can comprise at least one portion structured for at least one passage of a connection linked to the at least one structure.
Moreover, the at least one cap can be perforated, as described above.
The mould can comprise silicon atoms.
Each cap can comprise a metallic layer in contact with the fluorinated polymer.
The invention also relates to an encapsulation mould for an encapsulation device according to the invention and for an encapsulation method according to the invention, said mould comprising:
a mould substrate comprising at least one mould cavity, an adhesion layer deposited on one face of the mould substrate carrying the at least one mould cavity,
characterized in that the adhesion layer comprises a fluorinated polymer.
The fluorinated polymer preferably comprises a fluorocarbon polymer, and more particularly preferably polytetrafluoroethylene.
The mould substrate can comprise silicon atoms.
The mould according to the invention can carry a cap on the adhesion layer, in each mould cavity. Each cap preferably comprises a metallic layer in contact with the fluorinated polymer. The break-away force required to separate the mould substrate and the adhesion layer is preferably greater than the break-away force required to separate the adhesion layer and the at least one cap. At least one of the caps can be perforated as described above.
In general, the invention relates to a mould obtained by a method for producing a mould according to the invention.
The invention also relates to a method for producing an encapsulation mould according to the invention, comprising:
etching a mould substrate, in order to form at least one mould cavity, depositing an adhesion layer onto a face of the mould substrate carrying the at least one mould cavity,
characterized in that the adhesion layer comprises a fluorinated polymer.
The fluorinated polymer preferably comprises a fluorocarbon polymer, and particularly preferably polytetrafluoroethylene.
After the deposition of the adhesion layer, the mould substrate can comprise silicon atoms.
The mould production method according to the invention can moreover comprise depositing a cap onto the adhesion layer, in each mould cavity. Each cap can comprise a metallic layer in contact with the fluorinated polymer. The break-away force required in order to separate the mould substrate and the adhesion layer is preferably greater than the break-away force required to separate the adhesion layer and the at least one cap. At least one of the caps can be perforated as described above.
The deposition of the adhesion layer preferably comprises exposing the mould substrate to a C 4 F 8 plasma (this compound comprising four carbon atoms for eight fluorine atoms) such as octafluorobutene, perfluorobutene, octafluorocyclobutane or other.
BRIEF DESCRIPTION OF THE DRAWING FIGURES
Other advantages and characteristics of the invention will become apparent on reading the detailed description of implementations and embodiments which are in no way limitative, and from the attached diagrams as follows:
FIG. 1 is a cross-sectional profile view of a mould according to the invention for an encapsulation device according to the invention,
FIG. 2 is a three-quarter view of the mould in FIG. 1 ,
FIG. 3 is a diagrammatic view of a first preferred embodiment of the encapsulation device according to the invention, comprising the mould in FIGS. 1 and 2 ,
FIGS. 4 to 6 illustrate a mould, caps, and a carrier substrate of the device in FIG. 3 for different stages of an encapsulation method according to the invention.
DETAILED DESCRIPTION OF THE INVENTION
A description will firstly be given, with reference to FIGS. 1 and 2 , of a mould 1 according to the invention for an encapsulation device and method according to the invention and a production method according to the invention for producing such a mould 1 .
The production method comprises the chemical etching of a mould substrate 2 initially having the form of a plate with parallel faces 4 , 5 . The mould substrate 2 is etched in order to form at least one mould cavity 3 on one of these parallel faces 5 . The mould substrate 2 is typically a wafer made of glass or silicon
This etching is carried out by an etching method that is usual in the field of lithography, and comprises for example drawing a pattern on the face 5 of the mould substrate 2 using a mask. Thus, etching the mould is carried out:
by wet etching (for example using an etching solution of KOH, EDP, TMAH, etc.), in which case the areas not protected by the Si 3 N 4 or SiO 2 mask are etched, or by dry etching (for example of the “DRIE” type), in which case the mask can be a photosensitive resin, an SiO 2 mask, or a layer of aluminium.
After the etching, an adhesion layer 6 is deposited on the face 5 of the mould substrate 2 carrying the at least one mould cavity 3 . The adhesion layer 6 is made from a fluorinated polymer, and therefore comprises said fluorinated polymer. By fluorinated polymer is meant a polymer comprising fluorine atoms. The fluorinated polymer here comprises a carbonated chain and along this chain several bonds of the C—F type between a carbon atom C and a fluorine atom F. The adhesion layer is shown by dotted lines on the cross-sectional views in FIGS. 1 and 3 to 6 , and is shown as a layer filled with small dots in FIG. 2 . The fluorinated polymer comprises a fluorocarbon polymer, and more particularly comprises polytetrafluoroethylene (or “PTFE”) having the general chemical formula:
where:
n is an integer, typically comprised between 1 and an almost infinite number equal to several thousand, several million or more, and the groups R 1 and R 2 comprise for example atoms of carbon C, oxygen O, fluorine F and/or other and therefore comprise for example CF, CH 3 , CF 3 groups, or other.
The deposition of the adhesion layer comprises exposure of the mould substrate 2 to a C 4 F 8 plasma in an RIE (Reactive Ion Etching) chamber or in a DRIE (Deep Reactive Ion Etching) chamber.
The thickness of this adhesion layer is comprised between several nanometres and several micrometres. The contact angle between a drop of deionized water and the adhesion layer 6 has a value comprised between 100° and 115°.
Then, thick resin lithography 17 is carried out on the mould 1 , more particularly on the adhesion layer 6 . The resin 17 is shown only in FIG. 1 , and not in FIG. 2 .
Then, several caps 7 are deposited onto the mould 1 , more particularly onto the adhesion layer 6 , a cap 7 being deposited in each mould cavity 3 , such that each cap 7 adopts the shape of a mould cavity 3 and thus has the form of a cap cavity 8 . Each cap 7 has the form of a plate of substantially constant thickness forming a cap cavity 8 . The deposition of the caps 7 comprises a stack of films. The films are metallic films such as nickel, copper, and/or titanium films. Specifically, a thin titanium film is deposited on the mould substrate 2 using an evaporator or a spray, then a thin copper film using an evaporator or a spray, then a thick nickel film using an electrochemical bath, in succession one film over the other. The thick nickel film is thus facing the inside (i.e. the concave side) of each cap cavity 8 with respect to the other films, and constitutes the mass of each cap, i.e. most of the material of each cap.
The pattern of the resin 17 deposited during the thick resin lithography makes it possible to define the shape and size of each cap 7 , and to separate the caps 7 from each other. The pattern of the resin 17 is not necessarily continuous: in particular, the pattern of the resin 17 can comprise isolated parts 27 located in at least one of the mould cavities 3 .
The adhesion layer 6 is a layer that is non-adherent with respect to the caps. In other words, the adhesion between the mould substrate 2 and the adhesion layer 6 is greater than the adhesion between the adhesion layer 6 and the caps 7 . The mould substrate 2 made of glass or silicon comprises silicon atoms that are in direct contact mainly with the carbon atoms of the fluorocarbon polymer 6 . Thus, the mould can adhere to the fluorinated polymer due to its silicon atom content, in particular via Si—C bonds between silicon atoms of the mould and carbon atoms of the fluorocarbon polymer. Each cap 7 comprises a metallic layer made of titanium that is in direct contact mainly with the fluorine atoms of the fluorocarbon polymer. The break-away force required to separate the mould substrate 2 and the adhesion layer 6 is greater than the break-away force required to separate the adhesion layer 6 and each cap 7 . This phenomenon is even more pronounced due to the use of C 4 F 8 plasma to produce the adhesion layer 6 .
Then, the resin 17 is removed, for example by dissolving it. FIG. 2 shows the mould 1 after dissolution of the resin 17 . After dissolution of the isolated parts 27 , at least one mould is obtained that is provided with holes 37 through which the adhesion layer 6 appears.
Finally, for each cap 7 , a seal 9 is deposited:
that is located on the cap 7 in question, on the opposite side of the cap 7 with respect to the adhesion layer 6 , and that surrounds the cavity 8 of the cap 7 in question.
In a variant, the seals 9 are eutectic seals, comprising an alloy the melting point of which is less than that of each of its constituent elements. This alloy consists for example of a silicon-gold alloy.
In another variant, the seals 9 comprise a polymer seal comprising, for example benzo-cyclo-butene (BCB) or an epoxy resin, particularly of the SU8 type.
The encapsulation mould 1 resulting from the production method is shown in FIGS. 1 and 2 , and comprises:
the mould substrate 2 made of glass or silicon, comprising several mould cavities 3 , is the adhesion layer 6 deposited on the face 5 of the mould substrate 2 carrying the mould cavities, this adhesion layer comprising a fluorinated polymer comprising polytetrafluoroethylene.
The mould 1 is common to several caps 7 . The mould 1 carries a cap 7 on the adhesion layer 6 in each mould cavity 3 , so that each cap 7 is in direct contact with the adhesion layer 6 and is connected to the mould 1 via the adhesion layer. The caps 7 are separated, i.e. they are not directly connected to each other, but only via the mould 1 .
Finally, for each cap 7 , the mould carries the above-described seal 9 .
It is noted that in FIGS. 1-6 , the mould 1 comprises only two cap cavities 8 and can carry only two caps 7 . It will be understood that the sole purpose of this representation is to simplify and clarify these figures, as the mould 1 typically comprises several tens, hundreds, thousands or more cap cavities 8 such that it is arranged in order to carry the same number of caps 7 .
With reference to FIGS. 3 to 6 , a first preferred embodiment of an encapsulation device 10 according to the invention, implementing a first preferred embodiment of the encapsulation method according to the invention, will now be described. FIG. 3 is a diagrammatic view of the device 10 , and FIGS. 4 to 6 are enlargements of a portion of the device 10 showing the relative positions of the mould 1 , the caps 7 and the carrier substrate 12 for different stages of an encapsulation method according to the invention.
The device 10 comprises the mould 1 already described with reference to FIGS. 1 and 2 , comprising the polytetrafluoroethylene adhesion layer 6 and carrying caps 7 such that each cap is connected to the common mould via the adhesion layer 6 .
Moreover, the device 10 comprises:
means 13 for holding a carrier substrate 12 , for example by clamping or by suction of the carrier substrate 12 , said carrier substrate carrying structures 11 , a motorized plate 14 arranged in order to move the carrier substrate, held by the holding means 13 , along three orthogonal axes X, Y, Z. means 15 for holding the mould 1 , for example by clamping or by suction of the mould 1 , and a motorized plate 16 arranged in order to move the mould 1 , held by the holding means 15 , along the three orthogonal axes X, Y, Z.
The carrier substrate 12 is typically a glass or silicon wafer. Each structure 11 is a microstructure, more particularly a microsystem such as a microelectromechanical system or MEMS. The MEMS 11 comprise for example a sensor, an actuator, or a “released” MEMS (i.e. comprising a movable, unconnected or vibrating part) such as a resonator.
Before applying the caps 7 carried by the mould 1 onto the carrier substrate 12 , accurate alignment of the mould 1 and of the carrier substrate 12 in a plane defined by the X and Y axes is controlled by an alignment control device that is preferably independent of the encapsulation device according to the invention, but which in some variants can form part thereof. The mould 1 , like the carrier substrate 12 , comprises optical markers such as alignment crosses. The alignment control is managed by alignment cross recognition software, the software cooperating with the means for moving the carrier substrate 12 with respect to the caps 7 carried by the mould 1 , or the alignment control is carried out manually by a user.
It is considered hereafter that the Z axis is substantially perpendicular to the mould 1 and to the carrier substrate 12 and links the mould 1 to the carrier substrate 12 . In the device according to the invention, the plates 14 and 16 are arranged in order to move the mould 1 towards the carrier substrate 12 along the Z axis as shown in FIG. 4 , until the caps 7 carried by the mould 1 are applied onto the carrier substrate 12 . Thus, by means of these plates 14 , 16 , the caps 7 carried by the mould are applied onto the carrier substrate 12 by maintaining a certain pressure of the mould 1 and of the caps 7 on the carrier substrate 12 . This application is shown in FIG. 5 . The plates 14 , 16 are micrometric plates with precision of the order of one micron. By means of these plates, the caps 7 are applied onto the carrier substrate 12 so that the concave face of each mould cavity 3 and each cap cavity 8 is oriented towards the carrier substrate 12 so as to cap, encapsulate and protect at least one of structures 11 . In other words, each cap 7 is applied onto the carrier substrate 12 so that each structure 11 is encapsulated and protected within a cavity 8 .
The device 10 comprises moreover means for bonding the caps 7 onto the carrier substrate when the caps 7 are applied onto the carrier substrate. The bonding means include an emission source 18 . During the application of the caps 7 onto the carrier substrate 12 shown in FIG. 5 , the caps 7 are thus bonded onto the carrier substrate 12 by means of the seals 9 and the source 18 . The bonding thus comprises a weld by seals 9 carried out at low temperature and low pressure, so as not to impair the performance of the microsystems 11 .
In the variant in which the seals are eutectic seals, the source 18 emits heat in order to melt the seals 9 so as to weld the caps 7 to the carrier substrate 12 . The advantages of eutectic seals are a moderate weld temperature (typically around 300°), very good adhesion and the ability to produce cavities 8 encapsulating the structures 11 in a vacuum.
In the preferred variant in which the seals are polymer seals, the source 18 emits heat and/or an ultraviolet radiation that transforms the seals 9 by changing them from a liquid phase or a viscoelastic phase to a “solid” phase that is crosslinked or gelled by heating and/or exposure to UV radiation, so as to weld the caps 7 to the carrier substrate 12 . The polymer seals 9 have very good tolerance to the topography of the carrier substrate 12 and a low welding temperature range from ambient temperature to approximately 250° C. Thus, bonding via a polymer seal limits the risks of melting the adhesion layer 6 . On the other hand, polymer seals do not allow vacuum cavities to be produced, as polymers are generally insufficiently hermetic.
The seals 9 have structured parts in some places, so that when the caps 7 are applied onto the carrier substrate 12 , these seals 9 are structured at passages for electrical connections linked to the structures 11 and carried by the carrier substrate. Each connection starts from a microstructure 11 and extends to the exterior of the cavity 8 encapsulating the microstructure 11 . Apart from the structured parts, the seals 9 have a smooth outer surface and a constant thickness. At the structured parts, the seals 9 have the same thickness as at the non-structured parts, but have a structured outer surface having for example a grid shape or embossing comprising grooves and recesses. When the seals 9 melt during the bonding of the caps 7 to the carrier substrate 12 , the lack of material at the embossed recesses compensates for the additional thickness due to the electrical connections.
Finally, the device 10 comprises means for separating the mould 1 and the caps 7 , after the caps 7 have been bonded to the carrier substrate 12 .
The separation means are arranged in order to mechanically separate the mould and each cap, by pulling the mould 1 from each cap 7 . As shown in FIG. 6 , the mould 1 and the caps 7 are separated by pulling the mould 1 from the caps 7 by means of motorized plates 16 , 14 that pull in opposite directions along the Z axis on the one hand, the mould 1 and on the other hand, the caps 7 bonded to the carrier substrate 12 , until mechanical break-away occurs between the adhesion layer 6 and the caps 7 . After mechanical break-away, the polytetrafluoroethylene layer 6 remains on the mould substrate 2 , and the caps 7 remain bonded to the carrier substrate 12 so as to form a substrate 12 carrying structures 11 encapsulated by caps 7 .
Thus a transfer of the caps 7 is carried out from the mould 1 to the carrier substrate 12 , using a reusable mould 1 . The mould 1 is reusable as the adhesion layer 6 limits the adhesion between the mould 1 and the caps 7 , and the adhesion layer 6 thus remains bonded to the mould substrate 2 . In order to reuse the mould 1 , it is sufficient to deposit new caps 7 in each mould cavity 3 , which considerably simplifies encapsulations carried out on an industrial scale.
Moreover, as the mould 1 comprises several cavities 3 and carries several caps 7 , it is noted that the encapsulation that has just been described is a collective encapsulation, i.e. a simultaneous encapsulation in parallel of several structures 11 by several cavities 8 , which has the advantage of being much faster than a series of successive individual encapsulations over time.
Finally, the encapsulation that has just been described is compatible with the release of the microsystems 11 before their encapsulation, as the carrier substrate 12 is not handled during the making of the caps 7 . By release of a microsystem is meant the fact of giving mobility or freedom of movement to the parts of the microsystem that must be mobile or have freedom of movement for its satisfactory operation.
The device 10 finally comprises a fuming nitric acid bath 19 , at a concentration of 99%, in which the encapsulated substrate 12 can be dipped by means of the motorized plate 14 . Thus, by dipping the substrate 12 carrying the encapsulated structures 11 , the caps are cleaned of any small residues of fluorinated polymer that may, unusually, accidentally remain on the caps 7 . It is also possible to clean the residues of fluorinated polymer using an oxygen plasma.
A second embodiment of an encapsulation device according to the invention will now be described, implementing a second embodiment of the encapsulation method according to the invention, only in respect of their difference in comparison with the first embodiments of the device and method according to the invention described above. In particular, references 1 to 19 will not be described again.
In this second embodiment, the separation means comprise the fuming nitric acid bath 19 at a concentration of 99%. After the caps 7 have been bonded to the substrate 12 , an assembly comprising the mould 1 , the caps 7 carried by the mould 1 and bonded to the carrier substrate 12 , and the carrier substrate 12 , is dipped into the bath 19 by means of the plates 14 and 16 . Thus the mould 1 and the caps are separated chemically, by dissolving the adhesion layer 6 in the bath 19 .
Of course, the invention is not limited to the examples that have just been described and numerous modifications can be made to these examples without departing from the scope of the invention.
In particular, the seals 9 can be deposited on the carrier substrate 12 around each structure 11 instead of being deposited on the caps 7 around each cap cavity 8 .
Moreover, in the description of the figures, the adhesion layer 6 is common to all of the caps 7 ; in a variant, the mould 1 can comprise separate adhesion layers deposited in each mould cavity 3 .
Similarly, instead of using caps 7 separate from each other, the caps can be connected directly to each other and thus be grouped onto a single plate forming several cap cavities 8 .
Moreover, the mould 1 can carry only a single cap 7 and only a single cap cavity 8 , so as to encapsulate only one structure at once in an individual and localized manner.
Moreover, in the first embodiment, instead of using the motors 14 and 16 , the step of pulling off the caps can be implemented for example using a claw system, a lever arm or pneumatic jack, or can be implemented manually by an operator using an equivalent instrument. It is noted moreover that in a variant of the production method of the mould 1 , the deposition of the adhesion layer 6 is carried out by spin coating or spray coating of PTFE in liquid phase.
Furthermore, each cap 7 can comprise a polymer such as benzo-cyclo-butene (BCB) or an epoxy resin, particularly of the SU8 type rather than metal. Each cap 7 can also comprise glass or silicon.
Finally, instead of welding using a eutectic or polymer seal, the caps 7 can be bonded to the carrier substrate 12 by means of:
direct silicon welding, comprising for example the emission of heat by the source 18 ; this type of welding is applicable if for example each cap 7 and the carrier substrate 12 are made of silicon, or anode welding comprising for example the emission of heat by the source 18 and an application of an electrical voltage between each cap 7 and the carrier substrate 12 ; this type of welding is applicable if for example each cap 7 is made of glass and if the carrier substrate 12 is made of silicon, or a thermocompression weld comprising for example the emission of heat by the source 18 and the application of each cap 7 onto the carrier substrate with high pressure; this type of welding is applicable if for example each cap 7 and the carrier substrate 12 all comprise metallic seals made of copper arranged to be superimposed when each cap 7 is applied onto the carrier substrate.
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A method for encapsulating structures ( 11 ) (typically MEMS structures) supported by a carrier substrate ( 12 ) (typically made of glass or silicon), includes: application, on the carrier substrate ( 12 ), of at least one cover ( 7 ) supported by a mould ( 1, 2, 6 ), the mould including a catching layer ( 6 ), each cover ( 7 ) being in contact with the catching layer ( 6 ); then fastening of at least one cover ( 7 ) onto the carrier substrate ( 12 ); and then separation of the mould ( 1, 2, 6 ) from the at least one cover ( 7 ). The catching layer ( 6 ) includes a fluoropolymer. Preferably, the mould ( 1, 2, 6 ) is mechanically separated from the at least one cover ( 7 ), by pulling the mould ( 1, 2, 6 ) away from the at least one cover ( 7 ). Thus, the mould ( 1 ) can be reused, which considerably simplifies encapsulating operations carried out on an industrial scale.
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This application claims the benefit of U.S. Provisional Application(s) Ser. No(s). 60/072,713, filed on Jan. 13, 1998.
TECHNICAL FIELD
The present invention relates, in general, to a paint roller frame having a cage assembly attached thereto and, more particularly, to a paint roller frame and cage assembly which securely retains a paint roller cover thereon during painting and which permits the paint roller cover to be easily removed therefrom after usage or for replacement purposes.
BACKGROUND ART
There are numerous types of paint roller frames and cage assemblies that permit the removal of the roller cover therefrom for replacement purposes. Such removal and/or replacement entails varying degrees of difficulty since if it is relatively easy to remove the roller cover from the cage assembly, the roller cover is usually not positively retained in place on the cage assembly and thus can move longitudinally relative thereto during painting. Conversely, if the roller cover is securely retained on the cage assembly, it is relatively difficult to remove it therefrom for replacement purposes or at the time painting has been completed. Such is the case with the paint roller frame disclosed in U.S. Pat. No. 5,345,648 (Graves) wherein the paint roller cover is retained on the cage assembly by a Belleville type washer having a plurality of radially extending prongs which grip the inner surface of the roller cover. Since the prongs become embedded in the inner surface of the roller cover, it is extremely difficult to remove the roller cover from the cage assembly in this case.
Another inherent disadvantage of most paint roller frames is that the cage assemblies used to support the roller cover include areas where paint may become entrapped, thus making the cage assemblies difficult to clean. Also, some cage assemblies do not provide uniform support for the roller cover permitting the roller cover to develop flat spots or become out of round making the roller cover less effective in spreading paint.
Because of the foregoing inherent disadvantages associated with presently available paint roller frames, it has become desirable to develop a paint roller frame which positively retains the roller cover thereon during painting while allowing the roller cover to be quickly and easily removed therefrom for replacement purposes or when painting has been completed. Furthermore, the resulting paint roller frame should be easy to clean and should provide substantial uniform support to the surface of the roller cover.
SUMMARY OF THE INVENTION
The present invention solves the problems associated with the prior art paint roller frames and other problems by providing a paint roller frame having a cage assembly which positively retains the roller cover thereon during painting and still permits the roller cover to be easily removed therefrom when desired. The cage assembly includes a cage body comprising a plurality of circumferentially spaced-apart, longitudinally extending roller cover support bars joined together by a plurality of arcuate ribs interposed between the support bars. An outboard end cap is received over the outboard end of the cage body while an inboard end cap is received over the inboard end thereof. A centrally located bore is provided in the hub portions of each of the aforementioned end caps permitting the shaft portion of the paint roller frame to be received therethrough allowing rotation of the cage assembly about the shaft of the paint roller frame. The inboard end cap has a plurality of circumferentially spaced-apart longitudinally extending ribs which grippingly engage the inner surface of the inboard end of the roller cover to securely retain the roller cover on the cage assembly. When painting has been completed or when it is desired to replace the roller cover, the paint roller frame with the roller cover thereon can be oriented vertically with the outboard end cap being located lower than the inboard end cap and by rapping the inboard side of the paint roller frame against a solid surface, the weight of the paint roller cover, with the paint retained therein, causes the roller cover to become disengaged from the longitudinally extending ribs on the inboard end cap resulting in the roller cover dropping from the cage assembly.
Accordingly, an object of the present invention is to provide a paint roller frame which securely retains the roller cover thereon during painting and still permits the roller cover to be quickly and easily removed therefrom for replacement purposes or after painting has been completed.
Another object of the present invention is to provide a paint roller frame having a structure which permits paint to easily drain therefrom and which minimizes the amount of paint entrapped therein.
Still another object of the present invention is to provide a paint roller frame which provides substantial uniform support for the paint roller cover over the length thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of the paint roller frame and cage assembly of the present invention.
FIG. 2 is a front elevational view of the paint roller frame and cage assembly of the present invention with a roller cover received thereon.
FIG. 3 is a cross-sectional view of the inboard end cap of the cage assembly taken across section-indicating lines 3 — 3 in FIG. 2 .
FIG. 3A is an enlarged cross-sectional view of the inboard end cap shown in FIG. 3 and illustrates a longitudinally extending rib thereon.
FIG. 3B is a cross-sectional view taken across section-indicating lines 3 B— 3 B in FIG. 3 A.
FIG. 4 is a cross-sectional view of the cage assembly taken across section-indicating lines 4 — 4 in FIG. 2 .
FIG. 5 is a cross-sectional view of the outboard end cap of the cage assembly taken across section-indicating lines 5 — 5 in FIG. 2 .
FIG. 6 is a cross-sectional view of the paint roller frame and cage assembly taken across section-indicating lines 6 — 6 in FIG. 2 .
DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings where the illustrations are for the purpose of describing the preferred embodiment of the present invention and are not intended to limit the invention described herein, FIG. 1 is a perspective view of a paint roller frame 10 with a cage assembly, shown generally by the numeral 12 , attached thereto. The frame 10 is formed from heavy gauge wire or rod that is bent so as to provide a handle portion 14 at one end thereof and the shaft portion 16 at the other end thereof for rotatably supporting the cage assembly 12 thereon. Typically, a hand grip (not shown), which may be made of plastic or wood, is attached to the end of the handle portion 14 to assist in gripping the paint roller frame 10 with one hand. A threaded socket (not shown) may be provided in the outer end of the hand grip to permit attachment of an extension pole, if desired.
The cage assembly for the present invention can be any structure that can support a roller cover thereon. For illustration purposes only, as shown in FIG. 2, the cage assembly 12 may be molded of a nylon material, such as Delrin or the like, and includes a substantially rigid one-piece cage body 18 having a substantially circular cross-section and comprised of a plurality of circumferentially spaced, longitudinally extending roller cover support bars 20 joined together at a plurality of axially spaced-apart locations by arcuate ribs 22 interposed between the support bars 20 . The support bars 20 are substantially straight and of uniform height over their entire length, the height of the ribs 22 corresponding to the height of the support bars 20 , and the ribs 22 are joined to the bars 20 forming axially spaced annular rings 24 each having an outer diameter that is slightly less than the inner diameter of a paint roller cover resulting in the outer diameter of the cage body 18 being slightly less than the inner diameter of the paint roller cover to be received thereon.
As shown in FIG. 6, the cage body 18 has an axial opening 26 therethrough to receive the shaft portion 16 of the frame 10 . The outboard end of the cage body 18 is provided with a longitudinally extending circumferential surface 28 terminating in a chamfered surface 30 . A circumferential groove 32 is provided in the longitudinally extending circumferential surface 28 . The inboard end of the cage body 20 is similarly provided with a longitudinally extending circumferential surface 34 terminating in a chamfered surface 36 . As in the case of the outboard end of the cage body 18 , a circumferential groove 38 is also provided in the longitudinally extending circumferential surface 34 .
An end cap 50 , which may also be molded of a nylon material, such as Delrin or the like, and having a substantially circular cross-section with an outer diameter approximating the inner diameter of the paint roller cover to be received thereon, is provided to cover the outboard end of the cage body 18 . The end cap 50 has an annular recess 52 formed therein. The diameter of circumferential surface 54 defining annular recess 52 approximates the outer diameter of the longitudinally extending circumferential surface 28 on cage body 18 . An inwardly directed circumferential lip 56 , having a configuration complementary to circumferential groove 32 in the longitudinally extending circumferential surface 28 on cage body 18 , is provided on the circumferential surface 54 of end cap 50 . The inner diameter of the inwardly directed circumferential lip 56 approximates the root diameter of circumferential groove 32 . A centrally located bore 58 is provided in hub portion 60 of end cap 50 and terminates in a blind bore 62 on the outboard side of end cap 50 . End cap 50 is received over the longitudinally extending circumferential surface 28 on cage body 18 permitting the longitudinally extending circumferential surface 28 to be received in annular recess 52 in end cap 50 and allowing inwardly directed circumferential lip 56 to be received in circumferential groove 32 on the longitudinally extending circumferential surface 28 . In this manner, end cap 50 is lockingly engaged with longitudinally extending circumferential surface 28 on cage body 18 . Chamfered surface 30 on the end of longitudinally extending surface 28 on cage body 18 acts as a pilot surface for the receipt of end cap 50 thereon. The shaft portion 16 of the frame 10 is received through bore 58 in hub portion 60 of end cap 50 so that its end is positioned in blind bore 62 . A cap nut 64 is received on the end of shaft portion 16 of frame 10 and is positioned within blind bore 62 and abuts the surface 66 which defines the bottom of blind bore 62 . A cap (not shown) may be provided to cover the opening to blind bore 62 .
Similarly, an end cap 70 , which may also be formed of Delrin or the like and having a substantially circular cross-section, is provided to cover the inboard end of the cage body 18 . The end cap 70 has an annular recess 72 therein. The diameter of circumferential surface 74 defining annular recess 72 approximates the outer diameter of the longitudinally extending circumferential surface 34 on cage body 18 . An inwardly directed circumferential lip 76 , having a configuration complementary to circumferential groove 38 in the longitudinally extending surface 34 on cage body 18 , is provided on circumferential surface 74 of end cap 70 . The inner diameter of inwardly directed lip 76 approximates the root diameter of the circumferential groove 38 . A bore 78 is provided in hub portion 80 of end cap 70 . End cap 70 is received over the longitudinally extending circumferential surface 34 on cage body 18 permitting the longitudinally extending circumferential surface 34 to be received within annular recess 72 in end cap 70 and allowing inwardly directed circumferential lip 76 to be received in circumferential groove 38 on longitudinally extending circumferential surface 34 . In this manner, end cap 70 is lockingly engaged with longitudinally extending circumferential surface 34 on cage body 18 . Chamfered surface 36 on the end of longitudinally extending surface 34 on cage body 18 acts as a pilot surface for the receipt of end cap 70 thereon. The shaft portion 16 of the frame 10 is received through bore 78 in hub portion 80 and is staked outwardly thereof forming oppositely disposed ears 82 . A washer 84 is received over shaft portion 16 of frame 10 and is interposed between oppositely disposed ears 82 and end 86 of end cap 70 .
End 86 of inboard end cap 70 is provided with an outwardly directed circumferential flange 88 . As shown in FIG. 3, the outer surface of inboard end cap 70 is provided with four (4) circumferentially spaced-apart longitudinally extending ribs 90 which originate adjacent the inboard end of end cap 70 and terminate at the outwardly directed circumferential flange 88 . The diameter across oppositely positioned longitudinally extending ribs 90 is slightly greater than the inner diameter of the paint roller cover to be received thereon. The diameter across oppositely disposed longitudinally extending ribs 90 should be sufficient to tightly and frictionally engage the paint roller cover to be received thereon, yet allow an easy disengagement during the removal process. Typically, the diameter across oppositely disposed longitudinally extending ribs 90 is at least 0.020 inches greater than the inner diameter of the paint roller cover.
In order to install a paint roller cover 100 on paint roller frame 10 , the paint roller cover 100 is slidingly received over outboard end cap 50 , roller cover support bars 20 , and inboard end cap 70 until the end 102 of paint roller cover 100 abuts outwardly directed circumferential flange 88 on end cap 70 . When the paint roller cover 100 is so installed on paint roller frame 10 , the longitudinally extending ribs 90 on end cap 70 engage the inner surface of the paint roller cover 100 preventing the roller cover 100 from becoming disengaged from the frame 10 . When painting has been completed, the paint roller frame 10 , with the paint roller cover 100 thereon, is oriented vertically with outboard end cap 50 being positioned so as to be located lower than inboard end cap 70 . By rapping the inboard side of the shaft portion 16 of the paint roller frame against a solid surface, the weight of the paint roller cover 100 , with the paint retained therein, causes the roller cover 100 to become disengaged from the longitudinally extending ribs 90 and to drop from the roller frame 10 . Since the ribs 90 are oriented in the same direction as longitudinal axis of the roller cover 100 , and thus, in the direction of motion of the roller cover 100 during the removal process, the paint roller cover 100 , with the paint retained therein, can be easily removed from frame 10 for disposal purposes without the painter touching the roller cover 100 .
Certain modifications and improvements will occur to those skilled in the art upon reading the foregoing. It should be understood that all such modifications and improvements have not been expressly set forth herein for the sake of conciseness and readability, but are properly within the scope of the following claims.
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A paint roller frame which securely retains a paint roller cover thereon during painting and which permits the roller cover to be easily removed therefrom is disclosed. The paint roller frame includes a cage assembly comprising a cage body and oppositely disposed end caps having bores therein permitting the passage of the paint roller frame therethrough. The inboard end cap includes a plurality of circumferentially spaced-apart longitudinally extending ribs which securely engage the inner surface of the paint roller cover during the painting process and which permit the easy removal of the roller cover therefrom when painting has been completed or when the roller cover needs replacement.
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This is a divisional of application Ser. No. 08/734,384, filed on Oct. 17, 1996, now U.S. Pat. No. 5,813,658, which is a continuation of Ser. No. 08/344,447, filed on Nov. 23, 1994, now abandoned.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates generally to the field of cable installation and specifically to an apparatus for feeding cable into a conduit.
2. Description of the Related Art
Cables are continually being installed to replace or supplement existing cables. For instance, fiber optic cables are installed to support growing communications networks. The fiber optic cables are installed in new locations or to replace electrical cables in existing locations.
The cables are commonly installed in passages, such as conduits or ducts, by applying an axial force to the cable. The axial force may be a tensile force applied at a leading part of the cable to pull the cable through the conduit. Alternatively, the axial force may be a compressive force applied to a trailing part of the cable to push the cable into the conduit. A preferred method utilizes both tensile and compressive forces.
Conduits or ducts are commonly plastic, metal, or concrete tubes defining an elongated passage in an aerial, submerged, underground, or other installation. A conduit may extend for several kilometers and includes curves and slopes. The interior surface of the conduit is preferably a low friction material or is provided with a low friction coating. The passage in the conduit should be free from obstructions to permit the cable to pass therethrough without interference.
Different apparatus and methods are known for applying the tensile and/or compressive axial forces on the cable for installation in the conduit. In some configurations, a fluid, such as air, is forced along the outer surface of the cable to create a drag force. The drag force tends to propel the cable through the conduit. In other configurations, the leading end of the cable is provided with a dart, also known as a pig, plug, drogue, etc. The dart is pushed by the fluid and pulls the cable. Some configurations are also provided with a driver, such as rotating wheels or belts, that engages the outer surface of the cable and pushes the cable into the conduit. Examples of these configurations and related components are shown in U.S. Pat. Nos. 4,756,510, 4,850,569, 4,934,662, 5,121,644, 5,156,376, 5,163,657, 5,197,715, 5,211,377, and 5,308,041, all incorporated herein by reference.
According to some prior art systems for installing cables, low pushing forces are utilized with high volumes of compressed air (350 cubic feet per minute or more). Such systems require large compressors to propel the cable through the conduit. Even with high volumes of air, inflexibility of the cable, obstructions, or curved conduit paths limit the effectiveness of the installation. In practice, these systems are limited to installing cables of about 2000 to 3500 feet in length and additional compressors are required along the installation path. Smaller compressors can be used when a more powerful pushing tractor is used. However, such tractors increase the risk of damaging the cable, which is designed to endure tensile and radial loads, not axial compressive loads. The resulting damage involves redistribution of the fibers, as well as excessive bending or kinking. In addition, the tractor belts are prone to slipping on the cable, thereby damaging the cable jacket.
It is desirable to maximize the length of cable that can be installed without interruption, and to reduce the size and number of air compressors required. As the length increases, the force required to continue installation increases. Fiber optic cables are often more delicate than metal cables. Therefore, the method and apparatus used for installation of fiber optics must not damage the cable while providing the necessary installation forces. In addition, the installation should be automatically controlled and use a minimum amount of equipment to improve efficiency.
These problems are largely solved in the present invention by using a lower air volume and a greater pushing force. Damage to the cable from the greater force is prevented by sensing the force applied to the cable. A feed back system controls the pushing force based on the force sensed. Pushing is also controlled based on the velocity of the cable. Damage is further prevented by limiting the radial force applied.
The number of compressors required is reduced by providing a "mid-assist" cable feeder with a by-pass pipe to convey pressurized air from one conduit or duct to a succeeding conduit or duct. With the present invention, distances exceeding 5,000 feet between cable feeders can be achieved and compressors are not required at mid-assist locations.
SUMMARY OF THE INVENTION
The present invention provides a cable installation apparatus and method that reduce the chances of cable damage. The radial force applied to the cable is limited, and feedback sensors control installation to prevent excessive axial force being applied to the cable. Greater pushing force is applied to the cable, and smaller and fewer air compressors are required. A mid-assist configuration provides a by-pass for compressed air from a first conduit to a succeeding conduit.
According to one embodiment of the invention, the apparatus for installing the cable into a conduit includes a driver adapted to engage the cable to propel the cable forwardly into the conduit; and a sensor for measuring axial force, in particular, the axial compressive load, applied to the cable by the driver. The driver is a pair of opposed rotating members, such as belts, adapted to frictionally engage the cable. The opposed rotating members are separable to permit insertion of the cable therebetween. At least one of the rotating members is radially adjustable relative to the cable.
The sensor is a strain gauge or other device adapted to measure the axial force based on relative movement of the conduit and the driver. The strain gauge is rigidly mounted relative to the driver and the conduit is rigidly mounted in a duct clamp, the duct clamp being movably mounted relative to the driver and operatively in contact with the strain gauge so that the strain gauge measures the force tending to move the conduit. The driver is controlled responsive to the force sensed by the sensor by discontinuing propelling of the cable when the force sensed by the sensor exceeds a specified limit.
The apparatus also includes a fluid power system for powering the driver. The fluid power system is hydraulic, and the sensor comprises a hydraulic pressure detector for sensing pressure delivered to the driver. The hydraulic system is adapted to divert hydraulic fluid from the driver when the force sensed by the sensor exceeds a specified limit. A by-pass is connected to divert hydraulic fluid from the driver.
A fitting is adapted to be connected to a compressed air source, said fitting directing the air into the conduit to propel the cable through the conduit. An injection block defining a plenum is adapted for communicating compressed air from the source to the conduit. A seal disposed around the conduit and a seal disposed around the cable isolate the plenum from ambient air. A clamp secures the conduit adjacent the driver. The seals comprise generally symmetrical components that are separable for installation of the conduit and cable, respectively. The seals also comprise inserts that are replaceable according to the respective sizes of the conduit and cable.
A radial force limiter, such as a spring, limits radial force applied to the cable by the rotating members. A threaded member is adapted to position at least one of said rotating members, said spring being operatively disposed between the threaded member and the rotating member. A calibrated stop limits travel of the threaded member to limit a force of the spring applied to the rotating member.
The apparatus also includes a sensor for measuring velocity of the cable passing through the driver. The driver is controlled responsive to velocity sensed by the velocity sensor. The driver is adapted to discontinue propelling the cable when a velocity sensed by the sensor exceeds a specified limit. The hydraulic system powering the driver is adapted to divert hydraulic fluid from the driver when a velocity sensed by the sensor exceeds a specified limit. The velocity exceeds the specified limit when the velocity falls below a minimum or rises above a maximum.
According to another embodiment of the invention, the apparatus is adapted for installing cable from a first conduit into a succeeding conduit, said cable being propelled through said first conduit by compressed air in the first conduit. The driver is adapted to engage the cable to propel the cable forwardly into the succeeding conduit. A pipe is connected to define an airtight passage between the first conduit and the succeeding conduit. The pipe is adapted to direct the compressed air into the succeeding conduit to propel the cable through the succeeding conduit. An exit seal is provided for mounting an end of the first conduit from which the cable projects adjacent an entrance end of the driver. An entrance seal for mounting an end of the succeeding conduit into which the cable is to be installed is located adjacent an exit end of the driver. The seals define respective plena communicating the conduits with the pipe and isolating the driver from the compressed air. Seals are provided around the cable to isolate the plena from ambient air. The sensor measures axial force applied to the cable by the driver.
The invention also provides a method of installing cable in a conduit. The steps include propelling the cable through the conduit with a driver; sensing axial force applied to the cable; and controlling the driver in response to sensed forces. An additional step includes propelling the cable through the conduit with compressed air. The step of controlling the driver includes the step of diverting hydraulic fluid from the driver when an axial force exceeding a specified maximum is sensed. The step of sensing includes measuring relative axial movement of the driver and conduit and/or sensing a pressure of hydraulic fluid being delivered to the driver.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a schematic diagram of a cable installing operation using a cable feeder in a feed configuration according to the present invention;
FIG. 2 shows a partially cut away elevational front view of a cable feeder according to the invention;
FIG. 3 shows an elevational rear view of the cable feeder;
FIG. 4 shows a detailed front sectional view of an air injection block and exit duct clamp on the cable feeder shown in FIG. 2;
FIG. 5 shows a schematic diagram of a hydraulic system of the cable feeder;
FIG. 6 shows a schematic diagram of a control system of the cable feeder;
FIG. 7 shows a perspective view of a cable pulling dart; and
FIG. 8 shows a partially cut away elevational front view of the cable feeder in a mid-assist configuration.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Referring to FIG. 1, a reel 10 of cable 12 is to be installed in a conduit 14, such as a duct, defining an underground passage 16. A port 18 allows access to an entrance 20 of the conduit 14. The cable 12 is fed into the conduit 14 with a cable feeder 22. Sources of compressed air 24, hydraulics 26, and electric power 28 are connected to the cable feeder 22. Preferably, the compressed air 24 is provided at 175 to 375 cubic feet per minute (CFM) and 90 to 115 pounds per square inch (PSI). Alternatively, another fluid can be used instead of compressed air. The hydraulics are preferably provided at 2 to 5 gallons per minute (GPM) and 1500 PSI. The electrical source is preferably a 12 volt direct current (VDC) battery.
Referring to FIG. 2, the cable feeder 22 includes a support stand 30 having adjustable legs 32 resting on the ground or another suitable surface. Mounted on the support is a driver 33 such as a pair of opposed continuous drive belts 34. Alternatively, the driver 33 can be opposed wheels or a reel and guide. An air injection block 36 is located adjacent to an exit end of the driver 33. An encoder 38 is disposed adjacent to an entrance end of the driver 33. An entrance duct clamp 40 and an exit duct clamp 42 are located at opposite ends of the stand 30.
The entrance duct clamp 40 releasably holds a entrance duct 44 for guiding the cable 12 past the encoder 38 and toward the driver 33. Preferably, the entrance duct 44 is a cylindrical length of polyethylene tubing. The entrance duct clamp 40 includes a pair of opposed jaws 46 operated by a handle 48 and a threaded bolt or post.
The encoder 38 includes a wheel 50 that frictionally engages the cable 12. An opposed idler wheel 52 ensures engagement of the wheel 50 with the cable 12. The encoder, such as a Balluff Part No. BES-5K-343-EO-C3, determines speed and length of cable 12 passing the encoder as measured by rotation of the wheel 50.
The drive belts 34 are separable to permit installation of the cable 12 therebetween. The drive belts 34 include segmented, contoured tractor treads 54 adapted to frictionally engage and capture the cable 12. The drive belts 34 are preferably endless chains driven by sprockets 55 and supported on rails 57. The treads 54 are preferably a flexible material, such as natural rubber or urethane. A load spring 56, such as McMaster Part No. 9297k92, operated by a handle 58 and threaded member positions the drive belts 34 so that the treads 54 firmly engage the cable 12 without crushing or damaging the cable. A stop 60, such as a calibrated limit cylinder, limits travel of the handle 58. The stop 60 and load spring 56 are calibrated to precisely set the radial force applied to the cable 12 by the drive belts 34 when the handle 58 is rotated down to the stop 60. The stop 60 is removable and replaceable with stops having different heights corresponding to the proper radial forces to be applied to different cables based on cable diameter, cable type, or other conditions. The drive belts are powered by hydraulic motors 62 or other power transmission devices, shown in FIG. 3 and discussed below.
The air injection block 36 is provided with an entrance seal insert 64 and an exit seal insert 65 adapted to permit passage of the cable 12 therethrough while maintaining an airtight seal. The injection block 36, entrance seal insert 64, and exit seal insert 65 are each separable into two generally symmetrical halves to permit installation of the cable 12 therebetween. The seal inserts 64, 65 and other seal inserts discussed below are removable and replaceable with similar inserts adapted for different cable and conduit diameters. Securing means, such as handles 63 and threaded bolts or shafts, are operable to secure the parts of the injection block 36 in a closed position. The entrance seal insert 64 provides a passage slightly larger than the cable 12. A pair of gaskets 67 are provided in the entrance seal insert 64 to seal around the cable. A fitting 66 is provided to permit injection of compressed air 24 into the injection block 36.
The exit duct clamp 42 is secured to the air injection block 36 to secure the duct 70 to the injection block 36. The injection block 36 defines a plenum 68 closed by the entrance seal insert 64 and the exit seal insert 65. A guide duct 70 is releasably held in the exit duct clamp 42. Preferably, the guide duct 70 is a cylindrical length of polyethylene tubing. The exit duct clamp 42 includes a pair of opposed jaws 72 operated by a handle 74 and a threaded post or bolt. A duct seal 76, such as a pair of gaskets, is provided to seal around the guide duct 70. The exit duct clamp 42 and duct seal 76 seal the injection block 36 and guide duct 70 to direct passage of air from the plenum 68 into the guide duct 70.
Referring to FIG. 3, the hydraulic motors 62 are mounted on the rear of the driver 33 and operatively connected to power the drive belts 34. The hydraulic motors 62 are connected to a hydraulic manifold 80, by suitable fluid conveying hoses and connectors. A solenoid operated by-pass valve 82 is connected in parallel with the motors 62. The hydraulic manifold 80 is provided with a pressure detector 84 (such as Barksdale Part No. 400H3-13CG-Q11), a pressure gauge 85, and a relief cartridge 86. The hydraulic source 26 (FIG. 1) is connectable to the hydraulic manifold 80 in a conventional manner. A junction box 88 is also provided for connection of electric power 28 to electrical components of the driver 33.
Referring to FIG. 4, the insert 64 and seal 67 are preferably made of materials having low coefficients of friction. As shown, the entrance seal insert 64 is tapered so that air inside the injection block 36 is directed toward the exit seal insert 65. The seal 90 and insert 64 do not substantially impede movement of the cable 12 and do not permit leakage of air from the injection block 36. Serrations 92 or teeth are provided on inner faces of the jaws 72 of the exit duct clamp 42 to firmly grip the guide duct 70.
A force transducer, such as a strain gauge 94 is rigidly mounted on a base 96 fixed to the support stand 30. The strain gauge 94 is operatively in contact with the exit duct clamp 42. The duct clamp 42 and injection block 36 are slidingly mounted on the base 96, for example with bolts 98 through slotted mounting holes 100. A tail section 102 of the cable seal insert 64 is slidingly received in an end of the driver 33. The cable 12 moving through the duct 70 tends to urge the injection block 36 and duct clamp 42 toward the strain gauge 94. The strain gauge 94 is a piezoresistive element or other device (e.g., A.L. Design model No. ALD-W-3) suitable for measuring the relative frictional force between the duct 70 and the cable 12 to determine the axial compressive force applied to the cable 12.
Referring to FIG. 5, the hydraulic source 26 comprises, for example, a pump having a capacity of about three gallons per minute of hydraulic fluid. The hydraulic source 26 is connected to power the hydraulic motors 62 through a hydraulic system 104. Alternatively, the driver 33 can be powered by another fluid power system or another source of power such as electricity. The hydraulic system 104 includes an actuator valve 106, a fixed restriction 108, and a pressure control 110 connected in series with the motors 62. The by-pass valve 82 is connected in parallel across the motors 62 and the other components of the system 104. The actuator valve 106 selectively directs hydraulic fluid toward the motors 62 or to a reservoir to respectively actuate or disable the motors 62. The fixed restriction 108 limits flow to the motors 62 to a maximum of about five gallons per minute. The pressure control 110 is preferably a manually adjustable, pressure regulating, reducing valve. As discussed in more detail below, the pressure control 110 limits the hydraulic pressure to the motors 62 to limit the force applied on the cable 12 by the drive belts 34. The normal pressure is typically about 500 to 1350 PSI at the motors, depending on cable characteristics. The pressure detector 84 is connected to measure pressure delivered to the hydraulic motors 62. The pressure detector 84 is calibrated to measure axial compressive force applied to the cable 12 by the drive belts 34 by correcting for internal friction of the mechanical parts of the motors 62 and belts, and the force required to pull the cable 12 from the reel 10. The by-pass valve 82 includes a solenoid 112 operated variable restriction 114 and a check valve 116. The variable restriction 114 is adjustable to divert part of the flow away from the motors 62 and to the reservoir, as discussed below.
Referring to FIG. 6, a control system 118 includes the strain gauge 94, pressure detector 84, encoder 38, and solenoid 112 located on the cable feeder 22, as discussed above. The control system 118 also includes a display and alarm panel 120 having a rate display 122 (e.g., Red Lion Co. Part No. 50020) connected to the encoder 38, and a strain/pressure display 124 (e.g., Ottotech Series 260) connected to the strain gauge 94 and pressure detector 84. A rate control 126 is operatively connected to the encoder 38 and is connected for automatic or manual adjustment of the solenoid 112. A drive control 128 is operatively connected to the strain gauge 94 and the pressure detector 84. The drive control 128 is also connected for automatic or manual adjustment of the solenoid 112. The displays 122, 124 and controls 126, 128 can be provided with audible and/or visible alarms indicating certain operating conditions. The control system 118 can also be provided with recorders to store data collected during operation.
Referring to FIG. 7, prior to installation in the cable duct 70, a leading end of the cable 12 is provided with a dart 130. For example, the dart 130 includes several cylindrical plugs 132 each having a diameter the same as or slightly larger than the inside diameter of the cable duct 70 and conduit 14. The plugs 132 are made of a rigid or slightly flexible, low friction material, such as rubber or thermoplastic. The plugs 132 are interconnected by a flexible cord 134 securely fastened to the cable 12. A loop 136 is formed in the cord by weaving, for example. The cord 134 is secured to the cable 12 by a pivot connector 138 or universal joint connector that firmly grasps the end of the cable 12.
To set up the cable feeder 22, as shown in FIGS. 1 and 2, a length of cable 12 is unrolled from the reel 10 and inserted in the entrance duct 44. The cable 12 is positioned so that it extends from the end of the entrance duct 44 approximately the length of the cable feeder 22. The dart 130 is installed on the cable 12 and inserted into the guide duct 70. The cable feeder 22 is positioned adjacent the cable 12. The drive belts 34, injection block 36, encoder 50, clamps 40, 42, and seal inserts 64, 65 are separated to provide a generally horizontal passage into which the cable 12 is transversely inserted. The separated parts are then reassembled, closed, and secured to secure the entrance duct 44, cable 12, and guide duct 70 in the cable feeder 22. Alternatively, the conduit 14 can be fastened directly in the exit duct clamp 42. The stop 60 is installed and the handle 58 is turned to engage the tractor treads 54 with the cable 12 at a specified radial force.
Referring to FIGS. 2, 5, and 6, the compressed air 24, hydraulic source 26, and electric power 28 are connected and initiated to pressurize the plenum 68 and to activate the hydraulic system 104 and the control system 118. Air pressure builds up behind the dart 130 and propels the dart forwardly, pulling the cable 12 through the conduit 14. The actuator 106 is switched on to provide hydraulic fluid to the motors 62, and the drive belts 34 rotate, driving the cable through the conduit 14.
During operation, the encoder 38 monitors the length of cable 12 passing through the cable feeder 22. The length of cable and the rate at which the cable travels are displayed on the rate display 122. Rate information is provided to the rate control 126, which operates the by-pass valve 82. The by-pass valve 82 can divert a selected amount of hydraulic fluid away from the motors 62 to control the rotational speed of the motors, thereby controlling the rotational speed of the drive belts 34. The rate control, thus, maintains the cable rate within a selected range manually input to the rate control 126 before or during a cable feeding operation to minimize installation time while avoiding damage to the cable 12 and conduit 14. If the encoder 38 senses that the cable 12 has stopped or excessively slowed, for example because of an obstruction, the by-pass valve 82 diverts fluid to stop the drive belts 34, thereby preventing the drive belts from damaging the cable 12 and to prevent excessive axial compression of the cable. Typical cable installation rates are between about 100 to 200 feet per minute (fpm). Exemplary limits triggering alarms and/or stopping the driver are about 25 fpm and 250 fpm.
The pressure detector 84 senses the pressure in the hydraulic system at the motors 62. The pressure is displayed on the pressure display 124 and pressure information is provided to the drive control 128, which operates the solenoid 112 of the by-pass valve 82 based on a selected range of hydraulic pressures input to the drive control before or during operation. The hydraulic pressure used to power the driver 33 depends on the characteristics of the cable 12. In most cases the pressure is between about 500 and 1350 PSI. Lower and upper limits are in the range of 200 to 2000 PSI and are determined by the minimum power required to drive the cable and the force at which unwanted bending, deflection or axial compression of the cable occurs. The pressure control 110 can be adjusted to maintain the hydraulic pressure within the selected range to provide sufficient force to drive the cable 12 through the conduit 14 while preventing damage to the cable.
The pressure display 124 also displays axial force applied to the cable based on information from the strain gauge 94. The axial force information is used to operate the by-pass valve 82 to limit the axial force applied to the cable 12 to prevent damage thereto. Again, the range of forces is determined by cable characteristics. Typical forces range from 30 to 300 pounds, with alarms being triggered outside the normal range. If the pressure detector 84 or strain gauge 94 senses an excessive axial force on the cable 12, the by-pass valve 82 stops the drive belts 34 to prevent the drive belts from damaging the cable 12 and to prevent excessive axial compression of the cable. The hydraulic system can be arranged to stop the motors, allow the motors to free-wheel or otherwise discontinue driving of the cable on the specified condition.
Cable installation is monitored and controlled by the control system 118 to provide efficient feeding of the cable 12 into the conduit 14. Parameters are set and adjusted to minimize installation time while preventing damage to the cable. The control system 118 is adapted to adjust or discontinue operation of the cable feeder 22 in the event of obstructions or other impediments to cable movement.
Referring to FIG. 8, the cable feeder 222 is arranged in a "mid-assist" configuration. The cable feeder 222 is substantially identical to the cable feeder 22 shown in FIG. 2, except for modifications discussed below. In fact, the cable feeder 22 of FIG. 2 is designed to be easily adapted for the configuration shown in FIG. 8. A downstream end of the conduit 14, or a duct in communication with the conduit, is firmly mounted in the entrance duct clamp 240. The cable 12 passes from the conduit 14 into the cable feeder 222. An air ejection block 223 is disposed between the entrance duct clamp 240 and the encoder 238. The ejection block 223 is similar in construction to the injection block 236 and has an entrance seal insert 225 including, for example, a pair of gaskets 227 engaging the conduit 14. An exit seal insert 229 has a pair of gaskets 231 engaging the cable 12. The ejection block 223, seals 225, 229, and duct clamp 240 are each separable into halves and secured together by handles 263 and threaded members. The ejection block 223 defines a plenum 235 therein in communication with the conduit 14. The plenum communicates with an ejection fitting 237 connectable to one end of a by-pass pipe 239, such as a rigid tube or flexible hose. The other end of the by-pass pipe 239 is connectable to the fitting 266 of the air injection block 236 to place the conduit 14 in communication with a succeeding duct 70a. The cable 12 is driven by the drive belts 234 and passes into the succeeding cable duct 70a where pressurized air conveyed by the by-pass pipe 239 propels the cable 12 forwardly through a succeeding conduit.
To set up the mid-assist cable feeder 222, the cable 12 is positioned so that it extends from the end of the conduit 14 approximately the length of the cable feeder 222. The dart 130 is inserted into the succeeding cable duct 70a. The cable feeder 222 is positioned adjacent the cable 12. The drive belts 234, ejection block 223, injection block 236, clamps 240, 242, and seal inserts 225, 229, 264, 265 are separated to provide a generally horizontal passage into which the cable 12 is transversely inserted. The separated parts are then reassembled, closed, and secured to secure the conduit 14, cable 12, and duct 70a in the cable feeder 222.
Operation of the mid-assist cable feeder 222 in the mid-assist configuration is substantially the same as described above for the cable feeder 22, except that the compressed air is transferred from the upstream conduit 14 to the succeeding conduit 70a, thus, no additional compressed air source is required. The mid-assist feeder 222 should not be operated without the by-pass pipe 239. To coordinate the drive belts 34, 234, controls from the cable feeders 22, 222 can be connected together.
The present disclosure describes several embodiments of the invention, however, the invention is not limited to these embodiments. Other variations are contemplated to be within the spirit and scope of the invention and appended claims. Terms for such elements as the seals, inserts, pipe, conduits, and ducts are selected to distinguish among different parts of the invention and are not intended to limit the materials or configurations of these elements, as will be apparent to one skilled in the art.
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An improved cable feeder uses tractor type drive belts and compressed air to propel cable through a conduit. The axial force applied to the cable is sensed with a strain gauge near the conduit or a pressure detector in a hydraulic system powering the drive belts. If excessive force is applied, hydraulic fluid is diverted from the drive belts. The radial force applied to the cable is limited by a calibrated spring. The feeder can also be arranged in a mid-assist configuration. Conduits and the cable are sealed to maintain air pressure. A by-pass pipe is provided to convey pressurized air from a first conduit to a succeeding conduit.
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This invention was made in part with government support under grant HL58713 from the National Institutes of Health. The government has certain rights in the invention.
FIELD OF THE INVENTION
This invention generally relates to a novel composition comprising myoblasts and growth factors. The growth factors may include, for example, basic fibroblast growth factor (bFGF) and fibronectin (FN). The invention also relates to a novel composition comprising myoblasts transfected with vectors expressing metalloproteases and growth factors. Additionally, the invention relates to the use of these compositions in assays for the identification of agents which are antagonistic or agonistic for myoblast migration either in vivo or in vitro. Furthermore, the invention relates to the use of these compositions for the treatment of degenerative muscle diseases. Further still, the invention relates to the therapeutic use of these compositions and methods in gene therapy.
BACKGROUND
The ability of myoblasts to migrate through connective tissue barriers has important implications for muscle development, muscle regeneration, and myoblast-mediated gene transfer. During embryonic development, myogenic precursor cells migrate out of the somites and into the developing limb buds to form the limb musculature (Christ et al. “Experimental analysis of the origin of the wing musculature in avian embryos” Anat. Embrylo. 150:171-186, 1977), and myoblasts retain the ability to traverse the myofiber basal lamina during postnatal development (Hughes and Blau “Migration of myoblasts across basal lamina during skeletal muscle development” Nature 345:350-352, 1990). A number of studies have also demonstrated migration of myoblasts both within (Schultz et al. “Absence of exogenous satellite cell contribution to regeneration of frozen skeletal muscle” J. Muscle Res. Cell Motil 7:361-367, 1986; Philips et al. “Migration of myogenic cells in the rat extensor digitorum longus muscle studied with a split autograft model” Cell Tissue Res 262:81-88, 1990) and between adult muscles (Watt et al. “The movement of muscle precursor cells between adjacent regenerating muscles in the mouse” Anat. Embryol. 175:527-536, 1987; Watt et al. “Migration of LacZ positive cells from the tibialis anterior to the extensor digitorum longus muscle of the X-linked muscular dystrophic (MDX) mouse” J. Muscle Res. Cell Motil. 14:121-132, 1993; Watt et al. “Migration of muscle cells” Nature 368:496-407, 1994; Moens et al. “Lack of myoblast migration between transplanted and host muscle of mdx and normal mice” J. Muscle Res. Cell Motil. 17:37-43, 1996). These studies have shown that in order to produce myoblast migration between muscles there must first be disruption of the thick outer epimysium on one or both muscles, combined with some sort of chemotactic stimulus or stimuli generated by conditions such as inflammation or regeneration of muscle.
In recent years, myoblast cell therapy and myoblast-mediated gene transfer therapy have been extensively explored for both muscle disorders, such as muscular dystrophy (Karpati et al. “Myoblast transfer in Duchenme muscular dystrophy” Ann. Neurol 34:8-17, 1993; Morgan et al. “Normal myogenic cells from newborn mice restore normal histology to degenerating muscles of the mdx mouse” J. Cell. Biol 111:2437-2449, 1990), and for disorders which require production of systemic protein factors such as factor IX (Yao and Kurachi “Expression of human factor IX in mice after injection of genetically modified myoblasts” Proc. Natl. Acad. Sci USA 89:3357-3361, 1992; Roman et al. “Circulating human or canine factor IX from retrovirally transduced primary myoblasts and established myoblast cell lines grafted into murine skeletal muscle” Somatic Cell Mol. Genetics 18:247-258, 1992; Yao et al. “Primary myoblast-mediated gene transfer: persistent expression of human factor IX in mice” Gene Therapy 1:99-107, 1994; Wane, et al. “Persistent systematic production of human factor IX in mice by skeletal myoblast-mediated gene transfer: feasibility of repeat application to obtain therapeutic levels” Blood 90:1075-1082, 1997). The implanted myoblasts not only fuse with the existing myofibers, but can also remain as satellite cells (Yao and Kurachi “Implanted myoblasts not only fuse with myofibers but also survive as muscle precursor cells” J. Cell Sci. 105:957-963, 1993), but in both cases these myoblasts must traverse the basal lamina. However, the results from clinical trials using myoblast cell therapy for Duchenne's muscular dystrophy (DMD) have been equivocal, with some reporting success (Law et al. “Human gene therapy with myoblast transfer” Transplant. Proc. 29:2234-2237, 1990; Huard et al. “Human myoblast transplantation: preliminary results of 4 cases” Muscle & Nerve 15:550-560, 1992) and others reporting less encouraging results (Karpati et al. “Myoblast transfer in Duchenne muscular dystrophy” Ann. Neural. 34:8-17, 1993; Mendell et al. “Myoblast transfer in the treatment of Duchenne's muscular dystrophy” New England J. Med. 333:832-838, 1995). It is evident from these studies that substantial improvements are needed before such therapies will become practical as a therapeutic intervention for human disorders.
One of the primary limiting factors in myoblast therapy is the overall efficiency of incorporation of myoblasts into the myofibers. Estimates have suggested that only 5-10% of the implanted myoblasts become incorporated and contribute to transgene expression (Gussoni et al. “The fate of individual myoblasts after transplantation into muscles of DMD patients” Nature Medicine 3:970-977, 1997; Wang et al “Persistent systemic production of human factor IX in mice by skeletal myoblast-mediated gene transfer: feasibility of repeat application to obtain therapeutic levels” Blood 90:1075-1082, 1997). Evidence from human clinical trials of myoblast implantation to correct DMD has suggested that even when the immune system is suppressed by cyclosporine treatment, myoblast incorporation into the host myofibers is still low, and only minimal long term effects were noted (Karpati et al. “Myoblast transfer in Duchenne muscular dystrophy” Ann. Neurol. 34:8-17, 1993). These studies suggested that another barrier to successful myoblast incorporation is the presence of connective tissue sheaths surrounding both fascicles and individual myofibers. Myoblasts must first traverse these barriers to access the myofiber surface in order to fuse with and incorporate into the myofiber syncytium. Moreover, human muscle contains thicker connective tissue sheaths than that of smaller organisms, and therefore this barrier may be even greater in humans than in experimental animal models such as mice. Thus the ability of myoblasts to cross connective tissue barriers may have a major effect on the overall efficiency of the gene transfer process. Recent studies have also demonstrated that the myofiber basal lamina is a significant barrier to viral-mediated in vivo gene transfer as well (Huard et al. “The basal lamina is a physical barrier to herpes simplex virus-mediated gene delivery to mature muscle fibers” J. Virol. 70:8117-8123, 1996).
Physical and chemical disruption of the basal lamina by damaging the muscle would allow implanted myoblasts to cross the basal lamina and merge with the concomitant regeneration program, regenerating the muscle fibers with a mosaic of endogenous and implanted myonuclei. Most studies on myoblast transfer in animal models have used either physical injury (Wernig et al. “Formation of new muscle fibers and tumors after injection of cultured myogenic cells” J. Neurocytol. 20:982-997, 1991; Morgan et al. “Normal myogenic cells from newborn mice restore normal histology to degenerating muscles of the mdx mouse” J. Cell Biol. 111:2437-2449, 1990) or myotoxic agents (Salminen et al. “Implantation of recombinant rat myocytes into adult skeletal muscle: a potential gene therapy” Human Gene Therapy 2:15-26, 1991; Bonham et al. “Prolonged expression of therapeutic levels of human granulocyte-stimulating factor in rats following gene transfer to skeletal muscle” Human Gene Therapy 7:1423-1429, 1996) to produce this effect. However, these approaches may be too harmful and destructive for gene therapy in patients, particularly those suffering from disorders such as DMD or hemophilia.
Therefore, what is needed is a less destructive method for delivering genetically engineered therapeutics to muscles in the body.
SUMMARY OF THE INVENTION
The present invention generally relates to novel compositions comprising myoblasts and various growth factors. Additionally, the invention relates to novel compositions comprising myoblasts genetically engineered to express certain proteins (e.g. various metalloproteases (MMP) and various therapeutic proteins) and various growth factors. In one preferred embodiment the invention generally relates to novel compositions comprising myoblasts transfected with constructs expressing MMP-1 and MMP-2. In another embodiment, the invention relates to novel compositions comprising said transfected myoblasts and various growth factors. The selection of growth factors may include, but are not limited to, basic fibroblast growth factor (bFGF) and fibronectin (FN). Furthermore, the present invention relates to the use of said compositions to induce the migration of myoblasts and the invasion of myoblasts into myofibrils. Further still, the present invention relates to using said compositions to screen for agents that are agonistic or antagonistic to myoblast migration and invasion into myofibrils. Further still, the present invention relates to methods for treatment of degenerative muscular diseases and to delivery of therapeutic proteins by utilizing said transfected and untransfected myoblasts and growth factors.
In one embodiment, the present invention contemplates a composition, comprising myoblasts transfected with a gene encoding a metalloprotease. It is not intended that the present invention be limited to the degree of expression. However, it is preferred that the level of expression of the metalloprotease exceeds that of the untransfected myoblast. The present invention contemplates embodiments, wherein the gene is part of a vector which encodes at least one metalloprotease (i.e. vectors encoding more than one metalloprotease are contemplated—in addition, transfections with more than one vector, each comprising a gene encoding a metalloprotease is also contemplated).
In a preferred embodiment, said myoblasts have been co-transfected with a gene encoding a therapeutic gene product. Alternatively, two populations of myoblasts are mixed: one population transfected with the gene encoding the metalloprotease and the other population transfected with the gene encoding a therapeutic gene product.
The present invention also contemplates a host, said host comprising myoblasts transfected with a gene encoding a metalloprotease. Again, it is preferred that said myoblasts have been co-transfected with a gene encoding a therapeutic gene product. Again, multiple vectors and multiple metalloproteases are contemplates as well.
The present invention also contempaltes a method, comprising: a) providing i) transfected myoblasts, said transfected myoblasts transfected with a gene encoding a therapeutic gene product, ii) a host, and iii) fibroblast growth factor and fibronectin; b) culturing said transfected myoblasts in the presence of said fibroblast growth factor and said fibronectin to create cultured, transfected myoblasts; and c) introducing said cultured, transfected myoblasts into said host. The present invention contemplates variations on this embodiment, such as where said myoblasts have been co-transfected with a gene encoding a metalloprotease.
In one embodiment, myoblast migration assays are established, comprising: a) providing i) myoblasts from a donor, ii) one or more growth factors selected from the group consisting of bFGF and FN, iii) one or more compounds suspected of being agonistic or antagonistic to myoblast migration; b) culturing said myoblasts under conditions to measure cell migration, wherein migration of myoblasts is measured in the presence and absence of said one or more growth factors and compounds. The present invention contemplates using the above named compositions, and variations thereof, in screening assays for the detection of substances that are agonistic or antagonistic to myoblast invasion of myofibrils. High-throughput in vitro screening techniques are also contemplated in this invention.
In another embodiment, compounds suspected of inhibiting or promoting myoblast migration may be screened in vivo using, for example, mouse models, with the assay comprising: a) providing a host (e.g. a living animal); b) extracting myoblasts from said host; c) culturing said myoblasts with and without a compound suspected of being agonistic or antagonistic to myoblast migration so as to create a first and second preparation of cultured myoblasts; d) introducing at least a portion of said first and second preparations of cultured myoblasts into the said host under conditions such that the migration of said first and second preparations of said cultured myoblasts can be compared. In a preferred embodiment said cultured cells would be marked for easy identification after reintroduction into the host. Said means of identification would be known by those practiced in the art and may include transfection into said myoblasts of constructs that express a marker protein (e.g. green fluorescent protein (GFP), beta-galactosidase (β-gal), luciferase or an expression product (antigen) detectable with a specific antibody), incorporation into said myoblasts of radioactive markers and incorporation into said myoblasts of easily assayable marker proteins or chemicals. In another preferred embodiment said cultured cells would be transfected with constructs that express metalloproteases including, but not limited to, MMP-1, and MMP-2. Then said transfected myoblasts would be assayed as described herein above.
Furthermore, the present invention contemplates using the above named compositions, and variations thereof, to enhance the migration of myoblasts either in vivo or in vitro. In one embodiment, comprising, a) providing i) a patient, ii) one or more growth factors selected from the group consisting of bFGF and FN, and iii) myoblasts (e.g. immunocompatible myoblasts) from a donor; b) contacting said myoblasts ex vivo with said growth factor under conditions to promote myoblast migration; and c) introducing said myoblasts into said patient.
While not limited to any mechanism, it is believed that, in part, culturing the cells in the manner proposed results in the expression by the cells of various metalloproteases, the expression of which permit the myoblasts to transverse the epimysium (connective tissue) surrounding the muscle. In this regard, the present invention provides a method of treatment of human muscular degenerative diseases (e.g. muscular dystrophy) comprising: a) providing a human patient diagnosed with a muscular degenerative disease; b) obtaining myoblasts from the patient or an immunocompatable donor; c) culturing said myoblasts in a culture medium, said culture medium comprising one or more of the above mentioned cytokines; and d) introducing at least a portion of said myoblasts into said patient so as to induce an in vivo therapeutic reaction. In another embodiment the method further comprises additional introductions or administrations of said myoblasts into said patient. The invention shall not be limited by the selection of cytokines used to promote migration of myoblasts and invasion by myoblasts into myofibrils.
In yet another embodiment, the invention comprises: a) providing i) myoblasts from a host and ii) a vector comprising MMP-1 and MMP-2 in an operable combination with a promoter; b) transfecting said myoblasts with said vector under conditions such that metalloproteases are expressed; c) culturing said transfected myoblasts with bFGF and FN so as to create treated transfected myoblasts, and; d) introducing at least a portion of said treated transfected myoblasts into said host.
Furthermore, the invention embodies the delivery of various therapeutic peptides via the introduction of genes into the myoblasts prior to the stimulation of the myoblasts with the cytokines that induce migration. One embodiment comprises: a) providing i) myoblasts obtained from the host and ii) a DNA vector which encodes the therapeutic peptide; b) transfecting said myoblasts with said vector to create transfected myoblasts; c) culturing said transfected myoblasts with bFGF and FN so as to create treated transfected myoblasts; and d) introducing at least a portion of said treated, transfected myoblasts into said host. In another embodiment, the method further comprises additional introductions of the said myoblasts into said patient. The invention shall not be limited by the selection of cytokines used to promote migration of myoblasts and invasion by myoblasts into myofibrils. In yet another embodiment, the invention comprises: a) providing i) myoblasts from a host and ii) a first vector which encodes a therapeutic peptide, and iii) a second vector that encodes a metalloproteases (e.g. MMP-1 and MMP-2); b) transfecting said myoblasts with said first and second vectors; c) culturing said transfected myoblasts with bFGF and FN so as to create treated, transfected myoblasts, and; d) introducing at least a portion of said treated transfected myoblasts into said host.
For culturing, the bFGF may be used at concentrations in a range from about 0.1 to 10 μg/ml bFGF. Likewise, the FN may be used at concentrations in a range from about 5 μg/ml to 500 μg/ml. In one embodiment, the culture medium contains bFGF at 1 μg/ml and FN at 50 μg/ml.
In other embodiments, said transfected and cultured cells may be cryogenically stored by methods known to those practiced in the art for later use in screening assays or for therapeutic purposes.
DESCRIPTION OF THE FIGURES
FIG. 1 shows the effect of growth factor and fibronectin stimulation of mouse myoblast migration and invasion in vitro. Panel a, mouse myoblast migration at 12 hours; panel b, mouse myoblast invasion at 24 hours.
FIG. 2 shows the migration and invasion of mouse myoblasts in response to MMP activators and inhibitors. Panels a and c, mouse myoblast migration assays with various stimulants as labeled; panels b and d, mouse myoblast invasion assays with various stimulants as labeled at. Migration and invasion were assayed at 12 and 24 hours, respectively.
FIG. 3 shows a gelatin zymogram for MMP expression by mouse myoblasts. Panel a, gelatin zymogram of culture medium samples following treatment of cells with various growth factors for 24 hours; panels b and c, quantification of the zymograms for MMP-2 and MMP-9, respectively.
FIG. 4 shows a gelatin zymography showing effects of fibronectin fragments on MMP-2 activation.
FIG. 5 shows MMP over-expression. Panel a, gelatin zymogram of myoblasts transiently transfected with expression vectors for human MMP-1, MMP-2, or MMP-9. Panels b, c and d show Northern blot analysis.
FIG. 6 shows the effects of overexpressed MMP-1, -2 and -9 on migration and invasion of mouse myoblasts. Panel a, effects on migration. Panel b, invasion of mouse myoblasts transfected MMP expression vectors. Bars represent mean±SEM from three individual experiments.
FIG. 7 shows the migration and invasion of human myoblasts in response to growth factors and fibronectin in vitro. Panel a, effects on migration (12 hours); panel b, effects on invasion (24 hours); panel c, effects of plasmin and N-acetyl cysteine (NAC) on migration induced by PDGF-BB; panel d, effects of plasmin and NAC on invasion induced by PDGF-BB. Bars represent mean±SEM of at least three separate experiments.
FIG. 8 shows a gelatin zymogram of human myoblasts treated with various stimulants. Similar conditions described for mouse myoblasts (FIG. 3) were used. Panel a, zymogram for control cells and cells transfected with MMP expression vectors; panel b, relative levels of MMP-2 compared to the DMEM control panel c, relative level of MMP-9 compared to the DMEM control. Activated forms of MMP-2 are shown by bracket with asterisk.
FIG. 9 shows histochemical analyses of transverse sections of SCID mouse muscles implanted with myoblasts carry β-galactosides expression vector (BAG).
FIG. 10 shows the effects of bFGF and fibronectin on myoblast incorporation in vivo.
FIG. 11 shows the effects of bFGF and fibronectin on myoblast-mediated β-GAL gene transfer in vivo. Panel a, myoblasts treated with DMEM alone (control); panel b, myoblasts treated with a combination of bFGF and fibronectin.
DEFINITIONS
To facilitate understanding of the invention, a number of terms are defined below.
As used herein, the term “purified” or “to purify” refers to the removal of contaminants from a sample. The present invention contemplates purified compositions (discussed above).
As used herein, the term “substantially purified” refers to the removal of a portion of the contaminants of a sample to the extent that the substance of interest is recognizable as the dominant species (in amount) by techniques known to those skilled in the art.
As used herein, the term “portion” when used in reference to a protein (as in “a portion of a given protein”) refers to fragments of that protein. The fragments may range in size from four amino acid residues to the entire amino acid sequence minus one amino acid.
As used herein the term “portion” when in reference to cells (as in “a portion of the cells”) refers to any amount less than the total number of cells available.
“Staining” shall be defined as any number of processes known to those in the field that are used to better visualize, distinguish or identify a specific component(s) and/or feature(s) of a cell or cells.
“Antibody” shall be defined as a glycoprotein produced by B cells that binds with high specificity to the agent (usually, but not always, a peptide), or a structurally similar agent, that generated its production. Antibodies may be produced by any of the known methodologies [Current Protocols in Immunology (1998) John Wiley and Sons, Inc., N.Y.] and may be either polyclonal or monoclonal.
“Antigen” shall be defined as a protein, glycoprotein, lipoprotein, lipid or other substance that is reactive with an antibody specific for a portion of the molecule.
“Immunofluorescence” is a staining technique used to identify, mark, label, visualize or make readily apparent by procedures known to those practiced in the art, where a ligand (usually an antibody) is bound to a receptor (usually an antigen) and such ligand, if an antibody, is conjugated to a fluorescent molecule, or the ligand is then bound by an antibody specific for the ligand, and said antibody is conjugated to a fluorescent molecule, where said fluorescent molecule can be visualized with the appropriate instrument (e.g. a fluorescent microscope). Said antigen may be the product of a transfected expression vector.
“Morphology” shall be defined as the visual appearance of a cell or organism when viewed with the eye, a light microscope, a confocal microscope or an electronmicroscope, as appropriate.
“Patient” shall be defined as a human or other animal, such as a guinea pig or mouse and the like, capable of donating and receiving myoblasts.
“Myoblast” shall be defined as an muscle cell that has not fused with other myoblasts to form a myofibril and has not fused with an existing myofibril.
“Metalloprotease (MMP)” shall be defined as a member of a group of proteases that are capable of degrading various extracellular matrix and connective tissue proteins (e.g. collagens and proteoglycans).
“Vector” shall be defined as a circular double-strand DNA molecule capable of having any genes therein encoded transcribed when put into the appropriate environment in vivo or in vitro.
“Expression” shall be defined as the transcription and translation of a gene. Such transcription and translation may be in vivo or in vitro.
“Constitutive” shall be defined as the level of expression of a genomic gene in vivo.
“Overexpression” shall be defined as expression at a level above the level normally expressed by an untransfected cell and is reflected by the combined expression level of a genomic gene along with a similar gene transfected into a cell.
“Transfect” shall be defined as the introduction of a vector into a cell by means such as, e.g., eletroporation of lipofectamine.
“In operable combination”, “in operable order” and “operably linked” as used herein refer to the linkage of nucleic acid sequences in such a manner that a nucleic acid molecule capable of directing the transcription of a given gene and/or the synthesis of a desired protein molecule is produced. The term also refers to the linkage of amino acid sequences in such a manner so that a functional protein is produced.
A “gene encoding a therapeutic gene product” is a gene that encodes a product having a therapeutic benefit. It is not intended that the present invention be limited to any particular therapeutic gene product. A variety of such genes and gene products are contemplated, including but not limited to, a gene encoding dystrophin. Dystrophin is therapeutic, for example, in dystrophin-deficient recipients. This, of course is not to say that the present invention only contemplates the dystrophin gene. For example, the gene may encode coagulation factors, (such as Factor IX), enzymes involved in specific metabolic defects, (such as urea cycle enzymes, especially ornithine transcarbamylase, argininosuccinate synthase, and carbamyl phosphate synthase); receptors, (e.g., LDL receptor); membrane transporters (e.g., glucose transporter); and a variety of cytoskeletal proteins. The gene may be of synthetic, cDNA or genomic origin, or a combination thereof. The gene may be one which occurs in nature, a non-naturally occurring gene which nonetheless encodes a naturally occurring polypeptide, or a gene which encodes a recognizable mutant of such a polypeptide. The present invention contemplates that such genes can be used with success with a variety of animals. Particular therapeutic success is achieved with humans.
GENERAL DESCRIPTION OF THE INVENTION
Research has demonstrated a central role for matrix metalloproteinases (MMPs) in cell migration and invasion, particularly during tumor metastasis (Stetler-Stevenson et al. “Extracellular matrix 6: Role of matrix metalloproteinases in tumor invasion and metastasis” FASEB J. 7:1434-1441, 1993). Human myoblasts have been shown to constitutively secrete MMP-2 (Guerin and Holland “Synthesis and secretion of matrix-degrading metalloproteinases by human skeletal muscle satellite cells” Devel. Dynamics 202:91-99, 1995), but currently there is only limited knowledge available on the basic biology underlying the fate of implanted myoblasts, the importance of MMPs and their relationship to physiological stimuli in myoblast migration and invasion in vitro and in vivo.
The present invention would utilize the endogenous physiological ability of cells to cross protein barriers. In this regard, the present invention pertains to novel compositions and methods for the enhancement of myoblast migration both in vitro and in vivo. The development of these compositions and methods allows for the screening and testing of compounds that are suspected of being agonistic or antagonistic for myoblast migration. Additionally, the present invention pertains to the delivery of therapeutic proteins by introduction into patients of myoblasts that were transfected with a vector encoding the therapeutic protein and then cultured by the methods of the present invention. Furthermore, the invention pertains to the treatment of degenerative muscle diseases.
A. Cytokines and Growth Factors in Myoblast Migration
Gene therapy is emerging as a powerful tool in the development of new treatments for hereto untreatable diseases. In this regard, the present invention relates to compositions and methodologies needed for the advancement of therapeutic intervention in muscular degenerative diseases. We previously reported that treatment of skeletal myoblasts with certain growth factors, particularly bFGF, substantially increases myoblast-mediated factor IX gene transfer in mice (Yao et al. “Primary myoblast-mediated gene transfer: persistent expressing of human factor IX in mice” Gene Therapy 1:99-107, 1994), and similar effects of bFGF were also described for myoblast cell therapy (Kinoshita et al. “Pretreatment of myoblast cultures with basic fibroblast growth factor increases the efficacy of their transplantation in MDX mice” Muscle Nerve 18:834-841, 1995). However, the ability of bFGF to be of any use in modulating the migration and transplantation of myoblasts has remained unclear. The present invention pertains to the use of various growth factors (e.g. bFGF and FN) in vitro and in vivo in regards to their ability to induce myoblast migration and invasion and greatly enhance myoblast transplantation.
The growth factors tested here are known to have significant effects on proliferation, differentiation or survival of myoblasts (Collins et al. “Growth factors as survival factors: regulation of apoptosis” Bioessays 16:133-138, 1994). Growth factors such as PDGF-BB and bFGF strongly stimulate myoblast proliferation and suppress differentiation, while others such as TGF-β suppress proliferation. Their effect on myoblast migration and invasion is much less well understood. It is possible that these growth factors may effect myoblast migration and invasion (FIG. 1) through enhancing cell proliferation and survival, as suggested in the literature. However, the major effects of growth factors on cell migration and invasion observed in the present studies can not be completely due to such activities because the duration of the in vitro assay is too short to produce significant effects on cell proliferation and/or differentiation.
B. Effect of Growth Factors in Murine Myoblast Migration
Among the growth factors tested with mouse myoblasts, bFGF reproducibly showed the strongest stimulatory effects on mouse myoblast migration and invasion in vitro (FIG. 1 ). This agrees with the importance of bFGF in migration in murine myoblasts, though no significant effects of bFGF were reported on rat myoblast migration (Bischoff “Chemotaxis of skeletal muscle satellite cells” Devel. Dynamics 208:505-515, 1997). This suggests possible species differences of bFGF effects on myoblasts. The different effects of bFGF and other growth factors observed with mouse and human cells in the present studies also agree with such species differences. These combined results demonstrate the unpredictable nature of the effect of these factors on the migration and invasion of myoblasts from different species prior to actual testing.
In addition to bFGF, fibronectin also has strong augmenting effects on both migration and invasion of mouse myoblasts. It is important to note that the combination of bFGF and fibronectin has an additive stimulatory effect on mouse myoblast migration and invasion (FIG. 1 ). This strong effect may be due to 1) an induction of greater MMP-2 expression compared with bFGF alone (bFGF also induces low level activation of MMP-2 and a moderate level MMP-9 expression), and 2) induction and activation of MMP-2 by fibronectin. Together, these results support the critical role of MMP-2 in these cell processes. This is further supported by the MMP-2 over-expression experiment, which showed that the elevated MMP-2 expression substantially increases the migration and invasion capacity of myoblasts, while N-acetyl cycteine (NAC) effectively suppressed the effects (FIG. 7 ). The importance of the activated form of MMP-2 for migration and invasion of mouse myoblasts is also supported by the substantial enhancement of bFGF effects by plasmin treatment, which proteolytically activates MMPs, (Reich et al. “Effects of inhibitors of plasminogen activator, serine proteinases and collagenase IV on the invasion of basement membrane by metastatic cells” Cancer Research 48:307-3312, 1988), and also by substantial suppression of positive bFGF effects by N-acetyl cysteine (NAC) (FIG. 2 ). MMP-2 can also be activated by MT-MMP, a cell-membrane bound MMP (Strongin et al. “Mechanism of cell surface activation of 72-kDa type IV collagenase” J. Biol. Chem. 270:5331-5338, 1995). Therefore, the effects of growth factors and fibronectin on MMP-2 may also be conferred via their effects on MT-MMP. Activated MMP-2 has also been implicated in tumor cell invasion and metastatic potential (Deryugina et al. “Tumor cell invasion through Matrigel® is regulated by activated matrix metalloproteinase-2” Anticancer Res. 17:3201-3210, 1997; Corcoran et al. “MMP-2: Expression, activation and inhibition” Enzyme Protein 49:7-19, 1996).
Although none of the reagents tested in the present studies had any noticeable effects on MMP-1 expression, transient over-expression of MMP-1 produced an increase, almost equivalent to that of MMP-2, in the migration and invasion of mouse myoblasts (FIG. 7 ). Such activities are also substantially suppressed by NAC. MMP-1 has been implicated in the invasion of other cells including tumor cells (Durko et al. “Suppression of basement membrane type IV collagen degradation and cell invasion in human melanoma cells expressing an antisense RNA for MMP-1” Biochimica et Biophysica Acta 1356:271-280, 1997). Interestingly, co-transfection of MMP-1 and MMP-2 is less effective than transfection with each MMP alone, suggesting that their mechanisms of action are moderately competitive in the nature, rather than neutral or synergistic.
The minimal role of MMP-9 in murine myoblast migration and invasion is demonstrated by the marginal effects of TNF-α, which can strongly induce MMP-9 expression and only negligibly increased MMP-2 expression (FIG. 4 ). This is supported by the lack of an effect of over-expression of MMP-9 on myoblast migration and invasion (FIG. 5 ). However, the possibility that MMP-9 may induce or suppress myoblast migration and/or invasion through cooperation with other as-yet unidentified factors or conditions remains to be tested. Since bFGF, which strongly stimulates both migration and invasion of mouse myoblasts, can also increase MMP-9 expression in addition to its effects on MMP-2, MMP-9 apparently does not function to override the positive effects of MMP-2 on migration and invasion.
Together, these data indicate that the increased expression and activation of MMP-2 or MMP-1, but not of MMP-9, play a critical role in migration and invasion of myoblasts. Although this is one of the important conclusions obtained in the present studies, it is important to note that the increased expression and activation of MMP-2 alone does not account for all of the results observed. Regardless of the absence or presence of plasmin, migration and invasion of the control myoblasts (treated only with BSA), which constitutively express a substantial level of MMP-2 (FIG. 3) (Guerin and Hollard “Synthesis and secretion of matrix-degrading metalloproteinases by human sketal muscle satellite cells” Devel. Dynamics 202:91-99, 1995), was minimal. regardless of the absence or presence of plasmin, migration and invasion of the control Furthermore, bFGF has only a moderate effect on the MMP-2 expression level, yet it has substantial effects on mouse myoblast migration and invasion. These results suggest that myoblast migration and invasion require some other, as yet unidentified factor(s) in addition to MMP-2 and MMP-1. This notion is consistent with the results obtained from the MMP over-expression experiments, where a low dose of fibronectin is needed to prime cell migration to amplify the effects of over-expressed MMPs (FIG. 6 ). Without this directional priming, MMP over-expression alone gives only a small increase in migration and invasion over the basal control levels. It is therefore necessary to point out that the combination of elements that we have deduced is novel and unexpected.
C. Effect of Growth Factors in Human Myoblast Migration
Human myoblasts responded to growth factor treatment differently from mouse myoblasts. Treatment of human myoblasts with any growth factors, including TNF-α and bFGF, had no appreciative effects on MMP-1, MMP-2 or MMP-9 expression. The high basal level of MMP-2 expression of human cells may make them less sensitive to additional treatment with these growth factors, which primarily function to increase MMP-2 expression. This is further supported by the observation that fibronectin induces significant activation of MMP-2, and increases its effects on migration of human myoblasts (FIG. 7 a ). Interestingly, the effect of fibronectin alone on human myoblast invasion is small, but together with bFGF, its effect is synergistic increasing to several fold higher than the BSA control level. These results indicate that the factors and conditions which affect migration and invasion of human myoblasts are somewhat different from those of mouse cells. Human myoblasts have a great potential for migration, presumably due to the high constitutive MMP-2 expression, though an appropriate priming stimulus by treatment with growth factors or fibronectin is still needed for cells to initiate migration (FIG. 7 a ). Invasion of human myoblasts across MATRIGEL® is less than mouse cells (FIG. 7 b ). The differences observed between mouse and human cells appear not to be dependent on the age of the individual from which cells were isolated, as myoblasts from individuals 44 and 8 years old behaved similarly (data not shown).
D. Effect of Growth Factors on Metalloprotease Expression
It is noteworthy that soluble fibronectin, but not the substrate-bound fibronectin, can substantially increase MMP-2 expression and induce proteolytic activation of MMP-2 in both mouse and human myoblasts. Fibronectin, however, does not significantly affect the expression levels of MMP-1 and MMP-9. Interestingly, fibronectin sub-fragments which contain critical binding sites for integrins, heparin and collagen, were unable either alone or in combination to elevate MMP-2 expression and activation in mouse myoblasts any significantly (FIG. 5 ). Similarly, these fibronectin sub-fragments were also unable to increase migration and invasion of mouse cells any significantly (data not shown). This is also consistent with the observation that the strong stimulatory effects of fibronectin in combination with bFGF or MMP over-expression is almost completely abolished by addition of plasmin, presumably due to fragmentation of fibronectin. This suggests that the fibronectin signal transduction pathway leading to the elevated MMP-2 expression and activation may require the small amino terminal distal portion of the molecule, which is the only part of fibronectin absent in these fragments. Alternatively, the structures responsible for MMP-2 activation may be required to be on the same molecule, but not supplied in trans by separate molecules. Yet another possibility is that the selection of fragments that we used were not of the proper length nor of the proper segment to activate MMP-2 expression.
Fibronectin regulation of migration, invasion and MMP expression has been demonstrated for other cell types (Akiyama et al. “Fibronectin and integrins in invasion and metastasis” Cancer Met Rev 14:173-189, 1995). Werb et al. (“Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression” J. Cell Biol 109:877-889, 1989) reported that plating of rabbit synovial fibroblasts on fragments of fibronectin which interact with the α5β1 integrin, induce collagenase (MMP-1) expression, while fragments which interact with (α4β1 integrin suppresses MMP-1 expression. Intact fibronectin, which contains both domains, had no significant effect on MMP-1 expression (Werb et al. “Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression” J. Cell Biol 109:877-889, 1989; Huhtala et al. “Cooperative signaling by α5β and α5β1 integrins regulates metalloproteinase gene expression in fibroblasts adhering to fibronectin” J Cell Biol 129:867-879, 1995). Since proliferating myoblasts express α5β1 (Gullberg et al. “Analysis of fibronectin and vitronectin receptors on human fetal skeletal muscle cells upon differentiation” Exper Cell Res 220:112-123, 1995), but not α4β1 integrin (Rosen et al. “Roles for the integrin VLA-4 and its counter receptor VCAM-1 in myogenesis” Cell 69:1107-1119, 1992), fibronectin would have inductive, but not suppressive effects on MMP-1. The lack of an increase in MMP-1 expression in response to fibronectin observed in the present studies may suggest the existence of cell type-specific and/or species-specific differences between fibroblasts and myoblasts in integrin-mediated regulation of MMP expression.
E. In vivo Implantation of Murine Myoblasts
When implanted intramuscularly (I.M.) in mice, myoblasts can fuse with the host myofiber cells (FIG. 9 a ), as has been described (Yao and Kurachi “Expression of human factor IX in mice with myoblasts but also survive as muscle precursor cells” Proc Natl Acad Sci USA 89:3357-3361, 1992; Yao and Kurachi “Implanted myoblasts not only fuse with myoblasts but also survive as muscle precursor cells” J Cell Sci 105:957-963, 1993; Yao et al. “Primary myoblast-mediated gene transfer: persistent expression of human factor IX in mice” Gene Therapy 1:99-107, 1994; Rando et al. “The fate of myoblasts following transplantation into mature muscle” Exper Cell Res 220:383-389, 1995; Wang et al. “Persistent systemic production of human factor IX in mice by skeletal myoblast-mediated gene transfer: feasibility of repeat application to obtain therapeutic levels” Blood 90:1075-1082, 1997). However, the efficiency of incorporation is poor and only a small fraction of the implanted cells actually participate in transgene expression as mentioned above (Gussoni et al. “The fate of individual myoblasts after transplantation into muscles of DMD patients” Nature Medicine 3:970-977, 1997; Wang et al. “Persistent systemic production of human factor IX in mice by skeletal myoblast-mediated gene transfer: feasibility of repeat application to obtain therapeutic levels” Blood 90:1075-1082, 1997). A substantial fraction of implanted myoblasts actually remain trapped within the connective tissues, and unable to cross basal lamina to fuse with myofibers. These myoblasts form new myotubes in the connective tissue (FIG. 9 b,c ). Whether or not these newly formed myotubes within the connective tissues can eventually mature, become innervated and form an integral part of muscle tissue is not known, and must be determined. However, by pre-treating cells with bFGF, fibronectin or with both, before implantation, a substantial increase in incorporation of the implanted myoblasts into the existing host myofiber cells can be achieved (FIG. 10 ). This is observed in tissue sections prepared from the muscle tissue injected either with the myoblasts treated with medium (control) or pre-treated with bFGF and fibronectin (FIGS. 11 a and b, respectively). The former tissue contains a large number of newly formed myotubes (β-GAL positive) present within the connective tissues, while the latter contains a large number of β-GAL positive myofiber cells with fewer β-GAL positive myotubes trapped in the connective tissues.
F. Myoblast Mediated Gene Therapy
Together, these findings strongly suggest that a refined myoblast implantation procedure should be utilized to develop efficient and practical myoblast cell therapy and myoblast-mediated gene transfer. It is also noteworthy that characteristics of myoblast migration and invasion observed in response to bFGF, PDGF, HGF, fibronectin and MMP-2 are consistent with those described for migration of myogenic precursor cells during development (Daston et al. “Pax-3 is necessary for migration, not differentiation, of limb muscle precursors in the mouse” Development 122:1017-1027, 1996; Bladt et al. “Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud” Nature 376:768-771, 1995; Venkatsubramanian and Solursh “Chemotactic behavior of myoblasts” Devel Biol 104:406-407, 1984; Krenn et al. “Hyaluronic acid influences the migration of myoblasts within the avian embryo wing bud” Am J Anat 192:400-406, 1991; Brand-Saberi et al. “Differences in fibronectin-dependence of migrating cell populations” J Embyol 187:17-26, 1993; Chin and Werb “Matrix metalloproteinases regulate morphogenesis, migration and remodeling of epithelium, tongue skeletal muscle and cartilage in the mandibular arch” Development 124:1519-1530, 1997). This suggests that at least some of the mechanisms regulating myoblast migration may be conserved across developmental stages and into the adult animal, although, as seen in the present work, species differences will require the empirical determination of the combination necessary for any particular species.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
Generally, the nomenclature used hereafter and the laboratory procedures in cell culture, molecular genetics and nucleic acid chemistry and hybridization described below are those well known and commonly employed in the art. Standard techniques are used for recombinant nucleic acid methods, polynucleotide synthesis and microbial culture and transformation (e.g. electroporation and lipofection). Generally enzymatic reactions and purification steps are performed according to the manufacturer's specifications. The techniques and procedures are generally performed according to conventional methods in the art and various general references (see, generally, Sambrook et al. Molecular Cloning: A Laboratory Manual, 2d ed. (1989) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., and Current Protocols in Molecular Biology (1996) John Wiley and Sons, Inc., N.Y.).
The present invention contemplates assays for detecting the ability of agents to inhibit or enhance myoblast migration and invasion where high-throughput screening formats are employed together with large agent banks (e.g. compound libraries, peptide libraries and the like) to identify antagonists or agonists. Such myoblast migration and invasion antagonists and agonists may be further developed as potential therapeutics and diagnostic or prognostic tools for diverse types of acquired and hereditary degenerative muscle diseases.
1. Screens to Identify Agonists and Antagonists of Myoblast Migration and Invasion
A. In vitro Assays
There are several different approaches contemplated by the present invention to screen for small molecules that specifically inhibit or enhance the ability of myoblasts to migrate and invade tissue. One approach is to culture the myoblasts in the presence of the compound using standard culture procedures, and then assay for the mobility and invasiveness using assays known to those practiced in the art. The present invention would serve as a positive control and untreated or bovine serum albumin (BSA) treated cultures would serve as a negative control. Another approach would be to detect the expression of proteases suspected to be instrumental for the migration and invasion of myoblasts. After culturing as described above, MMP expression would be detected by zymogen assay, known to those practiced in the art. Furthermore, MMP expression could be detected by Northern or Western blotting. Further still, increased expression of other proteins or molecules induced by the culture conditions could also be determined.
Transfection assays allow for a great deal of flexibility in assay development. The wide range of commercially available transfection vectors will permit the expression of the MMPs. In one embodiment, cells are transiently transfected with an expression construct comprising nucleic acid encoding MMP-1 or MMP-2 that may include (in operable combination) an inducible promotor allowing for the expression of a metalloprotease to levels higher than in the untransfected cells. Increased expression of these metalloproteases may enhance migration and invasion of myoblasts in combination with the compounds to be screened. Cells can be exposed to the agent suspected of modulating myoblast migration and invasion, MMP expression would be turned on, if necessary, and migration and invasion can be measured by techniques known to those practiced in the art. The compositions of the present invention would be used as positive controls. Rates of migration and invasion of cells exposed to the compounds to be screened are compared to rates of migration and invasion of the cells exposed to the compounds of the invention. Transfection with a control expression vector (e.g. an empty expression vector) would serve to compare the effect of MMP over expression on migration and invasion. Rates of migration and invasion can be quantitated by any of a number of ways reported in the literature and known to those practiced in the art.
In another embodiment, stably transfected cell lines expressing MMP-1 or MMP-2 are produced as stocks for further assays. The use of an inducible promoter may be utilized in these systems. Screening assays for compounds suspected of modulating myoblast migration and invasion would be conducted in the same manner as with the transient transfection assays. Using stably transfected cell lines would allow for greater consistency between experiments and allow for inter-experimental comparisons.
B. In vivo Assays
In one embodiment cells will be transfected with a vector that expresses a protein suitable for use as a marker of migration and invasion (e.g. GFP, luciferase or β-gal). The cells will then be cultured with either 1) the compound suspected of being agonistic or antagonistic for myoblast migration and invasion, 2) a negative control or 3) positive control comprising the present invention. After culturing, at least a portion of the cells from each condition will be introduced into patients or laboratory animals. Myoblasts may be reintroduced into the patients, if necessary. After a suitable length of time muscle biopsies will be taken and assayed for migration and invasion by detecting cells that express the marker protein.
In another embodiment, compounds suspected of modulating myoblast migration and invasion may be given directly to the patient. Administration may be oral, intravenous, intraperitoneal, intramuscular or by other means as appropriate for the compound being administered. The suspected compound may be administered prior to, during or after introduction of the myoblasts into the patient. The myoblasts may be cultured with or without the compound suspected of modulating myoblast migration and invasion. The myoblasts will then be introduced into the patient. The suspected compound, as well as the cultured myoblasts, may be reintroduced into the patient, if necessary. Migration of the myoblasts will then be assayed as described herein above.
2. Methods of Treatment of Degenerative Muscle Diseases
The present invention demonstrates that cultured myoblasts can be induced to migrate and invade muscle tissue. Once there, the introduced myoblasts fuse to existing myofibrils. This technology may be used in the treatment of degenerative muscle diseases. In one embodiment, myoblasts are obtained from an immunocompatible donor or from the patient. The myoblasts are cultured with bFGF and FN, as described herein. Thereafter, at least a portion of the myoblasts are introduced into the patient. Reintroduction of myoblasts is also contemplated in this invention. In another embodiment, myoblasts would be transfected with a marker protein (e.g. GFP, luciferase or β-gal), prior to culturing with bFGF and FN, to permit the monitoring of the migration and invasion of the myoblasts. In yet another embodiment the myoblasts would be transfected with MMP-1 or MMP-2, prior to culturing with bFGF and FN, to permit enhanced migration and invasion.
3. Methods Related to Gene Therapy
The present invention demonstrates that cultured myoblasts can be induced to express peptides from transfected expression constructs. Additionally, the present invention demonstrates that cultured myoblasts can be induced to migrate and invade muscle tissue. This technology may be used in the delivery of therapeutic gene products thereby allowing for an effective method of gene therapy. In one embodiment, the myoblasts are obtained from an immunocompatable donor or from the patient. The myoblasts are transfected with the construct able to express the protein of interest. The myoblasts are then cultured with bFGF and FN, as described herein. Thereafter, at least a portion of the myoblasts would be introduced into the patient. In another embodiment myoblasts would be transfected with a marker protein (e.g. GFP, luciferase or β-gal), prior to culturing with bFGF and FN, to permit the monitoring of the migration and invasion of the myoblasts. In yet another embodiment the myoblasts would be transfected with MMP-1 or MMP-2, prior to culturing with bFGF and FN, to permit.enhanced migration and invasion. The latter embodiment, therefore, comprises myoblasts transfected with a first vector encoding a therapeutic gene product and a second vector encoding a metalloprotease gene.
Experimental
The following examples are intended to illustrate, but not limit, the present invention.
Materials and Methods
Cell Culture
Mouse myoblasts were previously isolated from hind limb muscles of 4-6 week old severe combined immunodeficient (SCID) mice and clonally purified from contaminating fibroblasts (Yao et al. “Primary myoblast-mediated gene: transfer: persistent expression of human factor IX in mice” Gene Therapy 1:99-107, 1994). Myoblasts (approximately 1×10 6 cells) were plated on 6 cm tissue culture plates coated with 0.5% gelatin (Sigma, St. Louis, Mo.) and grown in growth medium consisting of Dulbecco's Modified Eagle Medium (DMEM) (Gibco BRL, Gaithersburg Md.) supplemented with 20% fetal bovine serum (FBS; Gibco) and 0.5% chick embryo extract (CEE; Gibco). All animal studies were carried out following the institutional guidelines for ethical animal use. Human myoblasts were isolated using trypsin digestion from abdominal wall or chest wall muscle biopsies, and surgery. Written consent was obtained from all patients prior to biopsy isolation as approved by the University Hospital's Institutional Regulation Board on the use of human subjects. Cells were preplated on uncoated plates for 1 hour to separate muscle fibroblasts. Approximately 95% of the cells were desmin-positive following immunohistochemical staining of representative culture samples, and were capable of differentiation into myotubes, indicating high purity of the myoblast preparation. All experiments were done with myoblasts of passage 7 or lower.
In Vitro Migration and Invasion Assays
Myoblast migration and invasion were examined using a commercially available in vitro cell migration and invasion assay kit (Biocoat, Becton Dickinson, Franklin Lakes, N.J.) as described by Albini et al. (A rapid in vitro assay for quantitating the invasive potential of tumor cells Cancer Res 47:3239-3245, 1987). Myoblasts were grown to approximately 70% confluence, rinsed three times in serum-free DMEM, followed by incubation for 3 hours in 0.2% bovine serum albumin (BSA) in DMEM to eliminate the effects of serum. Cells were then trypsinized and collected by centrifugation. Cells were resuspended in serum-free DMEM at a density of 1×10 5 cells/ml, and 0.5 ml aliquots of cell suspension were added to the top chamber. The following stimuli, which were obtained from R&D (Minneapolis, Minn.) unless otherwise noted, were used: bovine basic fibroblast growth factor (bFGF), recombinant human tumor necrosis factor-α (TNF-α) (Sigma), purified human transforming growth factor-β1 (TGF-β1), recombinant human platelet-derived growth factor-BB (PDGF-BB), recombinant human insulin-like growth factor-I (IGF-I), recombinant hepatocyte growth factor (HGF); and human serum fibronectin (Sigma). Fibronectin subfragments of 45 KDa (Sigma), 120 kDa (Gibco), 63 kDa (Retronectin, Takara) and 70 KDa (Sigma) were used alone or in combination. The growth factor concentrations used were those which could produce maximal effects as examined in the present studies by extending from values reported by Bischoff (“Chemotaxis of skeletal muscle satellite cells” Devel. Dynamics 208:505-515, 1997). For migration studies, the upper chamber membrane was coated with 0.1% gelatin and cells were allowed to migrate for 8-12 hours, while for invasion studies, the upper membrane was coated with 5 μl of MATRIGEL® diluted to 5 mg/ml in sterile phosphate buffered saline (PBS) and cells were allowed to invade for 24 hours. The top side of the insert membrane was scrubbed free of cells using a cotton swab and the bottom side was stained using the Leukostat-I system (Fisher Diagnostics, Pittsburgh, Pa.). The number of cells per field was counted in 10 randomly selected fields and averaged for each condition.
To evaluate the effects of inactivation or activation of MMPs, aliquots (0.05 units in 50 μl PBS) of purified human plasmin (Sigma) or 50 mM N-acetyl cysteine (NAC; Sigma) were added with the cells to the top chamber of the migration assay and growth factor was added to the bottom. Plasmin is known to activate MMPs, (Reich et al. “Effects of inhibitors of plasminogen activator, serine proteinases and collagenase IV on the invasion of basement membranes by metastatic cells” Somatic Cell Mol. Genetics 18:247-258, 1988) while NAC is a general inhibitor for gelatinase, such as MMP-2 (gelatinase A) and MMP-9 (gelatinase B), and less strongly inhibits collagenases such as MMP-1 (Albini et al. “Inhibition of invasion, gelatinase activity, tumor take and metastasis of malignant cells by N-acetylcysteine” Int. J. Cancer 61:121-129, 1995).
Gelatin Zymography
Gelatin zymography for assaying MMPs was carried out as previously described (Guerin and Holland “Synthesis and secretion of matrix-degrading metalloproteinases by human skeletal muscle satellite cells” Devel. Dynamics 202:91-99, 1995) with minor modifications. Briefly, myoblasts were grown in 6 cm tissue culture plates to approximately 70% confluence, then rinsed three times with serum-free DMEM and incubated for 3 hours in DMEM containing 0.2% BSA to eliminate the effects of serum. Growth factors were added and cells were incubated for 24 hours. Culture medium was then collected, centrifuged to pellet detached cells, and concentrated ten- to twenty-fold using the Centricon-10 (Amicon, Beverly, Mass.) system. The protein concentration of the supernatants was determined using the Bio-Rad protein microassay system with BSA used as the standard. Samples were stored at −70° C. until use. For gelatin zymography, aliquots (10 μg as the total protein per sample) were electrophoresed at constant voltage on a 10% polyacrylamide gel containing 2 mg/ml gelatin. The gel was rinsed three times for 15 min in 2.5% Triton-X 100 to remove SDS and renature the proteins, then incubated in MMP activation buffer (0.05 M Tris-HCl, pH 7.5 with 5 mM CaCl 2 ) for 24 hours at 37° C. with constant shaking. Gels were stained overnight in 0.5% Coomassie blue R-250, and destained for 1 hour in 40% methanol:10% acetic acid. Proteinase activity was quantified by densitometric scanning of bands using a Bio-Rad Gel Doc 1000 video camera imaging system (Bio Rad, Hercules, Calif.).
Construction of MMP Expression Vectors
Expression vectors containing human MMP genes were generated with the plasmid pNGVL3, which contains the cytomegalovirus (CMV) immediate-early enhancer, 5 ′ untranslated region and intron, the rabbit β-globin poly(A) signal sequence and a kanamycin resistance marker. This plasmid vector was obtained from the Vector Center of the University of Michigan. The MMP-9 coding cDNA insert was excised from the vector PBS-92 with Xba I, and ligated into pNGVL3 at the Xba I site with T4 DNA ligase (Boehringer Mannheim, Indianapolis, Ind.), generating pNGVL3/MMP-9 . Competent bacteria (Top 10; Invitrogen, La Jolla, Calif.) were transformed and kanamycin-resistant colonies were selected.
PNGVL3/MMP-2 was prepared by removing the MMP-2 cDNA from the PBS-GEL plasmid vector by Not I/Eco RI digestion and ligating into pNGVL3 at the Not I/Eco RI sites. Expression vector pNGVL3/MMP-1 was prepared by inserting the MMP-1 cDNA isolated from pcD-X into pNGVL3 at the Sal I site. PBS-92 and PBS-GEL were kindly provided by Dr. Gregory Goldberg of Washington University School of Medicine, while pcD-X was obtained from ATCC. All constructs were examined by restriction mapping to confirm the correct structures and orientations.
Transient Transfection, Zymography and Migration/Invasion Assays
Transient over-expression of individual MMPs was carried out as follows. Myoblasts grown in growth medium to approximately 50% confluence in 6 well plates were transfected overnight by adding growth medium containing 1 μg expression vector DNA and 3 μl FUGENE 6® reagent according to the manufacturer's instructions (Boehringer Mannheim, Indianapolis, Ind.). Under similar conditions using pCH110 vector DNA (β-galactosidase expression plasmid), approximately 20-25% of mouse myoblasts could consistently be transfected. For co-transfection with MMP-1 and MMP-2 vectors, a total of 2 μg of vector DNAs composed of 1 μg of each expression vectors, were mixed with 6 μl of FUGENE6® for transfection. The following morning (12-14 hrs incubation), the transfection mixture was removed and the cells harvested for cell migration/invasion assays as described above except 10 μg/ml of fibronectin (10% of the regular concentration) was added to the bottom chamber to prime cell migration and invasion. The effects of NAC and plasmin on the transfected cells were assayed as described above. Zymography analysis of the culture medium of transfected cells was carried out as described above.
Northern Blot Analysis
Northern blot analysis of transiently transfected cells was carried out according to the standard method. Briefly, myoblasts were grown in 10-cm culture dishes to approximately 50% confluence, and were transfected with a mixture of 33 μl Fugene 6® (Boehringer Mannheim) and 11 μg MMP expression vector DNA according to the manufacture's instructions. After 36 hours, cells were harvested and total cellular RNA was isolated using the TRIzol total RNA isolation kit (GIBCO-BRL). Agarose gel electrophoresis was then carried out using 20 μg of the RNA preparation for each lane and the cDNA fragment for each MMP labeled with 32 P to 1×10 9 cpm/μg as specific probes for each MMPs. Filters were separately hybridized with each probe, washed and exposed to an X-ray film (Kodak, Rochester, N.Y.). Filters were rehybridized with an internal control probe, 32 P-labeled RNR18 (18S ribosomal RNA cDNA) to confirm equal RNA loading to the lanes.
Myoblast Implantation In Vivo
All animal studies were carried out following the institutional guideline for animal use. For in vivo studies, SCID mouse myoblasts transduced with a BAG retrovirus containing the beta-galactosidase (β-GAL) reporter gene and selected as previously described (Yao and Kurachi “Implanted myoblasts not only fuse with myofibers but also survive as muscle precursor cells” J. Cell Sci 105:957-963, 1993), were grown in growth medium on 15 cm plates. When cells reached 70% confluence they were harvested by trypsinization using standard methods, rinsed twice in phosphate buffered saline (PBS), and resuspended in DMEM containing either bFGF (1 μg/ml), fibronectin (50 μg/ml) or both, at a concentration of 2×10 7 cells/ml. Mice at 2.5 months of age were anesthetized with Metofane (Mallinckrodt Veterinary, Mundelein, Ill.) and the skin overlying the vastus musculature of the lower leg was exposed under aseptic conditions. Aliquots of cells (1×10 6 in 50 μl total solution) were injected into the midbelly of the vastus (thigh) musculature; the muscle was held closed with forceps for several seconds to avoid leakage of cell solution out of the muscle, and the skin was closed using surgical staples. Three weeks after cell implantation, animals were sacrificed and the vastus musculature was surgically removed, frozen in isopentane cooled in liquid nitrogen, and stored at − 70 ° C. until use. Transverse muscle sections (10 μm) were cut through the midbelly of the muscle group by the Morphology Core facility of this Medical School.
Muscle sections were stained for β-GAL activity using the standard histochemical staining procedure (Rando et al. “The fate of myoblasts following transplant into mature muscle” Exper. Cell Res. 220:383-389, 1995). Briefly, sections were fixed for 10 minutes in 2% formaldehyde in PBS then rinsed three times with PBS. Sections were incubated in X-GAL reaction medium (1 mg/ml 5 bromo-4 chloro-3 indolyl β D-galactopyrano-side, 5 mM K 3 Fe(CN) 6 , 5 mM K 4 Fe(CN) 6 , 2 mM MgCl 2 in PBS) for 18 h at 32° C. The total number of β-GAL-positive fibers (stained blue) per section was counted for 5 different sections spanning the entire injection site for each animal and averaged. For some animals, double staining of sections for the β-GAL activity and laminin immunohistochemistry was done to determine the localization of the β-GAL positive cells relative to the connective tissue. Sections were first immunohistochemically stained for laminin using polyclonal anti-laminin antibodies (Sigma) diluted 1:40 in PBS. Immunostaining was visualized using a horseradish peroxidase (HRP) enzyme immunostaining kit (Histostain; Zymed laboratories, San Francisco, Calif.). Sections were then fixed in formaldehyde and stained for β-GAL as described above.
EXAMPLE I
Mouse Myoblast Migration and Invasion in vitro
All of the growth factors (bFGF, TNF-α, PDGF-BB, TGF-β1, IGF-I, HGF) and fibronectin tested in vitro stimulated migration of mouse myoblasts to various degrees. Results are shown in FIG. 1 . Myoblasts (5×10 4 cells/well) were stimulated with various growth factors and fibronectin, and their ability to migrate or invade through a MATRIGEL® barrier (panel a, mouse myoblast migration at 12 hours; panel b, mouse myoblast invasion at 24 hours). Stimulants were used at the following final concentrations: 100 ng/ml TNF-α; 25 ng/ml bFGF at; 50 μg/ml human serum fibrone ctin (Fn); 20 ng/ml PDGF-BB; 2 ng/ml TGF-β1; 100 ng/ml IGF-I; 10 ng/ml HGF. Bars represent mean±SEM from a minimum of 3 separate experiments. The largest individual effects were seen in response to fibronectin and bFGF stimulation (14 and 12-fold over the DMEM control, respectively), while HGF and TGF-β1 had smaller, but significant effects (8 and 5-fold, respectively). The combination of bFGF and fibronectin produced an additive effect, stimulating migration >27-fold over the DMEM control. Unexpectedly, none of the fibronectin subfragments, which contain all known binding sites for cells, heparin, and collagen, showed effects on invasion and migration either alone or in combination (data not shown).
Further studies were done to elucidate the role of MMPs in cytokine-mediated mouse myoblast migration. Myoblast migration was assayed as described for FIG. 1 except 0.05 units/ml of purified human plasmin or final 50 mM NAC was added to the top chamber with the cells at the start of the assay (FIG. 2, panels a and c (at 12 hours), mouse myoblast migration assays with various stimulants as labeled; panels b and d (at 24 hours), mouse myoblast invasion assays with various stimulants as labeled). Bars represent mean±SEM from 4 separate experiments. Treatment of cells with both bFGF and plasmin, which is a proteolytic activator of MMPs (Reich et al. “Effects of inhibitors of plasminogen activator, serine proteinases and collagenase IV on the invasion of basement membranes by metastatic cells” Cancer Research 48:3307-3312, 1988), increased the migrational response to bFGF by nearly twofold. Unexpectedly, treatment with plasmin alone had a slightly negative effect on myoblast migration compared to the control (FIG. 2 a ). N-acetyl-cysteine (NAC), an inhibitor of gelatinases such as MMP-2 and MMP-9 (Albini et al. “Inhibition of invasion, gelatinase activity, tumor take and metastasis of malignant cells by N-acetylcysteine” Int. J. Cancer 61:121-129, 1995), efficiently reduced the effect of bFGF on mouse myoblast migration to a level similar to the BSA control. Moreover, addition of NAC resulted in a dramatic reduction of the effect seen by a combination of bFGF and plasmin, suggesting that the stimulatory effect of plasmin is likely attributable to proteolytic activation of gelatinases, and is not due to a direct effect of plasmin on cell migration (FIG. 2 a ). As expected, NAC attenuated the effects of treatment with bFGF and fibronectin in combination (FIG. 2 c ). Plasmin also attenuated the effect of this combination, presumably because of proteolytic fragmentation of fibronectin by plasmin. These results demonstrated the important role of a gelatinase(s) and its activation in the effects conferred by bFGF, fibronectin or their combination on migration of mouse myoblasts.
The same set of growth factors also stimulated MATRIGEL® invasion to various degrees (FIG. 1 b ). Basic FGF again had the largest effect on mouse myoblast invasion across a MATRIGEL® barrier, increasing it by approximately 7-fold over the control, while fibronectin gave a 4-fold increase. The combination of bFGF and fibronectin gave >8-fold higher invasion activity over the BSA control. As observed for migration, plasmin further increased the effects of bFGF, and NAC treatment drastically reduced such stimulatory effects to the control levels, supporting the important role of a gelatinase(s) and its activation on myoblast invasion (FIG. 2 b ). Addition of plasmin, however, lowered the greatly enhanced effects obtained by a combination of bFGF and fibronectin together (FIG. 2 d ), agreeing with its effect observed on migration.
EXAMPLE II
Zymography Analysis of Mouse Myoblasts
The effects of growth factors and fibronectin on MMP expression by mouse myoblasts are shown in FIG. 3 a. Mouse myoblasts grown in serum-free medium constitutively expressed MMP-2 (zymogen form, 72kDa), which still appears as a zymogram band due to its inherent gelatinase activity (Reich et al. “Effects of inhibitors of plasminogen activator, serine proteinases and collagenase IV on the invasion of basement membranes by metastatic cells” Cancer Research 48:3307-3312, 1998) (FIG. 3 ). Proteolytic degradation of gelatin due to MMPs appears as clear bands against the dark background. Bands marked with an asterisk (64 and 62 kDa) indicate the activated forms of MMP-2. The lane for fibronectin treatment was run simultaneously on a separate gel, and the scanned picture is placed in the order for comparison. Treatment of mouse myoblasts with bFGF, PDGF-BB, TGF-β and IGF-I had modest but consistent effects on total MMP-2 expression, increasing its expression by 49%, 35%, 36%, and 69%, respectively (FIG. 3 b ), while TNF-α and bFGF also greatly increased MMP-9 expression (110 kDa band) to approximately 30- and 10-fold over the DMEM control level, respectively (FIG. 3 c ). Values are arbitrary densitometric units, which are normalized to DMEM control for each experiment and shown as values±SEM representing a minimum of 3 experiments per condition. The subfragment of 120 kDa showed some MMP-2 activation, but only at a very low, insignificant level (not apparent in this Figure). Using gelatin zymography, MMP-1 expression (57 kDa) was not detected with or without growth factor treatment, although this does not exclude the possibility of its low level induction, which may have been below the limit of detection of the gelatin zymography system.
Treatment of mouse myoblasts with soluble plasma fibronectin resulted not only in increased MMP-2 expression by approximately 2-fold, but also its substantial proteolytic conversion to the activated and intermediate forms migrating as a doublet at 64 and 62 kDa, respectively (FIG. 3 a ). This effect was specific for soluble fibronectin, because cells grown on a fibronectin-coated substrate showed only constitutive expression of MMP-2 without any apparent proteolytic activation (DMEM control) (FIG. 3 ).
Most fibronectin subfragments of various sizes, essentially covering almost all domains of the molecule (the amino terminal small region not included in the test samples), neither increase MMP-2 expression nor its activation when used either separately or in combination. Mouse myoblasts were treated for 24 hours with either DMEM alone, fibronectin (50 μg/ml), or individual fragments (37.5 μg/ml) of 45, 120, 63 (Retronectin), 75 kDa and their combinations, 45 kDa/120 kDa and 120 kDa/63 kDa. These results suggest that either the responsible regions of the fibronectin molecule are not contained within these fragments, or that physical linkage of some or all of these fragments may be needed for conferring optimal induction of MMP-2 activation. This data is shown in FIG. 4 . MMP-1, MMP-2 and MMP-9 positions are shown on the right side. Bracket with asterisk indicates the 64 and 62 kDa activated forms of MMP-2, which are very prominent for the fibronectin-treated lane and at very low levels in lanes with 120 kDa fragment (even hard to see in the picture). Subfragment of 120 kDa, known to contain cell adhesion modules, showed MMP-2 activation activity, but at an extremely low level (not obvious in FIG. 4 ). Apparent sizes of MMPs observed in the present study agree with those previously reported by others (Aimes et al. “Cloning of a 72 kDa matrix metalloproteinase (gelatinase) from chicken embryo fibroblasts using gene family PCR: expression of the gelatinase increases upon malignant transformation” Biochem. J. 300:729-736, 1994; Masure et al. “Mouse gelatinase B: cDNA cloning, regulation of expression and glycosylation in WEHI-3 macrophages and gene organization” Eur. J. Biochem. 218:129-141, 1997; Chen et al. “Isolation and characterization of a 70-kDa metalloproteinase (gelatinase) that is elevated in Rous Sarcoma virus-transformed chicken embryo fibroblasts” J. Biol. Chem. 266:5113-5121, 1991).
EXAMPLE III
MMP Over-expression and Mouse Myoblast Migration and Invasion
Transient over-expression of MMP-1, MMP-2, and MMP-9 was tested in myoblasts to determine whether expression of individual MMPs was sufficient to produce increased migration and/or invasion. Transient transfection rather than stable transduction was used, because secretion of over-expressed MMPs by transfected cells (approximately 20-25% of the cells) should be sufficient to allow most, if not all, cells access to increased levels of secreted MMPs and avoid prolonged exposure of cells to over-expressed MMPs. Successful transfection of MMP-1, MMP-2 and MMP-9 were confirmed by gelatin zymography, showing dramatically increased intensity of bands of approximately 57, 72 and 92 kDa (human MMP-9 is smaller than the mouse counterpart), respectively (FIG. 5 a ), and by Northern blot analyses (FIG. 5 b, c, and d ) of the transfected cells. The high molecular weight bands within the bracketed region marked with + presumably represent complexes of the over-expressed MMP with metalloproteinase inhibitors. Gelatin zymography of the culture medium of cells transfected with the MMP-1 vector showed a substantial induction of MMP-1 expression from non-detectable levels in control (FIG. 5 a ). Though gelatin zymography is not optimal for demonstrating MMP-1 activity, the presence of elevated MMP-1 levels is clearly seen as a doublet (zymogen and activated form) migrating near 55-57 kDA. Expression levels of MMP-2 and MMP-9 in transfected cells, as assayed by zymography, were increased by >3.5- and 10-fold, respectively, over cells transfected with the control vector, pNGVL3 (FIG. 5 a ).
Overexpression of each MMP did not significantly affect the expression levels of the other two MMPs. Northern blot analysis further confirmed the elevation in mRNA levels for each MMPs (FIG. 5 b, c and d ). Lanes 1, 2 and 3 are for cells transfected with DMEM (control), pNGVL3 with no MMP inserts and pNGVL3 with MMP inserts, respectively, as indicated. Panels b, c and d are for MMP-1, MMP-2 and MMP-9, respectively. Positions for 28S and 18S RNAs are shown on the left, and those of MMP mRNA bands are shown on the right by arrows. MMP-9 has two mRNA bands. Because of the high level expression of MMPs for lanes 3, intrinsic MMP mRNA bands in lane 1 and 2 are not yet visible at this film exposure time. The presence of equal amount of total RNA in each lane is shown in the lower panels for the internal control RNA, RNR18 (18S ribosomal RNA cDNA).
Transfection of mouse myoblasts with MMP-1 or MMP-2 increased the migration of mouse myoblasts by 2.6- and 1.6-fold, respectively, over myoblasts transfected by the control plasmid vector (FIG. 6 a ), and invasion capability by 2-fold for both MMP-1 and MMP-2 (FIG. 6 b ). Transfection with MMP-9 had only marginal effects on both migration (FIG. 6 a ) or invasion (FIG. 6 b ) of mouse myoblasts. In FIG. 6 a, cells transfected with each expression vector were examined for their migration capability by assaying for 2 hours in the presence of BSA or a low level fibronectin (FN) (10 μg/ml) to prime cell migration. In FIG. 6 b the conditions used are similar to those for migration, except invasion was allowed to proceed for 6 hours.
NAC treatment decreased the migration capability of both MMP-1 and MMP-2 over-expressing myoblasts to 35% and 22% (n=4) of that of non-NAC treated cells, respectively. NAC also decreased the invasion of myoblasts over-expressing MMP-1 and MMP-2 to 40% and 28% (n=4) of the non-treated cells, respectively. These results further supported the involvement of MMP-1 and MMP-2 in myoblast migration and invasion. Co-transfection of MMP-1 and MMP-2 gave only 92.6% or 86% migration activity obtained by individual transfection of MMP-1 or MMP-2, respectively, demonstrating the competitive nature of their action with respect to conferring stimulatory effects on migration. The increased amount of FUGENE 6® used for the double transfections did not show any significant adverse effects on cell growth or morphology, eliminating the possibility of adverse effects of the transfection procedure. In these experiments, myoblast cell number as well as myotube number after differentiation were not significantly different between MMP-transfected and untransfected cells, indicating that MMP over-expression had little effect on myoblast proliferation and differentiation under the experimental conditions used (data not shown).
These results suggest that over-expression of MMP-2 and MMP-1, but not MMP-9, can facilitate myoblast migration and invasion in vitro. In each panel the bars represent mean±SEM from three individual experiments.
EXAMPLE IV
Human Myoblast Migration, Invasion and MMP Expression
The effects of growth factors on human myoblast migration in vitro (12 hour time point) were somewhat different from those observed with mouse myoblasts. All the growth factors tested showed substantial stimulatory effects over the BSA control, ranging from 20-100-fold. The greatly elevated level of migration of human myoblasts was due in part to the extremely low migration in the BSA control (basal level) of human cells compared to mouse cells. The largest effects on human myoblast migration were produced by fibronectin (100-fold), PDGF (about 62-fold), TGF-β (about 54-fold) and HGF (46-fold) over the control level, while bFGF produced only a 37-fold stimulation (FIG. 7 a ). Moreover, unlike mouse myoblasts, the combination of fibronectin and bFGF produced approximately the same effects as fibronectin alone. These effects were significantly increased by plasmin treatment, and greatly reduced by NAC (FIG. 7 c ), indicating the critical involvement of gelatinase activity.
The effects of growth factors on human myoblast invasion of MATRIGEL® are shown in FIG. 7 b (24 hour time point). All growth factors produced lower effects on human cells compared to mouse cells, while fibronectin alone or fibronectin/bFGF combination still produced a 2.3-fold or 6-fold stimulation, respectively, over the BSA control (FIG. 7 d ).
Human myoblasts showed a higher basal level of MMP-2 expression than that of mouse myoblasts. This level was approximately 3-fold higher than the basal MMP-2 expression level of mouse myoblasts (data not shown), thereby possibly explaining, in part, the higher migration rate. MMP-2 expression (72 kDa band), as assayed by zymography, was not significantly affected by any of the growth factors tested, while stimulation by intact fibronectin produced a significant increase in MMP-2 activation, similar to that observed in mouse cells (FIG. 8 a and b ). Unlike mouse cells, human myoblasts showed only marginal increases in MMP-9 expression (92 kDa band) with TNF-α or bFGF stimulation (FIG. 8 c ). Both mouse and human myoblasts were used at a similar passage number, and myoblasts from both species were obtained from mature muscle samples (4-6 weeks old for mouse, 8-44 years old for human), suggesting that passage and/or age differences may not account for the discrepancies observed between human and mouse myoblasts. These results strongly suggest that while there are similarities, there are also species-specific differences in basal MMP expression as well as induction of MMPs in response to growth factor stimulation.
EXAMPLE V
Mouse Myoblast Incorporation in vivo
Hindlimb muscles of SCID mice were injected with 5×10 5 BAG-SCID myoblasts, and analyzed 3 weeks later. Sections prepared from mouse hindlimb muscle injected with SCID mouse myoblasts carrying a β-GAL reporter gene were double stained for laminin (a component of the basal lamina) and for β-GAL, using laminin immunohistochemistry and X-GAL histochemistry, respectively. Myoblasts were able to incorporate into the muscle, resulting in numerous β-GAL-positive myofibers with normal diameters which were scattered throughout the muscle (FIG. 9 a ). However, myoblasts also remained trapped in areas of connective tissue such as fascicle sheaths, where they fused with one another to form new myotubes (FIG. 9 b ). In other cases, myoblasts appeared to migrate out of such barriers but were probably forced there due to the injection pressure where they were unable to cross the fiber basal lamina and, thus, remained outside the myofibers, again forming new myotubes (FIG. 9 c ; some typical representatives are shown by arrow heads). These results supported the hypothesis that the connective tissue structures surrounding fiber bundles and surrounding the fibers themselves may function as a barrier to the incorporation of myoblasts into the adult myofibers in vivo. Sections at 8 μm. The photographs were taken at an original magnification of 200-fold.
EXAMPLE VI
Effects of bFGF and Fibronectin in vivo
Stimulation of myoblasts prior to muscle implantation, with bFGF, fibronectin, or both together, resulted in substantial increases in myoblast incorporation into existing myofibers, as shown by 2.3-, 2-, and 5-fold increases in the number of β-GAL-positive myofibers, respectively, over that of the BSA treated control (FIG. 10 ). The number of β-GAL positive myofibers were quantified after implantation of BAG-transduced SCID myoblasts treated with DMEM alone (control), 1 μg/ml bFGF, 50 μg/ml fibronectin, or 1 μg/ml bFGF+50 μg/ml fibronectin. Bars indicated mean±SEM for 4 animals. Treatment with bFGF and bFGF+fibronectin stimulated increased incorporation of implanted myoblasts into myofibers compared to DMEM alone. Tissues were immunostained for visualizing laminin.
Effects of bFGF and fibronectin on myoblast incorporation were further visualized by staining representative sections of the muscle tissues after injection with untreated myoblasts (FIG. 11 a, BSA control) or myoblasts treated with bFGF plus β-GAL (FIG. 11 b ). Representative tissue sections used for analyses in FIG. 10 are shown. Arrows indicate some representative myofiber cells successfully fused with implanted β-GAL-marked myoblast cells. Arrow heads indicate some representative myotubes formed in connective tissues. No counter stain was done for the tissues. These photographs were taken at an original magnification of 100-fold. These results demonstrated that such stimuli can actually augment fusion efficiency of implanted myoblasts with the adult host myofiber cells. These results, however, do not rule out the possible contribution of mechanisms other than increased migration and invasion in the increased myoblast incorporation.
From the above, it is clear that the present invention provides a less destructive approch to myoblast gene transfer. The above-identified composition and methods can be readily employed ex vivo to prepare myoblasts for transfer into humans.
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A novel, empirically derived composition of cytokines and myoblasts is described, that allows for the migration of myoblasts through connective barriers, along with methods employing the composition in the in vivo migration of myoblasts for therapeutic purposes and gene therapy, as well as methods for the identification of agents that are agonistic or antagonistic to myoblast migration in vitro or in vivo.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a U.S. National-Stage entry under 35 U.S.C. §371 based on International Application No. PCT/EP2015/072513, filed Sep. 30, 2015, which was published under PCT Article 21(2) and which claims priority to German Application No. 10 2014 220 622.7, filed Oct. 10, 2014, which are all hereby incorporated in their entirety by reference.
TECHNICAL FIELD
[0002] The present disclosure relates to a method for laundering textiles in a washing machine comprising an activation device.
BACKGROUND
[0003] It is known that colored textiles can bleed during the washing process. Depending on the washing temperature, the selected washing program and the laundry detergent used, individual or multiple dyes may be washed out of the textiles in varying degrees. The solute dyes migrate into the washing liquid, which in general is suds, and in this way make contact with other textiles, to which the dyes may be transferred. This results in undesirable discolorations, in particular of light-colored textiles, and in the worst case, for example, can entirely ruin a piece of clothing.
[0004] The textile industry today uses a number of different dyes. These dyes vary drastically with respect to the chemical structure thereof, the properties thereof, and the binding thereof to a textile. A distinction can be made, for example, between direct dyes, reactive dyes, disperse dyes, acid acids, vat dyes and others. Different types of woven fabrics, such as cotton, polyamide or polyester, require different types of dyes to effectuate efficient and lasting coloring of these woven fabrics. This wide range of dyes used in the textile industry poses a major challenge in the quest for efficient measures against discoloration.
[0005] A variety of efforts have already been made to suppress the bleeding process, in particular in the area of laundry detergent compositions. Laundry detergents intended to be used for laundering colored textiles, for example, are usually mixed with dye transfer inhibitors, which are to prevent dyes from being transferred to other textiles. One disadvantage of these additives is that these are usually only effective against individual or few dyes, but not against a wider spectrum of dyes. Commercial dye transfer inhibitors, for example, exhibit good action with respect to red direct dye, but no action, or only low action, with respect to disperse, acid or vat dyes. Precisely such a wide color spectrum, however, can be found with common household colored laundry, since for efficiency reasons in general at most approximate (light/dark) sorting by colors is carried out, but typically not according to individual dues. So as to achieve an appropriate effectiveness with respect to such a mixture of dyes, it would be necessary to add numerous dye transfer inhibitors to the laundry detergent compositions. However, this would undesirably increase not only the complexity of the laundry detergent formulations, but also the costs for the laundry detergent.
[0006] A method for treating stains on textiles is known from the US patent specification U.S. Pat. No. 3,927,967, in which the textiles are subjected to a treatment using a laundry detergent solution, a photoactivator and oxygen and are irradiated with visible light during this treatment process. Such a method, however, is not suitable for treating dyed textiles, in particular for suppressing the bleeding process, since the treatment not only attacks dyes dissolved in the washing liquid, but also the dyes bound to the textiles, causing the textiles to undesirably bleach and lose color.
[0007] The international patent application WO 2009/067838 A2 describes a method for cleaning laundry using electrolyzed water by way of oxidative radicals. For this purpose, a water tank is provided in addition to the washing machine. The water present in the tank is electrolyzed by way of an electrolysis unit, thereby becoming enriched with radicals, which are highly reactive and thus, among other things, have a cleaning and disinfecting effect. The water thus treated is then supplied to the actual washing process. The disadvantage here is that the textiles to be laundered come in direct contact with radicals stemming from the electrolyzed water during the washing process, whereby not only soiling on the textiles is attacked, but also the dyes bound to the textiles, which can result in undesirable bleaching of the colors.
[0008] Bleaching performance-enhancing 3,4-dihydroisoquinoline derivatives are known from the international patent applications WO 03/104199 A2, WO 2005/047264 A1 and WO 2007/001262 A1.
BRIEF SUMMARY
[0009] A method for laundering textiles in a washing machine is provided herein. The washing machine includes a washing chamber for receiving a washing liquid and textiles to be cleaned The washing machine further includes an activation device, which includes an inlet for introducing washing liquid from the washing chamber into the activation device and an outlet for conducting washing liquid out of the activation device into the washing chamber. The activation device further includes at least one activation component suitable for triggering a process within the activation device for forming free radicals in the washing liquid.
[0010] The method includes the step of adding the textiles to be washed into the washing chamber of the washing machine. The method further includes the step of starting a washing cycle. The method further includes the step of introducing washing liquid from the washing chamber into the activation device. The method further includes the step of triggering a process in the activation device for forming free radicals in the washing liquid. The method further includes the step of breaking down dyes present in the washing liquid by way of the free radicals. The method further includes the step of conducting treated washing liquid out of the decolorization reservoir into the washing chamber. The washing liquid includes an organic bleach enhancer compound.
[0011] Surprisingly, it was found that the bleaching action of organic bleach enhancer compounds, and in particular of zwitterionic 3,4-dihydroisoquinoline derivatives, with respect to dyes detached from textiles increases when these are used in washing machines that comprise an activation device including an activation component, which is suitable for triggering a process within the activation device for forming free radicals in the washing liquid.
[0012] The disclosure thus relates to a method for laundering textiles in a washing machine ( 1 ) comprising a washing chamber ( 2 ) for receiving a washing liquid and textiles to be cleaned, and comprising an activation device ( 3 ), which includes an inlet ( 4 ) for introducing washing liquid from the washing chamber ( 2 ) into the activation device ( 3 ) and an outlet ( 5 ) for conducting washing liquid out of the activation device ( 3 ) into the washing chamber ( 2 ), and which additionally comprises at least one activation component suitable for triggering a process within the activation device ( 3 ) for forming free radicals in the washing liquid, comprising the following steps:
adding the textiles to be washed into the washing chamber ( 2 ) of the washing machine ( 1 ); starting a washing cycle; introducing washing liquid from the washing chamber ( 2 ) into the activation device ( 3 ); triggering a process in the activation device ( 3 ) for forming free radicals in the washing liquid; breaking down dyes present in the washing liquid by way of the free radicals; conducting treated washing liquid out of the decolorization reservoir ( 3 ) into the washing chamber ( 2 ),
characterized in that the, in particular aqueous, washing liquid comprises an organic bleach enhancer compound.
[0019] Organic bleach enhancer compounds are organic compounds that comprise no metals or transition metals, comprise no peroxo groups and in customary washing processes, in the presence of H 2 O 2 or H 2 O 2 precursors, do not form peroxocarboxylic acids or peroximidic acids by way of a perhydrolysis reaction, and when present in the washing process nonetheless enhance the bleaching performance.
[0020] Within the scope of the disclosure, the organic bleach enhancer compound is preferably selected from the compounds of general formula (I),
[0000]
[0000] in which R denotes a straight-chain or branched alkyl group having 2 to 20 carbon atoms, and in particular 8 to 12 carbon atoms, and the mixtures thereof. Preferably, the alkyl group R in the compounds of general formula (I) is branched at the 2-position and is in particular selected from the 2-methylhexyl, 2-ethylhexyl, 2-ethylheptyl, 2-propylheptyl, 2-butyloctyl, 2-butylnonyl, 2-pentylnonyl, 2-pentyldecyl and 2-hexyldecyl group and mixtures of these, although the n-dodecyl, n-tetradecyl, n-hexadecyl, n-octadecyl, iso-nonyl, iso-decyl, iso-tridecyl and iso-pentadecyl group and mixtures of these are also possibilities for R. Mixtures of general formula (I) can be produced from 3,4-dihydroisoquinoline, the sulfur trioxide-dimethylformamide complex and glycidyl ethers, as described in WO 03/104199 A2 or WO 2007/001262 A1.
[0021] The combination of an organic bleach enhancer compound, and in particular a compound according to general formula (I), and an activation component improves the oxidative destruction of the dyes detached from textiles. The measure as contemplated herein thus minimizes the risk of textile discolorations during the washing process since dyes detached from the textile are oxidatively from the washing liquor and cannot deposit on non-dyed or differently colored textiles, and additionally dyes present on the textile are generally not affected, and the textiles thus do not unacceptably alter the original color thereof as a result of the washing process.
[0022] The disclosure thus furthermore relates to the use of the aforementioned compounds for avoiding textile dyes from being transferred from dyed textiles to non-dyed or differently colored textile when these are laundered together in an, in particular surfactant-comprising, aqueous washing liquid in a washing machine ( 1 ) comprising a washing chamber ( 2 ) for receiving a washing liquid and textiles to be cleaned, and comprising an activation device ( 3 ), which includes an inlet ( 4 ) for introducing washing liquid from the washing chamber ( 2 ) into the activation device ( 3 ) and an outlet ( 5 ) for conducting washing liquid out of the activation device ( 3 ) into the washing chamber ( 2 ), and which additionally comprises at least one activation component suitable for triggering a process within the activation device ( 3 ) for forming free radicals in the washing liquid.
[0023] The washing machine used as contemplated herein can generally be a common household cuboid washing machine having a capacity of approximately 4 to 12 kg of laundry, but other washing machine types, for example industrial washing machine having deviating designs and considerably larger capacities are also possible. The washing chamber is the space through which washing liquid flows during a washing cycle. In a common household washing machine, this is generally a washing drum and the space directly surrounding the same.
[0024] It has been shown that the dyes having transferred into the washing liquid during a washing process can be broken down by free radicals, when these cooperate with an organic bleach enhancer compound, and in particular the compound according to general formula (I). Free radicals comprise at least one unpaired electron and, for this reason, are highly reactive and thus have a short live. They are able to react with dyes detached from the textile and present in the washing liquid, and to break these down. By way of example, the decomposition of the dye Acid Orange 7 shall be mentioned, which by the interaction with free radicals is broken down into colorless aromatic by-products, which if necessary in turn can be converted into aliphatic acids by way of further oxidation. A stronger decomposition of the dye molecules takes place in the presence of the organic bleach enhancer compound, and in particular of the compound according to general formula (I).
[0025] The washing machine used in the method as contemplated herein takes advantage of this property of free radicals. It comprises an activation device into which the washing liquid from the washing chamber can be conducted. The activation component is disposed in the activation device and is suitable for triggering a process within the activation device for forming free radicals in the washing liquid. The washing liquid thus treated is then conducted together with the organic bleach enhancer compound comprised therein back out of the activation device and into the washing chamber, and is supplied to the further washing process in the washing machine. A stronger decomposition of the dye molecules takes place in the presence of the organic bleach enhancer compound, and in particular of the compound according to general formula (I).
[0026] Both the inlet for introducing the washing liquid from the washing chamber into the activation device, and the outlet for conducting the washing liquid out and into the washing chamber are preferably configured such that it is not possible for textiles to find their way into the activation device. For this purpose, the inlet and/or the outlet of the activation device can be equipped with suitable filters or mesh, for example, which textiles cannot pass, while the washing liquid can. It is also possible for the dimensions, and in particular the cross-sectional surface area of the inlet and/or of the outlet, to be configured such that textiles are not able to enter the activation device.
[0027] In a preferred embodiment of the disclosure, the activation component comprises a UV radiation source, which is to say the process for forming free radicals in the activation device is triggered by UV irradiation. In this variant embodiment, suds comprising additional chemical components, such as hydrogen peroxide (H 2 O 2 ) or fine-particled titanium dioxide (TiO 2 ), can be used as the washing liquid. The UV radiation emitted by the radiation source in the activation device causes the hydrogen peroxide or titanium dioxide present in the suds to be activated, and highly reactive hydroxyl radicals (OH radicals) are created as short-lived products of this reaction, which together with the organic bleach enhancer compound are able to deliver the desired dye transfer inhibition performance. If present, the concentration of hydrogen peroxide in the washing liquid is preferably about 0.1 to about 50 mmol/l, and particularly preferably about 1 to about 20 mmol/l.
[0028] A quartz lamp or a UV light-emitting diode can be used as the UV radiation source. Other UV radiation sources such as gas discharge lamps, fluorescent lamps or lasers, however, are also conceivable.
[0029] If a UV radiation source is present as the activation component, it is generally preferred for this source to be disposed such in the activation device and/or for the activation device to be configured such that no direct UV radiation enters the washing chamber, so that dyes in the textiles present in the washing chamber are not damaged. This can take place, for example, by providing a panel or a curve at the inlet and the outlet in the direction of the washing chamber, forcing the washing liquid to flow around the panel or around the curve. The inlets and outlets of the activation device can be disposed in a direction that does not point in the direction of the washing chamber.
[0030] The preferred wavelength range of the emitted UV radiation is in the range of about 100 nm to about 400 nm, with about 250 nm to about 400 nm being particularly preferred.
[0031] In an alternative embodiment of the disclosure, the activation component comprises an electrode array, comprising an anode and a cathode. In this case, the free radicals are formed in the washing liquid by way of an electrochemical process. For this purpose, the anode and the cathode can be introduced into the activation device, and each can be connected to the positive or negative pole of a DC voltage source. Without being bound to this hypothesis, it is conceivable that the onsetting electrolysis will then split the water present in the washing liquid, forming OH radicals. The anode used can be, for example, an electrode made of graphite, steel, diamond, noble metals such as platinum or metal oxides or metal oxide mixtures. It is particularly preferred to use a possibly boron-doped diamond electrode as the anode. This generally involves a base body made of plastic material, metal or a semiconductor, such as silicon, which is coated with a thin, polycrystalline diamond layer. So as to achieve sufficient conductivity for the electrolysis, the diamond layer is doped with boron during production.
[0032] The effective surface area of the anode is preferably in the range of about 1 cm 2 to about 500 cm 2 , and particularly preferably between about 2 cm 2 and about 100 cm 2 . The electrolysis is preferably carried out at current intensities in the range of about 0.01 A to about 30 A, and preferably about 0.1 A to about 10 A.
[0033] The two aforementioned variant embodiments comprising a UV radiation source or electrode array as the activation component, in combination with the organic bleach enhancer compound, each already supply good results per se. Nonetheless, it is also possible as contemplated herein to combine the two variants so as to achieve even better bleaching performance. To this end, for example, both the UV radiation source and the electrode array can be disposed in a shared activation device. Alternative, a series or parallel connection of two activation devices, each comprising an activation component, is conceivable.
[0034] Preferably, at least one pump is provided in the washing machine used as contemplated herein, which pumps the washing liquid out of the washing chamber and into the activation device and/or out of the same.
[0035] The onset, the intensity, and the duration of the process for forming free radicals in the activation device can preferably be regulated. For example, the onset of the process can be coupled to achieving certain operating parameters, such as to a particular temperature of the washing liquid or a particular phase of the washing cycle. For a temperature-dependent regulation, a temperature sensor may be provided, for example, which can detect the temperature of the washing liquid. It is also possible for a purely time-based regulation to be provided, which prompts the radical forming process to start at a pre-set point in time. Likewise, the duration of the process can be set such that this process stops as soon as a certain bleaching result has been achieved. It is also possible for the onset of the process to be completely suppressed for washing cycles with textiles having no bleachable soiling and/or at a particularly low temperature at which it is not to be feared that dyes will wash out into the washing liquid. At high washing temperatures and when laundering particularly heavily soiled textiles, in contrast, the intensity and the duration of the process can be accordingly increased.
[0036] The temperature of the washing liquid at which the method as contemplated herein can be operated can be, if desired, in the range of about 10° C. to about 100° C., and preferably of about 20° C. to about 60° C. The activation device is preferably operated over a period of about 1 minute to about 240 minutes, and in particular of about 10 minutes to about 60 minutes.
[0037] According to one embodiment of the disclosure, the activation device can be fixedly installed in a housing of the washing machine. The power supply for the activation component and optionally for the pump can be coupled to the power supply of the washing machine. The activation device can be attached beneath the drum or on the inside of the door of the washing machine, for example. Appropriate lines, which can be connected to the inlet and the outlet of the activation device, can be provided in the washing machine to conduct the washing liquid into the activation device and back out of the same. For example, the washing chamber can comprise a washing liquid outlet, which can be connected to the inlet of the activation device. Accordingly, the outlet of the activation device can be connectable to a washing liquid inlet of the washing chamber, so that the treated washing liquid can be conducted out of the activation device and back into the washing chamber.
[0038] Alternatively, the activation device can also be designed as a separate, preferably battery-powered module. This can be attached to the inside of the door of the washing machine by way of an appropriate mounting, for example. The advantage of a separately introducible module is that this can be used only when needed and consequently is subject to less wear. Moreover, a separate module can also be installed subsequently into an existing washing machine, or can be removed from a defective washing machine and installed into a new washing machine.
BRIEF DESCRIPTION OF THE DRAWINGS
[0039] The present disclosure will hereinafter be described in conjunction with the following drawing figures, wherein like numerals denote like elements, and:
[0040] FIG. 1 shows a schematic representation of an exemplary embodiment of the activation device;
[0041] FIG. 2 shows a schematic representation of an alternative embodiment of the activation device;
[0042] FIG. 3 shows a schematic view of a washing machine comprising the activation device from FIG. 1 ; and
[0043] FIG. 4 shows a schematic view of a washing machine comprising the activation device from FIG. 2 .
DETAILED DESCRIPTION
[0044] The following detailed description is merely exemplary in nature and is not intended to limit the disclosure or the application and uses of the subject matter as described herein. Furthermore, there is no intention to be bound by any theory presented in the preceding background or the following detailed description.
[0045] FIG. 1 shows an exemplary embodiment of an activation device denoted in the overall by reference numeral 3 , which is suitable for receiving washing liquid. For this purpose, the activation device 3 comprises an inlet 4 and an outlet 5 . Washing liquid, which is not shown, can find its way from the environment of the activation device 3 into the interior space thereof through the inlet 4 . The washing liquid can exit the activation device 3 again via the outlet 5 . The flow direction of the washing liquid is schematically indicated by arrows.
[0046] A UV radiation source 6 is situated inside the activation device 3 . The arrangement of the UV radiation source 6 inside the activation device 3 is shown only schematically in FIG. 1 , and in particular the representation of the electrical connections of the UV radiation source 6 were dispensed with. The UV radiation source 6 can be a UV quartz lamp, which emits UV radiation having a wavelength of about 254 nm.
[0047] If a washing liquid comprising hydrogen peroxide or fine-particled titanium dioxide is now introduced through the inlet 4 into the activation device 3 , H 2 O 2 molecules are activated by the UV radiation emitted by the quartz lamp, creating short-lived, highly reactive hydroxyl radicals. Together with the washing liquid, these are conducted back out of the activation device 3 through the outlet 5 can develop the bleaching action in cooperation with the organic bleach enhancer compound, and in particular the compound according to general formula (I).
[0048] FIG. 2 shows an alternative embodiment of the activation device 3 . Identical components are denoted by identical reference numerals and, to avoid repetition, are not described again separately. An electrode array 7 , which is composed of an anode 8 and a cathode 9 , is located inside the activation device 3 shown in FIG. 2 .
[0049] The anode 8 is connected to the positive pole of an electrical DC voltage source, and the cathode 9 is connected to the negative pole. The representation of the electrode array is again only schematic. The anode 8 can be a boron-doped diamond anode, and the cathode 9 can be a stainless steel electrode. When washing liquid enters the activation device 3 via the inlet 4 , the water present in the washing liquid undergoes electrolysis. This results in the creation of hydroxyl radicals, which similarly to the exemplary embodiment already shown for FIG. 1 , can be conducted out of the activation device 3 via the outlet 5 .
[0050] FIGS. 3 and 4 each show a washing machine comprising an activation device.
[0051] The washing machine 1 shown in simplified form in FIG. 3 comprises a drum 13 , which is part of a washing chamber 2 and beneath which the activation device 3 according to FIG. 1 , comprising a UV quartz lamp, is disposed. The washing chamber 2 is composed of the washing drum 13 and the space directly surrounding the same, through which the washing liquid flows during the washing process. The flow of liquid through the activation device 3 is indicated by arrows. It is likewise possible to dispose the activation device 3 in the alternative embodiment together with the electrode array 7 in a region beneath the drum 13 . In the example shown, the activation device 3 is an integral part of the washing machine 1 .
[0052] Alternatively, the activation device 3 can also be disposed in the region of a door 12 of the washing machine 1 , as shown in FIG. 4 . In FIG. 4 , the activation device 3 is mounted on the inside of the door 12 of the washing machine 1 . The example shown is the embodiment of the activation device 3 comprising the electrode array 7 . It is also possible, of course, to mount the embodiment of the activation device 3 comprising the UV radiation source 6 in the region of the door 12 of the washing machine 1 . In this example, the activation device 3 is introduced into the washing machine 1 as a separate, battery-powered module and can be removed, if necessary.
[0053] The use as contemplated herein and the method as contemplated herein are preferably carried out at temperatures in the range of about 10° C. to about 95° C., in particular about 20° C. to about 60° C., and particularly preferably at temperatures below 30° C. The water hardness of the water used to prepare the aqueous liquor is preferably in the range of 0° dh to about 21° dH, and in particular 0° dH to about 3° dH. The water hardness in the washing liquor is preferably in the range of 0° dH to about 23° dH, and in particular 0° dH to about 6° dH, which can be achieved by using customary builder materials or water softeners, for example. The use as contemplated herein and the method as contemplated herein are preferably carried out at pH values in the range of about pH 2 to about pH 13, and in particular about of pH 7 to about pH 11.
[0054] The organic bleach enhancer compound, and in particular the compound of general formula I), can be introduced into the washing machine in addition to a laundry detergent that otherwise has a customary composition; however, preferably, it can be part of the laundry detergent used in the method as contemplated herein and within the scope of the use as contemplated herein. The concentration of the organic bleach enhancer compound in the, in particular aqueous, washing liquid is preferably in the range of about 0.5 μmol/l to about 500 μmol/l, and in particular of about 5 μmol/l to about 200 μmol/l. So as to create the, in particular aqueous, washing liquid, preferably a laundry detergent comprising an organic bleach enhancer compound, and in particular a compound according to general formula (I), is used.
[0055] In addition to the organic bleach enhancer compound, which is preferably present in amounts of about 0.001 wt. % to about 2 wt. %, and in particular about 0.03 wt. % to about 0.2 wt. %, a laundry detergent used within the scope of the present invention can comprise customary ingredients that are compatible with this component.
[0056] Laundry detergents, which may be present in particular in the form of powdery solids, in post-compacted particle form, as homogeneous solutions or suspensions, can, in principle, comprise all known ingredients common in such detergents, in addition to the active ingredient used as contemplated herein. The detergents as contemplated herein can in particular comprise builder substances, surfactants, bleaching agents based on organic and/or inorganic peroxygen compounds, other bleach activators, water-miscible organic solvents, enzymes, sequestering agents, electrolytes, pH regulators and further auxiliary agents, such as optical brighteners, graying inhibitors, foam regulators, dyes and odorants.
[0057] The detergents preferably comprise one or more surfactants, wherein in particular anionic surfactants, non-ionic surfactants, and the mixtures thereof, but also cationic, zwitterionic and amphoteric surfactants may be used.
[0058] Suitable non-ionic surfactants are in particular alkylglycosides and ethoxylation and/or propoxylation products of alkylglycosides or linear or branched alcohols, each having 12 to 18 carbon atoms in the alkyl part and 3 to 20, preferably 4 to 10 alkyl ether groups. Furthermore, corresponding ethoxylation and/or propoxylation products of N-alkyl amines, vicinal diols, fatty acid esters and fatty acid amides, which with respect to the alkyl part correspond to the described long-chain alcohol derivatives, and of alkyl phenols having 5 to 12 carbon atoms in the alkyl group may be used.
[0059] Alkoxylated, advantageously ethoxylated, in particular primary alcohols having preferably 8 to 18 carbon atoms and on average 1 to 12 moles ethylene oxide (EO) per mole of alcohol, in which the alcohol residue can be linear or preferably methyl-branched at the 2-position or can comprise linear and methyl-branched residues in the mixture, such as those usually present in oxo alcohol groups, are preferred as non-ionic surfactants. However, in particular, alcohol ethoxylates comprising linear groups of alcohols of native origin having 12 to 18 carbon atoms, for example of coconut, palm, tallow fatty or oleyl alcohol, and an average of 2 to 8 EO per mole of alcohol are preferred. The preferred ethoxylated alcohols include, for example, C 12 -C 14 alcohols having 3 EO or 4 EO, C 9 -C 11 alcohols having 7 EO, C 13 -C 15 alcohols having 3 EO, 5 EO, 7 EO, or 8 EO, C 12 -C 18 alcohols having 3 EO, 5 EO, or 7 EO, and mixtures thereof, such as mixtures of C 12 -C 14 alcohol having 3 EO and C 12 -C 18 alcohol having 7 EO. The degrees of ethoxylation indicated represent statistical averages that can correspond to an integer or a fractional number for a specific product. Preferred alcohol ethoxylates exhibit a restricted distribution of homologs (narrow range ethoxylates, NRE). In addition to these non-ionic surfactants, fatty alcohols having more than 12 EO can also be used. Examples of these are (tallow) fatty alcohols having 14 EO, 16 EO, 20 EO, 25 EO, 30 EO or 40 EO. Extremely foamable compounds are typically used in particular in detergents for use in mechanical processes. These preferably include C 12 -C 18 alkyl polyethylene glycol/polypropylene glycol ethers, each having up to 8 moles ethylene oxide and propylene oxide units in the molecule. It is also possible, however, to use other known low-foam non-ionic surfactants, such as C 12 -C 18 alkyl polyethylene glycol/polybutylene glycol ethers, each having up to 8 moles ethylene oxide and butylene oxide units in the molecule, and end group-capped alkyl polyalkylene glycol mixed ethers. Particularly preferred are also the hydroxyl group-comprising alkoxylated alcohols, known as hydroxy mixed ethers. The non-ionic surfactants also include alkyl glycosides of the general formula RO(G) x , where R represents to a primary straight-chain or methyl-branched, in particular methyl-branched at the 2-position, aliphatic group having 8 to 22, preferably 12 to 18 carbon atoms, and G denotes a glycose unit having 5 or 6 carbon atoms, preferably glucose. The degree of oligomerization x, which indicates the distribution of monoglycosides and oligoglycosides, is an arbitrary number, which as a quantity to be analytically determined may also take on fractional values, between 1 and 10; x is preferably about 1.2 to about 1.4. Likewise suitable are polyhydroxy fatty acid amides of formula
[0000]
[0060] in which R 1 CO denotes an aliphatic acyl group having 6 to 22 carbon atoms, R 2 denotes hydrogen, an alkyl or hydroxyalkyl group having 1 to 4 carbon atoms, and [Z] denotes a linear or branched polyhydroxyalkyl group having 3 to 10 carbon atoms and 3 to 10 hydroxyl groups.
[0061] The polyhydroxy fatty acid amides are preferably derived from reducing sugars having 5 or 6 carbon atoms, and in particular from glucose. The group of polyhydroxy fatty acid amides also includes compounds of formula
[0000]
[0062] in which R 3 denotes a linear or branched alkyl or alkenyl group having 7 to 12 carbon atoms, R 4 denotes a linear, branched or cyclic alkylene group or an arylene group having 2 to 8 carbon atoms, and R 5 denotes a linear, branched or cyclic alkyl group or an aryl group or an oxy alkyl group having 1 to 8 carbon atoms, wherein C 1 -C 4 alkyl or phenyl groups are preferred, and [Z] denotes a linear polyhydroxy alkyl group, the alkyl chain of which is substituted with at least two hydroxyl groups, or alkoxylated, preferably ethoxylated or propoxylated, derivatives of this group. [Z] is again preferably obtained by the reductive amination of a sugar, such as glucose, fructose, maltose, lactose, galactose, mannose or xylose. The N-alkoxy- or N-aryloxy-substituted compounds can be converted, in the presence of an alkoxide as the catalyst, to the desired polyhydroxy fatty acid amides by reacting these compounds with fatty acid methyl esters. Another class of non-ionic surfactants that is preferably used, which can be used either as the sole non-ionic surfactant or in combination with other non-ionic surfactants, in particular together with alkoxylated fatty alcohols and/or alkyl glycosides, is alkoxylated, preferably ethoxylated or ethoxylated and propoxylated, fatty acid alkyl esters, preferably having 1 to 4 carbon atoms in the alkyl chain, in particular fatty acid methyl esters. Non-ionic surfactants of the amine oxide type, for example N-cocoalkyl-N—N-dimethylamine oxide and N-tallowalkyl-N,N-dihydroxyethylamine oxide, and of the fatty acid alkanolamide type may also be suitable. The quantity of these non-ionic surfactants is preferably no more than that of the ethoxylated fatty alcohols, in particular no more than half thereof. Further possible surfactants are those known as gemini surfactants. These are generally understood to mean compounds that comprise two hydrophilic groups per molecule. These groups are generally separated from one another by a so-called “spacer.” This spacer is in general a carbon chain, which should be long enough for the hydrophilic groups to have sufficient distance from one another to be able to act independently of one another. Such surfactants are generally characterized by an unusually low critical micelle concentration and the capability of drastically reducing the surface tension of the water. In exceptions, the expression ‘gemini surfactants’ is understood to mean not only such “dimeric,” but also corresponding “trimeric” surfactants. Suitable gemini surfactants are, for example, sulfated hydroxy mixed ethers or dimer alcohol bis- and trimer alcohol tris-sulfates and -ether sulfates. End group-capped dimeric and trimeric mixed ethers are characterized in particular by the bifunctionality and multifunctionality thereof. The above-mentioned end group-capped surfactants, for example, exhibit good wetting properties, while being low-foaming, whereby they are suitable in particular for use in mechanical washing or cleaning processes. However, it is also possible to use gemini polyhydroxy fatty acid amides or poly-polyhydroxy fatty acid amides.
[0063] Suitable anionic surfactants are in particular soaps and those that comprise the sulfate or sulfonate groups. Surfactants of the sulfonate type that can be used are preferably C 9 -C 13 alkylbenzene sulfonates, olefin sulfonates, which is to say mixtures of alkene and hydroxyalkane sulfonates, and disulfonates, as they are obtained, for example, from C 12 -C 18 monoolefins having a terminal or internal double bond by way of sulfonation with gaseous sulfur trioxide and subsequent alkaline or acid hydrolysis of the sulfonation products. Also suited are alkane sulfonates obtained from C 12 -C 18 alkanes, for example by way of sulfochlorination or sulfoxidation with subsequent hydrolysis or neutralization. Also suitable are esters of α-sulfo fatty acids (ester sulfonates), for example the α-sulfonated methyl esters of hydrogenated coconut, palm kernel or tallow fatty acids, which are produced by the α-sulfonation of methyl esters of fatty acids of vegetable and/or animal origin having 8 to 20 carbon atoms in the fatty acid molecule and subsequent neutralization to yield water-soluble mono-salts. Preferably, these are the α-sulfonated esters of hydrogenated coconut, palm, palm kernel or tallow fatty acids, wherein it is also possible for sulfonation products of unsaturated fatty acids, such as oleic acid, to be present in small amounts, and preferably in amounts not above approximately about 2 to about 3 wt. %. In particular, α-sulfo fatty acid alkyl esters that comprise an alkyl chain having no more than 4 carbon atoms in the ester group are preferred, such as methyl esters, ethyl esters, propyl esters and butyl esters. Particularly advantageously, the methyl esters of α-sulfo fatty acid (MES) are used, but also the saponified di-salts thereof. Further suitable anionic surfactants are sulfated fatty acid glycerol esters, which represent the monoesters, diesters and triesters and the mixtures thereof, as they are obtained during production by way of the esterification of a monoglycerol with 1 to 3 moles fatty acid or during the transesterification of triglycerides with 0.3 to 2 moles glycerol. The alkali salts, and in particular the sodium salts of the sulfuric acid half-esters of C 12 to C 18 fatty alcohols, for example from coconut fatty alcohol, tallow fatty alcohol, lauryl, myristyl, cetyl or stearyl alcohol, or of C 10 to C 20 oxoalcohols and the half-esters of secondary alcohols having this chain length are preferred alk(en)yl sulfates. Furthermore preferred are alk(en)yl sulfates having the described chain length that comprise a synthetic straight-chain alkyl group produced on a petrochemical basis, and that have a similar degradation behavior as the adequate compounds based on fatty chemical raw materials. From a washing perspective, the C 12 to C 16 alkyl sulfates, C 12 to C 15 alkyl sulfates, and C 14 to C 15 alkyl sulfates are preferred. The sulfuric acid monoesters of straight-chain or branched C 7 -C 21 alcohols ethoxylated with 1 to 6 moles of ethylene oxide, such as 2-methyl-branched C 9 -C 11 alcohols comprising, on average, 3.5 moles ethylene oxide (EO) or C 12 -C 18 fatty alcohols comprising 1 to 4 EO, are also suited. The preferred anionic surfactants also include the salts of alkyl sulfosuccinic acid, which are also referred to as sulfosuccinates or as sulfosuccinic acid esters and represent monoesters and/or diesters of sulfosuccinic acid with alcohols, preferably fatty alcohols, and in particular ethoxylated fatty alcohols. Preferred sulfosuccinates comprise C 8 to C 18 fatty alcohol groups or mixtures of these. In particular, preferred sulfosuccinates comprise a fatty alcohol group that is derived from ethoxylated fatty alcohols, which taken alone represent non-ionic surfactants. Among these, in turn, sulfosuccinates comprising fatty alcohol groups that derive from ethoxylated fatty alcohols exhibiting a restricted distribution of homologs are particularly preferred. Likewise, it is also possible to use alk(en)yl succinic acid having preferably 8 to 18 carbon atoms in the alk(en)yl chain, or the salts thereof. Further possible anionic surfactants are fatty acid derivatives of amino acids, such as of N-methyltaurine (taurides) and/or of N-methylglycine (sarcosides). In particular, the sarcosides or sarcosinates are preferred, and among these especially sarcosinates of higher and optionally monounsaturated or polyunsaturated fatty acids, such as oleyl sarcosinate. Further anionic surfactants that can also be used are in particular soaps. In particular, saturated fatty acid soaps are suitable, such as the salts of lauric acid, myristic acid, palmitic acid, stearic acid, hydrogenated erucic acid and behenic acid, and in particular soap mixtures derived from natural fatty acids, such as coconut, palm kernel, or tallow fatty acids. Together with these soaps or as a substitute for soaps, it is also possible to use the known alkenyl succinic acid salts.
[0064] The anionic surfactants, including the soaps, can be present in the form of the sodium, potassium or ammonium salts thereof, or as soluble salts of organic bases, such as monoethanolamine, diethanolamine or triethanolamine. The anionic surfactants are preferably present in the form of the sodium or potassium salts thereof, and in particular in the form of the sodium salts. Surfactants are normally present in the laundry detergents in proportions of about 1 wt. % to about 50 wt. %, and in particular of about 5 wt. % to about 30 wt. %.
[0065] A laundry detergent preferably comprises at least one water-soluble and/or water-insoluble, organic and/or inorganic builder. The water-soluble organic builder substances include polycarboxylic acids, in particular citric acid, saccharic acids, monomeric and polymeric aminopolycarboxylic acids, in particular glycine diacetic acid, methylglycine diacetic acid, nitrilotriacetic acid, iminodisuccinates such as ethylenediamine-N,N′-disuccinic acid and hydroxyiminodisuccinates, ethylenediaminetetraacetic acid and polyaspartic acid, polyphosphonic acids, in particular aminotris(methylenephosphonic acid), ethylenediaminetetrakis(methylenephosphonic acid), lysine tetra(methylenephosphonic acid) and 1-hydroxyethane-1,1-diphosphonic acid, polymeric hydroxy compounds such as dextrin and polymeric (poly-)carboxylic acids, in particular polycarboxylates accessible by oxidation of polysaccharides, polymeric acrylic acids, methacrylic acids, maleic acids, and mixed polymers of the same, which may also have small fractions of polymerizable substances having no carboxylic acid functionality polymerized into the same. The relative average molar mass of the homopolymers of unsaturated carboxylic acids is generally between about 5,000 g/mol and about 200,000 g/mol, that of the copolymers is between about 2,000 g/mol and about 200,000 g/mol, preferably about 50,000 g/mol to about 120,000 g/mol, each based on free acid. A particularly preferred acrylic acid/maleic acid copolymer has a relative average molar mass of about 50,000 to about 100,000. Suitable, albeit less preferred compounds of this class are copolymers of acrylic acid or methacrylic acid with vinyl ethers, such as vinyl methyl ethers, vinyl esters, ethylene, propylene and styrene, in which the proportion of the acid is at least 50 wt. %. It is also possible to use terpolymers comprising two unsaturated acids and/or the salts thereof as the monomers, and vinyl alcohol and/or a vinyl alcohol derivative or a carbohydrate as the third monomer, as water-soluble organic builder substances. The first acid monomer or the salt thereof is derived from a monoethylenically unsaturated C 3 -C 8 carboxylic acid and preferably from a C 3 -C 4 monocarboxylic acid, in particular from (meth)acrylic acid. The second acid monomer or the salt thereof can be a derivative of a C 4 -C 8 dicarboxylic acid, wherein maleic acid is particularly preferred. The third monomeric unit is formed in this case by vinyl alcohol and/or preferably an esterified vinyl alcohol. In particular, vinyl alcohol derivatives which represent an ester of short-chain carboxylic acids, for example of C 1 -C 4 carboxylic acids, with vinyl alcohol are preferred. Preferred polymers comprise about 60 wt. % to about 95 wt. %, in particular about 70 wt. % to about 90 wt. %, (meth)acrylic acid or (meth)acrylate, particularly preferably acrylic acid or acrylate, and maleic acid or maleinate, and about 5 wt. % to about 40 wt. %, preferably about 10 wt. % to about 30 wt. %, vinyl alcohol and/or vinyl acetate. Especially particularly preferred are polymers in which the weight ratio of (meth)acrylic acid or (meth)acrylate to maleic acid or maleinate ranges between about 1:1 and about 4:1, preferably between about 2:1 and about 3:1, and in particular about 2:1 and about 2.5:1. Both the amounts and the weight ratios are based on the acids. The second acid monomer or the salt thereof can also be a derivative of an allyl sulfonic acid, which at the 2-position is substituted with an alkyl group, preferably a C 1 -C 4 alkyl group, or an aromatic group, which is preferably derived from benzene or benzene derivatives. Preferred terpolymers comprise about 40 wt. % to about 60 wt. %, in particular about 45 wt. % to about 55 wt. %, (meth)acrylic acid or (meth)acrylate, particularly preferably acrylic acid or acrylate, about 10 wt. % to about 30 wt. %, preferably about 15 wt. % to about 25 wt. %, methallyl sulfonic acid or methallyl sulfonate, and, as the third monomer, about 15 wt. % to about 40 wt. %, preferably about 20 wt. % to about 40 wt. % of a carbohydrate. This carbohydrate can be a mono-, di-, oligo- or polysaccharide, for example, wherein mono-, di- or oligosaccharides are preferred. Sucrose is particularly preferred. As a result of the use of the third monomer, predetermined breaking points are presumably introduced into the polymer, which are responsible for the good biodegradability of the polymer. These terpolymers generally have a relative average molecular mass between about 1,000 g/mol and about 200,000 g/mol, preferably between about 200 g/mol and about 50,000 g/mol. Further preferred copolymers are those that comprise acrolein and acrylic acid/acrylic acid salts or vinyl acetate as monomers. The organic builder substances can be used in the form of aqueous solutions, and preferably in the form of about 30 to about 50 percent by weight aqueous solutions, in particular for the production of liquid detergents. All aforementioned acids are generally used in the form of the water-soluble salts thereof, in particular the alkali salts thereof.
[0066] Such organic builder substances can be present in amounts of up to 40 wt. %, in particular up to 25 wt. %, and preferably from about 1 wt. % to about 8 wt. %, if desired. Amounts close to the aforementioned upper limit are preferably used for pasty or liquid, in particular hydrous, agents.
[0067] Water-soluble inorganic builder materials that can be used are in particular polyphosphates, and preferably sodium triphosphate. Water-insoluble inorganic builder materials that are used are in particular crystalline or amorphous, water-dispersible alkali aluminosilicates, in amounts not above 25 wt. %, preferably from about 3 wt. % to about 20 wt. %, and in particular in amounts from about 5 wt. % to about 15 wt. %. Among these, the crystalline sodium aluminosilicates in detergent quality, in particular zeolite A, zeolite P and zeolite MAP, and optionally zeolite X, are preferred. Amounts close to the aforementioned upper limit are preferably used for solid, particulate agents. Suitable aluminosilicates in particular comprise no particles having a particle size above 30 μm, and preferably have a content of at least 80 wt. % of particles having a size of less than 10 μm. The calcium-binding capacity is generally in the range of about 100 to about 200 mg CaO per gram.
[0068] In addition or as an alternative to the described water-insoluble aluminosilicate and alkali carbonate, further water-soluble inorganic builder materials may be present. In addition to the polyphosphates such as sodium triphosphate, these include in particular the water-soluble crystalline and/or amorphous alkali silicate builders. The detergents preferably comprise such water-soluble inorganic builder materials in amounts of about 1 wt. % to about 20 wt. %, in particular about 5 wt. % to about 15 wt. %. The alkali silicates that can be used as builder materials preferably have a molar ratio of alkali oxide to SiO 2 of less than 0.95, in particular of about 1:1.1 to about 1:12 and can be present in amorphous or crystalline form. Preferred alkali silicates are sodium silicates, in particular the amorphous sodium silicates, having a molar ratio of Na 2 O:SiO 2 of about 1:2 to about 1:2.8. Crystalline silicates that are used, which may be present either alone or in a mixture with amorphous silicates, are preferably crystalline phyllosilicates of general formula Na 2 Si x O 2x-1 ·y H 2 O, where x, the so-called module, is a number from about 1.9 to about 4, and y is a number from 0 to 20, and preferred values for x are 2, 3 or 4. Preferred crystalline phyllosilicates are those in which x in the above-mentioned general formula takes on the value 2 or 3. In particular, both β- and δ-sodium disilicates (Na 2 Si 2 O 5 ·y H 2 O) are preferred. Practically anhydrous crystalline alkali silicates, produced from amorphous alkali silicates, of the above general formula, in which x denotes a number from about 1.9 to about 2.1, can also be used in the detergents. In a further preferred embodiment, a crystalline sodium phyllosilicate having a module from 2 to 3 is used, as it can be produced from sand and soda. Sodium silicates having a module in the range from about 1.9 to about 3.5 are used in a further embodiment. In a preferred embodiment of such detergents, a granular compound composed of alkali silicate and alkali carbonate is used, as it is commercially available under the name Nabion® 15, for example.
[0069] The detergents can comprise peroxygen-based bleaching agents, in particular if they are used in connection with activation component comprising a UV radiation source. Possible suitable peroxygen compounds include in particular organic peroxy acids or peracid salts of organic acids, such as phthalimidopercaproic acid, perbenzoic acid, monoperoxyphthalic acid and diperdodecanoic diacid and the salts thereof, such as magnesium monoperoxyphthalate, hydrogen peroxide and inorganic salts giving off hydrogen peroxide under the usage conditions, such as alkali perborate, alkali percarbonate and/or alkali persilicate, and hydrogen peroxide clathrates, such as H 2 O 2 urea adducts. Hydrogen peroxide may also be created by way of an enzymatic system, which is to say an oxidase and the substrate thereof. To the extent that solid peroxygen compounds are to be used, these may be used in the form of powders or granules, which may also be coated in the manner known per se. Particularly preferably, alkali percarbonate, alkali perborate monohydrate or hydrogen peroxide is used in the form of aqueous solutions comprising 3 wt. % to 10 wt. % hydrogen peroxide. If a laundry detergent used within the scope of the disclosure comprises peroxygen compounds, these are preferably present in amounts of up to 50 wt. %, in particular of about 2 wt. % to about 45 wt. %, and particularly preferably of about 5 wt. % to about 20 wt. %. Preferred peroxygen concentrations (calculated as H 2 O 2 ) in the liquor are in the range of about 0.001 g/l to about 10 g/l, in particular o about f 0.02 g/l to about 1 g/l, and particularly preferably of about 0.03 g/l to about 0.5 g/l, in particular when the activation component are UV radiation sources.
[0070] In particular, compounds that, under perhydrolysis conditions, yield optionally substituted perbenzoic acid and/or aliphatic peroxocarboxylic acids having 1 to 12 carbon atoms, and in particular 2 to 4 carbon atoms, either alone or in mixtures, can be used as compounds that enhance a bleaching process, but in contrast to an organic bleach enhancer compound, yield peroxocarboxylic acid under perhydrolysis conditions, in addition to the organic bleach enhancer compound, and in particular the compound according to general formula (I). Suitable bleach activators are those that carry O- and/or N-acyl groups, in particular having the described carbon atomic number and/or optionally substituted benzoyl groups. Polyacylated alkylenediamines, in particular tetra acetyl ethylene diamine (TAED), acylated glycolurils, in particular tetraacetyl glycoluril (TAGU), acylated triazine derivatives, in particular 1,5-diacetyl-2,4-dioxohexahydro-1,3,5-triazine (DADHT), N-acyl imides, in particular N-nonanoyl succinimide (NOSI), acylated phenolsulfonates or phenolcarboxylates or the sulfonic or carboxylic acids of these, in particular nonanoyl or iso-nonanoyl or lauroyl oxybenzene sulfonate (NOBS or iso-NOBS or LOBS), or decanoyloxybenzoate (DOBA), the formal carboxylic acid ester derivatives thereof, such as 4-(2-decanoyloxyethoxycarbonyloxy)benzene sulfonate (DECOBS), acylated polyhydric alcohols, in particular triacetin, ethylene glycol diacetate and 2,5-diacetoxy-2,5-dihydrofuran, and acetylated sorbitol and mannitol and the mixtures thereof (SORMAN), acylated sugar derivatives, in particular penta-acetyl glucose (PAG), penta-acetyl fructose, tetra-acetyl xylose and octa-acetyl lactose, acetylated, optionally N-alkylated glucamine and gluconolactone, and/or N-acylated lactams, for example N-benzoyl caprolactam, are preferred.
[0071] In addition to the compounds that, under perhydrolysis conditions, form peroxocarboxylic acids, further bleach-activating compounds, such as nitriles, which yield perimidic acids under perhydrolysis conditions, may be present. These include in particular aminoacetonitrile derivatives comprising a quaternized nitrogen atom according to formula
[0000]
[0072] in which R 1 denotes —H, —CH 3 , a C 2-24 alkyl or alkenyl group, a substituted C 1-24 alkyl group or C 2-24 alkenyl group comprising at least one substituent from the group —Cl, —Br, —OH, —NH 2 , CN and —N (+) —CH 2 —CN, an alkyl or alkenyl aryl group having a C 1-24 alkyl group, or a substituted alkyl or alkenyl aryl group having at least one, preferably two, optionally substituted C 1-24 alkyl groups and optionally further substituents on the aromatic ring, R 2 and R 3 , independently of one another, are selected from —CH 2 —CN, —CH 3 , —CH 2 —CH 3 , —CH 2 —CH 2 —CH 3 , —CH(CH 3 )—CH 3 , —CH 2 —OH, —CH 2 —CH 2 —OH, —CH(OH)—CH 3 , —CH 2 —CH 2 —CH 2 —OH, —CH 2 —CH(OH)—CH 3 , —CH(OH)—CH 2 —CH 3 , —(CH 2 CH 2 —O) n H, where n=1, 2, 3, 4, 5 or 6, R 4 and R 5 , independently of one another, have a meaning stated above for R 1 , R 2 or R 3 , wherein at least two of the aforementioned groups, in particular R 2 and R 3 , may be linked to one another so as to close the ring, including the nitrogen atom and optionally further heteroatoms, and then preferably form a morpholino ring, and X is a charge-equalizing anion, preferably selected from benzene sulfonate, toluene sulfonate, cumol sulfonate, the C 9-15 alkylbenzene sulfonates, the C 1-20 alkyl sulfates, the C 8-22 carboxylic acid methyl ester sulfonates, sulfate, hydrogen sulfate, and the mixture thereof, can be used. Bleach activators forming peroxocarboxylic acids or perimidic acids under perhydrolysis conditions are preferably present in amounts over 0 wt. % up to 10 wt. %, in particular about 1.5 wt. % to about 5 wt. % in the laundry detergents used within the scope of the disclosure.
[0073] The presence of bleach-catalyzing transition metal complexes is also possible. These are preferably selected among the cobalt, iron, copper, titanium, vanadium, manganese and ruthenium complexes. Possible ligands in such transition metal complexes are either inorganic or organic compounds, which in addition to carboxylates, include in particular compounds having primary, secondary and/or tertiary amine and/or alcohol functions, such as pyridine, pyridazine, pyrimidine, pyrazine, imidazole, pyrazole, triazole, 2,2″-bispyridyl amine, tris-(2-pyridylmethyl)amine, 1,4,7-triazacyclononane, 1,4,7-trimethyl-1,4,7-triazacyclononane, 1,5,9-trimethyl-1,5,9-triazacyclododecane, (bis-((1-methylimidazol-2-yl)-methyl))-(2-pyridylmethyl)amine, N,N′-(bis-(1-methylimidazol-2-yl)-methyl)ethylenediamine, N-bis-(2-benzimidazolylmethyl)aminoethanol, 2,6-bis-(bis-(2-benzimidazolylmethyl)aminomethyl)-4-methylphenol, N,N,N′,N′-tetrakis-(2-benzimidazolylmethyl)-2-hydroxy-1,3-diaminopropane, 2,6-bis-(bis-(2-pyridyl-methyl)aminomethyl)-4-methylphenol, 1,3-bis-(bis-(2-benzimidazolylmethyl)aminomethyl)benzene, sorbitol, mannitol, erythritol, adonitol, inositol, lactose, and optionally substituted salenes, porphins and porphyrins. The inorganic neutral ligands include in particular ammonia and water. If not all coordination sites of the central transition metal atom are occupied by neutral ligands, the complex comprises further, preferably anionic and, among these, in particular monodentate or bidentate, ligands. These include in particular the halides, such as fluoride, chloride, bromide and iodide, and the (NO 2 ) − group, which is to say a nitro ligand or a nitrito ligand. The (NO 2 ) − group can also be bound to a transition metal in a chelating manner, or it may asymmetrically or η 1 -O bridge two transition metal atoms. In addition to the above-mentioned ligands, the transition metal complexes can carry further ligands, which generally have simpler structures, and in particular monovalent or polyvalent anionic ligands. For example, nitrate, acetate, trifluoroacetate, formate, carbonate, citrate, oxalate, perchlorate and complex anions such as hexafluorophosphate may be used. The anionic ligands are to ensure the charge equalization between the central transition metal atom and the ligand system. The presence of oxo ligands, peroxo ligands and imino ligands is also possible. In particular, these ligands may also have a bridging effect, whereby multinuclear complexes are created. In the case of bridged, binuclear complexes, the two metal atoms in the complex do not have to be identical. It is also possible to use binuclear complexes in which the two central transition metal atoms have differing oxidation numbers. If anionic ligands are absent or the presence of anionic ligands does not result in charge equalization in the complex, anionic counterions are present in the transition metal complex compounds to be used as contemplated herein, which neutralize the cationic transition metal complex. These anionic counterions include in particular nitrate, hydroxide, hexafluorophosphate, sulfate, chlorate, perchlorate, the halides such as chloride, or the anions of carboxylic acids such as formate, acetate, oxalate, benzoate or citrate. Examples of transition metal complex compounds that can be used are Mn(IV) 2 (μ-O) 3 (1,4,7-trimethyl-1,4,7-triazacyclononane)-di-hexafluorophosphate, [N,N′-bis[(2-hydroxy-5-vinylphenyl)-methylene]-1,2-diaminocyclohexane] manganese(III) chloride, [N,N′-bis[(2-hydroxy-5-nitrophenyl)-methylene]-1,2-diaminocyclohexane] manganese(III) acetate, [N,N′-bis[(2-hydroxyphenyl)-methylene]-1,2-phenylenediamine] manganese(III) acetate, [N,N′-bis[(2-hydroxyphenyl)-methylene]-1,2-diaminocyclohexane] manganese(III) chloride, [N,N′-bis[(2-hydroxyphenyl)-methylene]-1,2-diaminoethane] manganese(III) chloride, [N,N′-bis[(2-hydroxy-5-sulfonatophenyl)-methylene]-1,2-diaminoethane] manganese(III) chloride, manganese oxalate complexes, nitropentammine cobalt(III) chloride, nitritopentammine cobalt(III) chloride, hexammine cobalt(III) chloride, chloropentammine cobalt(III) chloride and the peroxo complex [(NH 3 ) 5 Co—O—O—Co(NH 3 ) 5 ]Cl 4 .
[0074] Enzymes that can be used in the detergents include those of the class of amylases, proteases, lipases, cutinases, pullulanases, hemicellulases, cellulases, oxidases, laccases and peroxidases, and the mixtures thereof. Particularly suited are enzymatic active ingredients obtained from fungi or bacteria, such as Bacillus subtilis, Bacillus licheniformis, Bacillus lentus, Streptomyces griseus, Humicola lanuginosa, Humicola insolens, Pseudomonas pseudoalcaligenes, Pseudomonas cepacia or Coprinus cinereus . The enzymes can be adsorbed on carrier substances and/or be embedded in coating substances to protect them against premature inactivation. These are preferably present in the laundry detergents or cleaning agents as contemplated herein in amounts of up to 5 wt. %, and in particular of about 0.2 wt. % to about 4 wt. %. If the detergent as contemplated herein comprises protease, this preferably has a proteolytic activity in the range of approximately 100 PE/g to approximately 10,000 PE/g, and in particular about 300 PE/g to about 8000 PE/g. If several enzymes are to be used in the detergent as contemplated herein, this may be carried out by incorporating two or more enzymes that are separate or separately formulated in the known manner, or by two or more enzymes that are formulated together in granules.
[0075] The organic solvents that can be used, in addition to water, in the laundry detergents, in particular if these are present in liquid or pasty form, include alcohols having 1 to 4 carbon atoms, in particular methanol, ethanol, isopropanol, and tert. butanol., diols having 2 to 4 carbon atoms, in particular ethylene glycol and propylene glycol, and the mixtures thereof and the ethers derivable from the above-mentioned compound classes. Such water-miscible solvents are preferably present in the detergents as contemplated herein in amounts not above 30 wt. %, in particular of about 6 wt. % to about 20 wt. %.
[0076] To set a desired pH value that does not result on its own by virtue of mixing the remaining components, the detergents as contemplated herein can comprise system compatible and environmentally compatible acids, in particular citric acid, acetic acid, tartaric acid, malic acid, lactic acid, glycolic acid, succinic acid, glutaric acid and/or adipic acid, but also mineral acids, in particular sulfuric acid, or bases, in particular ammonium or alkali hydroxides. Such pH regulators are preferably present in the detergents as contemplated herein in amounts not above 20 wt. %, in particular of about 1.2 wt. % to about 17 wt. %.
[0077] The task of graying inhibitors is to maintain the dirt dissolved from the textile fibers suspended in the liquor. Water-soluble colloids, usually of an organic nature, are suitable for this purpose, such as starch, glue, gelatin, salts of ether carboxylic acids or ether sulfonic acids of starch or cellulose, or salts of acidic sulfuric acid esters of cellulose or starch. Water-soluble, acidic group-comprising polyamides are also suitable for this purpose. Furthermore, starch derivatives other than those mentioned above may be used, for example aldehyde starches. The use of cellulose ethers, such as carboxymethyl cellulose (Na salt), methyl cellulose, hydroxyalkyl cellulose and mixed ethers, such as methyl hydroxyethyl cellulose, methyl hydroxypropyl cellulose, methyl carboxymethyl cellulose and the mixtures thereof, for example in amounts of 0.1 to 5 wt. %, based on the agents, is preferred.
[0078] If desired, the detergents can comprise a customary dye transfer inhibitor, preferably in amounts of up to 2 wt. %, and in particular of about 0.1 wt. % to about 1 wt. %, which in a preferred embodiment is selected from the polymers of vinylpyrrolidone, vinylimidazole, vinylpyridine-N-oxide, or the copolymers of these. It is possible to use both polyvinylpyrrolidones having molecular weights of about 15,000 g/mol to about 50,000 g/mol and polyvinylpyrrolidones having higher molecular weights of more than 1,000,000 g/mol, and in particular of about 1,500,000 g/mol to about 4,000,000 g/mol, for example, N-vinylimidazole/N-vinylpyrrolidone copolymers, polyvinyloxazolidones, copolymers based on vinyl monomers and carboxylic acid amides, pyrrolidone group-comprising polyesters and polyamides, grafted polyamidoamines and polyethylene imines, polyamine-N-oxide polymers and polyvinyl alcohols. However, it is also possible to use enzymatic systems, comprising a peroxidase and hydrogen peroxide or a substance yielding hydrogen peroxide in water. The addition of a mediator compound for the peroxidase, for example of an acetosyringone, a phenol derivative or a phenothiazine or phenoxazine, is preferred in this case, wherein in addition the above-mentioned polymeric dye transfer inhibitor active ingredients can also be used. Polyvinylpyrrolidone preferably has an average molar mass in the range of about 10,000 g/mol to about 60,000 g/mol, and in particular in the range of about 25,000 g/mol to about 50,000 g/mol. Among the copolymers, those composed of vinylpyrrolidone and vinylimidazole in a molar ratio of about 5:1 to about 1:1, having an average molar mass in the range of about 5,000 g/mol to about 50,000 g/mol, and in particular of about 10,000 g/mol to about 20,000 g/mol, are preferred. In preferred embodiments of the disclosure, however, the laundry detergents are free from such added dye transfer inhibitors.
[0079] Laundry detergents can comprise derivatives of diaminostilbene disulfonic acid or the alkali metal salts thereof, for example, as optical brighteners, although they are preferably free from optical brighteners when used as color laundry detergents. For example, salts of 4,4′-bis(2-anilino-4-morpholino-1,3,5-triazinyl-6-amino)stilbene-2,2′-disulfonic acid or similarly structured compositions are suitable, which carry a diethanolamino group, a methylamino group, an anilino group or a 2-methoxyethylamino group instead of the morpholino group. Moreover, brighteners of the type of substituted diphenylstyryls can be present, for example the alkali salts of 4,4′-bis(2-sulfostyryl)biphenyl, 4,4′-bis(4-chloro-3-sulfostyryl)biphenyl, or 4-(4-chlorostyryl)-4′-(2-sulfostyryl)biphenyls. It is also possible to use mixtures of the aforementioned optical brighteners.
[0080] In particular when used with mechanical processes, it may be advantageous to add customary foam inhibitors to the detergents. For example, soaps of natural or synthetic origin having a high content of C 18 -C 24 fatty acids are suitable foam inhibitors. Suitable non-surfactant-type foam inhibitors are, for example, organopolysiloxanes and the mixtures thereof with micro-fine, optionally silanized silica and paraffins, waxes, microcrystalline waxes and the mixtures thereof with silanized silica or bis-fatty acid alkylene diamides. Advantageously, mixtures of different foam inhibitors are also used, for example those composed of silicones, paraffins or waxes. The foam inhibitors, and in particular silicone-comprising and/or paraffin-comprising foam inhibitors, are preferably bound to a granular carrier substance that is soluble or dispersible in water. In particular, mixtures of paraffins and ethylene distearylamide are preferred.
[0081] The production of solid detergents does not pose any difficulties and be carried out in the known manner, for example by spray drying or granulation, wherein enzymes and potential further thermally sensitive ingredients, such as bleaching agents, are optionally added separately later. To produce detergents having increased bulk density, in particular in the range of 650 g/L to 950 g/L, a method comprising an extrusion step is preferred.
[0082] So as to produce detergents in tablet form, which can be single-phase or multi-phase, single-color or multi-color and in particular can be composed of one layer or of multiple, in particular of two, layers, the procedure is preferably such that all components—optionally of a respective layer—are mixed with each other in a mixer, and the mixture is compressed using conventional tablet presses, such as eccentric presses or rotary tablet presses, using pressures in the range of approximately about 50 to about 100 kN, preferably about 60 to about 70 kN. In particular, in the case of multi-layer tablets, it may be advantageous if at least one layer is pre-compressed. This is preferably carried out at pressures between about 5 and about 20 kN, and in particular at about 10 to about 15 kN. This readily yields break-resistant tablets that nonetheless dissolve sufficiently quickly under usage conditions, with breaking and flexural strengths of normally about 100 to about 200 N, preferably however above 150 N. A tablet thus produced preferably has a weight of about 10 g to about 50 g, in particular of about 15 g to about 40 g. The physical shape of the tablets is arbitrary and can be round, oval or angular, intermediate shapes also being possible. Corners and edges are advantageously rounded. Round tablets preferably have a diameter of about 30 mm to about 40 mm. In particular, the size of angular or cuboid tablets, which are predominantly introduced via the dosing device of the washing machine, is dependent on the geometry and the volume of this dosing device. Preferred embodiments by way of example have a base area of (20 to 30 mm)×(34 to 40 mm), and in particular of about 26×36 mm or of about 24×38 mm.
[0083] Liquid or pasty detergents in the form of solutions comprising customary solvents are generally produced by simple mixing of the ingredients, which can be placed into an automatic mixer in substance or as a solution.
EXAMPLES
Example 1
[0084] The internal salt of sulfuric acid mono-[2-(3,4-dihydro-isoquinolin-2-yl)-1-(2-ethylhexyloxy-methyl)-ethyl] ester was prepared as in Example 4 of WO 03/104199 A2. An aqueous solution comprising 16 ppm of the dye Acid Blue 113 was mixed with the aforementioned dihydroisoquinoline compound, so that the concentration thereof was 50 mg/L, and was electrolyzed for 3 hours at 23° C. and a pH of 2.5 at a potential difference of 1.35 V (Ag/AgCl) using a working electrode made of boron-doped graphite and a counter electrode made of stainless steel. For comparison, the same solution was electrolyzed under the same conditions without adding the dihydrosioquinoline. Thereafter, the concentration of the dye in each solution was photometrically (wavelength 548 nm) determined. In the dihydroisoquinoline-comprising solution, the breakdown of the dye was 10% higher than in the solution without the compound. Neither in the absence nor in the presence of the dihydroisoquinoline compound was a decomposition of the dye observed in solutions that were kept without electrolysis for an identical duration for comparison purposes.
Example 2
[0085] Example 1 was repeated, except that now no electrolysis device was used, but the aqueous solutions, which had previously been mixed with H 2 O 2 (to a concentration of 10 mmol/l), were exposed for 10 minutes to radiation of a UV lamp (supplier Benda, Wiesloch; type NU-15 KL, 220 volt, 15 watt, 1 ampere; wavelength set to 254 nm). In the dihydroisoquinoline-comprising solution, the breakdown of the dye was 21.4% higher than in the solution without the compound.
[0086] While at least one exemplary embodiment has been presented in the foregoing detailed description, it should be appreciated that a vast number of variations exist. It should also be appreciated that the exemplary embodiment or exemplary embodiments are only examples, and are not intended to limit the scope, applicability, or configuration of the various embodiments in any way. Rather, the foregoing detailed description will provide those skilled in the art with a convenient road map for implementing an exemplary embodiment as contemplated herein. It being understood that various changes may be made in the function and arrangement of elements described in an exemplary embodiment without departing from the scope of the various embodiments as set forth in the appended claims.
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The disclosure relates to a method of washing textiles in a washing machine having a washing chamber for accommodating a washing liquid and textiles to be cleaned and having an activating unit possessing an inlet or introduction of washing liquid from the washing chamber into the activating unit and possessing an outlet for guiding washing liquid out of the activating unit into the washing chamber, and additionally having at least one means of activation suitable for setting in motion a process for forming free radicals in the washing liquid within the activating unit, wherein the washing liquid comprises an organic bleach booster compound, especially a zwitterionic 3,4-dihydroisoquinolinium derivative.
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CROSS-REFERENCE TO RELATED APPLICATION
This application is a divisional application of prior application Ser. No. 10/888,862, filed Jul. 9, 2004, now U.S. Pat. No. 7,191,017, issued Mar. 13, 2007, which is herein incorporated by reference in its entirety.
TECHNICAL FIELD
The present invention is related to implantable cardiac leads used with a cardiac function management device such as a pacemaker, a defibrillator, or a cardiac resynchronization therapy device to monitor and control heart function.
BACKGROUND
Cardiac function management devices, including implantable pacemakers and implantable defibrillators, include at least one cardiac lead having an electrode for making contact with a portion of the heart. Such leads are typically connected to a pulse generator at their proximal end and to cardiac tissue at their distal end. When such a lead is positioned so as to stimulate the left ventricle, it is common to advance the lead deep into the cardiac veins in order to effectively sense and stimulate in the left ventricle. However, traditional leads are not well suited for implantation in the coronary veins because the veins are narrow and traditional leads are often too large in diameter. Therefore, it is desirable to have a cardiac lead of a smaller size for placement in the coronary vein for left ventricle sensing and stimulation.
One such smaller size lead comprises a two-part bipolar lead where the first part of the lead includes an insulated conductive coil with an electrode at the distal end and the second part of the lead includes a wire or cable with an electrically conductive surface at its distal tip, which is delivered down the center of the conductive coil. There is a need in the art for a connector for such a lead that connects and secures the conductive cable to the conductive surface. There is a further need for such a device including a terminal connector compatible with standard cardiac function management devices.
SUMMARY
The present invention, according to one embodiment, is a method of implanting a cardiac lead. The method comprises advancing an outer lead portion into a coronary vessel, the outer lead portion having a longitudinal lumen and a terminal connector located at a proximal end. The terminal connector defines an internal bore and is adapted to couple with a cardiac function management device. A conductive member of an inner lead portion is advanced through the longitudinal lumen. A pin is attached to a proximal end of the conductive member such that the pin mechanically engages the internal bore of the terminal connector.
The present invention, according to another embodiment, is a method of implanting a cardiac lead. The method comprises advancing an outer lead portion into a heart or a coronary vessel, the outer lead portion having a longitudinal lumen, a terminal connector located at a proximal end, and a sleeve connected to the terminal connector. The terminal connector defines an internal bore and is adapted to couple with a cardiac function management device. A conductive member of an inner lead portion is advanced through the longitudinal lumen. A pin is attached to a proximal end of the conductive member such that the pin mechanically engages and couples to the sleeve and is electrically insulated from the terminal connector by the sleeve.
The present invention, according to yet another embodiment, is a method of implanting a cardiac lead. The method comprises advancing a guide catheter to a desired location in or near a heart. An inner lead portion having a conductive member is advanced through the guide catheter. An outer lead portion having a longitudinal lumen and a terminal connector located at a proximal end of the outer lead portion is advanced over the inner lead portion. The terminal connector defines an internal bore and is adapted to couple with a cardiac function management device. The outer lead portion is advanced over the inner lead portion. A pin is attached to a proximal end of the conductive member such that the pin mechanically engages and couples to the internal bore of the terminal connector.
While multiple embodiments are disclosed, still other embodiments of the present invention will become apparent to those skilled in the art from the following detailed description, which shows and describes illustrative embodiments of the invention. As will be realized, the invention is capable of modifications in various obvious aspects, all without departing from the spirit and scope of the present invention. Accordingly, the drawings and detailed description are to be regarded as illustrative in nature and not restrictive.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a perspective view of a cardiac function management system in accordance with the present invention.
FIG. 2 is a sectional view of a cardiac lead of FIG. 1 , according to one embodiment of the present invention.
FIG. 3 is a partial sectional view of the proximal end and first portion of the cardiac lead of FIG. 2 , according to one embodiment of the present invention.
FIGS. 4A-4B are partial sectional views of the proximal end and first portion of the cardiac lead of FIG. 2 , according to another embodiment of the present invention.
FIGS. 4C-4D show side plan view of the portion of FIG. 4B indicated as 4 C- 4 D.
FIGS. 5A-5B are partial sectional views of the proximal end and first portion of the cardiac lead of FIG. 2 , according to a third embodiment of the present invention.
FIG. 6 is a partial sectional view of the proximal end and first portion of the cardiac lead of FIG. 2 , wherein the pin is threadably engaged with the sleeve, according to a fourth embodiment of the present invention.
FIG. 7 is a partial sectional view of the proximal end and first portion of the cardiac lead of FIG. 2 , according to a fifth embodiment of the present invention.
FIG. 8 is a partial sectional view of the proximal end and first portion of the cardiac lead of FIG. 2 , according to a sixth embodiment of the present invention.
FIGS. 9A-9C are partial sectional views of the proximal end and first portion of the cardiac lead of FIG. 2 , according to a seventh embodiment of the present invention.
FIGS. 10A-10C are partial sectional views of the jaws of FIGS. 9A-9B , wherein the jaws include mechanisms for gripping the conductive member, according to alternative embodiments of the present invention.
FIGS. 11A-11C are sectional views of the distal end of the cardiac lead of FIG. 2 , according to yet other alternative embodiments of the present invention.
FIG. 12 is a flowchart showing an implantation process for implanting the cardiac lead of FIG. 2 into the human heart.
DETAILED DESCRIPTION
FIG. 1 is a perspective view of a cardiac function management system 10 for delivering a treatment or therapy to a human heart. The cardiac function management system 10 may, for example, be a pacemaker, an ICD, or a cardiac resynchronization device. The system 10 includes a pulse generator 22 and a cardiac lead 24 . The pulse generator 22 includes a power source, circuitry for receiving and delivering electrical signals through the cardiac lead 24 , and circuitry for determining an appropriate therapy.
As shown in FIG. 1 , the lead 24 is implanted into a human heart 25 through a coronary vein 26 . The lead 24 operates to convey electrical signals between the heart 25 and the pulse generator 22 . A proximal end 28 of the lead 24 is coupled to the pulse generator 22 and a distal end 30 includes to a surface electrode 32 . In the embodiment shown in FIG. 1 , the cardiac lead 24 of the present invention extends through the superior vena cava 34 , the right atrium 36 , and the coronary sinus 38 into the coronary vein 26 , so that the surface electrode 32 is located in a branch of the coronary vein 26 . When positioned as above, the electrode 32 can be used to sense the electrical activity of the heart 25 or to apply a stimulating pulse to the left ventricle 40 . In other embodiments, the cardiac lead 24 of the present invention can also be implanted in any other portion of the heart as known in the art of cardiac function management. For example, it may be implanted in right atrium 36 , the left atrium 41 , the right ventricle 42 , or the pulmonary artery 43 .
FIG. 2 shows a sectional view of the cardiac lead 24 in accordance with the present invention. As shown in FIG. 2 , the cardiac lead 24 includes an inner or first portion 44 and an outer or second portion 46 . The first portion 44 is sized to fit into and couple with the second portion 46 . The first portion 44 , shown from left to right in FIG. 2 , includes a conductive member 50 , a connector assembly 51 , and a front seal 52 . As shown from left to right on the bottom portion of FIG. 2 , the second portion 46 includes the surface electrode 32 , a lead body 54 , a rear seal 56 , and a terminal connector 58 .
The connector assembly 51 electrically and mechanically connects the cardiac lead 24 to the pulse generator 22 . The connector assembly 51 includes a pin 60 , which is configured to mechanically couple to the terminal connector 58 (or a tube or sleeve 62 as shown in FIGS. 3-8 ). The pin 60 , which is made from an electrically conductive material, is adapted to connect electrically and mechanically to the cable or conductive member 50 . The connection can be pre-formed or formed upon coupling with the terminal connector 58 . In embodiments where the connection is formed upon coupling with the terminal connector 58 , the connection can be permanent or reversible. The pin 60 , however, is electrically insulated from the terminal connector 58 . In one embodiment, the conductive member 50 is a wire or a cable. The conductive member 50 may include an insulating sheath 61 . The insulating sheath 61 can be a polymer or other insulating material surrounding the conductive member 50 . As shown in FIG. 2 , the front seal 52 surrounds a proximal end 64 of the pin 60 . The front seal 52 is a standard seal as is known in the industry, such as an IS-1 seal. The front seal 52 may have any other standard terminal configuration known in the art.
The lead body 54 of the second portion 46 is sized to allow cannulation of the coronary sinus and coronary veins. The lead body 54 includes an outer sheath 70 that substantially extends from a proximal end 72 of the lead body 54 to a distal end 74 of the lead body 54 and can be made of polyurethane tubing or any other material known in the art. The outer sheath 70 encapsulates a flexible conductive coil 76 . In one embodiment, the outer sheath 70 encapsulates one or more cables or both cables and a conductive coil 76 . In one embodiment, the conductive coil 76 may be coated with any biocompatible, polymeric material, such as, for example, ETFE, PTFE, silicone rubber, or polyurethane. In various embodiments the conductive coil 76 is made from any biocompatible material, such as stainless steel, MP35N, Platinum/Tantalum, and DFT.
A lumen 78 is located inside the lead body 54 and extends from the proximal end 72 to the distal end 74 . Upon assembly of the first portion 44 and the second portion 46 , the conductive member 50 extends through the lumen 78 from the proximal end 28 of the cardiac lead 24 to near the distal end 30 of the cardiac lead 24 . In one embodiment, the conductive member 50 extends beyond the distal end 30 and has a tip 80 serving as an electrode 31 . The conductive member 50 can be used convey sense electrical activity from the heart 25 or to convey electrical signals to the heart 25 , or both. Alternatively, the conductive member 50 may not extend beyond the distal end 30 of the cardiac lead 24 , but instead may couple to an electrode on the lead body 54 (see, for example, FIGS. 11B and 11C .) In one embodiment, a spiral fixation shape is incorporated into the distal end 74 of the lead body 54 , which can facilitate fixation of the lead inside of the coronary vein. In another embodiment, fixation is accomplished using tines coupled to the distal end 74 of the lead body 54 .
The terminal connector 58 , as shown in FIG. 2 , includes a tab 82 that is inserted into the proximal end 72 of the lead body 54 . The tab 82 of the terminal connector 58 is electrically connected to the conductive coil 76 . The rear seal 56 surrounds a portion of the conductive coil 76 that overlaps with the tab 82 . The surface electrode 32 is located at the distal end 30 of the cardiac lead 24 . The surface electrode 32 can be a terminal connector electrically connected to the conductive coil 76 or alternatively can be created by removing an annular portion of outer sheath 70 , thus exposing a portion of conductive coil 76 . The position of the surface electrode 32 along the cardiac lead 24 can vary. In one embodiment, the lead 24 includes more than one surface electrode 32 .
FIG. 3 shows a partial sectional view of the proximal end 72 of the lead body 54 and the first portion 44 of the cardiac lead 24 , in accordance with one embodiment of the present invention. As shown in FIG. 3 , the first portion 44 includes the conductive member 50 , the connector assembly 51 , and the front seal 52 . The connector assembly 51 includes the pin 60 , which is adapted for insertion into the sleeve 62 . The sleeve 62 is generally shaped like a hollow cylinder and is adapted for insertion into and coupling with the terminal connector 58 . The sleeve may be formed, for example, for PEEK, tecothane, or other biocompatible polymers. In one embodiment, the sleeve 62 is adapted to snap fit into the terminal connector 58 . In another embodiment, the sleeve 62 is formed directly on the interior surface of the terminal connector 58 . In another embodiment, the sleeve 62 is formed directly on the pin 60 .
As shown in FIG. 3 , the sleeve 62 includes a leading surface 84 which contacts a shoulder 86 of the terminal connector 58 when the sleeve 62 is inserted into the terminal connector 58 . The sleeve 62 also includes an inner surface 88 and an outer surface 90 . The outer surface 90 has protrusions 92 , which mate with indentations 94 on the terminal connector 58 . The protrusions 92 encircle the sleeve 62 and fit into the grooves comprising the indentations 94 on the terminal connector 58 . The protrusions 92 and indentations 94 could be of any configuration that effects mechanical coupling between the sleeve 62 and the terminal connector 58 . The inner surface 88 of the sleeve 62 has an angled surface 96 , which forms a triangular groove within the sleeve 62 . The inner surface 88 of the sleeve 62 also has indentations 98 adapted for mating with the pin 60 . The indentations 98 could be grooves or any other receptive feature as is known in the art.
The pin 60 has a generally cylindrical shape and has a pin proximal end 100 , a pin distal end 102 , a pin tip 104 , and pin protrusions 106 . As shown in FIG. 3 , the pin distal end 102 is tapered. In an alternative embodiment, the pin distal end 102 need not be tapered. The pin distal end 102 is electrically and mechanically connected or coupled to the conductive member 50 . The pin protrusions 106 have an attaching end 108 and an engaging end 110 and are interposed between the pin tip 104 and the pin proximal end 100 . The attaching end 108 is resiliently attached to the pin 60 so that the pin protrusions 106 are compressed toward the pin 60 as the pin 60 is inserted into the sleeve 62 and expand outward into the indentations 98 upon reaching the indentations 98 , thereby locking the pin 60 into place in the sleeve 62 . The embodiment of FIG. 3 shows two protrusions 106 but any number of protrusions could be used. In an alternative embodiment, pin protrusions 106 could be one or more solid protrusions encircling the pin 60 , or the pin protrusions 106 could be some other attachment feature as is known in the art, such as leaf springs. In one embodiment, the sleeve 62 (or terminal connector 58 ) supports a seal 111 near the proximal end. In this embodiment, the seal 111 functions to contact a leading portion of the front seal 52 , such that when the first portion 44 is inserted into the second portion 46 , the two portions form a sealed interface.
FIGS. 4A-4B show partial sectional views of the interface between the pin 60 of the first portion 44 and the terminal connector 58 of the second portion 46 . In one embodiment, the conductive member 50 is fixed with respect to the pin 60 , such that the pin 60 and the conductive member 50 are inserted into the second portion 46 simultaneously. In another embodiment, the pin 60 is adapted for insertion over the conductive member 50 , after the conductive member 50 is properly positioned within the second portion 46 . As shown in FIG. 4A , the pin 60 includes a lumen 112 extending along the longitudinal axis 114 of the pin 60 . The conductive member 50 is positioned in the lumen 112 . The pin 60 engages with the sleeve 62 , locking the pin 60 and the conductive member 50 into place. In the embodiment shown in FIG. 4A , pin protrusions 106 are attached at the pin distal end 102 . In the alternative embodiment shown in FIG. 4B , the pin protrusions 106 are attached at a location further from the pin tip 104 .
FIGS. 4C and 4D show side views of the portion of FIG. 4B marked 4 C- 4 D. FIGS. 4C and 4D show the jaws 102 in further detail. As shown, as the jaws 102 close, they cut through the insulating sheath 61 thereby creating both a mechanical and an electrical connection between the pin 60 and the conductive member 50 . In the embodiment shown in FIG. 4C , the jaws 102 include substantially flat edges 115 for cutting through the insulating sheath 61 . In another embodiment shown in FIG. 4D , the jaws 128 have serrated edges 115 . In this embodiment, the pin tip 104 may be composed of 2, 3, 4, or more jaw members 102 .
FIGS. 5A-5B show partial sectional views of the interface between the pin 60 of the first portion 44 and the terminal connector 58 of the second portion 46 , wherein the pin 60 is removably coupled to the sleeve 62 . As shown in FIG. 5A , the pin protrusions 106 include a bend 116 having an angle 118 . The angle 118 is such that when the pin 60 is pulled out of the sleeve 62 , a contact area 120 acts against a top surface 122 of the protrusion 106 to compress the protrusion 106 toward the pin 60 , thereby releasing the pin 60 from the sleeve 62 and allowing removal of the pin 60 and repositioning of the conductive member 50 . In the embodiment shown in FIG. 5A , the pin protrusions 106 are attached at the pin distal end 102 . In the alternative embodiment shown in FIG. 5B , the pin protrusions 106 are attached at a position further from the pin tip 104 .
FIG. 6 shows a partial sectional view of an alternative embodiment of the present invention, wherein the conductive member 50 is removable from the pin 60 . As shown in FIG. 6A , the pin 60 is threadably engagable with the sleeve 62 . In the embodiment shown in FIG. 6A , the pin 60 has external threads 124 and the sleeve 62 has mating internal threads 126 . When the pin 60 is screwed into the sleeve 62 , a leading angled surface 96 of jaws 128 contact the angled surface 96 , which causes the jaws 128 to close on the conductive member 50 .
FIG. 7 shows a partial sectional view of yet another alternative embodiment of the present invention. As shown in FIG. 7 , the pin 60 includes both threads 124 and protrusions 106 . The sleeve 62 includes the sleeve inner surface indentations 98 and threads 126 . In the embodiment shown in FIG. 7 , the protrusions 106 are shaped in the form of a chamfer so that as the pin 60 is screwed into the sleeve 62 , the protrusions 106 mechanically engage with the sleeve inner surface indentations 98 , locking the pin 60 into place in sleeve 62 . In an alternative embodiment, the pin 60 and sleeve 62 include pin protrusions 106 and sleeve inner surface indentations 98 of the type shown in FIGS. 3-5B . The location of the protrusions 106 and inner sleeve indentations 98 can vary along the longitudinal axis 114 .
FIG. 8 shows a partial sectional view of yet another alternative embodiment of the present invention, wherein the pin 60 and the sleeve 62 act to sever the conductive member 50 when the pin 60 is mechanically engaged with the sleeve 62 . As shown in FIG. 8 , the pin 60 includes cutting edges 134 and a shoulder 136 . The sleeve 62 includes a protrusion 138 . The shoulder 136 and protrusions 138 are located at a distance along the longitudinal axis 114 such that when the shoulder 136 reaches the protrusions 138 , the protrusions 138 act against the shoulder 136 , causing the cutting edges 134 to compress, thereby severing the conductive member 50 . In the embodiment shown in FIG. 8 , the protrusions 138 have an arcuate shape, but other shapes are within the scope of the present invention, including a chamfer encircling the inner surface 88 of the sleeve 62 . The number of protrusions 138 and cutting points 134 can also vary as needed.
FIGS. 9A-9B show an alternative embodiment of the present invention wherein the jaws 128 include cutting points 134 , gripping points 140 , and a jaw indentation 142 . The cutting points could be made using any technique known in the art, including, for example, wire EDM. The pin 60 includes a leading surface 144 and the sleeve 62 includes a shoulder 146 . In this embodiment, as the pin 60 is advanced into the sleeve 62 , the angled surface 96 acts to compress the jaws 128 together. As the jaws 128 are compressed together, gripping points 140 retain the conductive member 50 in the jaws 128 and cutting points 134 sever the conductive member 50 . In one embodiment, as shown in FIG. 9C , the jaws 128 act in conjunction with the sleeve 62 to constrain the cable or conductive member 50 , such that when it is gripped by gripping points 140 or cut at cutting points 134 , the cable does not flatten, which would impede this gripping or cutting action.
The conductive member 50 is forced into the jaw indentation 142 and can then be removed from the pin 60 in the direction shown by the arrow in FIG. 9B . When the pin 60 is inserted into the sleeve 62 , the leading surface 144 contacts the sleeve shoulder 146 to stop the pin from advancing further into the sleeve 62 . In the embodiment shown in FIGS. 9A-9B , pin protrusions 106 mechanically engage with sleeve inner surface indentations 98 to lock the pin 60 into place. Alternatively, the pin 60 and sleeve 62 could be threadably engaged as shown in FIGS. 6A-6C , or engaged using threads and a snap fit as shown in FIG. 7 .
FIGS. 10A-10C show alternative embodiments of the jaw gripping mechanism. In FIG. 10A , the jaws 128 have inner surfaces 148 having sinusoidal shapes and gripping points 140 that are sharp enough to cut through the insulating sheath 61 of the conductive member 50 . In FIG. 10B , the inner surfaces 148 are substantially flat so as to better control the depth of the cut into the insulating sheath 61 . In the embodiment shown in FIG. 10C , the inner surfaces 148 have a proximal end 150 and a distal end 152 . The proximal end 150 includes gripping points 140 that cut through the insulating sheath 61 . The distal end 152 includes curves 154 that act to hold the conductive member 50 into place without penetrating the insulating sheath 61 .
FIGS. 11A-11C show alternative embodiments of the distal end of the cardiac lead 24 . In the embodiment shown in FIG. 11A , the conductive member 50 extends beyond the distal end 30 of the lead body 54 . The conductive member 50 has a generally spherically-shaped tip 80 . The tip 80 can also be canted or biased to one side to improve contact with the coronary vein 26 . In this embodiment, the tip 80 of the conductive member 50 functions as the surface electrode 31 . In one embodiment, the lead body further includes a drug collar 155 .
In an alternative embodiment shown in FIGS. 11B and 11C , the surface electrode 32 includes a first surface electrode 158 located near the distal end 30 of the cardiac lead 24 and a second surface electrode 159 located further from the distal end 30 . As shown in FIG. 11C , the first surface electrode 158 includes recesses 160 , a proximal surface 162 , and a distal surface 164 . The proximal diameter 166 is slightly larger than the distal diameter 168 so that the conductive member 50 can pass through the proximal diameter 166 but not the distal diameter 168 . The distal diameter 168 is large enough that a guidewire (not shown) can pass through it.
As further shown in FIG. 11C , the conductive member 50 includes a cable conductor 170 and tines 174 . As shown in FIG. 11C , the tines 174 are resiliently attached to the tip 176 of the cable conductor 170 . When the conductive member 50 is inserted through the lumen 78 of the lead body 54 sufficiently far that the tines 174 reach the recesses 160 , the tines 174 expand outward into the recesses 160 , thereby electrically and mechanically attaching to the surface electrode 158 . Two tines 174 are shown in FIG. 11B , but any number could be used as needed for retention properties. In this embodiment, the conductive member 50 can be used to electrically couple the first surface electrode 158 to the pin 60 . In other embodiments, any other configuration known in the art can be used to couple the distal end of the conductive member to either of the surface electrodes 158 , 159 . In one embodiment, the conductive member 50 is fixed with respect to the lead body 54 , such that the conductive member 50 can be used as a stylet for delivering the lead body 54 . In one embodiment, the conductive member 50 is fixed rotationally, such that it can be used to apply torque for steering the lead body 54 during delivery. In one such embodiment, the conductive member 50 has a pre-formed shape to assist in delivery and cannulation.
FIG. 12 depicts an exemplary implantation process 200 for implanting the cardiac lead 24 into the human heart 25 . As shown, the second portion 46 of the cardiac lead 24 is advanced, using a stylet or over a guide wire, to the desired position in the coronary vein 26 (block 206 ). In one embodiment, the cardiac lead 24 is advanced through a previously-placed guide catheter extending through the vasculature to the coronary sinus. The stylet or guide wire is then removed from the lumen 78 of the second portion 46 (block 208 ). Next, the first portion 44 of the cardiac lead 24 is inserted into the lumen 78 and advanced to the desired position in the coronary vein 26 (block 210 ). The conductive member 50 is then advanced through a lumen in the first portion 44 . In one embodiment, the conductive member 50 is advanced to a position extending beyond the distal end of the lead body 54 , such that the tip 80 can act directly as a surface electrode 31 (see FIG. 11A ). In another embodiment, the distal end of the conductive member 50 couples to a surface electrode 32 located on the lead body 54 (see FIGS. 11B-11C ). The first portion 44 and the second portion 46 are then connected using the connector assembly 51 at the proximal end 28 of the cardiac lead 24 (block 212 ). If needed, any excess portion of the conductive member 50 can be removed (block 214 ). In an alternative embodiment, the connector assembly 51 is pre-affixed to the conductive member 50 , such that insertion of the conductive member 50 and coupling of the connector assembly 51 to the second portion 46 occur simultaneously. In yet another alternative method, the conductive member 50 can be used as a stylet to deliver the second part 46 of the cardiac lead 24 .
Although the present invention has been described with reference to exemplary embodiments, persons skilled in the art will recognize that changes may be made in form and detail without departing from the spirit and scope of the invention.
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Methods of implanting a two-part cardiac lead in a heart are disclosed. The two-part cardiac lead has inner and outer portions and a pin. The inner and outer lead portions are separately advanced to a location of interest within the vasculature of a patient. The pin is attached to a proximal end of the inner lead portion and can provide a connection between the inner and outer lead portions.
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CROSS-REFERENCES TO RELATED APPLICATIONS
[0001] This application is a Continuation of U.S. application Ser. No. 11/589,123, filed on Oct. 27, 2006, which is a Continuation of U.S. application Ser. No. 10/886,151, filed on Jul. 6, 2004, now U.S. Pat. No. 7,261,913 B2, which claims the benefit of U.S. provisional patent application No. 60/485,425, filed on Jul. 7, 2003; the contents of each of which are hereby incorporated by reference thereto.
BACKGROUND OF THE INVENTION
[0002] The present invention relates to aerated multiphase systems containing an aqueous continuous fluid phase which may include solutes, thus forming an aqueous syrup and disperse phases like gas/air cells, water ice crystals and solid/semi-solid fat globules or aggregates thereof, whereas the disperse phases are that finely structured that their mean diameters are below phase specific critical maximum values and thereby generate a most preferred by consumers, full rich silky-creamy mouth feel at much lower fat content than usual in conventional related products like premium and super premium ice creams, and processes for their manufacture.
[0003] In conventional frozen and aerated water-based ice slurries of the ice cream type, creaminess is mainly generated by a disperse fat phase forming globules with diameters between 0.5 and 2 microns, preferably below 1 micron, and/or fat globule aggregates built due to partial coalescence of the primary fat globules. Such interconnected fat globules/fat globule aggregates can form a three-dimensional network thus stabilizing the air cells in the ice cream structure, most obviously when the ice crystals are melted. Fat globule networking in particular at the air cell interface is supported by more hydrophobic fat globule surfaces. Those are more available if emulsifiers like mono-/diglycerides containing a larger fraction of unsaturated fatty acids support the de-hulling of initially protein covered fat globules in the temperature range where a major portion of the fat fraction crystallizes. In ice creams, milk fat is generally used as the main fat component for which the related relevant crystallizing temperature range is below 5 to 8° C. The well stabilized air cells are mainly responsible for the creaminess and texture sensation during ice cream melting in the mouth. The more stable the air cell/foam structure in the melted state during shear treatment between tongue and palate, the more pronounced the creaminess is perceived. Another but smaller direct contribution to the creaminess is derived from medium sized fat globule aggregates below 30 micron. If the fat globule aggregates become too large (larger than about 30-50 microns) the creamy sensation turns into a buttery, fatty mouth feel.
[0004] It has been demonstrated how the diameter reduction of the fat globules by applying higher homogenization pressure in ice cream mix preparation supports the build-up of a fat globule network, improving air cell/foam structure stability and related creaminess.
[0005] The scoop ability of frozen, aerated slurries like ice cream is mainly related to the ice crystal structure, in particular the ice crystal size and their inter-connectivity. Scoop ability is a very relevant quality characteristic of ice creams in the low temperature range between −20° C. and −15° C., right after removing from the freezer. In conventional ice cream manufacture partial freezing is done in continuous or batch freezers (=cooled scraped surface heat exchangers) down to outlet temperatures of about −5° C. Then the ice cream slurry is filled into cups or formed e.g. at the outlet of extrusion dies. Following this the products are hardened in freezing systems with coolant temperatures of around −40° C. until a product core temperature of about −20° C. is reached. Then the products are stored and/or distributed. After the pre-freezing step in the scraped surface heat exchanger (=ice cream freezer) in conventional ice cream recipes, about 40-45% of the freezable water is frozen as water ice crystals. Another fraction of about 25-30% is still liquid. Most of this fraction freezes during further cooling in the hardening system. In this production step, the ice cream is in a state of rest. Consequently the additionally frozen water crystallizes at the surfaces of the existing ice crystals, thus causing their growth from about 20 microns to 50 microns and larger. Some of the initial ice crystals are also interconnected thus forming a three-dimensional ice crystal network. If such a network is formed the ice cream behaves like a solid body and the scoop ability becomes very poor.
[0006] It has been shown that the ice crystal growth during cooling/hardening is claimed to be restricted by the use of anti-freeze proteins. This is also expected to have a positive impact on the ice crystal connectivity with respect to improved scoop ability.
[0007] It has also been claimed that the use of other specific ingredients like low melting vegetable fat, polyol fatty acid polyesters or specific sugars like sucrose/maltose mixtures are claimed to soften the related ice cream products thus improving scoop ability and creaminess.
[0008] Finally reference has been made to specific processing equipment, mostly single or twin screw cooled extruders, in order to modify the ice cream microstructure for improving the texture and stability properties.
[0009] It has not yet been recognized that all of the disperse phases in aerated frozen ice cream-like slurries can be reduced or modified in size and/or connectivity on the basis of a mechanical shear treatment principle. Thus the mechanical shear treatment principle can effectively contribute to the adjustment of microstructure related quality characteristics like scoop ability and creaminess.
SUMMARY OF THE INVENTION
[0010] The present invention provides products that are aerated multiphase systems containing an aqueous continuous fluid phase which may include solutes thus forming an aqueous syrup and disperse phases like gas/air cells, water ice crystals and solid/semi-solid fat globules or aggregates thereof, whereas the disperse phases are that finely structured that their mean diameters are below phase specific critical maximum values and thereby generate a most preferred by consumers, full rich silky-creamy mouth feel at much lower fat content than usual in conventional related products like premium and super premium ice creams.
[0011] The present invention also provides a process that may use a variety of mechanical moving tools like stirrers, rollers, bands, blades and the-like as the mechanical first major component to generate a uniform shear flow field between them or between them and fixed walls. The second major component of the inventive process is a thermal cooling system which cools the moving or fixed tools/walls down to temperatures slightly warmer than the glass transition temperature Tg′ of the multiphase fluid system. According to the inventive idea the mechanical stresses acting in the process are applied in such a way that each volume unit of the fluid system experiences the same stress history (=same stresses and same stress-related residence times). At the same time the applied shear treatment is adjusted such, that the heat transfer from the fluid to the cooling agent in a final treatment state of the fluid system, with more than 60-70% of the freezable watery fluid phase forming ice crystals, and/or the total disperse solids content in the non aerated material fraction (water ice crystals+fat globules+eventually other disperse solids) exceeding 50% vol., is still sufficient to transfer the heat generated by viscous friction due to shearing of the material to the cooling agent without re-melting the partially frozen aerated system.
[0012] Surprisingly it was found, that when shear stresses within a distinct range of 5000-75000 Pa, preferably 10000-15000 Pa, act on the microstructure of frozen aerated slurries like ice cream [in which more than 50-60% of the freezable continuous liquid phase, in general water, is frozen], all typical disperse structuring components like ice crystals, air cells and fat globules or agglomerates thereof are more finely structured. This happens to such an extent, that scoop ability and creaminess characteristics are most positively influenced, as long as the dissipated viscous friction energy is efficiently transferred to a cooling system at the same time.
[0013] This principle works independent of the apparatus choice and apparatus geometry if the presumptions of homogeneous shear force input, heat transfer and narrow residence time distribution are fulfilled for all volume units.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is a graph illustrating ice crystal diameter vs. cumulative number distribution of the present invention vs. a conventional freezer;
[0015] FIG. 2 is a graph illustrating aircell diameter of the present invention vs. a conventional freezer;
[0016] FIG. 3 is a graph illustrating milk fat particle diameter of the present invention vs. a conventional freezer for 8% milk fat ice cream formulation;
[0017] FIG. 3A is another graph illustrating particle diameter of the present invention vs. a conventional freezer for 5.5% milk fat ice cream formulation;
[0018] FIG. 4 is a graph illustrating storage/loss moduli vs. temperature of the present invention vs. a conventional freezer;
[0019] FIG. 5 illustrates an oscillatory shear rheometer;
[0020] FIG. 6 is a graph illustrating storage/loss moduli vs. temperature of the present invention vs. a conventional freezer;
[0021] FIG. 7 is a graph illustrating sensory scores of the present invention vs. conventional products; and
[0022] FIGS. 8 and 9 illustrate test market scores of the present invention vs. conventional products.
DETAILED DESCRIPTION OF THE INVENTION
[0023] The present invention relates to frozen or partially frozen concentrated water based aerated slurries like e.g. ice cream or other frozen deserts which are mechanically treated by means of mechanical tools generating shear flow with large acting shear stresses, thus reducing contained disperse phases like ice crystals/ice crystal agglomerates, gas/air cells and fat globules/fat globule aggregates in size. According to the present invention this shear treatment is applied to such an extent that in the final product the ice crystal mean diameter (mean value of the volume distribution) does not exceed 30 microns, 10 microns are not exceeded for the gas/air cell mean diameter and 100 microns for the fat globule aggregate diameter.
[0024] At the same time, the energy dissipation rate is kept smaller than the heat transfer rate to the cooling agent, because otherwise the ice crystals would partially or fully re-melt. Furthermore this mechanical treatment of the frozen aerated slurry is uniform with respect to the acting stresses and treatment time for each volume element of the mass.
[0025] According to the present invention, this is realized by applying the high shear forces at such low temperatures where more than 50 to 60% of the freezable water fraction is in the frozen ice crystal state.
[0026] The maximum freezable water fraction cg′ is recipe-specific. For a pure watery sucrose solution between 75 to 80% are measured for cg′. If this maximum freeze concentration state is reached the remaining liquid water fraction is a highly concentrated sucrose syrup which solidifies in a glassy state if the temperature is further reduced thus undergoing the so-called glass transition temperature Tg′. If the added sugars have a lower molecular weight compared to sucrose, Tg′ is shifted to lower temperatures, if larger e.g. oligo- and/or polysaccharide molecules are added Tg′ is accordingly shifted to higher Tg′ values. All molecules dissolved or colloidally dispersed in the continuous watery phase of the frozen aerated slurry have a related influence on the glass transition temperature Tg′ of the mass. cg′, denoting the freezable water fraction depends as well on the composition of the molecule species, which are solved in the continuous water phase.
[0027] If the ice crystal concentration reaches 50-60% of cg′ (=50-60% of the freezable water in the frozen state), the liquid watery continuous phase is already in a highly concentrated syrup state containing e.g. sugars, polysaccharides and proteins in regular ice cream recipes.
EXAMPLES
Example 1
[0028] In a typical ice cream recipe with total dry matter content of about 40% (related to total mass) and 60% of water, a total freezable water fraction of 75% (cg′=0.75; related to the pure water phase) is equivalent to 45% of maximum frozen water content related to the total mass. If in such a system 50% of the freezable water are frozen, this is consequently equivalent to 22.5% of frozen water, related to the total mass. If the total non-dissolved solids fraction is calculated related to the total mass about 10% of fat globules/fat globule aggregates have to be added to the disperse ice crystal fraction of 22.5% (for this example). Such a slurry containing 32.5 weight % (=equal to about 32.5 volume % due to the density of the solids close to water density) of disperse phase is a highly concentrated suspension in which the solid particles sterically interact with each other if a shear flow is applied.
[0029] If such a concentrated suspension is additionally aerated with typically about 50% of gas/air volume related to the total volume under atmospheric pressure conditions, the liquid fluid phase is additionally, partially immobilized within the foam lamellae which leads to a further increase in aerated slurry viscosity.
[0030] According to these structure/phase conditions frozen aerated water slurries like conventional ice cream form a highly viscous mass with dynamic viscosities in the range of about 500-1500 Pas at shear rates of about 10 l/s, if 50% of the freezable water are frozen. Depending on freezing point depression and glass transition temperature Tg′ which depend on the composition of ingredients which are soluble in the continuous water phase, the 50% frozen state (related to the freezable water fraction) is reached at different temperatures. For conventional ice creams this is in the range of around −10 to −11° C. Related mean dynamic viscosities are around 1000 Pas (at shear rate of 10 l/s) as stated before. Further decrease in temperature related to further increase in frozen ice fraction, increases viscosity exponentially up to about 3000 Pas (shear rate 10 l/s) at −15° C. The related acting shear stresses at shear rates of 10 l/s are given by the product of dynamic viscosity and shear rate, which results in a shear stress of 30000 Pa at −15° C. for the example given before.
[0031] If such large shear forces are applied to the aerated frozen slurries, the specific mechanical power input (power per volume of the slurry) which is transferred into micro-structuring work as well as into viscous friction heat is approximately proportional to the dynamic viscosity and proportional to the square of the shear rate. This means for the given example, that at −15° C. and a shear rate of 10 l/s a power of about 3 kW per liter slurry will be dissipated. For comparison, at −12° C. there will be about 0.6 kW/liter.
[0032] The power input or respectively related energy input (=power×residence time) will partially be consumed by micro-structuring work within the partially frozen slurry causing air cell, fat globule/fat globule agglomerate and ice crystal/ice crystal agglomerate deformation and/or break-up. Another second major part of the power/energy input during shear treatment will be consumed by Coulomb friction between the solid disperse components and viscous friction within the continuous fluid phase.
[0033] If the friction energy is not efficiently transferred to a cooling medium via cooled walls or cooled shearing tools, local heating and re-melting of ice crystals has to be expected. Consequently the shear treatment in the highly frozen state at >50-60% of frozen water fraction (related to the freezable water fraction) will be limited by the heat transfer to the cooling medium.
[0034] According to the present invention the micro-structuring which is relevant to change the microstructure of frozen aerated slurries to such an extent, that scoop ability and creaminess are remarkably and significantly (based on consumer tests) improved, is reached in the low shear rate range between 1-50 l/s preferably 1-20 l/s at shear stresses acting in the range of 2000 to 75000 Pa, preferably between 10000 and 15000 Pa at ice crystal fractions larger than 50-60% of the maximum freezable fraction of the liquid (water) phase.
[0035] Conventionally ice cream as a well known frozen aerated slurry is continuously partially frozen in scraped surface heat exchangers so-called ice cream freezers. Air is dispersed in parallel in the flow around the rotating scraper blades. At a conventional draw temperature of about −5° C. the relative amount of frozen water is about 40% related to the freezable water fraction. An additional water fraction of about 30-40% (related to the freezable water fraction) is subsequently frozen in a hardening tunnel (−40° C. air temperature, 2-6 hours residence time) and finally another 20% in a cold storage room (−25 to −30° C.).
[0036] In contrast in the shear treatment according to the invention the frozen aerated slurry (e.g. ice cream) is continuously frozen to draw temperatures of about −12 to −18° C. and related fractions of the freezable water of about 50 to 80%. When the mass temperature decreases from −5 to about −15° C., viscosity increases by 2 to 3 decades.
[0037] High shear forces at low temperatures are forming a finely disperse microstructure (ice crystals, air cells, fat globules and agglomerates thereof). To obtain improved product quality with respect to scoop ability and creaminess, two disperse structure-related criteria classes are of importance:
[0038] 1. Characteristic size below a critical size: ice crystals, air cells, fat globules and agglomerates thereof have to be smaller than specific critical diameters in order to avoid unwanted structure characteristics causing reduced consumer acceptance which were found to be about 50-60 microns to avoid iciness and roughness for the ice crystals and their agglomerates, about 30-40 microns for air cells to avoid too fast coalescence and structure break-down during melting in the mouth and about 30-100 microns for fat globule agglomerates to avoid a buttery and/or fatty mouthfeel. Due to the existence of size distributions these criteria have to be interpreted as 90% in number of the related disperse particles/agglomerates shall be below these critical diameter values.
[0039] 2. Increased fraction within a specific size range: ice crystals, air cells, fat globules and agglomerates thereof shall be in a specific diameter range in order to enhance positive sensory and stability characteristics. At least 50% in number of ice crystals/ice crystal agglomerates in a size range between 5 and 30 microns (or mean value below 8-10 microns) together with a low degree of ice crystal interconnectivity improve scoop ability and creaminess. At least 50% in number of air cells in the diameter range between 2-10 microns (or mean value below 8-10 microns) delays bubble coarsening by coalescence during melting in the mouth so strongly, that creaminess sensation is significantly enhanced. The volume of fat globules/fat globule agglomerates in the size range between 2-20 microns have a significant direct impact on improving creaminess sensation in the mouth and also contribute to increased air cell structure stability against coalescence thus supporting also indirectly the creaminess attribute.
[0040] The criteria under class 1 are partially fulfilled by existing processing techniques for ice cream. The criteria package under class 2 is only fulfilled by the present invention-based treatment of related aerated frozen slurries in shear flows according to the shear rate, shear stress, mechanical power consumption and heat transfer criteria described in detail herein.
Example 2
[0041] In the following using ice cream as a typical aerated frozen slurry example, the structure criteria given before as well as the relationship to the sensory characteristics of scoop ability and creaminess shall be exemplary described.
[0042] In micro-structuring studies in accordance with the present invention, the influence of low temperature, low shear treatment at ice crystal fractions larger than 50-60% has been investigated for a conventional vanilla ice cream with total dry matter content of 38% including 8% of milk fat and compared with conventionally treated/manufactured ice cream.
[0043] For this ice cream system it was shown that the mean ice crystal size in the freshly produced ice cream by low temperature, low shear treatment was reduced by the factor of 2-3 compared to a conventionally freezered (scraped surface heat exchanger) and hardened ice cream of the same recipe. The related size distribution functions of the ice crystals are given in FIG. 1 .
[0044] Air cell sizes were also reduced by a factor of 2.8 using the inventive low temperature low shear treatment as demonstrated in FIG. 2 .
[0045] The influence of low temperature low shear processing on the fat globule and fat globule aggregate structure is given in FIG. 3 for a 8% milk fat containing ice cream formulation. Most significant changes in the fat globule aggregate size distribution are seen in the size range of 2-20 microns where a two-fold increase with the inventive treatment is reached compared to the conventional Freezer treatment. Furthermore using two levels of high shear for the inventive treatment, both under required heat transfer conditions, increased shear stress leads to an increased fraction of fat globule aggregates in the denoted size range. Similar trends are shown in FIG. 3A for a 5.5% milk fat containing ice cream formulation. The size range of 2-20 micron is increased at least two-fold. Simultaneously the larger fat globule aggregate size distribution in the range of 20-100 micron, resulting in an unpleasant buttery and/or fatty mouthfeel, is significantly reduced.
[0046] Within the following paragraph, the relationships of disperse microstructure and sensory perception of scoop ability and creaminess shall be explained. A crucial analytical tool to describe the microstructure-sensory quality relationships is rheometry which deals with flow measurements in order to characterize viscous and elastic material functions which are then correlated with the sensory characteristics of scoop ability and creaminess received from consumer tests.
[0047] The relevant theological test is a small deformation shear test (oscillatory shear) which is adapted to the typical flow characteristics in the consumer's mouth between tongue and palate. Consequently two parallel plates, simulating tongue and palate are used between which a tablet like cut sample of the frozen aerated slurry (here: ice cream) is placed and slightly compressed to fix it. The surfaces of the two plates are of well-defined roughness in order to avoid wall slip effects. The shear frequency is also adapted to typical moving frequencies of the tongue relative to the palate in testing creaminess between 0.5 and 2 Hertz (here 1.6 Hz fixed). The shear amplitude is chosen rather small, such that non-linear effects in the stress-strain dependencies are minimized. During oscillatory shear the temperature of the sample is changed from −20 (initial storage state) up to +10° C. which represents the fully melted state in the mouth. The time for the temperature sweep is fixed to 1 hour in order to get the sample fully equilibrated for each temperature increment.
[0048] The theological characteristics measured are the so-called storage modulus G′ representing the elastic material properties and the loss modulus G″ describing the viscous properties of the sample. From the elastic modulus G′ the networking properties of the disperse structure like interconnectivity can be derived, from the viscous modulus G″ the viscous shear flow behavior is received.
[0049] It was shown that both moduli G′ and G″ show a typical dependency from temperature which consists of a more or less pronounced plateau value domain in the temperature range between −20° C. and −10° C. (zone I), a strong decrease of the moduli in the temperature range between −10° C. and 0° C. (zone II) and a plateau domain of the moduli in the “high temperature” range between 0° C. and +10° C. (zone III) as demonstrated in FIG. 4 .
[0050] Ice cream samples were drawn either after conventional freezing or low temperature low shear treatment exemplary carried out in an extruder device. In order to guarantee a high reproducibility of the rheological measurements a constant sample preparation procedure was performed prior to oscillation rheometry. At a temperature of about −20° C. ice cream tablets with a diameter of 25 mm and a height of 5 mm were formed a using cylindrical cutting device. The samples were then stored at a temperature of −20° C. and measured either directly after or 24 hours after preparation.
[0051] The oscillatory shear measurements were carried out using a rotational rheometer (Physica MCR 300, shown in FIG. 5 ) with a plate-plate geometry (diameter 25 mm). Using Peltier-elements at the upper and lower plate a negligible temperature gradient within the sample was achieved. A moveable hood covering the plate—plate geometry prevented the heat exchange with the environment.
[0052] The results of measurements with conventionally and low temperature low shear treated samples are given in FIG. 6 . These results are interpreted within the three zones I-III as follows taking the related microstructure into account:
[0053] Zone I: (−20° C. to −10° C.)
[0054] The ice crystal microstructure is dominating the rheological behavior. A more pronounced decrease of the elastic modulus G′ in comparison to G″ from −20° C. to −10° C. can be attributed to the decrease of the solid body like behavior and loss of interconnectivity of ice crystals with decreasing ice fraction. The loss modulus, shows an upper slightly pronounced plateau level, which corresponds to the viscous behavior and flow-ability of ice cream in the low temperature range ( FIG. 4 ). In sensory terms the level of G′ and G″ below a temperature of −10° C. can be correlated to the rigidity and scoop ability of ice cream. The samples which were treated according to the inventive procedure show a strongly reduced plateau value of the moduli in this temperature zone I compared to the conventionally processed samples (factor 4.5 at −15° C.) thus clearly indicating the reduced rigidity and reduced interconnectivity of the ice crystal structure ( FIG. 6 exemplary for the G″ temperature dependency).
[0055] Zone II: (−10° C. to 0° C.)
[0056] As the ice crystals are melting and losing connectivity completely with increasing temperature in this zone, G′ and G″ are decreasing more rapidly ( FIG. 4 ). The steeper the slope of the G′/G″—temperature functions the faster the ice cream melts. Faster melting requires a larger heat flux from the mouth to the ice cream sample. Consequently a steep slope corresponds to a more pronounced sensorial impression of coldness. The samples which were treated according to the inventive procedure show a reduced slope of the G″ temperature dependency ( FIG. 6 ) indicating the sensory impression of a “warmer” mouth feel during melting and/or a higher melting resistance.
[0057] Zone III:
[0058] In the temperature range between 0 and 10° C. G′ and G″ show a well-defined lower plateau level ( FIG. 4 ). All ice is melted in this temperature range, therefore only the disperse air- and fat-phases have an impact on the theological and quality characteristics. The loss modulus G″ plateau in this temperature zone is highly correlated to the perception of creaminess. The samples which were treated according to the inventive procedure show a strongly increased plateau value of G″ (factor 2) in this temperature zone III ( FIG. 6 ) compared to the conventionally processed samples thus indicating the increased foam structure stability of the melted system which is supported by smaller air cell size and improved stabilization of these air cells by more efficient fat globule aggregates in the size range between 2 and 20 microns.
[0059] The Correlation between Oscillation Thermo-Rheometry (OTR) and sensorial perception studies of ice cream scoop ability and creaminess were investigated with a trained panel of 7 experts. In the related sensorial studies it was shown that scoop ability and creaminess of ice cream can be closely correlated with the upper loss modulus G″—plateau values in the low temperature zone I (scoop ability) and the lower G″—plateau values in the high temperature zone III (creaminess). The scoop ability and creaminess were classified by the panelists according to a 6 point sensory scale with 6 being the highest positive score.
[0060] In FIG. 7 the average sensory score values of the 8 panelists is related to the measured G″ plateau values in the low temperature and high temperature zones I and III. Both characteristics for scoop ability and for creaminess fit to an exponential relationship as indicated by the straight approximation of the functional dependencies in the semi-logarithmic plot (log G″ versus sensory average score).
[0061] Scoop ability got a higher score for lower G″ plateau values in the low temperature zone I. The creaminess was evaluated the better the higher the G″ high temperature (zone III) plateau value measured in the molten state.
[0062] If conventionally processed ice cream was additionally treated with the inventive procedure the G″ plateau value decreased at a temperature of −15° C., but increased in the molten state ( FIG. 6 ). As indicated in FIG. 8 the inventive treatment increased the sensory quality score on the sensory scale by about 1 point on a 9 point scale. However the functional dependency (curve) was still fitted. This was found for the scoop ability as well as for the creaminess attributes.
[0063] These results clearly indicate the impression of the sensory panelists that the inventive low temperature shear (LTS) treatment of ice cream samples improves the scoop ability and creaminess behavior of frozen aerated slurries strongly ( FIG. 7 ). A shift of about 2 score points indicates the commercial and marketing related relevance of the inventive treatment.
[0064] In order to confirm this outlook, market tests with LTS treated ice cream samples and conventionally processed ice cream samples of the same recipe have been performed on a test market. The market overall acceptance scores significantly confirmed that the consumers of the test market gave clear preference to the LTS treated samples of the same recipes (indicated with “ET” in the list of tested products in FIGS. 8 and 9 ) compared to the conventionally produced ice creams.
[0065] The foregoing descriptions of specific embodiments of the present invention have been presented for purposes of illustration and description. They are not intended to be exhaustive or to limit the invention to the precise forms disclosed, and obviously many modifications and variations are possible in light of the above teaching. The embodiments were chosen and described in order to best explain the principles of the invention and its practical application, to thereby enable others skilled in the art to best utilize the invention and various embodiments with various modifications as are suited to the particular use contemplated. It is intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
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Products that are aerated multiphase systems containing an aqueous continuous fluid phase which may include solutes thus forming an aqueous syrup and disperse phases like gas/air cells, water ice crystals and solid/semi-solid fat globules or aggregates thereof, whereas the disperse phases are that finely structured that their mean diameters are below phase specific critical maximum values and thereby generate a most preferred by consumers, full rich silky-creamy mouth feel at much lower fat content than usual in conventional related products like premium and super premium ice creams.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application is a continuation application of International Patent Application No. PCT/CN2013/072331, filed Mar. 8, 2013, which itself claims the priority to Chinese Patent Application No. 201210060962.7, filed Mar. 9, 2012 in the State Intellectual Property Office of P.R. China, which are hereby incorporated herein in their entireties by reference.
[0002] Some references, if any, which may include patents, patent applications and various publications, may be cited and discussed in the description of this invention. The citation and/or discussion of such references, if any, is provided merely to clarify the description of the present invention and is not an admission that any such reference is “prior art” to the invention described herein. All references listed, cited and/or discussed in this specification are incorporated herein by reference in their entireties and to the same extent as if each reference was individually incorporated by reference.
FIELD OF THE INVENTION
[0003] The present invention relates generally to a slow release anti-icing material for a bituminous pavement, and more particularly to a slow release anti-icing material used in an upper layer of a bituminous pavement of an express way, and a preparation method thereof.
BACKGROUND OF THE INVENTION
[0004] In most of regions of China, it was cold in winter. Thus, especially in Yunnan province, Guizhou province, Sichuan province, Hubei province and Hunan province, a pavement is easy to ice in winter, affecting the anti-skid capability of the pavement, reducing traffic capacity, increasing a potential risk of traffic accidents, even causing traffic to be blocked in severe cases, and bringing about frightful troubles for normal travel of people and disturbance of normal living state of people. For the purpose of anti-skid effect, a conventional method involves spreading snow-melting agents for removal of snow and ice. Although it is capable of temporarily mitigating traffic and improving driving safety, it causes severe destruction and contamination on roadways and structures thereof, and surrounding environment such as soil and water bodies. If an anti-icing material which can actively inhibit icing on the pavement is developed, it would bring about favorable economic and social benefits in view of preventing roadway icing and enhancement of driving safety in winter.
[0005] With respect to chemical anti-icing materials for inhibition of pavement icing, as early as 1960s, an anti-icing salt called Verglimit was invented in Switzerland. Verglimit is a solid composite pavement anti-icing material derived by chemical processing of calcium chloride as a main ingredient, a small amount of sodium chloride and sodium hydroxide as an accessory ingredient, with linseed oil. The pavement anti-icing material was used in some trial pavements both in China and abroad, and had a certain anti-icing and anti-skid effect, but failed to be promoted in a large scale as a result of deficiencies. U.S. Pat. No. 6,982,044 discloses a method for encapsulating chlorate surface with thermo-sensitive phenolic resin. German Patent No. DE-OS 2426200, discloses a preparation method for modification of chloride with polyvinyl acetate, polyvinyl alcohol, epoxy or acrylic resins. In the foregoing patents, corrosion of steel bars by chloride ion was inevitable, and research on slow release materials was not disclosed. Accordingly, it is significant in economy to develop a slow release anti-icing material for the bituminous pavement having a relatively simple process for preparation and a low price without corroding the steel bars.
SUMMARY OF THE INVENTION
[0006] To solve the problem of corrosion of steel bars by chloride in the related art, in one aspect, the present invention is related to a slow release anti-icing material for a bituminous pavement that actively inhibits pavement icing and has an anti-corrosion effect, and a preparation method thereof.
[0007] In one embodiment of the present invention, a slow release anti-icing material for a bituminous pavement, essentially comprises X component, Y component and Z component. Parts by mass of these components are:
[0008] X component is chloride of 80-95 parts by mass;
[0009] Y component is an anti-corrosion agent, consisting of sodium silicate of 0.01-0.5 parts by mass, sodium gluconate of 0.01-0.5 parts by mass, and zinc dihydrogen phosphate of 0.01-0.5 parts by mass; and
[0010] Z component is an acrylate polymer of 5-10 parts by mass.
[0011] The chloride is one or a combination of two or more of sodium chloride, potassium chloride, calcium chloride and magnesium chloride. The acrylate polymer is polybutyl acrylate, polypropyl acrylate or polyisobutyl acrylate, obtained from polymerization of acrylate monomer, divinylbenzene as a cross-linking agent and hydrogen containing silicone oil in the presence of chloroplatinic acid as catalyst. Each of materials and its parts by mass in the polymerization are: the acrylate monomer of 5-10 parts, the cross-linking agent of 0.002-0.004 parts, the hydrogen containing silicone oil of 0.001-0.05 parts, the benzoyl peroxide initiator of 0.003-0.009 parts, and the chloroplatinic acid of 0.0005-0.001 parts. The hydrogen containing silicone oil includes hydrogen in a mass fraction of 0.01 wt %-0.2 wt %. The acrylate monomer is butyl acrylate, propyl acrylate or isobutyl acrylate.
[0012] In one embodiment, the chloride is in a form of particle with size of 0.1-5 mm.
[0013] In one embodiment, the sodium silicate is required to be white powder, with a passing rate of more than 80% through a 0.1 mm square mesh sieve.
[0014] In one embodiment, the sodium gluconate is required to be white powder, with a passing rate more than 90% through a 0.1 mm square mesh sieve.
[0015] In one embodiment, the zinc dihydrogen phosphate is required to be white powder, with a passing rate of more than 85% through a 0.1 mm square mesh sieve.
[0016] In one aspect, a method for preparing the slow release anti-icing material for the bituminous pavement according to the present invention includes the following steps.
[0017] 1) Preparation the X component: granulation and molding of the chloride, to produce particles of 0.1-5 mm.
[0018] 2) Preparation the Y component: mixing the sodium silicate of 0.01-0.5 parts, the sodium gluconate of 0.01-0.5 parts and the zinc dihydrogen phosphate of 0.01-0.5 parts with mechanical stirring at room temperature.
[0019] 3) Mechanically mixing the granular chloride of 80-95 parts from step 1) with the Y component from step 2), on a basis of parts by mass.
[0020] 4) Adding the mixture from step 3) to a 4-necked flask equipped with a thermometer, a stirrer and a refluxing condenser tube, adding petroleum ether of 100-300 parts as a reaction medium, stirring for 1-2 h at room temperature. Then adding the acrylate monomer of 5-10 parts, the cross-linking agent divinylbenzene of 0.002-0.004 parts, the initiator benzoyl peroxide of 0.002-0.006 parts, and reacting for 6-10 h at 60-80° C. Further adding the initiator benzoyl peroxide of 0.001-0.003 parts, the hydrogen containing silicone oil of 0.001-0.05 parts (including hydrogen in the mass fraction of 0.01 wt %-0.2 wt %), dropping a solution of chloroplatinic acid in isopropanol of 0.0005-0.001 parts as catalyst in 1-2 h, and continuing the reaction for 8-10 h. After recovering the solvent by filtration, drying in a vacuum for 3-4 h, the slow release anti-icing material for the bituminous pavement is produced. The acrylate monomer is butyl acrylate, propyl acrylate or isobutyl acrylate.
[0021] The X component is a principal component for preparing the anti-icing material, and it lowers the freezing point of road surface water by slowly releasing. The Y component is a ternary anti-corrosion agent, preventing corrosion of steel bars by chloride ion, and prolonging a service life of the roadways. The Z component is a layer of a uniform, compact, spatially reticular, thermostable, macromolecular coating material formed on the surface of the mixture of components X and Y, controlling a releasing rate thereof in the bituminous pavement.
[0022] In one aspect, the present application is related to a using of the anti-icing material product in the upper layer of the bituminous pavement.
[0023] In one embodiment, the using includes verifying indoor target mixing ratio for the anti-icing materials according to the additive addition method, and producing in bitumen mixing station according to production mixing ratio. The adding sequence is rock material→mineral powder→bitumen→anti-icing material. The anti-icing material is added in the amount of 5 wt %-8 wt % of bituminous concrete by mass. The wet mixing time for bitumen mixture is prolonged by 7-10 seconds prior to discharging. The construction process is the same as the routine construction method for bituminous concrete, with the field porosity being controlled within 3%-4%.
[0024] The anti-icing mechanism for the product according to the present invention is as follows.
[0025] In the upper layer of the bituminous pavement constructed with the product according to the present invention, as a result of loading effects such as wheel pressure, vibration, abrasion and the like, the anti-icing materials will migrate from varying depths by slow suction to the upper layer of pavement for release, by phenomena of porous osmotic pressure and capillary suction in pavement. At this point, the anti-icing material at about 5-10 mm in the upper layer of pavement is activated quickly, reacts with ice snow and dissolved quickly in water. As chloride ions in water increase, a vapor pressure of water in liquid phase is decreased, but a vapor pressure of solid ice is constant. According to a solid-liquid vapor pressure equilibrium principle in the ice water mixture, solid ice is melt into liquid water, thereby preventing and delaying pavement icing in winter.
[0026] The advantageous effects of the slow release anti-icing material for the bituminous pavement according to the present invention are: the components of the product are inexpensive, the production process is relatively simple, and the material is not corrosive to steel bars. The anti-icing effects are remarkable for the bituminous pavement, and the material has effects of completely preventing the pavement from icing at −5 to 0° C. In addition, the product does not corroding the steel bars, as verified by measurement according to JB/T 7901-1999 Metallic Material Uniform Corrosion Full Immersion Test Method in Lab, indicating that the product has a green environmental protection effect and is environmental-friendly.
[0027] These and other aspects of the present invention will become apparent from the following description of the preferred embodiment taken in conjunction with the following drawings, although variations and modifications therein may be effected without departing from the spirit and scope of the novel concepts of the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0028] The accompanying drawings illustrate one or more embodiments of the invention and together with the written description, serve to explain the principles of the invention. Wherever possible, the same reference numbers are used throughout the drawings to refer to the same or like elements of an embodiment.
[0029] FIG. 1 is a comparison diagram of a corrosion rate of a slow release anti-icing material solution for a bituminous pavement according to one embodiment of the present invention and a corrosion rate of tap water to a sheet steel (corrosion time of 7 days).
[0030] FIG. 2 is a photograph of a rut specimen added with an anti-icing material.
[0031] FIG. 3 is a photograph of a rut specimen without an anti-icing material.
DETAILED DESCRIPTION OF THE INVENTION
[0032] While there has been shown several and alternate embodiments of the present invention, it is to be understood that certain changes can be made as would be known to one skilled in the art without departing from the underlying scope of the present invention as is discussed and set forth above and below including claims. Furthermore, the embodiments described above and claims set forth below are only intended to illustrate the principles of the present invention and are not intended to limit the scope of the present invention to the disclosed elements.
Embodiment 1
[0033] Preparation of a slow release anti-icing material for bituminous pavement
[0034] The material essentially comprises X component, Y component and Z component. Parts by mass of the components are as follows:
[0035] X component is calcium chloride, in a form of particle with size of 0.1-5 mm, of 92 parts;
[0036] Y component consisted of sodium silicate of 0.2 parts, sodium gluconate of 0.2 parts and zinc dihydrogen phosphate of 0.05 parts; and
[0037] Z component is polybutyl acrylate, synthesized from butyl acrylate, cross-linking agent and hydrogen containing silicone oil.
[0038] The method for preparing the slow release anti-icing material for the bituminous pavement includes the following steps:
[0039] 1. Preparing the X component: granulating and molding, to produce the granular chloride of 0.1-5 mm, of 92 parts.
[0040] 2. Preparing the Y component: mixing sodium silicate of 0.01 parts, sodium gluconate of 0.2 parts and zinc dihydrogen phosphate of 0.05 parts by mechanical stirring at room temperature.
[0041] 3. Mechanically mixing the granular chloride from step 1 with the Y component from step 2.
[0042] 4. Adding the mixture from step 3 to a 4-necked flask equipped with a thermometer, a stirrer and a refluxing condenser tube, adding petroleum ether of 150 parts as a reaction medium, and stirring for 1-2 h at room temperature. Then adding the acrylate monomer of 7 parts, the cross-linking agent divinylbenzene of 0.002 parts, initiator benzoyl peroxide (BPO) of 0.003 parts, and reacting for 6-10 h at 60-80° C.
[0043] Further adding the initiator BPO of 0.001 parts, the hydrogen containing silicone oil of 0.002 parts (including hydrogen in the mass fraction of 0.01 wt %-0.2 wt %), dropping a solution of chloroplatinic acid in isopropanol of 0.0005 parts as catalyst for 1-2 h, and continuing the reaction for 8-10 h. After recovering the solvent by filtration, drying in a vacuum for 3-4 h, the slow release anti-icing material for the bituminous pavement is produced.
Embodiment 2
[0044] Preparation of a slow release anti-icing material for bituminous pavement
[0045] The material essentially includes X component, Y component and Z component. Parts by mass of the components are as follows.
[0046] X component is granular calcium chloride: calcium chloride of 0.1-5 mm, 82 parts; and magnesium chloride of 0.1-5 mm, 10 parts;
[0047] Y component consisted of sodium silicate of 0.1 parts, sodium gluconate of 0.1 parts and zinc dihydrogen phosphate of 0.25 parts; and
[0048] Z component is polypropyl acrylate, synthesized from propyl acrylate, cross-linking agent and hydrogen containing silicone oil.
[0049] A method for preparing the slow release anti-icing material for the bituminous pavement is the same as that in Embodiment 1, except that propyl acrylate monomer is used instead of butyl acrylate monomer.
Embodiment 3
[0050] Preparation of a slow release anti-icing material for bituminous pavement
[0051] The material essentially comprises X component, Y component and Z component. Parts by mass of the components are as follows.
[0052] X component is granular chloride: calcium chloride of 0.1-5 mm, 75 parts; magnesium chloride of 0.1-5 mm, 10 parts; and sodium chloride of 0.1-5 mm, 7 parts; Y component consisted of sodium silicate of 0.3 parts, sodium gluconate of 0.1 parts and zinc dihydrogen phosphate of 0.05 parts; and
[0053] Z component is polyisobutyl acrylate, synthesized from isobutyl acrylate, the cross-linking agent and the hydrogen containing silicone oil.
[0054] The method for preparing the slow release anti-icing material for bituminous pavement is the same as that in Embodiment 1, except that isobutyl acrylate monomer was used, instead of butyl acrylate monomer.
Embodiment 4
[0055] Preparation of a slow release anti-icing material for bituminous pavement
[0056] The material essentially comprises X component, Y component and Z component. Parts by mass of the components are as follows.
[0057] X component was granular chloride: calcium chloride with 0.1-3 mm particle size, 17 parts; sodium chloride of 0.1-3 mm, 75 parts.
[0058] Y component consisted of sodium silicate of 0.05 parts, sodium gluconate of 0.15 parts and zinc dihydrogen phosphate of 0.1 parts; and
[0059] Z component is polybutyl acrylate, synthesized from butyl acrylate, the cross-linking agent and the hydrogen containing silicone oil.
[0060] The method for preparing the slow release anti-icing material for bituminous pavement includes the following steps:
[0061] 1. Preparing the X component: granulating and molding, to produce granular calcium chloride of 0.1-3 mm, 17 parts; granular sodium chloride of 0.1-3 mm, 75 parts.
[0062] 2. Preparing the Y component: homogeneously mixing sodium silicate of 0.05 parts, sodium gluconate of 0.15 parts and zinc dihydrogen phosphate of 0.1 parts by mechanical stirring at room temperature.
[0063] 3. Mechanically and homogeneously mixing the granular calcium chloride and sodium chloride from step 1 with the Y component from step 2.
[0064] 4. Adding the mixture from step 3 to a 4-necked flask equipped with a thermometer, a stirrer and a refluxing condenser tube, adding petroleum ether of 100 parts as reaction medium, and stirring for 1-2 h at room temperature. Then adding the butyl acrylate monomer of 5 parts, the cross-linking agent divinylbenzene of 0.004 parts, the initiator benzoyl peroxide (BPO) of 0.005 parts, and reacting for 6-10 h at 60-80° C. Further adding the initiator benzoyl peroxide of 0.002 parts, the hydrogen containing silicone oil of 0.004 parts (comprising hydrogen in the mass fraction of 0.01 wt %-0.2 wt %), dropping a solution of chloroplatinic acid in isopropanol of 0.001 parts as catalyst for 1-2 h, and continuing the reaction for 8-10 h. After recovering the solvent by filtration, drying under vacuum for 3-4 h, the slow release anti-icing material for bituminous pavement is produced.
[0065] For each of materials in the embodiment, dosage of each of parts is measured as 1 kg.
Embodiment 5
[0066] Preparation of a slow release anti-icing material for bituminous pavement
[0067] The material essentially comprises X component, Y component and Z component. Parts by mass of the components are as follows:
[0068] X component is granular chloride: calcium chloride with 0.1-3 mm particle size, 40 parts; sodium chloride of 0.1-3 mm, 40 parts;
[0069] Y component consisted of sodium silicate of 0.5 parts, sodium gluconate of 0.5 parts and zinc dihydrogen phosphate of 0.5 parts;
[0070] Z component is polyisobutyl acrylate, synthesized from isobutyl acrylate, the cross-linking agent and the hydrogen containing silicone oil.
[0071] The method for preparing the slow release anti-icing material for bituminous pavement includes the following steps:
[0072] 1. Preparing the X component: granulating and molding, to produce granular calcium chloride of 0.1-3 mm, 40 parts; granular sodium chloride of 0.1-3 mm, 40 parts.
[0073] 2. Preparing the Y component: homogeneously mixing sodium silicate of 0.5 parts, sodium gluconate of 0.5 parts and zinc dihydrogen phosphate of 0.5 parts by mechanical stirring at room temperature.
[0074] 3. Mechanically and homogeneously mixing the granular calcium chloride and sodium chloride from step 1 with the Y component from step 2.
[0075] 4. Adding the mixture from step 3 to the 4-necked flask equipped with a thermometer, a stirrer and a refluxing condenser tube, adding petroleum ether of 300 parts as reaction medium, and stirring for 1-2 h at room temperature. Then adding the isobutyl acrylate monomer of 9 parts, the cross-linking agent divinylbenzene of 0.003 parts, the initiator benzoyl peroxide of 0.006 parts, and reacting for 6-10 h at 60-80° C. Further adding the initiator benzoyl peroxide of 0.003 parts, the hydrogen containing silicone oil of 0.04 parts (comprising hydrogen in the mass fraction of 0.01 wt %-0.2 wt %), dropping a solution of chloroplatinic acid in isopropanol of 0.001 parts as catalyst for 1-2 h, and continuing the reaction for 8-10 h. After recovering the solvent by filtration, drying under vacuum for 3-4 h, the slow release anti-icing material for bituminous pavement is produced.
[0076] For each of materials in the embodiment, dosage of each of parts is measured as 1 kg.
Efficacy Assessment
[0077] 1. 5.5 g anti-icing materials prepared in Embodiments 1, 2 and 3 are respectively dissolved in 100 g water to form a solution. Corrosion rate of the produced solution to sheet steel is measured according to JB/T 7901-1999 Metallic Material Uniform Corrosion Full Immersion Test Method in Lab. Corrosion of the solution vs. tap water to sheet steel at day 7 is shown in FIG. 1 . It is indicated in FIG. 1 that the anti-icing material had no corrosion to sheet steel and had favorable environmental benefit.
[0078] 2. The anti-icing materials prepared in Embodiments 1, 2, 3, 4 and 5 are added into a bitumen mixture in an amount of 5 wt %-8 wt %. Rut specimen is molded with or without addition of the anti-icing material in laboratory. Water is sprayed onto the surface of rut specimen, and then the specimen is placed into a cryo-freezer at −5° C. and frozen for 10 h, allowing the surface of the specimen to ice up. From the testing results, it is seen that no icing is occurred on the surface of the bitumen mixture added with the anti-icing material, and obvious ice layer is found on the surface of the bitumen mixture without addition of the anti-icing material. In the experiments above, it is suggested that the anti-icing materials had favorable anti-icing effect at −5° C. The results are shown in FIGS. 2 and 3 .
[0079] 3. The anti-icing materials prepared in Embodiments 1, 2, 3, 4 and 5 are added into a bitumen mixture in an amount of 5 wt %-8 wt %. The anti-icing material is added in laboratory to mold rut specimen. In order to demonstrate the slow release property of the anti-icing material in the bitumen mixture, the molded rut specimen is exposed to the sun and rain in open air. The liquid layer on the surface of the specimen after raining is tested for chloride ion concentration at varying interval, thereby assessing the slow release property of the anti-icing material.
[0080] The results from assessment and testing were given in Table 1.
[0000]
TABLE 1
results from assessment and testing
Level of
Level of
Level of
Level of
Level of
Level of
Level of
chloride ion
chloride ion
chloride ion
chloride ion
chloride ion
chloride ion
chloride ion
released from
released from
released from
released from
released from
released from
released from
Assessment
the specimen
the specimen
the specimen
the specimen
the specimen
the specimen
the specimen
of anti-
at varying
at varying
at varying
at varying
at varying
at varying
at varying
icing
interval (g/m 2 )
interval (g/m 2 )
interval (g/m 2 )
interval (g/m 2 )
interval (g/m 2 )
interval (g/m 2 )
interval (g/m 2 )
Name
efficacy
0 d
50 d
100 d
150 d
200 d
250 d
300 d
Blank
Icing on
0.01
0
0
0
0
0
0
surface
The anti-icing
No
56.8
53.3
51.8
48.6
46.5
45.1
44.6
material from
icing on
Example 1
surface
The anti-icing
No
58.1
55.6
52.9
50.5
48.7
46.4
45.0
material from
icing on
Example 2
surface
The anti-icing
No
57.3
54.1
52.4
50.1
47.8
46.2
43.9
material from
icing on
Example 3
surface
The anti-icing
No
60.3
56.1
54.4
52.1
50.8
49.2
48.6
material from
icing on
Example 4
surface
The anti-icing
No
65.6
62.1
60.1
59.4
56.4
54.8
52.7
material from
icing on
Example 5
surface
[0081] It is indicated from table 1 that, the anti-icing materials from Embodiments 1, 2, 3, 4 and 5 have excellent anti-icing effect. Moreover, upon exposure of the specimen to the sun and rain in the open air for a long time, although the escaping rate of chloride ions in the bitumen mixture tended to decline, the loss rate of chloride ions is low, indicating that the chloride covered by the acrylate polymer has slow release performance and persisted for a long time.
[0082] The foregoing description of the exemplary embodiments of the invention has been presented only for the purposes of illustration and description and is not intended to be exhaustive or to limit the invention to the precise forms disclosed. Many modifications and variations are possible in light of the above teaching.
[0083] The embodiments were chosen and described in order to explain the principles of the invention and their practical application so as to enable others skilled in the art to utilize the invention and various embodiments and with various modifications as are suited to the particular use contemplated. Alternative embodiments will become apparent to those skilled in the art to which the present invention pertains without departing from its spirit and scope. Accordingly, the scope of the present invention is defined by the appended claims rather than the foregoing description and the exemplary embodiments described therein.
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A slow release anti-icing material for a bituminous pavement and a method of manufacturing the same. The material includes X, Y and Z components. The X component is a chloride of 80-95 parts. The Y component comprises sodium silicate sodium gluconate and zinc dihydrogen phosphate. The Z component is an acrylate polymer obtained from polymerization of an acrylate monomer, as a cross-linking agent, and a hydrogen containing silicone oil. The manufacturing method includes preparing the X component, preparation the Y component, mixing the X component and the Y component evenly, and encapsulating the surface of the mixture of component X and Y by the component Z evenly through polymerization, to produce the slow release anti-icing material for a bituminous pavement. The anti-icing effects are remarkable for the bituminous pavement, and the material has effects of completely preventing the pavement from icing at −5 to 0° C.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application is continuation of U.S. patent application Ser. no. 11/767,152, filed Jun. 22, 2007 and currently pending, which is a divisional application of U.S. patent application Ser. No. 11/444,491, filed Jun. 1, 2006 and currently pending, which is a continuation-in-part of U.S. patent application Ser. No. 11/177,480, filed Jul. 11, 2005 and currently pending, which in turn is a continuation-in-part of U.S. patent application Ser. No. 10/937,304, filed on Sep. 10, 2004 and issued on Dec. 25, 2007 as U.S. Pat. No. 7,311,276, the entire contents of which are all incorporated herein by reference. U.S. patent application Ser. No. 11/444,491, filed Jun. 1, 2006 and currently pending is also a continuation-in-part of U.S. patent application Ser. No. 11/385,864, filed on Mar. 22, 2006 and currently pending, the entire content of which is also incorporated herein by reference.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The present invention relates to shredders for destroying articles, such as documents, compact discs, etc.
[0004] 2. Description of Related Art
[0005] Shredders are well known devices for destroying articles, such as documents, compact discs (“CDs”), expired credit cards, etc. Typically, users purchase shredders to destroy sensitive articles, such as credit card statements with account information, documents containing company trade secrets, etc.
[0006] A common type of shredder has a shredder mechanism contained within a housing that is removably mounted atop a container. The shredder mechanism typically has a series of cutter elements that shred articles fed therein and discharge the shredded articles downwardly into the container. The shredder typically has a stated capacity, such as the number of sheets of paper (typically of 20 lb. weight) that may be shredded at one time; however, the feed throat of a typical shredder can receive more sheets of paper than the stated capacity. A common frustration of users of shredders is to feed too many papers into the feed throat, only to have the shredder jam after it has started to shred the papers. To free the shredder of the papers, the user typically reverses the direction of rotation of the cutter elements via a switch until the papers become free.
[0007] In addition, shredders that are subjected to a lot of use should have periodic maintenance done to them. For example, the cutter elements may become dull over time. It has been found that lubricating the cutter elements may improve the performance of cutter elements, particularly if the shredder is used constantly over a long period of time.
[0008] The present invention endeavors to provide various improvements over known shredders.
BRIEF SUMMARY OF THE INVENTION
[0009] It is an aspect of the invention to provide a shredder that does not jam as a result of too many papers, or an article that is too thick, being fed into the shredder.
[0010] In an embodiment, a shredder is provided. The shredder includes a housing having a throat open to an exterior of the housing for permitting a user to feed at least one article to be shredded, and a shredder mechanism received in the housing and including an electrically powered motor and cutter elements. The shredder mechanism enables the at least one article fed into the throat to be shredded to be fed into the cutter elements and the motor is operable to drive the cutter elements in a shredding direction so that the cutter elements shred the articles fed therein. The shredder includes a thickness detector device that includes a contact portion in the throat, the contact portion being movable by a thickness between opposing major surfaces of the at least one article being received by the throat, a detectable portion movable by the contact portion, and a detector for detecting at least one position of the detectable portion. The at least one position of the detectable portion includes a position when the detectable portion has been moved by the contact portion by an amount that correlates to a predetermined maximum thickness. The shredder includes a controller coupled to the thickness detector. The controller is operable to prevent the motor from driving the cutter elements in the shredding direction responsive to the detector detecting that the detectable portion has been moved by the amount that correlates to the predetermined maximum thickness. The controller is configured to vary the predetermined maximum thickness based on receiving an input parameter.
[0011] In an embodiment, there is provided a method of operating a shredder that includes: (a) a housing having a throat open to an exterior of the housing for permitting a user to feed at least one article to be shredded; (b) a shredder mechanism received in the housing and including an electrically powered motor and cutter elements, the shredder mechanism enabling the at least one article fed into the throat to be shredded to be fed into the cutter elements and the motor being operable to drive the cutter elements in a shredding direction so that the cutter elements shred the articles fed therein; (c) a thickness detector device comprising (i) a contact portion in the throat, the contact portion being movable by a thickness between opposing major surfaces of the at least one article being received by the throat, (ii) a detectable portion movable by the contact portion, and (iii) a detector for detecting at least one position of the detectable portion, the at least one position of the detectable portion including a position when the detectable portion has been moved by the contact portion by an amount that correlates to a predetermined maximum thickness; and (d) a controller coupled to the thickness detector; wherein the controller is operable to prevent the motor from driving the cutter elements in the shredding direction responsive to the detector detecting that the detectable portion has been moved by the amount that correlates to the predetermined maximum thickness; and wherein the controller is configured to vary the predetermined maximum thickness based on receiving an input parameter. The method includes the controller receiving the input parameter and varying the predetermined maximum thickness; detecting with the detector when the detectable portion has moved the amount that correlates to the predetermined maximum thickness; and the controller preventing the motor from driving the cutter elements in the shredding direction responsive to the detector detecting when the detectable portion has moved the amount that correlates to the predetermined maximum thickness.
[0012] In an embodiment, there is provided a shredder that includes a housing having a throat open to an exterior of the housing for permitting a user to feed at least one article to be shredded, and a shredder mechanism received in the housing and including an electrically powered motor and cutter elements. The shredder mechanism enables the at least one article fed into the throat to be shredded to be fed into the cutter elements and the motor being operable to drive the cutter elements in a shredding direction so that the cutter elements shred the articles fed therein. A thickness detector device is configured to detect a thickness between opposing major surfaces of the at least one article being received by the throat. The thickness detector device includes a first portion in the throat, a second portion that is configured to rotate upon movement of the first portion, and an optical detector configured to detect a position of the second portion. The shredder includes a controller coupled to the thickness detector device. The optical detector is configured to detect at least one position of the second portion and to communicate such detection to the controller, the at least one position including a position when the thickness of the at least one article is at least equal to a predetermined maximum thickness. The controller is operable to prevent the motor from driving the cutter elements in the shredding direction responsive to the detector detecting that the thickness of the at least one article is at least equal to the predetermined maximum thickness. The controller is configured to vary the predetermined maximum thickness based on receiving an input parameter.
[0013] Other aspects, features, and advantages of the present invention will become apparent from the following detailed description, the accompanying drawings, and the appended claims.
BRIEF DESCRIPTION OF THE DRAWINGS
[0014] FIG. 1 is a perspective view of a shredder constructed in accordance with an embodiment of the present invention;
[0015] FIG. 2 is an exploded perspective view of the shredder of FIG. 1 ;
[0016] FIG. 3 is a schematic illustration of an oiling mechanism in accordance with an embodiment of the present invention;
[0017] FIG. 4 is a perspective view of a shredder having an oiling mechanism in accordance with an embodiment of the present invention;
[0018] FIG. 5 is a perspective view of a shredder having an oiling mechanism in accordance with an embodiment of the present invention;
[0019] FIG. 6 is a schematic of interaction between a controller and other parts of the shredder;
[0020] FIG. 7 is a schematic of an embodiment of an indicator located on the shredder;
[0021] FIG. 8 is a schematic of an embodiment of a detector configured to detect a thickness of a article to be shredded by the shredder;
[0022] FIG. 9 is a schematic of another embodiment of a detector configured to detect a thickness of a article to be shredded by the shredder;
[0023] FIG. 10 is a schematic of another embodiment of a detector configured to detect a thickness of a article to be shredded by the shredder;
[0024] FIG. 11 is a schematic of another embodiment of the detector of FIG. 10 ; and
[0025] FIG. 12 is a flow diagram of an embodiment of a method for shredding an article.
DETAILED DESCRIPTION OF THE INVENTION
[0026] FIGS. 1 and 2 illustrate a shredder constructed in accordance with an embodiment of the present invention. The shredder is generally indicated at 10 . In the illustrated embodiment, the shredder 10 sits atop a waste container, generally indicated at 12 , which is formed of molded plastic or any other material. The shredder 10 illustrated is designed specifically for use with the container 12 , as the shredder housing 14 sits on the upper periphery of the waste container 12 in a nested relation. However, the shredder 10 may also be designed so as to sit atop a wide variety of standard waste containers, and the shredder 10 would not be sold with the container. Likewise, the shredder 10 could be part of a large freestanding housing, and a waste container would be enclosed in the housing. An access door would provide for access to and removal of the container. Generally speaking, the shredder 10 may have any suitable construction or configuration and the illustrated embodiment is not intended to be limiting in any way. In addition, the term “shredder” is not intended to be limited to devices that literally “shred” documents and articles, but is instead intended to cover any device that destroys documents and articles in a manner that leaves each document or article illegible and/or useless.
[0027] As shown in FIG. 2 , in an embodiment, the shredder 10 includes a shredder mechanism 16 that includes an electrically powered motor 18 and a plurality of cutter elements 19 . “Shredder mechanism” is a generic structural term to denote a device that destroys articles using at least one cutter element. Such destroying may be done in any particular way. For example, the shredder mechanism may include at least one cutter element that is configured to punch a plurality of holes in the document or article in a manner that destroys the document or article. In the illustrated embodiment, the cutter elements 19 are generally mounted on a pair of parallel rotating shafts 20 . The motor 18 operates using electrical power to rotatably drive the shafts and the cutter elements through a conventional transmission 23 so that the cutter elements shred articles fed therein. The shredder mechanism 16 may also include a sub-frame 21 for mounting the shafts, the motor 18 , and the transmission 23 . The operation and construction of such a shredder mechanism 16 are well known and need not be described herein in detail. Generally, any suitable shredder mechanism 16 known in the art or developed hereafter may be used.
[0028] The shredder 10 also includes the shredder housing 14 , mentioned above. The shredder housing 14 includes top wall 24 that sits atop the container 12 . The top wall 24 is molded from plastic and an opening 26 is located at a front portion thereof. The opening 26 is formed in part by a downwardly depending generally U-shaped member 28 . The U-shaped member 28 has a pair of spaced apart connector portions 27 on opposing sides thereof and a hand grip portion 28 extending between the connector portions 27 in spaced apart relation from the housing 14 . The opening 26 allows waste to be discarded into the container 12 without being passed through the shredder mechanism 16 , and the member 28 may act as a handle for carrying the shredder 10 separate from the container 12 . As an optional feature, this opening 26 may be provided with a lid, such as a pivoting lid, that opens and closes the opening 26 . However, this opening in general is optional and may be omitted entirely. Moreover, the shredder housing 14 and its top wall 24 may have any suitable construction or configuration.
[0029] The shredder housing 14 also includes a bottom receptacle 30 having a bottom wall, four side walls and an open top. The shredder mechanism 16 is received therein, and the receptacle 30 is affixed to the underside of the top wall 24 by fasteners. The receptacle 30 has an opening 32 in its bottom wall through which the shredder mechanism 16 discharges shredded articles into the container 12 .
[0030] The top wall 24 has a generally laterally extending opening, which is often referred to as a throat 36 , extending generally parallel and above the cutter elements. The throat 36 enables the articles being shredded to be fed into the cutter elements. As can be appreciated, the throat 36 is relatively narrow, which is desirable for preventing overly thick items, such as large stacks of documents, from being fed into cutter elements, which could lead to jamming. The throat 36 may have any configuration.
[0031] The top wall 24 also has a switch recess 38 with an opening therethrough. An on/off switch 42 includes a switch module (not shown) mounted to the top wall 24 underneath the recess 38 by fasteners, and a manually engageable portion 46 that moves laterally within the recess 38 . The switch module has a movable element (not shown) that connects to the manually engageable portion 46 through the opening. This enables movement of the manually engageable portion 46 to move the switch module between its states.
[0032] In the illustrated embodiment, the switch module connects the motor 18 to the power supply. Typically, the power supply will be a standard power cord 44 with a plug 48 on its end that plugs into a standard AC outlet. The switch 42 is movable between an on position and an off position by moving the portion 46 laterally within the recess 38 . In the on position, contacts in the switch module are closed by movement of the manually engageable portion 46 and the movable element to enable a delivery of electrical power to the motor 18 . In the off position, contacts in the switch module are opened to disable the delivery of electric power to the motor 18 .
[0033] As an option, the switch 42 may also have a reverse position wherein contacts are closed to enable delivery of electrical power to operate the motor 18 in a reverse manner. This would be done by using a reversible motor and applying a current that is of a reverse polarity relative to the on position. The capability to operate the motor 18 in a reversing manner is desirable to move the cutter elements in a reversing direction for clearing jams. In the illustrated embodiment, in the off position the manually engageable portion 46 and the movable element would be located generally in the center of the recess 38 , and the on and reverse positions would be on opposing lateral sides of the off position.
[0034] Generally, the construction and operation of the switch 42 for controlling the motor 42 are well known and any construction for such a switch 42 may be used.
[0035] In the illustrated embodiment, the top cover 24 also includes another recess 50 associated with an optional switch lock 52 . The switch lock 52 includes a manually engageable portion 54 that is movable by a user's hand and a locking portion (not shown). The manually engageable portion 54 is seated in the recess 50 and the locking portion is located beneath the top wall 24 . The locking portion is integrally formed as a plastic piece with the manually engageable portion 54 and extends beneath the top wall 24 via an opening formed in the recess 50 .
[0036] The switch lock 52 causes the switch 42 to move from either its on position or reverse position to its off position by a caroming action as the switch lock 52 is moved from a releasing position to a locking position. In the releasing position, the locking portion is disengaged from the movable element of the switch 42 , thus enabling the switch 42 to be moved between its on, off, and reverse positions. In the locking position, the movable element of the switch 42 is restrained in its off position against movement to either its on or reverse position by the locking portion of the switch lock 52 .
[0037] Preferably, but not necessarily, the manually engageable portion 54 of the switch lock 52 has an upwardly extending projection 56 for facilitating movement of the switch lock 52 between the locking and releasing positions.
[0038] One advantage of the switch lock 52 is that, by holding the switch 42 in the off position, to activate the shredder mechanism 16 the switch lock 52 must first be moved to its releasing position, and then the switch 42 is moved to its on or reverse position. This reduces the likelihood of the shredder mechanism 16 being activated unintentionally. Reference may be made to U.S. Patent Application Publication No. 2005-0218250 A1, which is incorporated herein by reference, for further details of the switch lock 52 . This switch lock is an entirely optional feature and may be omitted.
[0039] In the illustrated embodiment, the shredder housing 14 is designed specifically for use with the container 12 and it is intended to sell them together. The upper peripheral edge 60 of the container 12 defines an upwardly facing opening 62 , and provides a seat 61 on which the shredder 10 is removably mounted. The seat 61 includes a pair of pivot guides 64 provided on opposing lateral sides thereof. The pivot guides 64 include upwardly facing recesses 66 that are defined by walls extending laterally outwardly from the upper edge 60 of the container 12 . The walls defining the recesses 66 are molded integrally from plastic with the container 12 , but may be provided as separate structures and formed from any other material. At the bottom of each recess 66 is provided a step down or ledge providing a generally vertical engagement surface 68 . This step down or ledge is created by two sections of the recesses 66 being provided with different radii. Reference may be made to U.S. Pat. No. 7,025,293, which is incorporated herein by reference, for further details of the pivotal mounting. This pivotal mounting is entirely optional and may be omitted.
[0040] As schematically illustrated in FIG. 3 , in order to lubricate the cutter elements 19 of the shredder 10 , a lubrication system 80 may be included for providing lubrication at the cutter elements 19 . The system includes a pump 82 , that draws lubricating fluid, such as oil, from a reservoir 84 . In a typical application, the reservoir 84 will have a fill neck 86 that extends through the top wall 24 of the shredder housing 14 to allow for easy access for refilling the reservoir (see FIG. 5 ).
[0041] The pump 82 communicates through a series of conduits 88 to one or more nozzles 90 that are positioned proximate the cutter elements 19 . In one embodiment, the nozzles can be positioned such that oil forced through the nozzles is dispersed as sprayed droplets in the throat of the shredder 10 . In another embodiment, the oil is dispersed in back of the throat of the shredder 10 . Generally, the nozzles have openings small relative to the conduits, thereby creating a high speed flow at the nozzle, allowing the oil to be expelled at a predictable rate and pattern.
[0042] As shown in FIG. 4 , a system in accordance with an embodiment of the present invention may be a retrofit device. In this embodiment, the reservoir 84 is mounted to an outside surface of the shredder 10 . It is connected via a conduit 92 to the main unit 94 . The main unit 94 may include a power supply (not shown) and the pump 82 (not shown in FIG. 4 ). In any embodiment, the reservoir 84 may be designed to be removed and replaced, rather than re-filled.
[0043] An alternate embodiment includes the system 80 built into the housing of the shredder 10 . In this embodiment, shown in FIG. 5 , the fill neck 86 can be designed to extend through the top wall 24 of the shredder housing 14 . Operation of the system 80 does not depend on whether it is retrofit or built-in.
[0044] In operation, a controller 96 (shown in FIG. 6 ) for the lubrication system 80 is programmed with instructions for determining when to lubricate the cutter elements 19 . The controller processes the instructions and subsequently applies them by activating the pump 82 to cause fluid from the reservoir to be delivered to the nozzles 90 under pressure. The nozzles are positioned and arranged to spray the pressurized lubricating oil to the cutter elements 19 . In general, the oil will be dispersed in a predetermined pattern directly onto the cutter elements and/or the strippers. In a particular arrangement, it may be useful to array the nozzles below the cutter elements so that lubrication is sprayed from below. In an alternate embodiment, the oil is sprayed onto an intermediate surface 98 (shown in FIG. 3 ) and allowed to drip from there onto the cutter elements 19 and the strippers (which are generally located on the outward or post-cutting side of the cutting mechanism and include a serrated member or a comb type member having teeth that protrude into the spaces between the individual cutting disks). The illustrated embodiments of the lubrication system 80 are not intended to be limiting in any way. Reference may be made to U.S. patent application Ser. No. 11/385,864, which is hereby incorporated by reference, for further details of an oiling mechanism. The lubrication system 80 is an optional feature of the shredder 10 .
[0045] In an embodiment of the invention, the shredder 10 includes a thickness detector 100 to, detect overly thick stacks of documents or other articles that could jam the shredder mechanism 16 , and communicate such detection to a controller 200 , as shown in FIG. 6 . Upon such detection, the controller 200 may communicate with an indicator 110 that provides a warning signal to the user, such as an audible signal and/or a visual signal. Examples of audible signals include, but are not limited to beeping, buzzing, and/or any other type of signal that will alert the user that the stack of documents or other article that is about to be shredded is above a predetermined maximum thickness and may cause the shredder mechanism 16 to jam. This gives the user the opportunity to reduce the thickness of the stack of documents or reconsider forcing the thick article through the shredder, knowing that any such forcing may jam and/or damage the shredder.
[0046] A visual signal may be provided in the form of a red warning light, which may be emitted from an LED. It is also contemplated that a green light may also be provided to indicate that the shredder 10 is ready to operate. In an embodiment, the indicator 110 is a progressive indication system that includes a series of indicators in the form of lights to indicate the thickness of the stack of documents or other article relative to the capacity of the shredder is provided, as illustrated in FIG. 7 . As illustrated, the progressive indication system includes a green light 112 , a plurality of yellow lights 114 , and a red light 116 . The green light 112 indicates that the detected thickness of the item (e.g. a single paper, a stack of papers, a compact disc, a credit card, etc.) that has been placed in the throat 36 of the shredder 10 is below a first predetermined thickness and well within the capacity of the shredder. The yellow lights 114 provide a progressive indication of the thickness of the item. The first yellow light 114 , located next to the green light 112 , would be triggered when the detected thickness is at or above the first predetermined thickness, but below a second predetermined thickness that triggers the red light 116 . If there is more than one yellow light 114 , each additional yellow light 114 may correspond to thicknesses at or above a corresponding number of predetermined thicknesses between the first and second predetermined thicknesses. The yellow lights 114 may be used to train the user into getting a feel for how many documents should be shredded at one time. The red light 116 indicates that the detected thickness is at or above the second predetermined thickness, which may be the same as the predetermined maximum thickness, thereby warning the user that this thickness has been reached.
[0047] The sequence of lights may be varied and their usage may vary. For example, they may be arranged linearly in a sequence as shown, or in other configurations (e.g. in a partial circle so that they appear like a fuel gauge or speedometer. Also, for example, the yellow light(s) 114 may be lit only for thickness(es) close to (i.e., within 25% of) the predetermined maximum thickness, which triggers the red light 116 . This is a useful sequence because of most people's familiarity with traffic lights. Likewise, a plurality of green lights (or any other color) could be used to progressively indicate the detected thickness within a range. Each light would be activated upon the detected thickness being equal to or greater than a corresponding predetermined thickness. A red (or other color) light may be used at the end of the sequence of lights to emphasize that the predetermined maximum thickness has been reached or exceeded (or other ways of getting the user's attention may be used, such as emitting an audible signal, flashing all of the lights in the sequence, etc.). These alert features may be used in lieu of or in conjunction with cutting off power to the shredder mechanism upon detecting that the predetermined maximum thickness has been reached or exceeded.
[0048] Similarly, the aforementioned indicators of the progressive indicator system may be in the form of audible signals, rather than visual signals or lights. For example, like the yellow lights described above, audible signals may be used to provide a progressive indication of the thickness of the item. The audible signals may vary by number, frequency, pitch, and/or volume in such a way that provides the user with an indication of how close the detected thickness of the article is to the predetermined maximum thickness. For example, no signal or a single “beep” may be provided when the detected thickness is well below the predetermined maximum thickness, and a series of “beeps” that increase in number (e.g. more “beeps” the closer the detection is to the predetermined maximum thickness) and/or frequency (e.g. less time between beeps the closer the detection is to the predetermined maximum thickness) as the detected thickness approaches the predetermined maximum thickness may be provided. If the detected thickness is equal to or exceeds the predetermined maximum thickness, the series of “beeps” may be continuous, thereby indicating to the user that such a threshold has been met and that the thickness of the article to be shredded should be reduced.
[0049] The visual and audible signals may be used together in a single device. Also, other ways of indicating progressive thicknesses of the items inserted in the throat 36 may be used. For example, an LCD screen with a bar graph that increases as the detected thickness increases may be used. Also, a “fuel gauge,” i.e., a dial with a pivoting needle moving progressively between zero and a maximum desired thickness, may also be used. As discussed above, with an audible signal, the number or frequency of the intermittent audible noises may increase along with the detected thickness. The invention is not limited to the indicators described herein, and other progressive (i.e., corresponding to multiple predetermined thickness levels) or binary (i.e., corresponding to a single predetermined thickness) indicators may be used.
[0050] The aforementioned predetermined thicknesses may be determined as follows. First, because the actual maximum thickness that the shredder mechanism may handle will depend on the material that makes up the item to be shredded, the maximum thickness may correspond to the thickness of the toughest article expected to be inserted into the shredder, such as a compact disc, which is made from polycarbonate. If it is known that the shredder mechanism may only be able to handle one compact disc at a time, the predetermined maximum thickness may be set to the standard thickness of a compact disc (i.e., 1.2 mm). It is estimated that such a thickness would also correspond to about 12 sheets of 20 lb. paper. Second, a margin for error may also be factored in. For example in the example given, the predetermined maximum thickness may be set to a higher thickness, such as to 1.5 mm, which would allow for approximately an additional 3 sheets of paper to be safely inserted into the shredder (but not an additional compact disc). Of course, these examples are not intended to be limiting in any way.
[0051] For shredders that include separate throats for receiving sheets of paper and compact discs and/or credit cards, a detector 100 may be provided to each of the throats and configured for different predetermined maximum thicknesses. For example, the same shredder mechanism may be able to handle one compact disc and 18 sheets of 20 lb. paper. Accordingly, the predetermined maximum thickness associated with the detector associated with the throat that is specifically designed to receive compact discs may be set to about 1.5 mm (0.3 mm above the standard thickness of a compact disc), while the predetermined maximum thickness associated with the detector associated with the throat that is specifically designed to receive sheets of paper may be set to about 1.8 mm. Of course, these examples are not intended to be limiting in any way and are only given to illustrate features of embodiments of the invention.
[0052] Similarly, a selector switch may optionally be provided on the shredder to allow the user to indicate what type of material is about to be shredded, and, hence the appropriate predetermined maximum thickness for the detector. A given shredder mechanism may be able to handle different maximum thicknesses for different types of materials, and the use of this selector switch allows the controller to use a different predetermined thickness for the material selected. For example, there may be a setting for “paper,” “compact discs,” and/or “credit cards,” as these materials are known to have different cutting characteristics and are popular items to shred for security reasons. Again, based on the capacity of the shredder mechanism, the appropriate predetermined maximum thicknesses may be set based on the known thicknesses of the items to be shredded, whether it is the thickness of a single compact disc or credit card, or the thickness of a predetermined number of sheets of paper of a known weight, such as 20 lb. The selector switch is an optional feature, and the description thereof should not be considered to be limiting in any way.
[0053] Returning to FIG. 6 , in addition to the indicator 110 discussed above, the detector 100 may also be in communication with the motor 18 that powers the shredder mechanism 16 via the controller 200 . Specifically, the controller 200 may control whether power is provided to the motor 18 so that the shafts 20 may rotate the cutter elements 19 and shred the item. This way, if the thickness of the item to be shredded is detected to be greater than the capacity of the shredder mechanism 16 , power will not be provided to the shredder mechanism 16 , thereby making the shredder 10 temporarily inoperable. This not only protects the motor 18 from overload, it also provides an additional safety feature so that items that should not be placed in the shredder 10 are not able to pass through the shredder mechanism 16 , even though they may fit in the throat 36 of the shredder 10 .
[0054] FIG. 8-11 show different embodiments of the detector 100 that may be used to detect the thickness of an article (e.g. a compact disc, credit card, stack of papers, etc.) that is placed in the throat 36 of the shredder. As shown in FIG. 8 , the detector 100 may include a contact member 120 that is mounted so that it extends into the throat 36 at one side thereof. The contact member 120 may be pivotally mounted or it may be mounted within a slot so that it translates relative to the throat 36 . The contact member 120 is mounted so that as the item to be shredded is inserted into the throat 36 , the item engages the contact member 120 and causes the contact member 120 to be pushed out of the way of the item. As shown in FIG. 8 , a strain gauge 122 is located on a side of the contact member 120 that is opposite the throat 36 . The strain gauge 122 is positioned so that it engages the contact member 120 and is able to measure the displacement of the contact member 120 relative to the throat 36 . Other displacement sensors may be used. The greater the displacement, the thicker the item being inserted into the throat 36 . The strain gauge 122 communicates this measurement to the controller 200 and the controller 200 determines whether the displacement measured by the strain gauge 122 , and hence thickness of the item, is greater than the predetermined maximum thickness, thereby indicating that the item that is being fed into the throat of the shredder 10 will cause the shredder mechanism 16 to jam. If the detected thickness is greater than the predetermined maximum thickness, the controller 200 may send a signal to the indicator 110 , as discussed above, and/or prevent power from powering the motor 18 to drive the shafts 20 and cutter elements 19 . This way, a jam may be prevented. Likewise, the measured displacement of the contact member 120 may be used by the controller 200 to output progressive amounts of thicknesses, as discussed above. Of course, different configurations of the strain gauge 122 and contact member 120 may be used. The illustrated embodiment is not intended to be limiting in any way.
[0055] In another embodiment, illustrated in FIG. 9 , the detector 100 includes the contact member 120 and a piezoelectric sensor 124 . In this embodiment, the contact member 120 is mounted such that it protrudes through one wall 126 of the throat and into the throat by a small amount, thereby creating a slightly narrower throat opening. A spring 128 may be used to bias the contact member 120 into the throat 36 . The narrower opening that is created by a tip 130 of the contact member 120 and a wall 132 opposite the spring 128 is less than the predetermined maximum thickness. Therefore, if an item that is too thick to be shredded enters the throat 36 , it will engage a top side 134 of the contact member 120 . Because the top side 134 of the contact member 120 is sloped, the contact member 120 will move against the bias of the spring 128 and into contact with the piezoelectric sensor 124 , thereby causing a voltage to be created within the piezoelectric sensor 124 . As the thickness of the item increases, the force applied by the contact member 120 to the piezoelectric sensor 124 increases, thereby increasing the voltage generated within the piezoelectric sensor 124 . The resulting voltage may be communicated to the controller 200 or directly to the indicator 110 , thereby causing the indicator 110 to indicate that the item is above the predetermined maximum thickness. In addition, the controller, upon sensing the voltage, may prevent power from powering the motor 18 to drive the shafts 20 and cutter elements 19 . Of course, different configurations of the piezoelectric sensor 124 and contact member 120 may be used. The illustrated embodiment is not intended to be limiting in any way.
[0056] In another embodiment, illustrated in FIG. 10 , the detector 100 includes the contact member 120 and an optical sensor 140 . In this embodiment, the contact member 120 is pivotally mounted such that one portion extends into the throat 36 and another portion, which has a plurality of rotation indicators 142 , extends away from the throat 36 . The optical sensor 140 may be configured to sense the rotation indicators 142 as the rotation indicators 142 rotate past the optical sensor 140 . For example, the optical sensor 140 may include an infrared LED 144 and a dual die infrared receiver 146 to detect the direction and amount of motion of the contact member 120 . As shown in FIG. 7 , the contact member 120 may be configured such that a small amount of rotation of the contact member is amplified at the opposite end of the contact member 120 , thereby improving the sensor's ability to sense changes in the thickness of the items that cause the contact member 120 to rotate. Of course, different configurations of the optical sensor 140 and contact member 120 may be used. The illustrated embodiment is not intended to be limiting in any way.
[0057] Another embodiment of the detector 100 that includes the optical sensor 140 is shown in FIG. 11 . As illustrated in FIG. 8 , the detector 100 is located above an infrared sensor 150 that detects the presence of an article. Of course, any such sensor may be used. The illustrated embodiment is not intended to be limiting in any way. The sensor 150 provides a signal to the controller 200 , which in turn is communicated to the motor 18 . When the sensor 150 senses that an article is passing through a lower portion of the throat 36 , the controller 200 signals the motor 18 to start turning the shafts 20 and cutter elements 19 . Of course, because the detector 100 is also in communication with the controller 200 , if the detector 100 detects that the thickness of the article that has entered the throat is too thick for the capacity of the shredder mechanism 16 , the shredder mechanism 16 may not operate, even though the sensor 150 has indicated that it is time for the shredder mechanism 16 to operate. Of course, this particular configuration is not intended to be limiting in any way.
[0058] Although various illustrated embodiments herein employ particular sensors, it is to be noted that other approaches may be employed to detect the thickness of the stack of documents or article being fed into the throat 36 of the shredder 10 . For example, embodiments utilizing eddy current, inductive, photoelectric, ultrasonic, Hall effect, or even infrared proximity sensor technologies are also contemplated and are considered to be within the scope of the present invention.
[0059] The sensors discussed above, and other possible sensors, may also be used to initiate the shredding operation by enabling the power to be delivered to the motor of the shredder mechanism. This use of sensors in the shredder throat is known, and they allow the shredder to remain idle until an item is inserted therein and contacts the sensor, which in turn enables power to operate the motor to rotate the cutting elements via the shafts. The controller 200 may be configured such that the insertion of an item will perform this function of enabling power delivery to operate the shredder mechanism motor. The motor may be cut-off or not even started if the thickness exceeds the predetermined maximum thickness.
[0060] Returning to FIG. 6 , for embodiments of the shredder 10 that include the lubrication system 80 , the controller 200 may be programmed to communicate with the controller 96 associated with the lubrication system 80 to operate the pump 82 in a number of different modes. The controller 200 and the controller 96 may be part of the same controller, or may be separate controllers that communicate with each another. In one embodiment, the controller 96 is programmed to operate according to a predetermined timing schedule. In another, the controller 96 activates the pump upon a certain number of rotations of the drive for the cutter elements. In another embodiment, the detector 100 at the throat 36 of the shredder 10 monitors the thickness of items deposited therein. Upon accumulation of a predetermined total thickness of material shredded, the controller 96 activates the pump to lubricate the cutter elements 19 . For example, if the predetermined total thickness of material is programmed in the controller 96 to be 0.1 m (100 mm), then once the total accumulated detected thickness of articles that have been shredder is at least equal to 0.1 m (e.g., one hundred articles with an average thickness of 1 mm, or fifty articles with an average thickness of 2 mm, etc.), the controller 96 will activate the pump 82 of the lubrication system 80 to lubricate the cutter elements 19 .
[0061] It is also possible to schedule the lubrication based on a number of uses of the shredder (e.g., the controller tracks or counts the number of shredding operations and activates the pump after a predetermined number of shredder operations). In each of the embodiments making use of accumulated measures, a memory 97 can be incorporated for the purpose of tracking use. Although the memory 97 is illustrated as being part of the controller 96 associated with the lubrication system, the memory may be part of the shredder controller 200 , or may be located on some other part of the shredder 10 . The illustrated embodiment is not intended to be limiting in any way.
[0062] In addition, the accumulated measures (e.g. the number of shredding operations or the accumulated thickness of the articles that have been shredded) may be used to alert the user that maintenance should be completed on the shredder. The alert may come in the form of a visual or audible signal, such as the signals discussed above, or the controller may prevent power from powering the shedder mechanism until the maintenance has been completed.
[0063] The ability to keep track of the accumulated use of the shredder may also be helpful in a warranty context, where the warranty could be based on the actual use of the shredder, rather than time. This is similar to the warranties that are used with automobiles, such as “100,000 miles or 10 years, whichever comes first.” For example, the warranty may be based on 100 uses or one year, whichever comes first, or the warranty may be based on shredding paper having a total sensed thickness of 1 meter or 2 years, whichever comes first, and so on.
[0064] FIG. 12 illustrates a method 300 for detecting the thickness of an item, e.g. a stack of documents or an article, being fed into the throat 36 of the shredder 10 . The method starts at 302 . At 304 , the item is fed into the throat 36 of the shredder 10 . At 306 , the detector 100 detects the thickness of the item. At 308 , the controller 200 determines whether the thickness that has been detected is greater than a predetermined maximum thickness. The predetermined maximum thickness may be based on the capacity of the shredder mechanism 16 , as discussed above. If the controller 200 determines that the thickness that has been detected is at least the predetermined maximum thickness, at 310 , a warning is provided. For example, to provide the warning, the controller 200 may cause the red light 116 to illuminate and/or causes an audible signal to sound and/or cause power to be disrupted to the motor 18 so that the shredder mechanism 16 will not shred the item. The user should then remove the item from the throat 36 of the shredder 10 at 312 , and reduce the thickness of the item at 314 before inserting the item back into the throat 36 at 304 .
[0065] If the controller 200 determines that the thickness that has been detected is less than the predetermined maximum thickness, the controller 200 may cause the green light 112 to illuminate and/or allows power to be supplied to the shredder mechanism 16 so that the shredder 10 may proceed with shredding the item at 316 .
[0066] In the embodiment that includes the plurality of yellow lights 114 as part of the indicator 100 , if the controller 200 determines that the thickness that has been detected is less than the predetermined maximum thickness, but close to or about the predetermined maximum thickness, the controller 200 may cause one of the yellow lights to illuminate, depending on how close to the predetermined maximum thickness the detected thickness is. For example, the different yellow lights may represent increments of about 0.1 mm so that if the detected thickness is within 0.1 mm of the predetermined maximum thickness, the yellow light 114 that is closest to the red light 116 illuminates, and so on. Although power will still be supplied to the shredder mechanism 16 , the user will be warned that that particular thickness is very close to the capacity limit of the shredder 10 . Of course, any increment of thickness may be used to cause a particular yellow light to illuminate. The example given should not be considered to be limiting in any way.
[0067] Returning to the method 300 of FIG. 9 , at 318 , the user may insert an additional item, such as another document or stack of documents, as the shredder mechanism 16 is shredding the previous item that was fed into the throat 36 of the shredder at 304 . If the user does insert an additional item into the throat 36 at 318 , the method returns to 304 , and the detector 100 detects the thickness of the item at the location of the detector 100 at 306 , and so on. If part of the previous item is still in the throat 36 , the cumulative thickness of the item being shredder and the new item may be detected. If the user does not add an additional item at 318 , the method ends at 320 . The illustrated method is not intended to be limiting in any way.
[0068] The foregoing illustrated embodiments have been provided to illustrate the structural and functional principles of the present invention and are not intended to be limiting. To the contrary, the present invention is intended to encompass all modifications, alterations and substitutions within the spirit and scope of the appended claims.
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A shredder includes a thickness detector device having a contact portion in a throat of a housing. The contact portion is movable by a thickness between opposing major surfaces of at least one article being received by the throat. The thickness detector device includes a detectable portion movable by the contact portion, and a detector for detecting at least one position of the detectable portion that includes a position when the detectable portion has been moved by the contact portion by an amount that correlates to a predetermined maximum thickness. A controller is coupled to the thickness detector, is operable to prevent a motor from driving cutter elements in a shredding direction responsive to the detector detecting that the detectable portion has been moved by the amount that correlates to the predetermined maximum thickness, and is configured to vary the predetermined maximum thickness based on receiving an input parameter.
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BACKGROUND OF THE INVENTION
The invention relates to a subcutaneous, intramuscular bearing for a rigid transcutaneous implant, which can be anchored intracorporally in a bone stump and which has an intermediate piece between the implant and an extracorporal coupling that can be coupled to this intermediate piece.
Such a bearing is known from German published patent application DE 100 40 590 A1. The bearing described in this publication comprises a flexible material and it has a bushing, which closely surrounds the implant distally. The bearing also has an intracorporally arranged coupling sleeve in the form of flexible pleated bellows, which is proximally connected to the bushing in a sealed manner with a molded collar, such that a hollow space of a minimum width remains free between the inner wall of the pleated bellows and the outer wall of the bushing. In this way, a flexible lattice network is arranged distally on the pleated bellows and is connected on the distal end to another lattice network with a higher modulus of elasticity.
With this bearing, the goal is achieved that soft parts can move relative to the rigid implant without exposing the point in the body-part stump where the implant emerges to an increased risk of inflammation.
Even if this known bearing is successfully inserted in practice, there is the risk that in the case, for example, when the point where the implant emerges through the thigh stump is cleaned with a hollow needle, the flexible material, in most cases silicone, is also pierced and a contamination occurs.
BRIEF SUMMARY OF THE INVENTION
Against this background, it is now an object of the present invention to improve a conventional subcutaneous, intramuscular bearing of the type mentioned at the outset, such that safety against contamination of the point in the body where the implant emerges (emergence point) and the adjacent regions of the thigh stump is significantly increased, and inadvertent removal of the germ barrier is prevented.
Accordingly, it is proposed according to a first embodiment that the bearing have a rigid bushing firmly connected to the intermediate piece, and that, between the wall of the bushing and the intermediate piece, an annular space be provided, which is closed in the intracorporal direction and in which the extracorporal coupling can be set. On the outer wall of the bushing there is an open-meshed, three-dimensional lattice structure, except for a region maintained in the distal region having a width B, preferably of up to about 2 cm. Furthermore, a spring ring is provided, which can be set into the annular space from the distal end, which can move with a telescoping motion, and which can be locked under exertion of its spring force.
Relative to the known bearing, the present bushing is a rigid element, which cannot be pierced, e.g., by hollow injection needles. The open-meshed, three-dimensional lattice structure provided on the outer wall of the bushing serves to allow connective tissue to form a structure therein and thus form a germ barrier. The distal region remains free from the three-dimensional lattice structure to allow movement of the surrounding connective tissue for compensating movements.
The spring ring is pressed together, for example with a spring chuck, and inserted into the annular space and pushed in, so that the layer of connective tissue starting at the end of the three-dimensional lattice structure on the bushing bridges over up to the skin of the thigh stump. The adjustability is tailored according to patient-specific conditions.
The surgery now proceeds so that, after the amputation of the thigh, the transcutaneous implant is first anchored in the bone stump, and the distal end is provided with the intermediate piece. Then, the thigh stump is closed until the transcutaneous implant has grown into the bone stump. Finally, after approximately 6 to 8 weeks, the thigh stump is opened with a skin cutting device and the spring ring is pressed together by means of a spring chuck, so that the spring ring can be guided into the annular space.
The spring ring is preferably a bent out ring with a radial slot. The outward flange then lies from the outside against the skin of the thigh stump. The radial slot is used for two purposes: first, the spring ring can be pressed together for insertion into the annular space. After removing the spring chuck, the ring expands in circumference and thereby generates the spring force necessary for the locking. In addition, the radial slot serves for drainage or discharge of internal bodily secretions.
The mesh spacings of the three-dimensional lattice structure on the bushing are preferably about 50 to 2500 μm. These mesh spacings are relatively large, but hold a sufficient amount of connective tissue surrounding the mesh, so that a reliable germ barrier can be produced.
The bushing can be connected firmly to the intermediate piece by heat-shrinking the bushing on the intermediate piece. Alternatively, it can also be fused with the intermediate piece. It is also possible for the bushing to be formed integrally as one piece with the intermediate piece. In each case, it must be guaranteed that the connection between the bushing and the bearing is tight and rigid and can withstand the applied loads.
A second embodiment provides a subcutaneous bearing: having a rigid bushing connected firmly to the intermediate piece with a coupling element, which is closed in the intracorporal direction and to which the extracorporal coupling can be coupled; having an open-meshed, three-dimensional lattice structure on the outer wall of the bushing while maintaining a free width B in the distal region; having an activatable device provided in the region where the implant emerges from the leg stump for application of bioactive material; and having a spring ring, which can be set into the coupling element from the distal end, which can move with a telescoping motion, and which can be locked by exerting its spring effect.
The bearing according to this second embodiment differs from that according to the first embodiment essentially by the activatable device provided in the region where the implant emerges from the leg stump for application of bioactive material. In this way, an optimal maintenance or care of the point where the implant emerges from the thigh stump is guaranteed. Here, the term “bioactive material” is understood to mean a medicine.
The critical region where the implant emerges from the thigh stump can thus be medicinally cared for with a view to an improved wound healing effect, but also with a view to a preventive effect against inflammation. The wound healing is greatly improved by the application of medicine.
According to a first preferred form of this second embodiment, the activatable device for application of bioactive material has at least one annular groove formed in the outer wall of the bushing and at least one hollow ring that can be set in the annular groove, the hollow ring being made of elastic and porous material with a molded inlet port, through which the hollow ring can be supplied with liquid bioactive material. Through the inlet port, the bioactive material is fed into the interior of the hollow ring. The material exits this ring over time due to the porosity, wets the regions of the open-meshed implant lying underneath, and then flows down in the direction towards the point where the implant emerges from the thigh stump. The hollow ring represents a certain reservoir. The storage capacity in terms of time is decisively influenced by the porosity of the material, from which it is made. Preferably, this is selected so that bioactive material need only be supplied approximately every week.
In an especially preferred refinement, the hollow ring and the inlet port comprise a silicone. Here, the hollow ring and the inlet port are preferably formed integrally.
According to a second preferred form of the second embodiment, the device for applying the bioactive material includes at least one annular groove formed in the outer wall of the bushing and at least one branch channel arranged laterally next to the coupling element in the bushing, which extends so that it intersects the periphery of the one or more annular grooves. The branch channel(s) serve for applying the bioactive material. After the application of the bioactive material, the branch channel(s) can be re-closed, preferably by a seal, for example by a screw. Therefore, this embodiment is concerned less with the long-term application of the bioactive material than with the instantaneous and short-term supply of material to the point where the implant emerges from the thigh stump.
In one especially preferred refinement of this embodiment, at least one branch channel, particularly preferred three branch channels, extend on the outer wall of the bushing in the lower region of the three-dimensional lattice structure, between the lowermost annular groove and the three-dimensional lattice free region of the bushing, for transporting the bioactive material to the point where the implant emerges from the leg stump.
According to a third concrete preferred form of the second embodiment, an annular space is arranged around the coupling element, in which space a supply of elastic film made from bioactive material is stored. Here, the film emerges from the annular space through an annular slot in the bushing and runs along the three-dimensional lattice structure-free region of the bushing to the point where the implant emerges from the leg stump. Here, it surrounds the bushing like a tube. In the three-dimensional lattice structure-free region, the film adheres to the tissue or skin surrounding it. Due to the growth of the skin and tissue, the film is pulled outwardly, wherein it carries possible germs and bacteria with it. The growth of the tissue and skin equals a maximum of about 1 mm per day. Correspondingly, the film is pulled from the intermediate piece by this measure. Storage times of up to one year for the film supply are possible before the annular space must be charged with a new film supply.
This embodiment is not targeted to an instantaneous short-term wound healing treatment. Instead, here the long-term preventive effect against possible infection is in the foreground.
All of the forms of the bearing according to the second embodiment can be improved even more advantageously by embodying the coupling element as a conical clamping sleeve. This permits a smaller overall size than a double cone, as was described in the scope of the first embodiment. In general, all refinements of the first embodiment can be applied to the second embodiment.
BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS
The foregoing summary, as well as the following detailed description of the invention, will be better understood when read in conjunction with the appended drawings. For the purpose of illustrating the invention, there are shown in the drawings embodiments which are presently preferred. It should be understood, however, that the invention is not limited to the precise arrangements and instrumentalities shown. In the drawings:
FIG. 1 is a longitudinal sectional view of a subcutaneous, intramuscular bearing, coupled to a transcutaneous implant according to a first embodiment of the invention;
FIG. 2 is a perspective view of an embodiment of the spring ring;
FIG. 3 is an exploded schematic sectional view of an intermediate piece of the bearing with bushing and spring ring;
FIG. 4 is a schematic side view of a transcutaneous implant with the intermediate piece according to a second embodiment of the invention;
FIG. 5 is an enlarged side view of the intermediate piece of FIG. 4 ;
FIGS. 6( a ) and 6 ( b ) are respectively top view (a) and side view (b) of the hollow ring shown in FIG. 4 ;
FIGS. 7( a ) and 7 ( b ) are respectively a schematic cross-sectional view (a) and a schematic view (b) of the intermediate piece according to the second embodiment; and
FIG. 8 is a cross-sectional view of the intermediate piece according to a third embodiment.
DETAILED DESCRIPTION OF THE INVENTION
FIG. 1 gives a first overview. A rigid transcutaneous implant 2 is inserted into a femur stump (not shown). The open meshed, three-dimensional lattice structure 28 is used in the present case for integrating bone material for secondary fixation of the implant 2 into the bone. It is sealed on the distal end by a metal sleeve 12 , which seals the femur stump. For this purpose, the metal sleeve 12 also carries a three-dimensional, open-meshed lattice structure 28 , in which bone material should grow.
In the interior of the metal sleeve 12 , a conical clamping sleeve 13 is formed. This is provided for manufacturing a conical clamp connecting with the intermediate piece 3 presently embodied as a double cone. The intermediate piece 3 has a cylindrical center section 11 , on which the bushing 5 is heat-shrunk. Another cone 14 connects to the center section 11 on the distal side for producing a conical clamp with a conical clamping sleeve in an adapter of the extracorporal coupling (not shown).
The bushing 5 is formed so that, between its wall and the intermediate piece 3 , there is an annular space 6 closed in the intracorporal or proximal direction. In this annular space 6 , the extracorporal coupling is set.
The outer side of the bushing 5 has in the proximal region an open-meshed, three-dimensional lattice structure 8 , into which the connective tissue surrounding the bushing 5 after implantation grows by granulation in order to form a germ barrier. In the distal region of the outer wall of the bushing 5 , there is no three-dimensional lattice structure in a region with a width B ( FIG. 3 ). This permits a compensating motion of the surrounding connective tissue without leading to stress in the tissue.
For the implantation, the transcutaneous implant 2 is first implanted in the femur stump with the metal sleeve 12 mounted thereon, and the thigh stump is then closed for setting the implant. After 6 to 8 weeks sufficient bone material has grown into the three-dimensional lattice structure 28 of the implant 2 , so that this remains stable even under loads in the femur stump. Simultaneously, connective tissue grows into the three-dimensional lattice structure 18 on the outer wall of the metal sleeve 12 to form a first germ barrier.
After the mentioned time span, the thigh stump is reopened and the intermediate piece 3 with the bushing 5 is guided into the opening in the femur stump and locked there by a conical clamp connection between the double cone and the clamping sleeve 13 . An additional securing device 17 (here in the form of a screw) serves for additional securing.
After opening the thigh stump, the spring ring 9 is pressed together by a spring chuck ( FIG. 2 ), wherein the radial slot 10 is provided and inserted into the annular space 6 . By telescopic insertion or shifting of the ring 9 in the annular space, the patient-specific distance between the distal end of the bushing 5 and the skin of the thigh stump can be set. The bent flange 19 of the spring ring 9 then contacts the skin of the thigh stump. The slot 10 serves, on the one hand, for the possibility of pressing the spring ring together with a spring chuck in order to generate a spring force when the spring chuck is released and, on the other hand, for discharge of possible bodily secretions.
A measurement bolt 20 is now inserted into the annular space 6 . With the help of this bolt, the required length for the extracorporal coupling can be determined.
The relationships are clearly seen again, enlarged in FIG. 3 . Here, the intermediate piece 3 with heat-shrunk bushing 5 is shown isolated (exploded view), so that an annular space 6 results between the cone 14 and the bushing 5 .
The heat-shrinking of the bushing 5 on the intermediate piece 3 is now especially successful due to the cylindrical center section 11 of the intermediate piece 3 . Clearly recognizable is also the open-meshed, three-dimensional lattice structure 8 on the outer wall of the bushing 5 , into which the connective tissue, surrounding it after implantation, grows for forming the germ barrier. Shown in FIG. 3 is also the width B, i.e., the width of the region, which is free of a three-dimensional lattice structure 8 on the distal end. From FIG. 3 it can also be seen, based on the indicating arrow, how the clamping ring 9 is inserted into the annular space 6 . After finding the correct insertion depth, the spring chuck is then released and the spring ring 9 expands, so that it lies against the inner wall of the bushing 5 and hardens in this position.
FIG. 4 again shows the rigid transcutaneous implant 102 , which can be anchored intracorporally in a bone stump. It again has an intermediate piece 103 between the implant 102 and an extracorporal coupling 107 that can be coupled to the implant.
A rigid bushing 105 is connected to the intermediate piece 103 . The bushing 105 has a coupling element 106 ( FIGS. 7 a and 8 ) closed in the intracorporal direction, to which the extracorporal coupling 107 is coupled.
The outer wall of the bushing 105 again carries an open-meshed, three-dimensional lattice structure 108 , in which connective tissue is integrated to form a germ barrier. The metal sleeve 119 closing the implant 102 similarly carries the three-dimensional, open-meshed lattice structure 118 for this same purpose.
An annular ring groove 110 is embedded in the outer wall of the bushing 105 , in the embodiment shown. In this annular groove 110 , a hollow ring 111 with a connected inlet port 112 is attached. Details of the hollow ring 111 can be seen from FIG. 6 .
The inlet port 112 is formed directly on the hollow ring 111 . Both preferably comprise silicone. The hollow ring 111 is porous or has small holes 120 , from which the supplied bioactive material can emerge and thus can perform its therapeutic effect in the region of the point where the implant emerges from the thigh stump.
FIGS. 7( a ) and ( b ) show a second embodiment of the intermediate piece 103 . The bushing 105 , again coated with the three-dimensional lattice structure 108 , now has an annular ring groove 110 . As one can see in the sectional view ( FIG. 7 a ), in the right side of the bushing 105 there is a branch channel 113 , which is presently closed with a tightened screw 121 . The branch channel 113 is formed in the bushing 105 , so that it intersects the periphery of the annular groove 110 , so that a bioactive material brought into the branch channel 113 can emerge from the branch channel 113 into the annular groove 110 to perform there its therapeutic effect. For applying the bioactive material, the screw 121 must be unscrewed from the branch channel 113 , after which the bioactive material can then be injected into the channel 113 , for example with a hollow needle. After successful treatment, the branch channel 113 is re-closed with the screw 121 .
So that a good distribution of the bioactive material can take place, three branch channels 114 are now provided ( FIG. 7 b ), which connect the annular groove 110 to the three-dimensional lattice structure region of the bushing 105 with the width B. The bioactive material then flows from the annular groove 110 through the branch channels 114 in the direction of the implant emergenece. point.
Finally, FIG. 8 shows the third preferred embodiment of the intermediate piece 103 . Here, an annular ring space 115 is formed around the coupling element 106 . In the annular space 115 , there is a supply of an elastic film 116 made of bioactive material.
The film in the form of a pressed-together tube emerges through a ring-shaped slot 117 from the annular space 115 and then runs along the three-dimensional lattice-free region of the bushing 105 up to the emergence point of the implant from the leg stump. The film 116 here surrounds this section of the sleeve 105 in the shape of a tube. In the bottom region, the film 116 adheres to the surrounding tissue or skin and is pulled outwards with the growth of the skin and the tissue through the region where the implant emerges. In this way, the film carries possible germs outwardly with it. The patient can then cut off the discharged film material 116 from time to time.
It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the present invention as defined by the appended claims.
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A subcutaneous, intramuscular bearing ( 1 ) for a rigid transcutaneous implant ( 2 ) is provided, for anchoring intracorporally in a bone stump and having an intermediate piece ( 3 ) between the implant ( 2 ) and an extracorporal coupling for coupling on the implant. A rigid bushing ( 5 ) is tightly connected to the intermediate piece ( 3 ), such that between the wall of the bushing ( 5 ) and the intermediate piece ( 3 ) an annular space ( 6 ) is formed, which is closed in the intracorporal direction, for receiving and setting the extracorporal coupling. The outer wall of the bushing ( 5 ) has an open-meshed, three-dimensional lattice structure ( 8 ) and a lattice-free distal region having a width B. A spring ring ( 9 ) is set in the annular space ( 6 ) from the distal end, moved with a telescoping motion, and locked under exertion of its spring effect.
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RELATED APPLICATIONS
[0001] This application is a divisional of U.S. patent application Ser. No. 12/789,306 filed May 27, 2010, entitled “Inverted Airfoil Pylon For An Aircraft,” which is a divisional of U.S. patent application Ser. No. 11/644,712 filed Dec. 22, 2006, entitled “Inverted Airfoil Pylon For An Aircraft,” now U.S. Pat. No. 7,770,841, issued Aug. 10, 2010.
FIELD OF THE INVENTION
[0002] The claimed invention relates generally to the field of aviation and more particularly, but not by way of limitation, to a method and apparatus for improved flight dynamics for an aircraft.
BACKGROUND
[0003] The optimization of flight dynamics for an aircraft is an important task typically undertaken by aeronautical engineers during the development and testing phases involved in bringing an aircraft to market. Following development, testing, and certification phases of the Series 20 LEARJET®, the aircraft was introduced to the market in 1964, and was followed by the introduction of the Series 30 LEARJET® in 1974.
[0004] The handling characteristics of LEARJET® Series 20 and 30 yield aircraft that is fairly complex to fly, which in the number of applications necessitates the presence of two pilots during flight. The drag acting on aircraft, the available lift provided by the wings, and available thrust provided by the engines each contribute to the aircraft's operating efficiency and its ability to take off, land, and avoid a stall condition during flight.
[0005] Two conditions known to be present in LEARJET® Series 20 and 30 aircraft from their introduction to the present are, their susceptibility of encountering a stall condition, and the susceptibility of the aircraft to dip its nose when additional thrust is provided during flight.
[0006] Accordingly, there is a long felt need for improvements in the flight dynamics of LEARJET® Series 20 and 30 aircraft.
SUMMARY OF THE INVENTION
[0007] In accordance with a preferred embodiment, an aircraft includes at least a fuselage supporting a wing, an engine for propelling said aircraft, and a pylon disposed between said engine and said fuselage and securing said engine to said fuselage, wherein said pylon provides an airfoil inverted from an airfoil of said wing.
[0008] In accordance with a preferred embodiment, an improvement for an aircraft selected from a group consisting of 20 Series and 30 Series LEARJET® that preferably includes at least increasing the horizontal distance between the leading edge of a wing of the selected aircraft and an intake of an engine of the selected aircraft. The increased horizontal separation between the leading edge of the wing and the intake of the engine reduces drag and increases lift provided by the wing for improved flight dynamics of the selected aircraft. The improvement preferably further includes a pylon (for use in securing the engine to the fuselage) that provides an airfoil inverted in form from a form of an airfoil provided by the wing. The inverted airfoil neutralizes the effect of the pylon, relative to lift and drag, for improved flight dynamic of the aircraft.
[0009] For the 20 Series LEARJET®, the preferred embodiment also preferably includes, the engine secured to the pylon such that a centerline passing through the engine is substantially parallel to a waterline of the aircraft. The substantially parallel alignment between the engine centerline and said waterline reduces drag effecting said aircraft flight dynamics. An increased distance between the centerline of the engine and the waterline of the aircraft is preferably incorporated within the improvement to increase lift provided by the wings of the aircraft, and an increased distance between the centerline of said engine and a centerline of the fuselage is included in the improvement to reduce drag effecting the flight dynamics of the aircraft.
[0010] In accordance with an alternate preferred embodiment, a method of improving flight dynamics of an aircraft selected from a group consisting of (a 20 Series LEARJET® and a 30 Series LEARJET®) is provided by steps that preferably include: removing an original engine from an original pylon of the aircraft; removing the original pylon from an original location adjacent a fuselage of the aircraft; and mounting a new pylon in a new location adjacent the fuselage, wherein the new location is located aft of said original location.
[0011] The alternate preferred embodiment preferably further includes the step of mounting a new engine to the new pylon such that the distance between a centerline of the new engine (which runs substantially parallel to the waterline) and the waterline of the aircraft is greater than a distance between a central point along a centerline of the original engine and the waterline. The alternate preferred embodiment also preferably further includes the steps of: mounting the new engine on the new pylon such that a distance between a centerline of the new engine and a centerline of the fuselage is greater than a distance between a centerline of the original engine and the centerline of the fuselage; and covering the pylon with a skin, wherein the skin provides an airfoil inverted in shape relative to an airfoil shape provided by the wing of said aircraft.
[0012] These and various other features and advantages, which characterize preferred embodiments of the present invention, will be apparent from reading the following detailed description in conjunction with reviewing the associated drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0013] FIG. 1 is a top plan view of prior art aircraft applicable to the present invention.
[0014] FIG. 2 provides a side elevational view of the prior art aircraft of FIG. 1 .
[0015] FIG. 3 provides a front elevational view of the prior art aircraft of FIG. 1 .
[0016] FIG. 4 is a top plan view of an aircraft of the present invention.
[0017] FIG. 5 provides a side elevational view of the aircraft of FIG. 4 .
[0018] FIG. 6 provides a front elevational view of the aircraft of FIG. 4 .
[0019] FIG. 7 shows a partial cross-sectional, side elevational view of a pylon and a wing of the aircraft of FIG. 4 .
[0020] FIG. 8 is a diagram of a flowchart of a method of making the present invention.
DETAILED DESCRIPTION
[0021] Reference will now be made in detail to one or more examples of the invention depicted in the accompanying figures. Each example is provided by way of explanation of the invention, and are not meant as, nor do they represent, limitations of the invention. For example, features illustrated or described as part of one embodiment may be used with another embodiment to yield still a different embodiment. Other modifications and variations to the described embodiments are also contemplated and lie within the scope and spirit of the invention.
[0022] Referring to the drawings, to provide an enhanced understanding of the present invention, a reader is encouraged to view prior art FIGS. 1 , 2 , and 3 in concert while proceeding with reading this description of the present invention. Collectively, prior art FIGS. 1 , 2 , and 3 depict prior art 20 and 30 Series LEARJET® aircraft applicable for use with the present invention.
[0023] Prior art FIG. 1 is useful for presenting a plan view of both a prior art 20 Series LEARJET® aircraft and a prior art 30 Series LEARJET® (collectively prior art aircraft 10 ) found useful in practicing the present invention. Prior art FIG. 2 shows the prior art aircraft 10 , in side elevational view, for a prior art 20 Series LEARJET® aircraft, and prior art FIG. 3 shows the front elevational view suitable for depicting either the 20 or 30 Series prior art LEARJET® aircraft. When collectively viewing prior art FIGS. 1 , 2 , and 3 , the reader's attention is drawn to the location of the engines 12 , relative to other sections and references of the aircraft, and in particular to the nacelle 13 inclosing each engine 12 .
[0024] Prior art FIG. 1 shows that engine inlets 14 , of the engines 12 , are correspondingly positioned at a predetermined distance 16 (of about 153 centimeters) from a corresponding leading edge 18 , of their corresponding wings 20 , and that each engine 12 is secured to a fuselage 22 , of the prior art aircraft 10 by a pylon 24 . Prior art FIG. 1 further shows centers of mass 26 , of the engines 12 , are correspondingly positioned at a predetermined distance 28 (of about 111 centimeters) from a centerline 30 , of the fuselage 22 , of the prior art aircraft 10 .
[0025] The prior art aircraft 10 , of FIG. 2 , depicts an orientation of the engine 12 , for a prior art 20 Series LEARJET® aircraft relative to the fuselage 22 via the relationship between a centerline 32 of the engine 12 , and a waterline 34 of the prior art aircraft 10 . In the prior art 20 Series LEARJET®; the engine 12 is set at a predetermined pitch angle 36 (of about 3°). That is, the engine 12 slopes from the engine inlet 14 to an engine outlet 38 at about a three-degree angle. Prior art FIG. 2 also shows the center of mass 26 , of the engine 12 , is positioned at a predetermined distance (of about 101 centimeters) from the waterline 34 .
[0026] For both the 20 and 30 Series prior art LEARJET® shown by FIG. 3 , nacelles 42 and fuselage skin 44 appear to abut one another. However, by referring back to FIG. 1 , it can be seen that the engines 12 are offset from the fuselage 22 by the pylons 24 . Nonetheless, FIG. 1 shows that a portion of the fuselage skin 44 and a portion of the nacelle 42 of the engine 40 lie coextensively with a cord line 46 (of FIG. 1 ).
[0027] The position of the engines 12 of the prior art aircraft 10 relative to the wings 20 and the fuselage 22 has a direct bearing on the flight dynamics of prior art aircraft 10 . The location of the engines 12 , relative to the wings 20 creates a partial air dam between wings 20 and the engines 12 . The effect of this partial air dam is a disruption in the fluid flow over the wings 20 , which decrease the effectiveness of the wings 20 . In other words, by partially disrupting the flow of fluid over the wing, the amount of available lift provided by the wing is diminished. The diminished availability of lift provided by wings 20 reduces the ability of prior art aircraft 10 to avoid stall conditions during flight.
[0028] The spacing of the engines 12 , relative to the fuselage 22 also creates a partial air dam for fluid flowing between the fuselage 22 and the engines 12 . The result of this disruption in fluid flow is an increase in the overall drag experienced by the prior art aircraft 10 .
[0029] For the 20 Series prior art LEARJET®, the problem of reduced lift capability of the wings 20 and increased drag created between the fuselage 22 in the engines 12 is exasperated by having the engines 12 mounted at a 3° pitch, relative to the waterline 34 . Mounting the engines 12 at a 3° pitch relative to the waterline 34 introduces additional drag and difficult handling characteristics into the flight dynamics of the prior art aircraft 10 . In addition to the increase in drag, the 3° pitch further affects the flight dynamics of the 20 Series LEARJET® by causing the nose of the prior art aircraft 10 to dip when additional throttle is applied to the engines 12 of the 20 Series LEARJET® during flight.
[0030] For ease in contrasting the present invention with the prior art, FIGS. 4 , 5 , and 6 are provided to depict the present invention in views comparable to FIGS. 1 , 2 , and 3 . Accordingly, viewing FIGS. 4 , 5 , and 6 together will provide an enhanced understanding of the present invention. Collectively, FIGS. 4 , 5 , and 6 depict structural changes made to the 20 and 30 Series LEARJET® aircraft to produce an improved present inventive aircraft 100 . FIG. 4 presents a plan view of an inventive aircraft 100 and is useful for showing a change in engine location between the prior art aircraft 10 (of FIG. 1 ) and the inventive aircraft 100 . FIG. 5 shows the inventive aircraft 100 in side elevational view, which is useful in helping with an understanding of a structural change made to the 20 Series LEARJET® in arriving at the present inventive aircraft 100 . FIG. 6 shows the front elevational view of the inventive aircraft 100 suitable for depicting an additional structural change employed in arriving at the present inventive aircraft 100 . When collectively viewing FIGS. 4 , 5 , and 6 , the reader's attention is drawn to the location of the engines 102 , relative to other sections and references of the inventive aircraft 100 .
[0031] In a preferred embodiment shown by FIG. 4 , engine inlets 104 of the engines 102 , are preferably positioned at a distance 106 (of about 194 centimeters) from corresponding leading edges 108 of corresponding wings 110 . Each engine 102 is preferably secured to a fuselage 112 by a pylon 114 . FIG. 4 further shows centers of mass 116 , of the engines 102 , are preferably correspondingly positioned at a distance 118 (of about 121.5 centimeters) from a centerline 120 , of the fuselage 112 of the inventive aircraft 100 .
[0032] The inventive aircraft 100 of FIG. 5 shows an orientation of the engine 102 (for an inventive aircraft 100 based on a 20 Series LEARJET®) relative to a centerline 122 of the engine 102 , and a waterline 124 of the inventive aircraft 100 . In the 20 Series LEARJET® prior art aircraft 10 (of FIG. 2 ), the engine 12 is set at a downwardly sloping 3° pitch. In a preferred embodiment shown by FIG. 5 , the relationship between the centerline 122 and the waterline 124 shows an absence of a pitch, i.e., the centerline 122 lies substantially parallel to the waterline 124 . FIG. 5 also shows the center of mass 116 , of the engine 102 , is positioned at a selected distance 126 (of about 109 centimeters) from the waterline 124 .
[0033] In a preferred embodiment of the inventive aircraft 100 shown by FIG. 6 , nacelles 128 are offset from a fuselage skin 130 such that a portion of the pylons 114 are brought into view when viewing the inventive aircraft 100 from a front elevational perspective. By referring back to FIG. 4 , it can be seen that the engines 102 are offset from the fuselage 112 by the pylons 114 at a distance sufficient to assure that the nacelle 128 does not lie coextensively with a cord line 132 , which lies tangent to the fuselage skin 130 .
[0034] The position of the engines 102 of the inventive aircraft 100 relative to the wings 110 and the fuselage 112 has a direct bearing on improved flight dynamics of the inventive aircraft 100 , when compared to the flight dynamics of the prior art aircraft 10 (of FIGS. 1-3 ). The location of the engines 102 , relative to the wings 110 alleviates the partial air dam present between wings 20 in the engines 12 of the prior art aircraft 10 . By alleviating the air dam, the amount of available lift provided by the wings 110 is greatly enhanced. The spacing of the engines 102 , relative to the fuselage 112 removes from the inventive aircraft 100 the partial air dam developed between the fuselage 22 in the engines 12 of prior art aircraft 10 , which decreases the overall drag experienced by the inventive aircraft 100 .
[0035] For the inventive aircraft 100 based on the 20 Series LEARJET®, removing the 3° pitch of the engines 12 , relative to the waterline 34 on the prior art aircraft 10 (of FIG. 2 ), alleviates the drag created by the 3° pitch, and the tendency of the nose to dip during in flight accelerations.
[0036] In a preferred embodiment, the following dimensional changes for engine location have been found useful in providing the inventive aircraft 100 based on either the 20 or 30 Series LEARJET®. Those dimensional changes for engine location include positioning the engines 102 : about 41 centimeters further back from the leading edge 108 of the wing 110 at a point adjacent the fuselage 112 ; about 8 centimeters further up from the waterline 124 ; and about 10.2 centimeters further out from the fuselage centerline 120 . It has been found that these improvements dramatically improve the flight dynamics of the inventive aircraft 100 , relative to the flight dynamics of the prior art aircraft 10 . The improvement includes a greatly enhanced ability to avoid stall conditions during in flight maneuvers.
[0037] FIG. 7 shows that in a preferred embodiment of the present invention, an airfoil 134 is provided by a skin 136 of the pylon 114 . Preferably, the shape of the airfoil 134 is inverted in form from the shape of an airfoil 138 provided by the wing 110 . By presenting the airfoil 134 to an air stream in an orientation inverted from the airfoil 138 of the wing 110 , an influence of the pylon 114 on the flight dynamics of the inventive aircraft 100 is neutralized. That is to say, by providing an inverted airfoil 134 covering the pylon 114 , the pylon 114 neither adds to the drag nor detracts from the lift of the inventive aircraft 100 . The shape of the airfoil of the pylon, i.e., inverted from the shape of the airfoil of the wing, has removed the pylon as a structural component effecting the aerodynamics of the aircraft.
[0038] Turning to FIG. 8 , the flow chart 200 depicts a process of forming an inventive aircraft (such as 100 ). The method commences at start step 202 and proceeds to process step 204 with the removal of an engine (such as 12 ). At process step 206 , a pylon (such as 24 ) is removed from a fuselage (such as 22 ) of the inventive aircraft. Following the removal of the pylon from the fuselage; providing a portion of fuselage skin (such as 44 ) to cover the portion of the fuselage left open by removal of the pylon; and removing a portion of fuselage skin from the airframe in preparation for mounting a new pylon (such as 114 ), the new pylon is secured to the fuselage at process step 208 .
[0039] At process step 210 , a new engine (such as 102 ) is mounted to the new pylon. At process step 212 , the new pylon is covered with a skin (such as 136 ) to provide an airfoil (such as 134 ) and the process concludes at end process step 214 .
[0040] It is to be understood that even though numerous characteristics and advantages of various embodiments of the present invention have been set forth in the foregoing description, together with details of the structure and function thereof, this detailed description is illustrative only, and changes may be made in detail, especially in matters of structure and arrangement of parts within the principles of the invention to the full extent indicated by the broad general meaning of the terms in which the appended claims are expressed. For example, the particular elements may vary depending on the particular application for a select engine, while maintaining the same functionality without departing from the spirit and scope of the invention.
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An aircraft including a wing and a pylon, wherein the pylon provides an airfoil inverted for an airfoil of the wing, and an improvement and method for improved flight dynamics for 20 and 30 Series LEARJET® is provided. The improvement includes an increased distance between a leading edge of a wing and an intake of an engine of the aircraft, which reduces drag and increases lift for improved flight dynamics of the aircraft. The inverted airfoil of the pylon negates an influence of the pylon on flight dynamics for improved overall flight dynamics of the aircraft. The method includes steps of removing an original engine from an original pylon, removing the original pylon from the fuselage of the aircraft, and mounting a new pylon in a new location adjacent to the fuselage, wherein the new location is aft of the original location.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of Invention
[0002] This invention pertains to a cardiac system with an implantable housing that can be selectively rendered to be active or passive. More particularly, the invention describes a cardiac system including housing with a header, a plug and/or a connector with a lead terminating with one or more electrodes and adapted to be inserted into the housing. The structure of the plug or connector defines whether the housing is active or passive.
[0003] 2. Description of the Prior Art
[0004] Implantable cardiac devices are used extensively to provide therapy to patients with various cardiac problems. The therapy from these types of devices usually consists of the application of electrical stimulation pulses to cardiac tissues. Typically, each such device typically consists of sensing circuitry used to sense intrinsic cardiac signals, generating circuitry used to generate electrical stimulation signals, control circuitry used to control the operation of the device, and various auxiliary circuitry used to perform other functions, such as telemetry, data logging, etc. This circuitry is contained in a housing suitable for implantation. The housing further includes a header used to connect the circuitry contained in the housing to one or more leads which extend into, or at least in the vicinity of, the patient's heart and terminate in one or more electrodes. Various header structures are disclosed in U.S. Pat. Nos. 5,545,189; 5,620,477; 5,899,930; 5,906,634; 6,167,314; 6,208,900; and 6,330,477, all incorporated herein by reference.
[0005] At least two electrodes are required for sensing, stimulation and some other functions of the device. In many instances, for example, when the housing is implanted pectorially, it is advantageous to have the housing act as one of the electrodes. In these instances, typically at least a portion of the housing's outer surface is exposed and is composed of a conductive material. This portion is then electrically connected to the circuitry within the housing and plays an active part in the operation of the circuitry (i.e., is used to provide stimulation, sensing and/or other functions). Such a housing is often referred to as an ‘active’ housing.
[0006] However, an active housing may not be desirable for all locations (e.g., abdominal) because it may be too distant from the heart to be effective, or because it may be, in some instances, adjacent to a muscle that is adversely affected by electrical stimulation.
[0007] A housing could be constructed from the start as an active or passive housing by providing an appropriate electrical link between the housing surface and its circuitry. However, this approach is impractical if the decision as to which kind of housing to use is made at the last minute, i.e., just prior to implantation. Since most cardiac devices are programmable, an electrically controlled switch could be used as the link and the decision as to whether to make a housing active or not could be another programming parameter. However, such electrically controlled switches use up space within the housing and add cost and complexity to the electrical circuitry.
[0008] U.S. Pat. No. 5,620,477 discloses a housing 12 that can be rendered selectively active and passive using a mechanical element. This housing makes use of a special header having two connector blocks 34 , 36 . Connector block 34 is connected to an internal circuit while connector block 36 is connected to the conductive surface 16 . The housing 12 is rendered active by a plug inserted into the header and having a long connector pin 54 which is positively attached to the connector blocks 34 , 36 , thereby effectively shorting the two connector blocks to each other. Alternatively, a lead connector is provided with its own connector pin 54 . The problem with this approach is that it requires a special design for both the housing header and the plug or lead connector. Thus, this housing cannot be used with standard multi-lead connectors conforming to specific standards, such as an IS-4 quadripollar lead connector.
SUMMARY OF THE INVENTION
[0009] The present invention provides a novel implantable cardiac housing that overcomes the deficiencies of such existing housings. More particularly, an implantable cardiac device is disclosed having a housing with a header. The header is structured to accept an external connector member such as a plug or a multiple conductor lead connector conforming to a pre-selected standard such as IS-4. The header includes a plurality of housing connector elements that come into contact with the external connector member. One of these housing connector elements is connected to a conductive portion of the housing. Another of the housing connector elements is connected to an internal electrical circuit disposed within the housing.
[0010] Each of the external connector members has a shaft with a plurality of external connector elements. The external connector elements are wired in a manner that connects distant electrodes to the internal electrical circuit. In addition, in certain embodiments of the present invention, the external connecting elements include a shorting wire to connect two housing connector elements, thereby rendering the housing active. Alternatively, If the housing is to remain passive, no shorting wire is provided.
BRIEF DESCRIPTION OF THE DRAWINGS
[0011] [0011]FIG. 1 shows a side view of the housing of a cardiac device and a shorting plug constructed in accordance to this invention;
[0012] [0012]FIG. 2 shows a partial cross-sectional of the shorting plug of FIG. 1;
[0013] [0013]FIG. 3 shows a partial cross-sectional view of a first lead connector similar to the connector of the shorting plug of FIG. 2;
[0014] [0014]FIG. 4 shows a partial cross-sectional view of a second lead connector used for an passive housing; and
[0015] [0015]FIG. 5 shows a partial cross-sectional view of a third lead connector in which the housing is active and is electrically connected to a remote electrode.
DETAILED DESCRIPTION OF THE INVENTION
[0016] Referring now to the drawings, a cardiac system 10 constructed in accordance with this invention includes a housing 12 with an external surface 14 . A portion 16 of the external surface 14 is made of an electrically conductive material, such as stainless steel, a titanium alloy, or other electrically conductive materials known in the art. Alternatively, the entire surface of the housing 10 could be made conductive. The housing 12 holds a power supply (not shown) and various electrical circuits 17 used to sense intrinsic cardiac signals, generate stimulation pulses and perform other similar conventional functions. These electrical circuits are provided on one or more circuit boards 18 . The housing 12 is hermetically sealed and includes a header 20 made of an epoxy or other similar non-conductive material.
[0017] The header 20 is formed with one or more access holes 22 to provide a means of interfacing the housing 12 with one or more external connector members. Examples of external connector members include a shorting plug 30 and a lead connector 40 . Furthermore, the header 20 is formed to enable these external connector members to be electrically coupled to the circuits contained within the housing 12 .
[0018] Each access hole 22 may be used to provide one or more connections. More particularly, several housing connector elements 24 A, 24 B, 24 C, 24 D are disposed axially along the access hole 22 . These housing connector elements may comprise contacting blades, springs, screws or any other similar conventional connecting mechanisms known in the art. Housing connector elements 24 A, 24 B, 24 C are electrically coupled to one of the circuits 17 on board 18 . Housing connector element 24 D is electrically coupled to the conductive portion 16 of the housing 12 .
[0019] The header 20 is arranged and constructed to electrically couple the external connector members (such as a shorting plug 30 or a lead connector 40 for a multi-electrode lead) to the electrical circuits 17 when the external connector members are inserted into the access hole 22 .
[0020] The shorting plug 30 includes a head 32 and a shaft 34 . The head 32 portion of the shorting plug 30 is used to hold and manipulate the shorting plug 30 during its insertion into the access hole 22 . The shaft 34 portion of the shorting plug 30 is constructed in accordance with standard guidelines set for multi-electrode connectors, such as IS-4.
[0021] The external connector elements 36 A, 36 B, 36 C, 36 D are disposed about the shaft 34 of the shorting plug 30 . In the configuration shown in FIG. 1, the connecting element 36 A forms the tip of the shaft 34 , while the connector elements 36 B, 36 C, 36 D are ring-shaped and are axially spaced from the shaft tip. The external connector elements 36 A- 36 D are formed of a conductive biocompatible material. The regions between the connector elements on the shaft 34 , however, are made of an insulating or non-conductive material.
[0022] When the shaft of the external connecting member (in this case, the shorting plug 30 ) is properly positioned within the access hole 22 , the external connector elements 36 A- 36 D couple to the housing connector element 24 A- 24 D located within the header 20 . This subsequent union provides an electrical connection between the external connector member and the cardiac system 10 .
[0023] The lead connector 40 similarly has a proximal end consisting of a shaft 44 . Disposed along the proximal end of the shaft 44 are external connector elements 46 A, 46 B, 46 C, 46 D. External connector elements 46 A- 46 D are constructed and function to the external connector elements 36 A- 36 D described with reference to the shorting plug 30 . Lead connector 40 is attached to a lead 42 which includes a plurality of conductors 48 . The plurality of conductors 48 terminate and are connected distally to an electrode 50 . Proximally, the plurality of conductors 48 are connected to one of the external connector elements 46 A- 46 D.
[0024] In one embodiment, the lead 42 is implanted with the electrodes 50 disposed in the patient's cardiac chambers. In an alternative embodiment, the lead is implanted with the electrodes 50 disposed subcutaneously within the patient's anatomy. Similarly, particular embodiments of the present invention include a combination of electrodes 50 disposed subcutaneously around the patient's thorax and transvenously within the patient's heart.
[0025] [0025]FIG. 2 shows a cross-sectional partial view of the shaft of an external connecting member. In particular, FIG. 2 depicts a portion of the shaft 34 of the shorting plug 30 . The shaft portion of the external connecting members is constructed to permit connections between external connector elements. For example, as depicted in FIG. 2, a shorting element 35 may be provided between external connector elements 36 C and 36 D. This design flexibility, in particular the electrical interactions between external connector elements, permits external connecting members to be used in mechanically programming a cardiac system 10 to have a housing that is active or passive.
[0026] In illustration, when the shorting plug 30 is fully inserted into the access hole 22 , the external connector elements 36 A- 36 D come into electrical contact with the respective housing connector elements 24 A- 24 D contained within the access hole 22 . If the housing connector elements 24 C and 24 D are coupled to the circuit board 18 and to the conductive portion 16 of the housing 12 respectively, when the shorting plug 30 depicted in FIG. 2 is inserted into the access hole 22 , the conductive portion 16 of the housing 12 is connected to the board 18 , thereby rendering the housing 12 active.
[0027] External connecting members may be used to mechanically program a cardiac system 10 having a single access hole 22 , or alternatively, having multiple access holes. When the cardiac system 10 possesses a single access hole 22 , a lead connector 40 is utilized to mechanically program the cardiac system 10 as active or passive. Alternatively, when the cardiac system includes multiple access holes 22 , a combination of shorting plugs 30 and lead connectors 40 can be utilized to mechanically program the cardiac system 10 to a desired configuration.
[0028] In a cardiac system 10 having two access holes 22 , there are at least five different combinations in which to arrange the external connecting members to mechanically program the cardiac system 10 as active or passive. One grouping of combinations utilizes two lead connectors 40 . In this grouping, both lead connectors 40 may be constructed to mechanically render the cardiac system 10 passive. Alternatively, one lead connector 40 may be constructed to render a passive cardiac system 10 , whereas the second lead connector 40 may be constructed for rendering the cardiac system 10 active. The result of such a lead connector 40 arrangement would be an active cardiac system 10 having two distally positioned electrodes.
[0029] A second grouping utilizes a single lead connector 40 and a single shorting plug 30 . In this grouping, both lead external connecting members may be constructed for mechanically rendering a passive cardiac system 10 . Alternatively, the lead connector 40 may be constructed for rendering the cardiac system 10 passive, whereas the shorting plug 30 may be constructed to render the cardiac system 10 active. Another conceivable arrangement is to have the lead connector 40 render the cardiac system 10 active and the shorting plug 30 render the cardiac system 10 passive. Again, in either of the last two examples, the result of such external connecting member arrangements would be an active cardiac system 10 having a distally positioned electrode.
[0030] FIGS. 2 - 5 further illustrate how within a single external connecting member, the interactions between external connecting elements may be configured to provide an array of mechanical programming for the cardiac system 10 .
[0031] [0031]FIG. 3 shows the structure of the lead connection 40 if the housing 12 is to be an active housing. As shown in this Figure, conductors 48 are attached to external connector elements 46 A, 46 B and a shorting wire 45 is provided between external connector elements 46 C and 46 D. In this manner, the circuit board 18 is connected to the housing portion 16 .
[0032] [0032]FIG. 4 shows alternative construction for a lead connection 40 . As seen in this Figure, the external connector elements 46 A, 46 B, 46 C are all connected to a respective conductor 48 while the external connection element 46 D is not connected to a conductor 48 . As a result, when the lead connector 40 ′ is inserted into the housing 12 , the housing 12 is passive.
[0033] [0033]FIG. 5 shows yet another alternate construction for a lead connector 40 ″. In this embodiment the external connector elements 46 C, 46 D are connected to each other by a wire 45 and to a conductor 48 . This arrangement may be advantageous if multiple current paths are desired.
[0034] While the invention has been described with reference to several particular embodiments, it is to be understood that these embodiments are merely illustrative of the principles of the invention. Accordingly, the embodiments described in particular should be considered as exemplary, not limiting, with respect to the following claims.
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The housing of an implantable cardiac device is selectively made active or passive by an external connector member, such as a shorting plug or lead connector inserted in its header. Advantageously, the header, the shorting plug, and the lead connector all are constructed and arranged to conform to a pre-selected standard in the industry, such as IS-4. The header includes an access hole that is provided with several housing connector elements connected either to the conductive surface or to an internal electrical circuit. The external connector members each have a shaft with external conductor elements. Each shaft includes conductors such as wires. The housing is made active by inserting into the header an external connector element having two of its external connector elements connected by a shorting wire.
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CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of priority to U.S. Provisional Patent Application No. 60/734,678, filed 7 Nov. 2005. The full disclosure of this application is incorporated herein by reference in its entirety and for all purposes.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] The invention provides compounds, pharmacutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families.
[0004] 2. Background
[0005] Peroxisome Proliferator Activated Receptors (PPARs) are members of the nuclear hormone receptor super family, which are ligand-activated transcription factors regulating gene expression. Certain PPARs are associated with a number of disease states including dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, atherogenesis, hypertriglyceridemia, heart failure, myocardial infarction, vascular diseases, cardiovascular diseases, hypertension, obesity, inflammation, arthritis, cancer, Alzheimer's disease, skin disorders, respiratory diseases, ophthalmic disorders, IBDs (irritable bowel disease), ulcerative colitis and Crohn's disease. Accordingly, molecules that modulate the activity of PPARs are useful as therapeutic agents in the treatment of such diseases.
SUMMARY OF THE INVENTION
[0006] In one aspect, the present invention provides compounds of Formula I:
[0000]
[0000] in which
[0007] n is selected from 0, 1, 2 and 3;
[0008] p is selected from 0, 1, 2 and 3;
[0009] Y is selected from O, S(O) 0-2 , NR 7a and CR 7a R 7b ; wherein R 7a and R 7b are independently selected from hydrogen and C 1-6 alkyl;
[0010] W is selected from O and S;
[0011] R 1 is selected from —X 1 CR 9 R 10 X 2 CO 2 R 11 , —X 1 SCR 9 R 10 X 2 CO 2 R 11 and —X 10 CR 9 R 10 X 2 CO 2 R 11 ; wherein X 1 and X 2 are independently selected from a bond and C 1-4 alkylene; and R 9 and R 10 are independently selected from hydrogen, C 1-4 alkyl and C 1-4 alkoxy; or R 9 and R 10 together with the carbon atom to which R 9 and R 10 are attached form C 3-12 cycloalkyl; and R 11 is selected from hydrogen and C 1-6 alkyl; each
[0012] R 2 is independently selected from halo, C 1-6 alkyl, C 2-6 alkenyl, C 1-4 alkoxy, C 1-4 alkylthio, C 3-12 cycloalkyl, C 3-8 heterocycloalkyl, C 6-10 aryl and C 5-10 heteroaryl; wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R 2 is optionally substituted with 1 to 3 radicals independently selected from halo, C 1-6 alkyl, C 1-6 alkoxy, C 2-6 alkenyl, C 1-6 alkylthio, halo-substituted-C 1-6 alkyl, halo-substituted-C 1-6 alkoxy, —C(O)R 14a and NR 14a R 14b ; wherein R 14a and R 14b are independently selected from hydrogen and C 1-6 alkyl;
[0013] R 3 and R 4 are independently selected from hydrogen and C 1-6 alkyl;
[0014] R 5 and R 6 are independently selected from hydrogen, C 1-6 alkyl, C 3-12 cycloalkyl, C 3-8 -heterocycloalkyl, C 6-10 aryl and C 5-13 heteroaryl;
[0015] wherein any aryl, heteroaryl, cycloalkyl and heterocycloalkyl of R 5 and R 6 is optionally substituted with 1 to 3 radicals independently selected from halo, nitro, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, hydroxy-C 1-6 alkyl, halo-substituted-C 1-6 alkyl, halo-substituted-C 1-6 alkoxy, C 3-12 cycloalkyl, C 3-8 heterocycloalkyl, C 6-10 aryl, C 5-13 heteroaryl, —XS(O) 0-2 R 12 , —XS(O) 0-2 XR 13 , —XNR 12 R 12 , —XNR 12 S(O) 0-2 R 12 , —XNR 12 C(O)R 12 , —XC(O)NR 12 R 12 , —XNR 12 C(O)R 13 , —XC(O)NR 12 R 13 , —XC(O)R 13 , —XNR 12 XR 13 and —XOXR 13 ; wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl substituent is further optionally substituted with 1 to 3 radicals independently selected from halo, nitro, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, hydroxy-C 1-6 alkyl, halo-substituted-C 1-6 alkyl and halo-substituted-C 1-6 alkoxy; wherein X is a bond or C 1-4 alkylene; R 12 is selected from hydrogen and C 1-6 alkyl; and R 13 is selected from C 3-12 cycloalkyl, C 3-8 heterocycloalkyl, C 6-10 aryl and C 5-10 heteroaryl; wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R 13 is optionally substituted with 1 to 3 radicals independently selected from halo, nitro, cyano, C 1-6 alkyl, C 1-6 alkoxy, halo-substituted-C 1-6 alkyl and halo-substituted-C 1-6 alkoxy; with the proviso that either R 5 or R 6 , but not both R 5 and R 6 , must be hydrogen or methyl;
[0016] R 7 is selected from hydrogen, C 1-6 alkyl, C 6-12 aryl-C 0-4 alkyl, C 3-12 cycloalkyl-C 0-4 alkyl, —XOR 14a and —XNR 14a R 14b ; wherein X is a bond or C 1-4 alkylene; and R 14a and R 14b are independently selected from hydrogen and C 1-6 alkyl; and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixture of isomers thereof; and the pharmaceutically acceptable salts and solvates (e.g. hydrates) of such compounds.
[0017] In a second aspect, the present invention provides a pharmaceutical composition that contains a compound of Formula I or a N-oxide derivative, individual isomers and mixture of isomers thereof; or a pharmaceutically acceptable salt thereof, in admixture with one or more suitable excipients.
[0018] In a third aspect, the present invention provides a method of treating a disease in an animal in which modulation of PPAR activity can prevent, inhibit or ameliorate the pathology and/or symptomology of the diseases, which method comprises administering to the animal a therapeutically effective amount of a compound of Formula I or a N-oxide derivative, individual isomers and mixture of isomers thereof, or a pharmaceutically acceptable salt thereof.
[0019] In a fourth aspect, the present invention provides the use of a compound of Formula I in the manufacture of a medicament for treating a disease in an animal in which PPAR activity contributes to the pathology and/or symptomology of the disease.
[0020] In a fifth aspect, the present invention provides a process for preparing compounds of Formula I and the N-oxide derivatives, prodrug derivatives, protected derivatives, individual isomers and mixture of isomers thereof, and the pharmaceutically acceptable salts thereof.
DETAILED DESCRIPTION OF TH E INVENTION
Definitions
[0021] “Alkyl” as a group and as a structural element of other groups, for example halo-substituted-alkyl and alkoxy, can be either straight-chained or branched. C 1-6 alkoxy includes, methoxy, ethoxy, and the like. Halo-substituted alkyl includes trifluoromethyl, pentafluoroethyl, and the like.
[0022] “Aryl” means a monocyclic or fused bicyclic aromatic ring assembly containing six to ten ring carbon atoms. For example, aryl can be phenyl or naphthyl, preferably phenyl. “Arylene” means a divalent radical derived from an aryl group. “Heteroaryl” is as defined for aryl where one or more of the ring members are a heteroatom. For example heteroaryl includes pyridyl, indolyl, indazolyl, quinoxalinyl, quinolinyl, benzofuranyl, benzopyranyl, benzothiopyranyl, benzo[1,3]dioxole, imidazolyl, benzo-imidazolyl, pyrimidinyl, furanyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazolyl, thienyl, etc. “C 6-10 arylC 0-4 alkyl” means an aryl as described above connected via a alkylene grouping. For example, C 6-10 arylC 0-4 alkyl includes phenethyl, benzyl, etc.
[0023] “Cycloalkyl” means a saturated or partially unsaturated, monocyclic, fused bicyclic or bridged polycyclic ring assembly containing the number of ring atoms indicated. For example, C 3-10 cycloalkyl includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc. “Heterocycloalkyl” means cycloalkyl, as defined in this application, provided that one or more of the ring carbons indicated, are replaced by a moiety selected from —O—, —N═, —NR—, —C(O)—, —S—, —S(O)— or —S(O) 2 —, wherein R is hydrogen, C 1-4 alkyl or a nitrogen protecting group. For example, C 3-8 heterocycloalkyl as used in this application to describe compounds of the invention includes morpholino, pyrrolidinyl, piperazinyl, piperidinyl, piperidinylone, 1,4-dioxa-8-aza-spiro[4.5]dec-8-yl, etc.
[0024] “Halogen” (or halo) preferably represents chloro or fluoro, but can also be bromo or iodo.
[0025] “Treat”, “treating” and “treatment” refer to a method of alleviating or abating a disease and/or its attendant symptoms.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0026] The present invention provides compounds, compositions and methods for the treatment of diseases in which modulation of one or more PPARs can prevent, inhibit or ameliorate the pathology and/or symptomology of the diseases, which method comprises administering to the animal a therapeutically effective amount of a compound of Formula I.
[0027] In one embodiment, with reference to compounds of Formula I:
[0028] n is selected from 0, 1, 2 and 3;
[0029] p is selected from 0, 1 and 2;
[0030] Y is selected from O, CH 2 and S(O) 0-2 ;
[0031] Z is selected from CR 8a R 8b and S; wherein R 8a and R 8b are independently selected from hydrogen and C 1-6 alkyl;
[0032] W is selected from O and S;
[0033] R 1 is selected from —X 1 CR 9 R 10 X 2 CO 2 R 11 , —X 1 SCR 9 R 10 X 2 CO 2 R 11 , and —X 1 OCR 9 R 10 X 2 CO 2 R 11 ; wherein X 1 and X 2 are independently selected from a bond and C 1-4 alkylene; and R 9 and R 10 are independently selected from hydrogen, C 1-4 alkyl and C 1-4 alkoxy; or R 9 and R 10 together with the carbon atom to which R 9 and R 10 are attached form C 3-12 cycloalkyl; and R 1 is selected from hydrogen and C 1-6 alkyl; each is independently selected from C 1-6 alkyl, C 2-6 alkenyl, C 1-4 alkoxy, C 1- 4 alkylthio, C 3-12 cycloalkyl, C 3-8 heterocycloalkyl, C 6-10 aryl and C 5-10 heteroaryl; wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl of R 2 is optionally substituted with 1 to 3 radicals independently selected from halo, C 1-6 alkoxy, C 1-6 alkylthio, halo-substituted-C 1-6 alkoxy, —C(O)R 14a and NR 14a R 14b ; wherein R 14a and R 14b are independently selected from hydrogen and C 1-6 alkyl;
[0034] R 3 and R 4 are independently selected from hydrogen and C 1-6 alkyl;
[0035] R 5 is C 6-10 aryl optionally substituted with 1 to 3 radicals independently selected from halo, nitro, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 alkylthio, hydroxy-C 1-6 alkyl, halo-substituted-C 1-6 alkyl, halo-substituted-C 1-6 alkoxy, C 3-12 cycloalkyl, C 3-8 heterocycloalkyl, C 6-10 aryl, C 5-13 heteroaryl and —XNR 12 R 12 ; wherein R 12 is selected from hydrogen and C 1-6 alkyl;
[0036] R 6 is selected from hydrogen and methyl; and
[0037] R 7 is selected from hydrogen, C 1-6 alkyl, C 6-12 aryl-C 0-4 alkyl, C 3-12 cycloalkyl-C 0-4 alkyl, —XOR 14a and —XNR 14a R 14b ; wherein X is a bond or C 1-4 alkylene; and R 14a and R 14b are independently selected from hydrogen and C 1-6 alkyl.
[0038] In another embodiment, R 1 is selected from —CH 2 CR 5 R 6 CO 2 H, —OCR 5 R 6 CO 2 H, —SCR 5 R 6 CO 2 H, —CR 5 R 6 CH 2 CO 2 H and —CR 5 R 6 CO 2 H; wherein R 5 and R 6 are independently selected from hydrogen, methyl, methoxy and ethoxy; or R 5 and R 6 together with the carbon atom to which R 5 and R 6 are attached form cyclopentyl.
[0039] In another embodiment, each R 2 is independently selected from methyl, ethyl, cyclopropyl, methoxy, furanyl, phenyl, pyridinyl, thienyl, pyrrolidinyl and benzo[1,3]dioxolyl; wherein said pyridinyl or phenyl of R 2 is optionally substituted with 1 to 3 radicals independently selected from halo, methyl-carbonyl, dimethyl-amino, methoxy, halo-substituted-methoxy, methyl-thio, ethenyl, hexenyl and propyloxy.
[0040] In another embodiment, R 7 is selected from hydrogen, methyl, isopropyl, propyl, pentyl, isobutyl, methoxy-ethyl, benzyl, phenethyl, cyclohexyl-methyl, cyclobutyl-methyl, cyclopropyl-methyl and diethyl-amino-ethyl.
[0041] Preferred compounds of Formula I are selected from: 2-Methyl-2-[2-methyl-4-(2-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-phenoxy]-propionic acid; 2-Methyl-2-(2-methyl-4-{2-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-ethoxy}-phenoxy)-propionic acid; 2-Methyl-2-[2-methyl-4-(2-{propyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-phenoxy]-propionic acid; 2-Methyl-2-[2-methyl-4-(2-{pentyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-phenoxy]-propionic acid; 2-[4-(2-{Isopropyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid; 2-[4-(2-{Isobutyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid; 2-[4-(2-{(2-Methoxy-ethyl)-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid; 2-[4-(2-{Benzyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid; 2-Methyl-2-[2-methyl-4-(2-{phenethyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-phenoxy]-propionic acid; 2-[4-(2-{Cyclohexylmethyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid; 2-[4-(2-{Cyclobutylmethyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]amino}-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid; 2-[4-(2-{Cyclopropylmethyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid; 2-[4-(2-{(2-Diethylamino-ethyl)-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(2-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-phenoxy]-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{2-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-ethoxy}-phenoxy)-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(3-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-propoxy)-phenoxy]-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{3-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-propoxy}-phenoxy)-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(4-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-butoxy)-phenoxy]-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{4-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-butoxy}-phenoxy)-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{2-[4-(4-trifluoromethoxy-phenyl)-thiazol-2-ylamino]-ethoxy}-phenoxy)-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(2-{methyl-[4-(4-trifluoromethoxy-phenyl)-thiazol-2-yl]-amino}-ethoxy)-phenoxy]-2-methyl-propionic acid; 2-(4-{2-[4-(4-Methoxy-phenyl)-thiazol-2-ylamino]-ethoxy}-2,5-dimethyl-phenoxy)-2-methyl-propionic acid; 2-[4-(2-{[4-(4-Methoxy-phenyl)-thiazol-2-yl]-methyl-amino}-ethoxy)-2,5-dimethyl-phenoxy]-2-methyl-propionic acid; 2-(4-{2-[(4-Biphenyl-4-yl-thiazol-2-yl)-methyl-amino]-ethoxy}-2,5-dimethyl-phenoxy)-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{2-[4-(4-trifluoromethyl-phenyl)-oxazol-2-ylamino]-ethoxy}-phenoxy)-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(2-{methyl-[4-(4-trifluoromethyl-phenyl)-oxazol-2-yl]-amino}-ethoxy)-phenoxy]-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{3-[4-(4-trifluoromethoxy-phenyl)-thiazol-2-ylamino]-propoxy}-phenoxy)-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(3-{methyl-[4-(4-trifluoromethoxy-phenyl)-thiazol-2-yl]-amino}-propoxy)-phenoxy]-2-methyl-propionic acid; 2-(4-{3-[4-(4-Methoxy-phenyl)-thiazol-2-ylamino]-propoxy}-2,5-dimethyl-phenoxy)-2-methyl-propionic acid; 2-[4-(3-{[4-(4-Methoxy-phenyl)-thiazol-2-yl]-methyl-amino}-propoxy)-2,5-dimethyl-phenoxy]-2-methyl-propionic acid; 2-{4-[3-(4-Biphenyl-4-yl-thiazol-2-ylamino)-propoxy]-2,5-dimethyl-phenoxy}-2-methyl-propionic acid; 2-(4-{3-[(4-Biphenyl-4-yl-thiazol-2-yl)-methyl-amino]-propoxy}-2,5-dimethyl-phenoxy)-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{3-[4-(4-trifluoromethyl-phenyl)-oxazol-2-ylamino]-propoxy}-phenoxy)-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(3-{methyl-[4-(4-trifluoromethyl-phenyl)-oxazol-2-yl]-amino}-propoxy)-phenoxy]-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{2-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-ethylsulfanyl}-phenoxy)-2-methyl-propionic acid; 2-(2,5-Dimethyl-4-{3-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-propylsulfanyl}-phenoxy)-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(2-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethylsulfanyl)-phenoxy]-2-methyl-propionic acid; 2-[2,5-Dimethyl-4-(3-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-propylsulfanyl)-phenoxy]-2-methyl-propionic acid; 3-(2,5-Dimethyl-4-{2-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-ethoxy}-phenyl)-2,2-dimethyl-propionic acid; 3-(2,5-Dimethyl-4-{3-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-propoxy}-phenyl)-2,2-dimethyl-propionic acid; 3-[2,5-Dimethyl-4-(2-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-phenyl]-2,2-dimethyl-propionic acid; 3-[2,5-Dimethyl-4-(3-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-propoxy)-phenyl]-2,2-dimethyl-propionic acid; 2-(2,5-Dimethyl-4-{2-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-ethoxy}-phenylsulfanyl)-2-methyl-propionic acid; 2-Methyl-2-(2-methyl-4-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-sulfamoyl}-phenoxy)-propionic acid; (2-Methyl-4-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-sulfamoyl}-phenoxy)-acetic acid; 2-(2,5-Dimethyl-4-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-sulfamoyl}-phenoxy)-2-methyl-propionic acid; and 2-(2,5-Dimethyl-4-{[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-methyl}-phenoxy)-2-methyl-propionic acid.
[0042] Further preferred compounds of Formula I are detailed in the Examples, infra.
Pharmacology and Utility
[0043] Compounds of the invention modulate the activity of PPARs and, as such, are useful for treating diseases or disorders in which PPARs contributes to the pathology and/or symptomology of the disease. This invention further provides compounds of this invention for use in the preparation of medicaments for the treatment of diseases or disorders in which PPARs contributes to the pathology and/or symptomology of the disease.
[0044] Such compounds may therefore be employed for the treatment of prophylaxis, dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, atherogenesis, hypertriglyceridemia, heart failure, hyper cholesteremia, myocardial infarction, vascular diseases, cardiovascular diseases, hypertension, obesity, cachexia, HIV wasting syndrome, inflammation, arthritis, cancer, Alzheimer's disease, anorexia, anorexia nervosa, bulimia, skin disorders, respiratory diseases, ophthalmic disorders, IBDs (irritable bowel disease), ulcerative colitis and Crohn's disease. Preferably for the treatment of prophylaxis, dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, atherogenesis, hypertriglyceridemia, cardiovascular diseases, hypertension, obesity, inflammation, cancer, skin disorders, IBDs (irritable bowel disease), ulcerative colitis and Crohn's disease.
[0045] Compounds of the invention can also be employed to treat long term critical illness, increase muscle mass and/or muscle strength, increase lean body mass, maintain muscle strength and function in the elderly, enhance muscle endurance and muscle function, and reverse or prevent frailty in the elderly.
[0046] Further, the compounds of the present invention may be employed in mammals as hypoglycemic agents for the treatment and prevention of conditions in which impaired glucose tolerance, hyperglycemia and insulin resistance are implicated, such as type-1 and type-2 diabetes, Impaired Glucose Metabolism (IGM), Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG), and Syndrome X. Preferably type-1 and type-2 diabetes, Impaired Glucose Metabolism (IGM), Impaired Glucose Tolerance (IGT) and Impaired Fasting Glucose (IFG).
[0047] In accordance with the foregoing, the present invention further provides a method for preventing or treating any of the diseases or disorders described above in a subject in need of such treatment, which method comprises administering to said subject a therapeutically effective amount (See, “ Administration and Pharmaceutical Compositions ”, infra) of a compound of the invention or a pharmaceutically acceptable salt thereof. For any of the above uses, the required dosage will vary depending on the mode of administration, the particular condition to be treated and the effect desired. The present invention also concerns: i) a compound of the invention or a pharmaceutically acceptable salt thereof for use as a medicament; and ii) the use of a compound of the invention or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for preventing or treating any of the diseases or disorders described above.
Administration and Pharmaceutical Compositions
[0048] In general, compounds of the invention will be administered in therapeutically effective amounts via any of the usual and acceptable modes known in the art, either singly or in combination with one or more therapeutic agents. A therapeutically effective amount can vary widely depending on the severity of the disease, the age and relative health of the subject, the potency of the compound used and other factors. In general, satisfactory results are indicated to be obtained systemically at daily dosages of from about 0.03 to 2.5 mg/kg per body weight. An indicated daily dosage in the larger mammal, e.g. humans, is in the range from about 0.5 mg to about 100 mg, conveniently administered, e.g. in divided doses up to four times a day or in retard form. Suitable unit dosage forms for oral administration comprise from ca. 1 to 50 mg active ingredient.
[0049] Compounds of the invention can be administered as pharmaceutical compositions by any conventional route, in particular enterally, e.g., orally, e.g., in the form of tablets or capsules, or parenterally, e.g., in the form of injectable solutions or suspensions, topically, e.g., in the form of lotions, gels, ointments or creams, or in a nasal or suppository form. Pharmaceutical compositions comprising a compound of the present invention in free form or in a pharmaceutically acceptable salt form in association with at least one pharmaceutically acceptable carrier or diluent can be manufactured in a conventional manner by mixing, granulating or coating methods. For example, oral compositions can be tablets or gelatin capsules comprising the active ingredient together with a) diluents, e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and/or glycine; b) lubricants, e.g., silica, talcum, stearic acid, its magnesium or calcium salt and/or polyethyleneglycol; for tablets also c) binders, e.g., magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and or polyvinylpyrollidone; if desired d) disintegrants, e.g., starches, agar, alginic acid or its sodium salt, or effervescent mixtures; and/or e) absorbents, colorants, flavors and sweeteners. Injectable compositions can be aqueous isotonic solutions or suspensions, and suppositories can be prepared from fatty emulsions or suspensions. The compositions can be sterilized and/or contain adjuvants, such as preserving, stabilizing, wetting or emulsifying agents, solution promoters, salts for regulating the osmotic pressure and/or buffers. In addition, they can also contain other therapeutically valuable substances. Suitable formulations for transdermal applications include an effective amount of a compound of the present invention with a carrier. A carrier can include absorbable pharmacologically acceptable solvents to assist passage through the skin of the host. For example, transdermal devices are in the form of a bandage comprising a backing member, a reservoir containing the compound optionally with carriers, optionally a rate controlling barrier to deliver the compound to the skin of the host at a controlled and predetermined rate over a prolonged period of time, and means to secure the device to the skin. Matrix transdermal formulations can also be used. Suitable formulations for topical application, e.g., to the skin and eyes, are preferably aqueous solutions, ointments, creams or gels well-known in the art. Such can contain solubilizers, stabilizers, tonicity enhancing agents, buffers and preservatives.
[0050] This invention also concerns a pharmaceutical composition comprising a therapeutically effective amount of a compound as described herein in combination with one or more pharmaceutically acceptable carriers.
[0051] Compounds of the invention can be administered in therapeutically effective amounts in combination with one or more therapeutic agents (pharmaceutical combinations).
[0052] Thus, the present invention also relates to pharmaceutical combinations, such as a combined preparation or pharmaceutical composition (fixed combination), comprising: 1) a compound of the invention as defined above or a pharmaceutical acceptable salt thereof; and 2) at least one active ingredient selected from:
[0053] a) anti-diabetic agents such as insulin, insulin derivatives and mimetics; insulin secretagogues such as the sulfonylureas, e.g., Glipizide, glyburide and Amaryl; insulinotropic sulfonylurea receptor ligands such as meglitinides, e.g., nateglinide and repaglinide; insulin sensitizer such as protein tyrosine phosphatase-1B (PTP-1B) inhibitors such as PTP-112; GSK3 (glycogen synthase kinase-3) inhibitors such as SB-517955, SB-4195052, SB-216763, N,N-57-05441 and N,N-57-05445; RXR ligands such as GW-0791 and AGN-194204; sodium-dependent glucose co-transporter inhibitors such as T-1095; glycogen phosphorylase A inhibitors such as BAY R3401; biguanides such as metformin; alpha-glucosidase inhibitors such as acarbose; GLP-1 (glucagon like peptide-1), GLP-1 analogs such as Exendin-4 and GLP-1 mimetics; DPPIV (dipeptidyl peptidase IV) inhibitors such as DPP728, LAF237 (vildagliptin—Example 1 of WO 00/34241), MK-0431, saxagliptin, GSK23A; an AGE breaker; a thiazolidone derivative (glitazone) such as pioglitazone, rosiglitazone, or (R)-1-{4-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-benzenesulfonyl}-2,3-dihydro-1H-indole-2-carboxylic acid described in the patent application WO 03/043985, as compound 19 of Example 4, a non-glitazone type PPARγ agonist e.g. GI-262570;
[0054] b) hypolipidemic agents such as 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, e.g., lovastatin, pitavastatin, simvastatin, pravastatin, cerivastatin, mevastatin, velostatin, fluvastatin, dalvastatin, atorvastatin, rosuvastatin and rivastatin; squalene synthase inhibitors; FXR (farnesoid X receptor) and LXR (liver X receptor) ligands; cholestyramine; fibrates; nicotinic acid and aspirin;
[0055] c) an anti-obesity agent or appetite regulating agent such as phentermine, leptin, bromocriptine, dexamphetamine, amphetamine, fenfluramine, dexfenfluramine, sibutramine, orlistat, dexfenfluramine, mazindol, phentermine, phendimetrazine, diethylpropion, fluoxetine, bupropion, topiramate, diethylpropion, benzphetamine, phenylpropanolamine or ecopipam, ephedrine, pseudoephedrine or cannabinoid receptor antagonists;
[0056] d) anti-hypertensive agents, e.g., loop diuretics such as ethacrynic acid, furosemide and torsemide; diuretics such as thiazide derivatives, chlorithiazide, hydrochlorothiazide, amiloride; angiotensin converting enzyme (ACE) inhibitors such as benazepril, captopril, enalapril, fosinopril, lisinopril, moexipril, perinodopril, quinapril, ramipril and trandolapril; inhibitors of the Na—K-ATPase membrane pump such as digoxin; neutralendopeptidase (NEP) inhibitors e.g. thiorphan, terteo-thiorphan, SQ29072; ECE inhibitors e.g. SLV306; ACE/NEP inhibitors such as omapatrilat, sampatrilat and fasidotril; angiotensin II antagonists such as candesartan, eprosartan, irbesartan, losartan, telmisartan and valsartan, in particular valsartan; renin inhibitors such as aliskiren, terlakiren, ditekiren, RO 66-1132, RO-66-1168; P-adrenergic receptor blockers such as acebutolol, atenolol, betaxolol, bisoprolol, metoprolol, nadolol, propranolol, sotalol and timolol; inotropic agents such as digoxin, dobutamine and milrinone; calcium channel blockers such as amlodipine, bepridil, diltiazem, felodipine, nicardipine, nimodipine, nifedipine, nisoldipine and verapamil; aldosterone receptor antagonists; and aldosterone synthase inhibitors;
[0057] e) a HDL increasing compound;
[0058] f) Cholesterol absorption modulator such as Zetia® and KT6-971;
[0059] g) Apo-A1 analogues and mimetics;
[0060] h) thrombin inhibitors such as Ximelagatran;
[0061] i) aldosterone inhibitors such as anastrazole, fadrazole, eplerenone;
[0062] j) Inhibitors of platelet aggregation such as aspirin, clopidogrel bisulfate;
[0063] k) estrogen, testosterone, a selective estrogen receptor modulator, a selective androgen receptor modulator;
[0064] l) a chemotherapeutic agent such as aromatase inhibitors e.g. femara, anti-estrogens, topoisomerase I inhibitors, topoisomerase II inhibitors, microtubule active agents, alkylating agents, antineoplastic antimetabolites, platin compounds, compounds decreasing the protein kinase activity such as a PDGF receptor tyrosine kinase inhibitor preferably Imatinib ({N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine}) described in the European patent application EP-A-0 564 409 as example 21 or 4-Methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide described in the patent application WO 04/005281 as example 92; and
[0065] m) an agent interacting with a 5-HT 3 receptor and/or an agent interacting with 5-HT 4 receptor such as tegaserod described in the U.S. Pat. No. 5,510,353 as example 13, tegaserod hydrogen maleate, cisapride, cilansetron;
[0066] or, in each case a pharmaceutically acceptable salt thereof; and optionally a pharmaceutically acceptable carrier.
[0067] Most preferred combination partners are tegaserod, imatinib, vildagliptin, metformin, a thiazolidone derivative (glitazone) such as pioglitazone, rosiglitazone, or (R)-1-{4-[5-methyl-2-(4-trifluoromethyl-phenyl)-oxazol-4-ylmethoxy]-benzenesulfonyl}-2,3-dihydro-1H-indole-2-carboxylic acid, a sulfonylurea receptor ligand, aliskiren, valsartan, orlistat or a statin such as pitavastatin, simvastatin, fluvastatin or pravastatin.
[0068] Preferably the pharmaceutical combinations contains a therapeutically effective amount of a compound of the invention as defined above, in a combination with a therapeutically effective amount of another therapeutic agent as described above, e.g., each at an effective therapeutic dose as reported in the art. Combination partners (1) and (2) can be administered together, one after the other or separately in one combined unit dosage form or in two separate unit dosage forms. The unit dosage form may also be a fixed combination.
[0069] The structure of the active agents identified by generic or trade names may be taken from the actual edition of the standard compendium “The Merck Index” or the Physician's Desk Reference or from databases, e.g. Patents International (e.g. IMS World Publications) or Current Drugs. The corresponding content thereof is hereby incorporated by reference. Any person skilled in the art is fully enabled to identify the active agents and, based on these references, likewise enabled to manufacture and test the pharmaceutical indications and properties in standard test models, both in vitro and in vivo.
[0070] In another preferred aspect the invention concerns a pharmaceutical composition (fixed combination) comprising a therapeutically effective amount of a compound as described herein, in combination with a therapeutically effective amount of at least one active ingredient selected from the above described group a) to m), or, in each case a pharmaceutically acceptable salt thereof.
[0071] A pharmaceutical composition or combination as described herein for the manufacture of a medicament for the treatment of for the treatment of dyslipidemia, hyperlipidemia, hypercholesteremia, atherosclerosis, hypertriglyceridemia, heart failure, myocardial infarction, vascular diseases, cardiovascular diseases, hypertension, obesity, inflammation, arthritis, cancer, Alzheimer's disease, skin disorders, respiratory diseases, ophthalmic disorders, inflammatory bowel diseases, IBDs (irritable bowel disease), ulcerative colitis, Crohn's disease, conditions in which impaired glucose tolerance, hyperglycemia and insulin resistance are implicated, such as type-1 and type-2 diabetes, Impaired Glucose Metabolism (IGM), Impaired Glucose Tolerance (IGT), Impaired Fasting Glucose (IFG), and Syndronie-X.
[0072] Such therapeutic agents include estrogen, testosterone, a selective estrogen receptor modulator, a selective androgen receptor modulator, insulin, insulin derivatives and mimetics; insulin secretagogues such as the sulfonylureas, e.g., Glipizide and Amaryl; insulinotropic sulfonylurea receptor ligands, such as meglitinides, e.g., nateglinide and repaglinide; insulin sensitizers, such as protein tyrosine phosphatase-1B (PTP-1B) inhibitors, GSK3 (glycogen synthase kinase-3) inhibitors or RXR ligands; biguanides, such as metformin; alpha-glucosidase inhibitors, such as acarbose; GLP-1 (glucagon like peptide-1), GLP-1 analogs, such as Exendin-4, and GLP-1 mimetics; DPPIV (dipeptidyl peptidase IV) inhibitors, e.g. isoleucin-thiazolidide; DPP728 and LAF237, hypolipidemic agents, such as 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, e.g., lovastatin, pitavastatin, simvastatin, pravastatin, cerivastatin, mevastatin, velostatin, fluvastatin, dalvastatin, atorvastatin, rosuvastatin, fluindostatin and rivastatin, squalene synthase inhibitors or FXR (liver X receptor) and LXR (farnesoid X receptor) ligands, cholestyramine, fibrates, nicotinic acid and aspirin. A compound of the present invention may be administered either simultaneously, before or after the other active ingredient, either separately by the same or different route of administration or together in the same pharmaceutical formulation.
[0073] The invention also provides for pharmaceutical combinations, e.g. a kit, comprising: a) a first agent which is a compound of the invention as disclosed herein, in free form or in pharmaceutically acceptable salt form, and b) at least one co-agent. The kit can comprise instructions for its administration.
[0074] The terms “co-administration” or “combined administration” or the like as utilized herein are meant to encompass administration of the selected therapeutic agents to a single patient, and are intended to include treatment regimens in which the agents are not necessarily administered by the same route of administration or at the same time. The term “pharmaceutical combination” as used herein means a product that results from the mixing or combining of more than one active ingredient and includes both fixed and non-fixed combinations of the active ingredients. The term “fixed combination” means that the active ingredients, e.g. a compound of Formula I and a co-agent, are both administered to a patient simultaneously in the form of a single entity or dosage. The term “non-fixed combination” means that the active ingredients, e.g. a compound of Formula I and a co-agent, are both administered to a patient as separate entities either simultaneously, concurrently or sequentially with no specific time limits, wherein such administration provides therapeutically effective levels of the 2 compounds in the body of the patient. The latter also applies to cocktail therapy, e.g. the administration of 3 or more active ingredients.
Processes for Making Compounds of the Invention
[0075] The present invention also includes processes for the preparation of compounds of the invention. In the reactions described, it can be necessary to protect reactive functional groups, for example hydroxy, amino, imino, thio or carboxy groups, where these are desired in the final product, to avoid their unwanted participation in the reactions. Conventional protecting groups can be used in accordance with standard practice, for example, see T. W. Greene and P. G. M. Wuts in “Protective Groups in Organic Chemistry”, John Wiley and Sons, 1991.
[0076] Compounds of Formula I, in which R 1 is defined by —X 1 CR 9 R 10 X 2 CO 2 R 11 (shown below), —X 1 SCR 9 R 10 X 2 CO 2 R 11 and —X 1 OCR 9 R 10 X 2 CO 2 R 11 , wherein R 7 is an alkyl group e.g., methyl or ethyl for a compound of formula 4 converting to hydrogen in formula I, can be prepared by proceeding as in reaction scheme 1:
[0000]
[0077] in which n, p, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 , X 1 , X 2 , Y, Z and W are as defined for Formula I. Compounds of Formula I are prepared by reacting a compound of formula 4 in the presence of a suitable base (e.g., lithium hydroxide, or the like) and a suitable solvent (e.g., THF, water or the like). The reaction is carried out in the temperature range of about 0° C. to about 50° C. and takes up to about 30 hours to complete.
[0078] Compounds of Formula II can be prepared by proceeding as in reaction scheme 2:
[0000]
[0079] in which n, p, R 1 , R 2 , R 3 , R 4 , Y and Z are as defined for Formula I in the Summary of the Invention; and Q is a halogen, preferably Cl, I or Br. Compounds of formula 11 are formed by reacting a compound of formula 5 with a compound of formula 9. The reaction proceeds in the presence of a suitable solvent (for example, acetonitrile, acetone, and the like), a suitable inorganic base (for example, Cs 2 CO 3 , K 2 CO 3 , and the like). The reaction is carried out in the temperature range of about 10 to about 100° C. and takes up to about 24 hours to complete.
[0080] Compounds of Formula 14 can be prepared by proceeding as in reaction scheme 3:
[0000]
[0081] in which R 5 , R 6 and W are as defined for Formula I in the Summary of the Invention; and Q is a halogen, preferably Cl, I or Br. Compounds of formula 14 are formed by reacting a compound of formula 12 with a compound of formula 13 in the presence of a suitable solvent (for example, acetone, and the like). The reaction is carried out in the temperature range of about 50 to about 80° C. and takes up to about 6 hours to complete.
[0082] Compounds of Formula I, where R 7 is hydrogen, can be prepared by proceeding as in reaction scheme 4:
[0000]
[0083] in which n, p, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , Y and W are as defined for Formula I. Compounds of Formula I are prepared by reacting a compound of 11 with a compound of formula 14 in the presence of a suitable solvent (for example, acetonitrile, and the like) and a suitable inorganic base (for example, K 2 CO 3 , and the like). The reaction is carried out in the temperature range of about 60 to about 120° C. and takes up to about 24 hours to complete.
[0084] Compounds of Formula I can be prepared by proceeding as in reaction scheme 5:
[0000]
[0085] in which n, p, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Y and W are as defined for Formula I; and Q is a halogen, preferably Cl, I or Br. Compounds of Formula I are prepared by reacting a compound of formula I (where R 7 is hydrogen) with a compound of formula 15 in the presence of a suitable solvent (for example, acetonitrile, and the like) and a suitable inorganic base (for example, Cs 2 CO 3 , and the like). The reaction is carried out in the temperature range of about 60 to about 120° C. and takes up to about 24 hours to complete.
[0086] Compounds of Formula 17, where R 7 is hydrogen, can be prepared by proceeding as in reaction scheme 6:
[0000]
[0000] in which n, p, R 1 , R 2 , R 5 , R 6 and W are as defined for Formula I. Compounds of Formula 17 are prepared by reacting a compound of 16 with a compound of formula 14 in the presence of a suitable solvent (for example, DCM, and the like) and a suitable inorganic base (for example, K 2 CO 3 , and the like) or organic base (for example, triethylamine, and the like). The reaction is carried out in the temperature range of about 0 to about 50° C. and takes up to about 24 hours to complete.
[0087] Compounds of Formula I can be prepared by proceeding as in reaction scheme 7:
[0000]
[0088] in which n, p, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , Y and W are as defined for Formula I. Compounds of Formula I are prepared by reacting a compound of 18 with a compound of formula 14 in the presence of a suitable solvent (for example, THF, and the like) and a suitable dehydrating agent (for example, triethylorthoacetate, and the like) and a suitable reducing agent (for example, sodium triacetoxyborohydride, and the like). The reaction is carried out in the temperature range of about 0 to about 50° C. and takes up to about 24 hours to complete.
[0089] Detailed reaction conditions are described in the examples, infra.
Additional Processes for Making Compounds of the Invention
[0090] A compound of the invention can be prepared as a pharmaceutically acceptable acid addition salt by reacting the free base form of the compound with a pharmaceutically acceptable inorganic or organic acid. Alternatively, a pharmaceutically acceptable base addition salt of a compound of the invention can be prepared by reacting the free acid form of the compound with a pharmaceutically acceptable inorganic or organic base. Alternatively, the salt forms of the compounds of the invention can be prepared using salts of the starting materials or intermediates.
[0091] The free acid or free base forms of the compounds of the invention can be prepared from the corresponding base addition salt or acid addition salt from, respectively. For example a compound of the invention in an acid addition salt form can be converted to the corresponding free base by treating with a suitable base (e.g., ammonium hydroxide solution, sodium hydroxide, and the like). A compound of the invention in a base addition salt form can be converted to the corresponding free acid by treating with a suitable acid (e.g., hydrochloric acid, etc.).
[0092] Compounds of the invention in unoxidized form can be prepared from N-oxides of compounds of the invention by treating with a reducing agent (e.g., sulfur, sulfur dioxide, triphenyl phosphine, lithium borohydride, sodium borohydride, phosphorus trichloride, tribromide, or the like) in a suitable inert organic solvent (e.g. acetonitrile, ethanol, aqueous dioxane, or the like) at 0 to 80° C.
[0093] Prodrug derivatives of the compounds of the invention can be prepared by methods known to those of ordinary skill in the art (e.g., for further details see Saulnier et al., (1994), Bioorganic and Medicinal Chemistry Letters, Vol. 4, p. 1985). For example, appropriate prodrugs can be prepared by reacting a non-derivatized compound of the invention with a suitable carbamylating agent (e.g., 1,1-acyloxyalkylcarbanochloridate, para-nitrophenyl carbonate, or the like).
[0094] Protected derivatives of the compounds of the invention can be made by means known to those of ordinary skill in the art. A detailed description of techniques applicable to the creation of protecting groups and their removal can be found in T. W. Greene, “Protecting Groups in Organic Chemistry”, 3 rd edition, John Wiley and Sons, Inc., 1999.
[0095] Compounds of the present invention can be conveniently prepared, or formed during the process of the invention, as solvates (e.g., hydrates). Hydrates of compounds of the present invention can be conveniently prepared by recrystallization from an aqueous/organic solvent mixture, using organic solvents such as dioxin, tetrahydrofuran or methanol.
[0096] Compounds of the invention can be prepared as their individual stereoisomers by reacting a racemic mixture of the compound with an optically active resolving agent to form a pair of diastereoisomeric compounds, separating the diastereomers and recovering the optically pure enantiomers. While resolution of enantiomers can be carried out using covalent diastereomeric derivatives of the compounds of the invention, dissociable complexes are preferred (e.g., crystalline diastereomeric salts). Diastereomers have distinct physical properties (e.g., melting points, boiling points, solubilities, reactivity, etc.) and can be readily separated by taking advantage of these dissimilarities. The diastereomers can be separated by chromatography, or preferably, by separation/resolution techniques based upon differences in solubility. The optically pure enantiomer is then recovered, along with the resolving agent, by any practical means that would not result in racemization. A more detailed description of the techniques applicable to the resolution of stereoisomers of compounds from their racemic mixture can be found in Jean Jacques, Andre Collet, Samuel H. Wilen, “Enantiomers, Racemates and Resolutions”, John Wiley And Sons, Inc., 1981.
[0097] In summary, the compounds of Formula I can be made by a process, which involves:
[0098] (a) that of reaction schemes 1 through 7; and
[0099] (b) optionally converting a compound of the invention into a pharmaceutically acceptable salt;
[0100] (c) optionally converting a salt form of a compound of the invention to a non-salt form;
[0101] (d) optionally converting an unoxidized form of a compound of the invention into a pharmaceutically acceptable N-oxide;
[0102] (e) optionally converting an N-oxide form of a compound of the invention to its unoxidized form;
[0103] (f) optionally resolving an individual isomer of a compound of the invention from a mixture of isomers;
[0104] (g) optionally converting a non-derivatized compound of the invention into a pharmaceutically acceptable prodrug derivative; and
[0105] (h) optionally converting a prodrug derivative of a compound of the invention to its non-derivatized form.
[0106] Insofar as the production of the starting materials is not particularly described, the compounds are known or can be prepared analogously to methods known in the art or as disclosed in the Examples hereinafter.
[0107] One of skill in the art will appreciate that the above transformations are only representative of methods for preparation of the compounds of the present invention, and that other well known methods can similarly be used.
EXAMPLES
[0108] The present invention is further exemplified, but not limited, by the following intermediates and examples that illustrate the preparation of compounds of Formula I according to the invention.
[0000]
Intermediate 1: 4-(4-Trifluoromethyl-phenyl)-thiazol-2-ylamine
[0109] 2-Bromo-1-(4-trifluoromethyl-phenyl)-ethanone (10 g, 37.4 mmol) and thiourea (2.85 g, 37.4 mmol) are dissolved in dry acetone (100 mL) and heated at reflux for 2 h. The solution is cooled and stirred at rt for 2 h, then filtered and washed with acetone to give 4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamine 1 (9.35 g, 100%) as white crystals. 1 H-NMR (400 MHz, DMSO-d 6 ) δ=8.30 (br. s, 2H), 7.98 (d, J=8.0 Hz, 2H), 7.84 (d, J=8.0 Hz, 2H), 7.42 (s, 1H). MS calcd. for C 10 H 8 F 3 N 2 S (M+H + ) 245.0, found 245.1.
[0000]
Intermediate 2: 4-(4-(Trifluoromethoxy)phenyl)thiazol-2-amine
[0110] Following the procedure for Intermediate 1, except substituting 2-bromo-1-(4-(trifluoromethoxy)phenyl)ethanone for 2-bromo-1-(4-trifluoromethyl-phenyl)-ethanone, the title compound is prepared as a white solid: 1 H-NMR (400 MHz, DMSO-d 6 ) δ=7.88 (d, J=8.8 Hz, 2H), 7.44 (d, J=8.4 Hz, 2H), 7.21 (s, 1H). MS calculated for C 10 H 8 F 3 N 2 OS (M+H + ) 261.0, found 261.0.
[0000]
Intermediate 3: 4-(4-methoxyphenyl)thiazol-2-amine
[0111] Following the procedure for Intermediate 1, except substituting 2-bromo-1-(4-methoxyphenyl)ethanone for 2-bromo-1-(4-trifluoromethyl-phenyl)-ethanone, the title compound is prepared as a white solid: 1 H-NMR (400 MHz, DMSO-d 6 ) δ=7.67 (d, J=8.8 Hz, 2H), 7.06 (s, 1H), 7.05 (d, J=8.8 Hz, 2H), 3.81 (s, 3H). MS calculated for C 10 H 11 N 2 OS (M+H + ) 207.0, found 207.0.
[0000]
Intermediate 4: 4-(4-Biphenyl)thiazol-2-amine
[0112] Following the procedure for Intermediate 1, except substituting 2-bromo-1-(4-biphenyl)ethanone for 2-bromo-1-(4-trifluoromethyl-phenyl)-ethanone, the title compound is prepared as a white solid: 1 H-NMR (400 MHz, DMSO-d 6 ) δ=7.84 (d, J=8.8 Hz, 2H), 7.79 (d, J=8.8 Hz, 2H), 7.73 (d, J=8.8 Hz, 2H), 7.50 (t, J=7.6 Hz, 2H), 7.40 (t, J=7.6 Hz, 1H), 7.28 (s, 1H). MS calculated for C 15 H 13 N 2 S (M+H + ), 253.1, found 253.0.
[0000]
Intermediate 5: 4-(4-(Trifluoromethyl)phenyl)oxazol-2-amine
[0113] Following the procedure for Intermediate 1, except substituting urea for thiourea, the title compound is prepared as a white solid: 1 H-NMR (400 MHz, DMSO-d 6 ) δ=8.07 (s, 1H), 7.84 (d, J=8.4 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H), 6.85 (s, 2H). MS calculated for C 15 H 13 N 2 S (M+H + ) 229.1, found 229.0.
[0000]
Intermediate 16: 2-[4-(2-Bromo-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid methyl ester
[0114] Step A: 4-Benzyloxy-phenol (32.04 g, 160.2 mmol) is dissolved in 550 mL of dichloromethane and 20 mL methanol. Powdered calcium carbonate (21.83 g, 218.1 mmol, 1.36 equiv.) is suspended in the solution. While the suspension is vigorously stirred, a solution of bromine (8.30 mL, 161.5 mmol, 1.01 equiv.) in 50 mL dichloromethane is added dropwise. After the addition is completed, the suspension is stirred at room temperature for 30 min, then the solids are filtered off. The filtrate is dried over solid NaHCO 3 and MgSO 4 , then filtered and concentrated to yield an oil. Precipitation of unreacted 4-benzyloxy-phenol using diethyl ether/petroleum ether at −20° C. yielded 4-benzyloxy-2-bromo-phenol 10 as a colorless oil that slowly solidified (43.65 g, 156.4 mmol, 97.6%). 1 H-NMR (400 MHz, CDCl 3 ) δ=7.38 (m, 5H), 7.10 (d, J=2.8 Hz, 1H), 6.94 (d, J=8.9 Hz, 1H), 6.87 (dd, J=8.9, 2.8 Hz, 1H), 4.99 (s, 2H).
[0115] Step B: 4-Benzyloxy-2-bromo-phenol 10 (43.6 g, 156.3 mmol) is dissolved in 400 mL dichloromethane. Imidazole (14.9 g, 218.9 mmol, 1.4 equiv.) is added; the mixture is stirred at room temperature until homogenous. tert-Butyl dimethylchlorosilane (23.6 g, 156.6 mmol, 1.0 equiv.) is added; the cloudy mixture is stirred at room temperature for 18 h. Washing with water, drying over MgSO 4 and concentration yielded (4-benzyloxy-2-bromo-phenoxy)-tert-butyl-dimethyl-silane 11 as an oil (60.91 g, 154.8 mmol, 99%). 1 H-NMR (400 MHz, CDCl 3 ) δ=7.40 (m, 5H), 7.10 (s, 1H), 6.79 (s, 2H), 4.98 (s, 2H), 1.03 (s, 9H), 0.22 (s, 6H).
[0116] Step C: (4-Benzyloxy-2-bromo-phenoxy)-tert-butyl-dimethyl-silane 11 (10.05 g, 25.6 mmol) is dissolved in 45 mL dimethylformamide. The mixture is degassed using argon. Dichloro bis(triphenylphosphino)palladium(II) (3.49 g, 4.97 mmol, 0.19 equiv.) is added, followed by tetramethyltin (5.0 mL, 36.3 mmol, 1.42 equiv.). The mixture is heated to 100° C. for 3 h, after which it became homogenous. Cooling, concentration, and silica gel chromatography purification (0-50% gradient, ethyl acetate in hexanes) yielded (4-benzyloxy-2-methyl-phenoxy)-tert-butyl-dimethyl-silane 12 as an oil that solidifies into a white solid (5.03 g, 15.3 mmol, 60%). 1 H-NMR (400 MHz, CDCl 3 ) δ=7.42 (m, 2H), 7.37 (m, 2H), 7.31 (m, 1H), 6.79 (d, J=2.2 Hz, 1H), 6.67 (m, 2H), 4.99 (s, 2H), 2.18 (s, 3H), 1.01 (s, 9H), 0.18 (s, 6H). MS calcd. for C 20 H 29 O 2 Si (M+H + ) 329.2, found 329.2.
[0117] Step D: (4-Benzyloxy-2-methyl-phenoxy)-tert-butyl-dimethyl-silane 12 (5.03 g, 15.3 mmol) is dissolved in 30 mL THF. A 1.0 M solution of tetra-(n-butyl)ammonium fluoride in THF (18 mL, 18 mmol, 1.5 equiv.) is added; the mixture is stirred at room temperature for 4 h. Concentration to dryness and purification by silica gel chromatography (10-30% gradient, ethyl acetate in hexanes) yielded 4-benzyloxy-2-methyl-phenol 13 (3.06 g, 14.3 mmol, 93%). 1 H-NMR (400 MHz, CDCl 3 ) δ=7.42 (m, 4H), 7.31 (m, 1H), 6.78 (s, 1H), 6.69 (s, 2H), 4.99 (s, 2H), 2.27 (s, 3H).
[0118] Step E: 4-benzyloxy-2-methyl-phenol 13 (3.06 g, 14.3 mmol) is dissolved in 60 mL acetonitrile. Powdered cesium carbonate (8.71 g, 26.7 mmol, 1.78 equiv.) is added to the vigorously stirring solution. 2-Bromo-2-methyl-propionic acid methyl ester (2.20 mL, 17.0 mmol, 1.13 equiv.) is added and the mixture is stirred at 60° C. for 6 h. Filtration and concentration yielded 2-(4-benzyloxy-2-methyl-phenoxy)-2-methyl-propionic acid methyl ester 14 as an oil (5.11 g, quantitative). The crude product is used as such in the next step. 1 H-NMR (400 MHz, CDCl 3 ) δ=7.37 (m, 5H), 6.80 (d, J=2.4 Hz, 1H), 6.65 (d, J=2.8 Hz, 1H), 6.64 (s, 1H), 4.98 (s, 2H), 3.80 (s, 3H), 2.21 (s, 3H), 1.54 (s, 6H). MS calcd. for C 19 H 22 NaO 4 (M+Na + ) 337.2, found 337.2.
[0119] Step F: 2-(4-Benzyloxy-2-methyl-phenoxy)-2-methyl-propionic acid methyl ester 14 from Step E above is dissolved in 120 mL ethanol. The solution is degassed using nitrogen, then treated with 5% palladium black on carbon (1.50 g, 0.70 mmol, 4 mol %). The solution is shaken under 60 psi hydrogen for 15 h. Filtration and concentration yielded an oil; silica gel chromatography (hexanes to 60% ethyl acetate in hexanes) yields 2-(4-hydroxy-2-methyl-phenoxy)-2-methyl-propionic acid methyl ester 15 as an oil (3.42 g, 15.3 mmol, quantitative). 1 H-NMR (400 MHz, CDCl 3 ) δ=6.64 (d, J=3.0 Hz, 1H), 6.59 (d, J=8.7 Hz, 1H), 6.51 (dd, J=8.7, 3.1 Hz, 1H), 4.62 (s, 1H), 3.80 (s, 3H), 2.19 (s, 3H), 1.53 (s, 6H). MS calcd. for C 12 H 16 NaO 4 (M+Na + ) 247.1, found 247.1.
[0120] Step G: Intermediate 15 (1.0 g, 4.5 mmol), 1,2-dibromoethane (3.8 mL, 44.6 mmol) and Cs 2 CO 3 (7.3 g, 22.3 mmol) are suspended in dry acetonitrile (25 mL). The mixture is heated to 80° C. overnight. The reaction mixture is cooled to room temperature, filtered and the solvent is removed in vacuo. The remainder is purified by flash chromatography (silica, DCM/MeOH gradient) to afford 2-[4-(2-bromo-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid methyl ester 16 (0.7 g, 47%) as a colourless oil: MS calculated for C 14 H 20 BrO 4 (M+H + ) 331.1, found 331.0.
[0000]
Intermediate 19: 2-[4-(2-Bromo-ethoxy)-2,5-dimethyl-phenoxy]-2-methyl-propionic acid methyl ester
[0121] Step A: 2,5-Dimethylquinone (5.41 g, 39.7 mmol) is suspended in diethyl ether (70 mL). Water (100 mL) is added, followed by solid sodium dithionite (20.30 g, 116.6 mmol). The resulting mixture is shaken vigorously. The initially yellow suspension slowly turned deep red, then colorless. Separation of the organic layer, followed by washing with water and brine, drying over Na 2 SO 4 and concentration yielded 2,5-dimethylhydroquinone 17 as a white solid (4.37 g, 31.6 mmol, 80%). 1 H-NMR (400 MHz, DMSO-d 6 ) δ=8.32 (s, 2H), 6.45 (s, 2H), 1.99 (s, 6H).
[0122] Step B: 2,5-Dimethylhydroquinone 17 (3.73 g, 27 mmol) is dissolved in dimethylformamide (20 mL) and acetonitrile (60 mL). Powdered cesium carbonate (9.16 g, 28.1 g, 1.04 equiv.) is added to the vigorously stirring solution, followed by 2-bromo-2-methyl-propionic acid methyl ester (3.50 mL, 27.0 mmol, 1 equiv.). The mixture is stirred at 75° C. for 18 h. Filtration and concentration, followed by purification by silica gel chromatography (5-30% gradient, ethyl acetate in hexanes) yielded 2-(4-hydroxy-2,5-dimethyl-phenoxy)-2-methyl-propionic acid methyl ester 18 as and oil (1.92 g, 8.06 mmol, 30%). The chromatography also yielded recovered hydroquinone 17 (1.20 g, 8.68 mmol, 32%). 18: 1 H-NMR (400 MHz, CDCl 3 ) δ=6.57 (s, 1H), 6.50 (s, 1H), 4.44 (s, 1H), 2.15 (s, 3H), 2.14 (s, 3H), 1.52 (s, 6H). MS calcd. for C 13 H 18 NaO 4 (M+Na + ) 261.1, found 261.1.
[0123] Step C: Intermediate 18 (0.25 g, 1.05 mmol), 1,2-dibromoethane (0.90 mL, 10.5 mmol) and Cs 2 CO 3 (1.7 g, 5.25 mmol) are suspended in dry acetonitrile (7 mL). The mixture is heated to 80° C. overnight. The reaction mixture is cooled to room temperature, filtered and the solvent is removed in vacuo. The remainder is purified by flash chromatography (silica, DCM/MeOH gradient) to afford 2-[4-(2-bromo-ethoxy)-2-methyl-phenoxy]-2-methyl-propionic acid methyl ester 19 (0.24 g, 66%) as a colourless oil: 1 H-NMR (400 MHz, CDCl 3 ) δ=6.59 (s, 1H), 6.52 (s, 1H), 4.22 (t, J=6.2 Hz, 2H), 3.80 (s, 3H), 3.62 (t, J=6.2 Hz, 2H), 2.18 (s, 3H), 2.15 (s, 3H), 1.53 (s, 6H). MS calculated for C 15 H 22 BrO 4 (M+H) 345.1, found 345.0.
[0000]
Intermediate 20: 2-[4-(3-Bromo-propoxy)-2,5-dimethyl-phenoxy]-2-methyl-propionic acid methyl ester
[0124] Following the procedure for Intermediate 19, except substituting 1,3-dibromopropane for 1,2-dibromoethane, the title compound is prepared as a clear oil: 1 H-NMR (400 MHz, CDCl 3 ) δ=6.49 (s, 1H), 6.40 (s, 1H), 3.90 (t, J=5.7 Hz, 2H), 3.68 (s, 3H), 3.49 (t, J=6.5 Hz, 2H), 2.18 (m, 2H), 2.07 (s, 3H), 1.99 (s, 3H), 1.40 (s, 6H). MS calculated for C 16 H 24 BrO 4 (M+H + ) 359.1, found 359.0.
[0000]
Intermediate 21: 2-[4-(4-Bromo-butoxy)-2,5-dimethyl-phenoxy]-2-methyl-propionic acid methyl ester
[0125] Following the procedure for Intermediate 19, except substituting 1,4-dibromobutane for 1,2-dibromoethane, the title compound is prepared as a clear oil: 1 H-NMR (400 MHz, CDCl 3 ) δ=6.55 (s, 1H), 6.49 (s, 1H), 3.90 (t, J=6.0 Hz, 2H), 3.78 (s, 3H), 3.47 (t, J=6.6 Hz, 2H), 2.16 (s, 3H), 2.09 (s, 3H), 2.05 (m, 2H), 1.90 (m, 2H), 1.49 (s, 6H). MS calculated for C 17 H 26 BrO 4 (M+H + ) 373.1, found 373.0.
[0000]
[0126] Intermediate 23: (4-Chlorosulfonyl-2-methyl-phenoxy)-acetic acid methyl ester.
[0127] Step A: o-Cresol (10.0 g, 0.092 mmol) is dissolved in dry DMF (100 mL). Bromoacetic acid methyl ester (15.0 g, 0.098 mmol) and cesium carbonate (40.0 g, 0.123 mmol) are added. The reaction is kept stirring at rt for 3 h. Water is added and the reaction is extracted three times with ethyl acetate. The organic phase is washed with brine and dried with MgSO 4 . The solvent is evaporated to give crude product 22. MS calcd. for C 10 H 13 O 3 (M+H + ) 181.08, found 181.10.
[0128] Step B: A round bottom flask is charged with o-tolyloxy-acetic acid methyl ester 22 (5.0 g, 27.8 mmol). Chlorosulfonic acid (13.05 g, 112.0 mmol) is added at rt over 5 min. The reaction mixture is poured onto ice, stirred for another 5 min. Then it is filtered, the residue dissolved in DCM and washed with water three times. The organic phase is washed with sat. NaHCO 3 and brine and dried by MgSO 4 . The solvent is evaporated. The crude product is purified by silica gel chromatography (ethyl acetate/hexane: 0-30%) to give 23 (4.8 g, 15.6 mmol, yield 78%) as a white solid: 1 H-NMR (400 MHz, CDCl 3 ) δ=7.78 (m, 2H), 6.72 (d, J=9.2 Hz, 1H), 4.71 (s, 2H), 3.76 (s, 3H), 2.30 (s, 3H). MS calcd. for C 10 H 11 O 5 S (M−Cl + ) 243.0, found 243.0.
[0000]
Intermediate 24: 2-(4-Chlorosulfonyl-2-methyl-phenoxy)-2-methyl-propionic acid methyl ester
[0129] Following the procedure for Intermediate 23, except substituting 2-bromo-2-methyl-propionic acid methyl ester for bromoacetic acid methyl ester, the title compound is prepared as a white solid: 1 H-NMR (400 MHz, CDCl 3 ) δ=7.82 (d, J=1.6 Hz, 1H), 7.77 (dd, J=2.8 Hz, 8.8 Hz, 1H), 6.64 (d, J=8.8 Hz, 1H), 3.77 (s, 3H), 2.31 (s, 3H), 1.70 (s, 6H). MS calcd. for C 12 H 16 ClO 5 S (M+H + ) 307.03, found 307.00.
[0000]
Intermediate 25: 2-(4-Chlorosulfonyl-2,5-dimethyl-phenoxy)-2-methyl-propionic acid methyl ester
[0130] Following the procedure for Intermediate 23, except using 2-bromo-2-methyl-propionic acid methyl ester and 2,5-dimethylphenol, the title compound is prepared as a white solid: 1H-NMR (400 MHz, CDCl 3 ) δ=7.51 (s, 1H), 6.31 (s, 1H), 3.71 (s, 3H), 2.40 (s, 3H), 2.10 (s, 3H), 1.51 (s, 6H). MS calcd. for C 13 H 18 ClO 55 S (M+H + ) 320.0, found 320.0.
[0000]
Intermediate 33: 2-[4-(2-Bromo-ethylsulfanyl)-2,5-dimethyl-phenoxy]-2-methyl-propionic acid methyl ester
[0131] Step A: 2,5-Dimethylphenol (10.04 g, 82.2 mmol) is dissolved in methanol (40 mL). Sodium thiocyanate (15.87 g, 195.8 mmol) and sodium bromide (7.37 g, 71.6 mmol) are added and the mixture is stirred at 0° C. Bromine (4.50 mL, 87.6 mmol) dissolved in methanol (40 mL) is added dropwise while stirring vigorously. Upon the completion of the addition, the mixture is stirred at 50° C. for 1 h. The mixture is cooled and concentrated. The residue is taken up in ethyl acetate and filtered. The filtrate is washed with saturated aqueous NaHCO 3 , water, and brine, dried over Na 2 SO 4 and concentrated to afford 2,5-dimethyl-4-thiocyanato-phenol 30 (11.54 g, 78%) as an oil that solidified upon drying under high vacuum: 1 H-NMR (400 MHz, CDCl 3 ) δ=7.38 (s, 1H), 6.73 (s, 1H), 5.22 (s, 1H), 2.45 (s, 3H), 2.21 (s, 3H).
[0132] Step B: 2,5-Dimethyl-4-thiocyanato-phenol 30 (5.75 g, 32.1 mmol) is dissolved in acetonitrile (25 mL). Powdered cesium carbonate (15.32 g, 47.0 mmol) is added. Then 2-bromo-2-methyl-propionic acid methyl ester (4.50 mL, 34.8 mmol) is added and the mixture is stirred at 60° C. for 18 h. Filtration and concentration, followed by silica gel chromatography (0-50% ethyl acetate in hexanes) yielded 2-(2,5-dimethyl-4-thiocyanato-phenoxy)-2-methyl-propionic acid methyl ester 31 (3.88 g, 43%) as an oil: 1 H-NMR (400 MHz, CDCl 3 ) (rotamers are present; the data given is for the most abundant isomer) δ=7.39 (s, 1H), 6.50 (s, 1H), 3.78 (s, 3H), 2.42 (s, 3H), 2.20 (s, 3H), 1.62 (s, 6H). MS calcd. for C 14 H 17 NNaO 3 S (M+Na + ) 302.1, found 302.1.
[0133] Step C: 2-(2,5-dimethyl-4-thiocyanato-phenoxy)-2-methyl-propionic acid methyl ester 31 (3.88 g, 13.9 mmol) is dissolved in methanol (50 mL). Potassium dihydrogenphosphate (0.23 g, 1.69 mmol), water (6 mL), and dithiothreitol (2.80 g, 18.2 mmol) are added and the mixture is stirred at reflux for 3 h. After cooling and concentration, the residue is taken up in ethyl acetate, washed with water and brine, dried over Na 2 SO 4 and concentrated to yield an oil. Silica gel chromatography purification (0-65% ethyl acetate in hexanes) afforded 2-(4-mercapto-2,5-dimethyl-phenoxy)-2-methyl-propionic acid methyl ester 32 as a colourless oil (1.92 g, 54%): 1 H-NMR (400 MHz, CDCl 3 ) δ=7.09 (s, 1H), 6.47 (s, 1H), 3.79 (s, 1H), 3.10 (s, 1H), 2.24 (s, 3H), 2.15 (s, 3H), 1.56 (s, 6H).
[0134] Step D: 2-(4-mercapto-2,5-dimethyl-phenoxy)-2-methyl-propionic acid methyl ester 32 (0.51 g, 2.0 mmol) is dissolved in acetonitrile (4 mL), followed by 1,2-dibromoethane (1.7 mL, 20 mmol) and potassium carbonate (0.53 mg, 4.0 mmol). The mixture is stirred at room temperature for 12 h, after which the acetonitrile is evaporated and the remaining solid dissolved in dichloromethane (20 mL) and washed with water. The solvent is removed and the crude oil is purified by preparatory HPLC to afford 2-[4-(2-bromo-ethylsulfanyl)-2,5-dimethyl-phenoxy]-2-methyl-propionic acid methyl ester 33 as a clear oil (0.5 g, 69%) MS calcd. for C 15 H 21 BrO 3 S (M+H + ) 361.0, found 361.1
[0000]
[0135] Intermediate 34: 2-[4-(3-Bromo-propylsulfanyl)-2,5-dimethyl-phenoxy]-2-methyl-propionic acid methyl ester. Following the procedure for Intermediate 33, except substituting 1,3-dibromopropane for 1,2-dibromoethane, the title compound is prepared as a clear oil. (0.6 g, 80%) MS calcd. for C 16 H 23 BrO 3 S (M+H + ) 375.1, found 375.1
[0000]
Intermediate 42: 3-[4-(2-Bromo-ethoxy)-2,5-dimethyl-phenyl]-2,2-dimethyl-propionic acid methyl ester
[0136] Step A: 4-Methoxy-2,5-dimethyl-benzaldehyde 35 (1.24 g, 7.55 mmol) is dissolved in dry dichloromethane (12 mL). Neat boron tribromide (1.75 g, 18.5 mmol) is added dropwise, with stirring. A tan-coloured precipitate started to form. The suspension is stirred at room temperature for 5 d. The homogenous mixture is poured over 150 g ice. After the ice melted, the solid phenol 36 is isolated by filtration and dried (1.28 g, quantitative). 1 H-NMR (400 MHz, dmso-d 6 ) δ=10.40 (s 1H), 9.98 (s, 1H), 7.54 (s, 1H), 6.68 (s, 1H), 3.36 (s, 1H), 2.49 (s, 3H), 2.13 (s, 3H).
[0137] Step B: 4-Hydroxy-2,5-dimethyl-benzaldehyde 36 (30.56 g, 0.2 mol) is dissolved in acetonitrile (150 mL). Benzyl bromide (24 mL, 0.2 mol) is added, followed by powdered potassium carbonate (36.92 g, 0.27 mol). The mixture is stirred at 60° C. for 18 h. Cooling and concentration, followed by silica gel chromatography (0-20% ethyl acetate in hexanes) yielded 4-benzyloxy-2,5-dimethyl-benzaldehyde 37 as a colorless oil (27.6 g, 57%). 1 H-NMR (400 MHz, CDCl 3 ) δ=10.13 (s, 1H), 7.61 (s, 1H), 7.43 (m, 5H), 6.72 (s, 1H), 5.15 (s, 2H), 2.63 (s, 3H), 2.28 (s, 3H). MS calcd. for C 16 H 17 O 2 (M+H + ) 241.1, found 241.1.
[0138] Step C: 4-Benzyloxy-2,5-dimethyl-benzaldehyde 37 (4.77 g, 20 mmol) is dissolved in diethyl ether (30 mL). Sodium borohydride (1.0 g, 27 mmol) is added in one portion, followed by 5 mL absolute ethanol. The mixture is vigorously stirred for 3 h at room temperature, then carefully poured over 100 mL 1N aqueous HCl. Extraction with ethyl acetate, washing with water and brine, then concentration yielded (4-benzyloxy-2,5-dimethyl-phenyl)-methanol 38 as a soft solid (4.79 g, 99%). 1 H-NMR (400 MHz, CDCl 3 ) δ=7.39 (m, 5H), 7.11 (s, 1H), 6.73 (s, 1H), 5.07 (s, 2H), 4.61 (s, 2H), 2.35 (s, 3H), 2.25 (s, 3H).
[0139] Step D: (4-Benzyloxy-2,5-dimethyl-phenyl)-methanol 38 (4.79 g, 19.7 mmol) and ethyl diisopropylamine (6.0 mL, 34.4 mmol) are dissolved in dichloromethane (80 mL). Acetic anhydride (2.5 mL, 26.4 mmol) is added in one portion and the mixture is stirred at room temperature for 18 h. Washing with 1N HCl, water, saturated aqueous NaHCO 3 , saturated aqueous NH 4 Cl and brine, followed by drying over MgSO 4 and concentration yields acetic acid 4-benzyloxy-2,5-dimethyl-benzyl ester 39 as an oil (4.93 g, quant.). 1 H-NMR (400 MHz, CDCl 3 ) δ=7.39 (m, 5H), 7.11 (s, 1H), 6.73 (s, 1H), 5.07 (s, 2H), 5.04 (s, 2H), 2.32 (s, 3H), 2.24 (s, 3H), 2.07 (s, 3H).
[0140] Step E: Acetic acid 4-benzyloxy-2,5-dimethyl-benzyl ester 39 (0.56 g, 2 mmol) is dissolved in dry dichloromethane (5 mL). (1-Methoxy-2-methyl-propenyloxy)-trimethylsilane (1 mL, 5 mmol) and magnesium perchlorate (0.09 g, 0.4 mmol) are added and the suspension is stirred overnight. Filtration and silica gel chromatography (0-30% ethyl acetate in hexanes) yielded 3-(4-benzyloxy-2,5-dimethyl-phenyl)-2,2-dimethyl-propionic acid methyl ester 40 as an oil (0.45 g, 69%). 1 H-NMR (400 MHz, CDCl 3 ) δ=7.37 (m, 5H), 6.81 (s, 1H), 6.67 (s, 1H), 5.02 (s, 2H), 2.82 (s, 3H), 2.25 (s, 3H), 2.20 (s, 3H), 1.18 (s, 6H).
[0141] Step F: 3-(4-Benzyloxy-2,5-dimethyl-phenyl)-2,2-dimethyl-propionic acid methyl ester 40 (0.45 g, 1.4 mmol) is dissolved in ethanol (20 mL). Palladium black on carbon (5%; 0.16 g, 5 mol %) is added and the mixture is vigorously stirred under 1 atm. hydrogen for 18 h. Filtration and concentration yielded 3-(4-hydroxy-2,5-dimethyl-phenyl)-2,2-dimethyl-propionic acid methyl ester 41 as an oil (0.11 g, 34%). 1 H-NMR (400 MHz, CDCl 3 ) δ=6.75 (s, 1H), 6.56 (s, 1H), 3.67 (s, 3H), 2.80 (s, 2H), 2.20 (s, 3H), 2.16 (s, 3H), 1.17 (s, 6H).
[0142] Step G: 3-(4-hydroxy-2,5-dimethyl-phenyl)-2,2-dimethyl-propionic acid methyl ester 41 (0.47 g, 2.0 mmol) is dissolved in acetonitrile (15 mL), followed by 1,2-dibromoethane (1.7 mL, 20 mmol) and cesium carbonate (3.25 g, 10 mmol). The mixture is stirred at room temperature for 8 h, followed by filtration and silica gel chromatography (0-30% ethyl acetate in hexanes) yielded 3-[4-(2-bromo-ethoxy)-2,5-dimethyl-phenyl]-2,2-dimethyl-propionic acid methyl ester 42 as a clear oil (0.5 g, 69%) MS calcd. for C 16 H 23 BrO 3 (M+H + ) 343.1, found 343.1
[0000]
[0143] Intermediate 43: 3-[4-(3-Bromo-propoxy)-2,5-dimethyl-phenyl]-2,2-dimethyl-propionic acid methyl ester Following the procedure for Intermediate 42, except substituting 1,3-dibromopropane for 1,2-dibromoethane, the title compound is prepared as a clear oil. (0.6 g, 84%) MS calcd. for C 17 H 25 BrO 3 (M+H + ) 357.1, found 357.1
[0000]
[0144] Intermediate 46: 2-[4-(2-Bromo-ethoxy)-2,5-dimethyl-phenylsulfanyl]-2-methyl-propionic acid methyl ester.
[0145] Step A: 2,5-Dimethyl-4-thiocyanato-phenol 30 (1.50 g, 8.4 mmol) is dissolved in methanol (30 mL). Potassium dihydrogenphosphate (0.32 g, 2.35 mmol), water (4 mL), and dithiothreitol (2.17 g, 14.1 mmol) are added and the mixture is stirred at reflux for 3 h. After cooling and concentration, the residue is taken up in ethyl acetate, washed with water and brine, dried over Na 2 SO 4 and concentrated to yield an oil. It is used as such in the next step: 1 H-NMR (400 MHz, CDCl 3 ) δ=7.10 (s, 1H), 6.63 (s, 1H), 4.81 (s, 1H), 3.08 (s, 1H), 2.28 (s, 3H), 2.17 (s, 3H). MS calcd. for C 8 H 11 OS (M+H + ) 155.1, found 155.0.
[0146] Step B: 4-Mercapto-2,5-dimethyl-phenol 44 obtained in step A above is dissolved in acetonitrile (30 mL). Powdered cesium carbonate (7.06 g, 21.7 mmol) is added, followed by 2-bromo-2-methyl-propionic acid methyl ester (2.40 mL, 18.5 mmol). The mixture is stirred at rt for 2 h. Filtration and concentration, followed by silica gel chromatography (0-50% ethyl acetate in hexanes) yielded 2-(4-hydroxy-2,5-dimethyl-phenylsulfanyl)-2-methyl-propionic acid methyl ester 45 (0.45 g, 13%) as a white waxy solid: 1 H-NMR (400 MHz, CDCl 3 ) δ=7.17 (s, 1H), 6.65 (s, 1H), 5.06 (s, 1H), 3.67 (s, 3H), 2.36 (s, 3H), 2.17 (s, 3H), 1.47 (s, 6H). MS calcd. for C 13 H 19 O 3 S (M+H + ) 255.1, found 255.1.
[0147] Step C: 2-(4-Hydroxy-2,5-dimethyl-phenylsulfanyl)-2-methyl-propionic acid methyl ester 45 (0.25 g, 1.0 mmol) is dissolved in acetonitrile (4 mL), followed by 1,2-dibromoethane (1.7 mL, 20 mmol) and potassium carbonate (0.90 mL, 4.6 mmol). The mixture is stirred at 50° C. for 18 h, after which the solids are filtered off and the acetonitrile is evaporated. Silicagel chromatography (10-60% ethyl acetate in hexanes) afforded 2-[4-(2-bromo-ethoxy)-2,5-dimethyl-phenylsulfanyl]-2-methyl-propionic acid methyl ester 46 as a clear oil (0.18 g, 51%): 1 H-NMR (400 MHz, CDCl 3 ) δ=7.19 (s, 1H), 6.66 (s, 1H), 4.28 (t, J=6.2 Hz, 2H), 3.67 (s, 3H), 3.64 (t, J=6.2 Hz, 2H), 2.41 (s, 3H), 2.18 (s, 3H), 1.46 (s, 6H). MS calcd. for C 15 H 21 BrO 3 S (M+H) 361.0, found 361.1.
[0000]
[0148] Intermediate 47: 4-Hydroxy-2,5-dimethyl-benzaldehyde 36 (7.18 g, 47.8 mmol) is dissolved in acetonitrile (60 mL). Powdered cesium carbonate (22.63 g, 69.5 mmol) is added, followed by 2-bromo-2-methyl-propionic acid methyl ester (7.00 mL, 54.1 mmol). The mixture is stirred at 50° C. for 8 h. Filtration and concentration, followed by silica gel chromatography (0-50% ethyl acetate in hexanes) yielded 2-(4-formyl-2,5-dimethyl-phenoxy)-2-methyl-propionic acid methyl ester 47 (3.50 g, 29%) as a white solid: 1 H-NMR (400 MHz, CDCl 3 ) δ=10.10 (s, 1H), 7.27 (s, 1H), 6.36 (s, 1H), 3.77 (s, 3H), 2.57 (s, 3H), 2.23 (s, 3H), 1.67 (s, 6H). MS calcd. for C 14 H 19 O 4 (M+H + ) 251.1, found 251.1.
[0000]
Example A1
2-Methyl-2-[2-methyl-4-(2-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-amino}-ethoxy)-phenoxy]-propionic acid
[0149] Step A: The aminothiazole 1 (0.61 g, 2.49 mmol), the bromide 16 (0.55 g, 1.66 mmol) and potassium carbonate (0.28 g, 1.99 mmol) are suspended in dry acetonitrile (15 mL) in a sealed tube. The mixture is stirred vigorously and heated to 120° C. overnight. Then the reaction mixture is cooled to room temperature, filtered and the solvent is removed in vacuo. The remainder is dissolved in ethyl acetate and washed with water twice, the organic layer is dried over MgSO 4 and concentrated. The remainder is purified by flash chromatography (silica, DCM/MeOH gradient) to afford 2-methyl-2-(2-methyl-4-{2-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-ethoxy}-phenoxy)-propionic acid methyl ester 90 (0.35 g, 43%) as a colourless oil: MS calculated for C 24 H 26 F 3 N 2 O 4 S (M+H + ) 495.2, found 495.1.
[0150] Step B: The 2-Methyl-2-(2-methyl-4-{2-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-ethoxy}-phenoxy)-propionic acid methyl ester 90 (50 mg, 0.10 mmol), iodomethane (32 μL, 0.48 mmol) and Cs 2 CO 3 (100 mg, 0.30 mmol) are suspended in dry acetonitrile (1 mL) in a sealed tube. The mixture is stirred vigorously and heated to 120° C. overnight, cooled to room temperature, and then used directly in the next step.
[0151] Step C: THF (3 mL) and 1 N LiOH (1 mL) are added to the solution derived from Step B. The mixture is stirred at 50° C. for 5 h, then acidified with 1 N HCl (˜1.5 mL). The reaction mixture is extracted with DCM (3 mL), the organic layer is separated and concentrated in vacuo. The remainder is taken up in DMSO (1 mL) and purified on reverse phase HPLC (H 2 O/MeCN gradient) to afford the title compound A1 (26 mg, 53%) as a white solid: 1 H-NMR (600 MHz, (CD 3 ) 2 SO) δ=7.89 (d, J=8.0 Hz, 2H), 7.63 (d, J=8.0 Hz, 2H), 6.82-6.63 (m, 4H), 4.24 (t, J=5.1 Hz, 2H), 4.02 (t, J=5.1 Hz, 2H), 3.29 (s, 3H), 2.20 (s, 3H), 1.54 (s, 6H). MS calculated for C 24 H 26 F 3 N 2 O 4 S (M+H + ) 495.2, found 495.1.
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Example B1
2-Methyl-2-(2-methyl-4-{methyl-[4-(4-trifluoromethyl-phenyl)-thiazol-2-yl]-sulfamoyl}-phenoxy)-propionic acid
[0152] Step A: The aminothiazole 1 (24 mg, 0.10 mmol), the sulfonyl chloride 24 (37 mg, 0.12 mmol) and triethylamine (28 μL, 0.20 mmol) are suspended in dry DCM (1 mL) and stirred at rt overnight. Then the reaction mixture is diluted with DCM and washed with water twice, the organic layer is separated, dried over MgSO 4 and concentrated. The remainder is used in the next step without further purification.
[0153] Step B: The crude 2-methyl-2-{2-methyl-4-[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylsulfamoyl]-phenoxy}-propionic acid methyl ester 92 is dissolved in DMF (1 mL) and cooled to 0° C. Sodium hydride (60% dispersion, 8 mg, 0.11 mmol) is added and the mixture is stirred for 5 min. Then iodomethane (7 μL, 0.11 mmol) is added, and the ice-bath is removed. The mixture is stirred for 6 h at rt and used directly in the next step.
[0154] Step C: THF (1 mL) and 1 N LiOH (1 mL) are added to the solution derived from Step B. The mixture is stirred at 40° C. for 5 h, then acidified with 1 N HCl (˜1.2 mL). The reaction mixture is extracted with DCM (3 mL), the organic layer is separated and concentrated in vacuo. The remainder is taken up in DMSO (1 mL) and purified on reverse phase HPLC (H 2 O/MeCN gradient) to afford the title compound B1 (13 mg, 25%) as a colourless glass: 1 H-NMR (600 MHz, (CD 3 ) 2 SO) δ=7.90 (d, J=8.2 Hz, 2H), 7.66-7.60 (m, 4H), 7.24 (s, 1H), 6.71 (d, J=8.7 Hz, 1H), 3.52 (s, 3H), 2.24 (s, 3H), 1.67 (s, 6H). MS calculated for C 22 H 22 F 3 N 2 O 5 S 2 (M+H + ) 515.1, found 515.0.
[0000]
Example C1
2-(2,5-Dimethyl-4-{[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-methyl}-phenoxy)-2-methyl-propionic acid
[0155] Step A: The aminothiazole 1 (85 mg, 0.34 mmol) and the aldehyde 47 (91 mg, 0.37 mmol) are dissolved in dry THF (3 mL). Triethylorthoacetate (0.2 mL, 1 mmol) is added, then the mixture is stirred at rt for 30 min. Solid sodium triacetoxyborohydride (0.15 mmol, 0.7 mmol) is added and the mixture is stirred overnight at rt. The reaction mixture is diluted with 1N HCl and extracted with ethyl acetate twice, the organic layer is washed with brine, dried (MgSO 4 ) and concentrated. The remainder is used in the next step without further purification.
[0156] Step B: The crude 2-(2,5-dimethyl-4-{[4-(4-trifluoromethyl-phenyl)-thiazol-2-ylamino]-methyl}-phenoxy)-2-methyl-propionic acid methyl ester 94 obtained in step A is dissolved in dimethoxyethane (2 mL). Lithium hydroxide monohydrate (0.10 g) is added, followed by water (0.5 mL). The mixture is vigorously stirred at 50° C. for 3 h. Purification on reverse phase HPLC (H 2 O/MeCN gradient) afforded the title compound C1 as a colourless glass:
[0157] 1 H-NMR (400 MHz, CDCl 3 ) δ=7.81 (d, J=8.2 Hz, 2H), 7.74 (d, J=8.7 Hz, 1H), 7.13 (s, 1H), 6.68 (s, 1H), 6.63 (s, 1H), 4.44 (s, 2H), 2.32 (s, 3H), 2.22 (s, 3H), 1.63 (s, 6H). MS calculated for C 23 H 24 F 3 N 2 O 3 S 2 (M+H + ) 465.2, found 465.2.
[0158] By repeating the procedure described in the above examples A1 and B1, using appropriate starting materials, the following compounds of Formula I, as identified in Table 1, are obtained.
[0000]
TABLE 1
Com-
pound
Compound
Physical Data
Number
Structure
1 H NMR 400 MHz and/or MS (m/z)
A2
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.81 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 6.82-6.60 (m, 4H), 4.20 (t, J = 5.0 Hz, 2H), 3.74 (t, J = 5.0 Hz, 2H), 2.21 (s, 3H), 1.54 (s, 6H). MS calculated for C 23 H 24 F 3 N 2 O 4 S (M + H + ) 481.1, found 481.1.
A3
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.85 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.9 Hz, 1H), 6.75 (s, 1H), 6.72 (d, J = 3.0 Hz, 1H), 6.63 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.24 (t, J = 5.2 Hz, 2H), 4.03 (t, J = 5.2 Hz, 2H), 3.55 (t, J = 7.7 Hz, 2H), 2.20 (s, 3H), 1.80 (m, 2H), 1.54 (s, 6H), 1.00 (t, J = 7.4 Hz, 3H). MS calculated for C 26 H 30 F 3 N 2 O 4 S (M + H + ) 523.2, found 523.1.
A4
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.87 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.9 Hz, 1H), 6.75 (s, 1H), 6.72 (d, J = 3.0 Hz, 1H), 6.63 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.23 (t, J = 5.2 Hz, 2H), 4.03 (t, J = 5.2 Hz, 2H), 3.57 (t, J = 7.7 Hz, 2H), 2.20 (s, 3H), 1.77 (m, 2H), 1.54 (s, 6H), 1.38 (m, 4H), 0.93 (t, J = 7.0 Hz, 3H). MS calculated for C 28 H 34 F 3 N 2 O 4 S (M + H + ) 551.2, found 551.1.
A5
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.89 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 6.81 (d, J = 8.9 Hz, 1H), 6.80 (s, 1H), 6.75 (d, J = 3.0 Hz, 1H), 6.70 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.23 (t, J = 6.1 Hz, 2H), 4.09 (m, 1H), 3.87 (t, J = 6.1 Hz, 2H), 2.21 (s, 3H), 1.54 (s, 6H), 1.37 (d, J = 6.6 Hz, 3H). MS calculated for C 26 H 30 F 3 N 2 O 4 S (M + H + ) 523.2, found 523.1.
A6
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.85 (d, J = 8.2 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.9 Hz, 1H), 6.75 (s, 1H), 6.71 (d, J = 3.0 Hz, 1H), 6.63 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.25 (t, J = 5.4 Hz, 2H), 4.05 (t, J = 5.4 Hz, 2H), 3.41 (d, J = 7.6 Hz, 2H), 2.25 (m, 1H), 2.20 (s, 3H), 1.54 (s, 6H), 1.01 (d, J = 6.6 Hz, 3H). MS calculated for C 27 H 32 F 3 N 2 O 4 S (M + H + ) 537.2, found 537.1.
A7
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.86 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.9 Hz, 1H), 6.77 (s, 1H), 6.72 (d, J = 3.0 Hz, 1H), 6.62 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.23 (t, J = 5.4 Hz, 2H), 4.03 (t, J = 5.4 Hz, 2H), 3.85 (t, J = 5.4 Hz, 2H), 3.72 (t, J = 5.4 Hz, 2H), 3.37 (s, 3H), 2.20 (s, 3H), 1.54 (s, 6H). MS calculated for C 27 H 30 F 3 N 2 O 5 S (M + H + ) 539.2, found 539.1.
A8
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.91 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 7.34 (m, 5H), 6.80 (d, J = 8.9 Hz, 1H), 6.80 (s, 1H), 6.70 (d, J = 3.0 Hz, 1H), 6.62 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.85 (s, 2H), 4.24 (t, J = 5.4 Hz, 2H), 3.99 (t, J = 5.4 Hz, 2H), 2.20 (s, 3H), 1.54 (s, 6H). MS calculated for C 30 H 30 F 3 N 2 O 4 S (M + H + ) 571.2, found 571.1.
A9
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.90 (d, J = 8.2 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H), 7.35-7.24 (m, 5H), 6.80 (d, J = 8.9 Hz, 1H), 6.80 (s, 1H), 6.71 (d, J = 3.0 Hz, 1H), 6.63 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.18 (t, J = 5.2 Hz, 2H), 3.92 (t, J = 5.2 Hz, 2H), 3.82 (t, J = 7.7 Hz, 2H), 3.08 (t, J = 7.7 Hz, 2H), 2.20 (s, 3H), 1.54 (s, 6H). MS calculated for C 31 H 32 F 3 N 2 O 4 S (M + H + ) 585.2, found 585.1.
A10
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.85 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 6.79 (d, J = 8.9 Hz, 1H), 6.74 (s, 1H), 6,71 (d, J = 3.0 Hz, 1H), 6.63 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.24 (t, J = 5.3 Hz, 2H), 4.04 (t, J = 5.3 Hz, 2H), 3.42 (d, J = 7.4 Hz, 2H), 2.20 (s, 3H), 1.90 (m, 1H), 1.76 (m, 4H), 1.70 (m, 1H), 1.54 (s, 6H), 1.22 (m, 6H), 1.03 (m, 4H). MS calculated for C 30 H 36 F 3 N 2 O 4 S (M + H + ) 577.2, found 577.1.
A11
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.85 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.9 Hz, 1H), 6.74 (s, 1H), 6.72 (d, J = 3.0 Hz, 1H), 6.64 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.22 (t, J = 5.4 Hz, 2H), 4.00 (t, J = 5.3 Hz, 2H), 3.63 (d, J = 7.3 Hz, 2H), 2.84 (m, 1H), 2.20 (s, 3H), 2.14 (m, 2H), 1.97-1.81 (m, 4H), 1.54 (s, 6H). MS calculated for C 28 H 32 F 3 N 2 O 4 S (M + H + ) 549.2, found 549.2.
A12
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.89 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 6.80 (d, J = 8.9 Hz, 1H), 6.78 (s, 1H), 6.72 (d, J = 3.0 Hz, 1H), 6.66 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.26 (t, J = 5.4 Hz, 2H), 4.09 (t, J = 5.3 Hz, 2H), 3.49 (d, J = 6.8 Hz, 2H), 2.20 (s, 3H), 1.54 (s, 6H), 1.21 (m, 1H), 0.64 (m, 2H), 0.38 (m, 2H). MS calculated for C 27 H 30 F 3 N 2 O 4 S (M + H + ) 535.2, found 535.2.
A13
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.86 (d, J = 8.2 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H), 6.88 (s, 1H), 6.78 (d, J = 8.9 Hz, 1H), 6.69 (d, J = 3.0 Hz, 1H), 6.54 (dd, J = 3.0 Hz, J = 8.9 Hz, 1H), 4.12 (m, 4H), 3.80 (t, J = 4.9 Hz, 2H), 3.41 (m, 2H), 3.23 (q, J = 7.2 Hz, 4H), 2.18 (s, 3H), 1.54 (s, 6H), 1.35 (t, J = 7.2 Hz, 6H). MS calculated for C 29 H 37 F 3 N 3 O 4 S (M + H + ) 580.2, found 580.2.
A14
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.93 (d, J = 8.1 Hz, 2H), 7.62 (d, J = 8.1 Hz, 2H), 6.82 (s, 1H), 6.70 (s, 1H), 6.61 (s, 1H), 4.23 (t, 1 =5.1 Hz, 2H), 4.01 (t, J = 5.1 Hz, 2H), 3.27 (s, 3H), 2.18 (s, 3H), 2.13 (s, 3H), 1.53 (s, 6H). MS calculated for C 25 H 28 F 3 N 2 O 4 S (M + H + ) 509.2, found 509.1.
A15
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.80 (d, J = 8.2 Hz, 2H), 7.66 (d, J = 8.2 Hz, 2H), 6.72 (s, 1H), 6.68 (s, 1H), 6.61 (s, 1H), 4,15 (t, J = 4.9 Hz, 2H), 3.74 (t, J = 4.9 Hz, 2H), 2.19 (s, 3H), 2.03 (s, 3H), 1.54 (s, 6H). MS calculated for C 24 H 26 F 3 N 2 O 4 S (M + H + ) 495.2, found 495.1.
A16
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.90 (d, J = 8.1 Hz, 2H), 7.60 (d, J = 8.1 Hz, 2H), 6.78 (s, 1H), 6.71 (s, 1H), 6.59 (s, 1H), 4.01 (t, J = 4.8 Hz, 2H), 3.78 (t, J = 7.0 Hz, 2H), 3.19 (s, 3H), 2,20 (s, 3H), 2.19 (m, 2H), 2.17 (s, 3H), 1.53 (s, 6H). MS calculated for C 26 H 30 F 3 N 2 O 4 S (M + H + ) 523.2, found 523.1.
A17
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.84 (d, J = 8.1 Hz, 2H), 7.70 (d, J = 8.1 Hz, 2H), 6.72 (s, 1H), 6.71 (s, 1H), 6.64 (s, 1H), 4.08 (t, J = 5.6 Hz, 2H), 3.58 (m, 2H), 2.26 (m, 2H), 2.20 (s, 3H), 2.18 (m, 2H), 2.18 (s, 3H), 1.54 (s, 6H). MS calculated for C 25 H 28 F 3 N 2 O 4 S (M + H + ) 509.2, found 509.1.
A18
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.91 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 8.1 Hz, 2H), 6.79 (s, 1H), 6.69 (s, 1H), 6.60 (s, 1H), 3.98 (t, J = 5.8 Hz, 2H), 3.64 (t, J = 6.9 Hz, 2H), 3.16 (s, 3H), 2.19 (s, 3H), 2.14 (s, 3H), 1.89 (m, 4H), 1.53 (s, 6H). MS calculated for C 26 H 30 F 3 N 2 O 4 S (M + H + ) 537.2, found 537.1.
A19
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.78 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.2 Hz, 2H), 6.72 (s, 1H), 6.68 (s, 1H), 6.58 (s, 1H), 3.93 (t, J = 5.5 Hz, 2H), 3.34 (t, J = 6.7 Hz, 2H), 2.20 (s, 3H), 2.08 (s, 3H), 1.92 (m, 4H), 1.55 (s, 6H). MS calculated for C 26 H 30 F 3 N 2 O 4 S (M + H + ) 523.2, found 523.1.
A20
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.73 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.68 (s, 1H), 6.63 (s, 1H), 6.60 (s, 1H), 4.17 (t, J = 5.2 Hz, 2H), 3.75 (t, J = 5.2 Hz, 2H), 2.20 (s, 3H), 2.08 (s, 3H), 1.53 (s, 6H). MS calculated for C 24 H 26 F 3 N 2 O 5 S (M + H + ) 511.1, found 511.2.
A21
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.78 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 6.70 (s, 1H), 6.66 (s, 1H), 6.62 (s, 1H), 4.24 (t, J = 5.2 Hz, 2H), 4.11 (t, J = 5.2 Hz, 2H), 3.43 (s, 3H), 2.19 (s, 3H), 2.12 (s, 3H), 1.53 (s, 6H). MS calculated C 25 H 28 F 3 N 2 O 5 S (M + H + ) 525.2, found 525.2.
A22
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.62 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.68 (s, 1H), 6.64 (s, 1H), 6.41 (s, 1H), 4.19 (t, J = 5.2 Hz, 2H), 3.85 (s, 3H), 3.74 (t, J = 5.2 Hz, 2H), 2.20 (s, 3H), 2.11 (s, 3H), 1.52 (s, 6H). MS calculated for C 24 H 29 N 2 O 5 S (M + H + ) 457.2, found 457.2.
A23
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.68 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 6.68 (s, 1H), 6.62 (s, 1H), 6.52 (s, 1H), 4.24 (t, J = 4.8 Hz, 2H), 4.13 (t, J = 4.8 Hz, 2H), 3.83 (s, 1H), 3.36 (s, 3H), 2.18 (s, 3H), 2.12 (s, 3H), 1.52 (s, 6H). MS calculated for C 25 H 31 N 2 O 5 S (M + H + ) 471.2, found 471.2.
A24
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.84 (d, J = 8.8 Hz, 2H), 7.63 (t, J = 8.4 Hz, 4H), 7.45 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.6 Hz, 1H), 6.69 (s, 2H), 6.64 (s, 1H), 4.28 (t, J = 5.2 Hz, 2H), 4.21 (t, J = 5.2 Hz, 2H), 3.39 (s, 3H), 2.19 (s, 3H), 2.13 (s, 3H), 1.52 (s, 6H). MS calculated for C 30 H 33 N 2 O 4 S (M + H + ) 517.2, found 517.3.
A25
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.70 (s, 4H), 7.52 (s, 1H), 6.68 (s, 1H), 6.60 (s, 1H), 4.10 (t, J = 5.2 Hz, 2H), 3.86 (t, J = 4.8 Hz, 2H), 2.20 (s, 3H), 2.12 (s, 3H), 1.53 (s, 6H). MS calculated for C 24 H 26 F 3 N 2 O 5 (M + H + ) 479.2, found 479.2.
A26
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.78 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.0 Hz, 2H), 7.55 (s, 1H), 6.69 (s, 1H), 6.62 (s, 1H), 4.18 (t, J = 5.0 Hz, 2H), 3.94 (t, J = 5.0 Hz, 2H), 3.31 (s, 3H), 2.19 (s, 3H), 2.10 (s, 3H), 1.52 (s, 6H). MS calculated for C 25 H 28 F 3 N 2 O 5 (M + H + ) 493.2, found 493.2.
A27
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.73 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 6.71 (s, 1H), 6.63 (s, 1H), 6.57 (s, 1H), 4.06 (t, J = 5.6 Hz, 2H), 3.54 (t, J = 6.8 Hz, 2H), 2.25 (m, 2H), 2.19 (s, 3H), 2.16 (s, 3H), 1.53 (s, 6H). MS calculated for C 25 H 28 F 3 N 2 O 5 S (M + H + ) 525.2, found 525.2.
A28
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.75 (d, J = 8.8 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 6.70 (s, 1H), 6.61 (s, 1H), 6.59 (s, 1H), 4.02 (t, J = 5.6 Hz, 2H), 3.82 (t, J = 7.2 Hz, 2H), 3.26 (s, 3H), 2.22 (m, 2H), 2.17 (s, 6H), 1.53 (s, 6H). MS calculated for C 26 H 30 F 3 N 2 O 5 S (M + H + ) 539.2, found 539.2.
A29
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.61 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 9.2 Hz, 2H), 6.70 (s, 1H), 6.63 (s, 1H), 6.39 (s, 1H), 4.06 (t, J = 5.6 Hz, 2H), 3.84 (s, 3H), 3.52 (t, J = 6.8 Hz, 2H), 2.27 (m, 2H), 2.20 (s, 3H), 2.16 (s, 3H), 1.53 (s, 6H). MS calculated for C 25 H 31 N 2 O 5 S (M + H + ) 471.2, found 471.2.
A30
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.65 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 9.2 Hz, 2H), 6.70 (s, 1H), 6.60 (s, 1H), 6.46 (s, 1H), 4.02 (t, J = 5.6 Hz, 2H), 3.83 (m, 5H), 3.28 (s, 3H), 2.23 (m, 2H), 2.18 (s, 6H), 1.53 (s, 6H). MS calculated for C 26 H 33 N 2 O 5 S (M + H + ) 485.2, found 485.2.
A31
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.76 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 8.4 Hz, 2H), 7.46 (t, J = 7.2 Hz, 2H), 7.38 (t, J = 7.2 Hz, 1H), 6.71 (s, 1H), 6.64 (s, 1H), 6.57 (s, 1H), 4.07 (t, J = 5.6 Hz, 2H), 3.55 (m, 2H), 2.29 (m, 2H), 2.20 (s, 3H), 2.17 (s, 3H), 1.54 (s, 6H). MS calculated for C 30 H 33 N 2 O 4 S (M + H + ) 517.2, found 517.3.
A32
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.76 (d, J = 8.4 Hz, 2H), 7.62 (t, J = 6.8 Hz, 4H), 7.45 (t, J = 7.6 Hz, 2H), 7.36 (t, J = 7.2 Hz, 1H), 6.71 (s, 1H), 6.63 (s, 1H), 6.61 (s, 1H), 4.04 (t, J = 5.6 Hz, 2H), 3.87 (t, J = 6.8 Hz, 2H), 3.33 (s, 3H), 2.25 (m, 2H), 2.18 (s, 6H), 1.53 (s, 6H). MS calculated for C 31 H 35 N 2 O 4 S (M + H + ) 531.2, found 531.2.
A33
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.69 (s, 4H), 7.47 (s, 1H), 6.70 (s, 1H), 6.62 (s, 1H), 4.05 (t, J = 5.6 Hz, 2H), 3.68 (m, 2H), 2.20 (s, 3H), 2.17 (m, 2H), 2.16 (s, 3H), 1.53 (s, 6H). MS calculated for C 25 H 28 F 3 N 2 O 5 (M + H + ) 493.2, found 493.2.
A34
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.77 (d, J = 8.8 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.45 (s, 1H), 6.70 (s, 1H), 6.62 (s, 1H), 4.04 (t, J = 5.6 Hz, 2H), 3.83 (m, 2H), 3.28 (s, 3H), 2.18 (s, 3H), 2.16 (s, 3H), 1.53 (s, 6H). MS calculated for C 26 H 30 F 3 N 2 O 5 (M + H + ) 507.2, found 507.2.
A35
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.76 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.23 (s, 1H), 6.66 (s, 1H), 6.65 (s, 1H), 3.47 (t, J = 6.8 Hz, 2H), 3.07 (t, J = 7.2 Hz, 2H), 2.33 (s, 3H), 2.15 (s, 3H), 1.60 (s, 6H). MS calcd. for C 24 H 26 F 3 N 2 O 3 S 2 (M + H + ) 511.1, found 511.2.
A36
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.89 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.15 (s, 1H), 6.68 (s, 1H), 6.65 (s, 1H), 3.42 (t, J = 6.8 Hz, 2H), 2.94 (t, J = 7.2 Hz, 2H), 2.33 (s, 3H), 2.16 (s, 3H), 2.11 (m, 2H), 1.60 (s, 6H). MS calcd. for C 25 H 28 F 3 N 2 O 3 S 2 (M + H + ) 525.1, found 525.2.
A37
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.75 (d, J = 8.0 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.18 (s, 1H), 6.72 (s, 1H), 6.66 (s, 1H), 3.75 (t, J = 6.8 Hz, 2H), 3.12 (t, J = 7.2 Hz, 2H), 3.10 (s, 3H), 2.29 (s, 3H), 2.11 (s, 3H), 1.63 (s, 6H). MS calcd. for C 25 H 28 F 3 N 2 O 3 S 2 (M + H + ) 525.1, found 525.2.
A38
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.78 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.4 Hz, 2H), 7.14 (s, 1H), 6.70 (s, 1H), 6.65 (s, 1H), 3.70 (t, J = 6.8 Hz, 2H), 3.23 (s, 3H), 2.86 (t, J = 7.2 Hz, 2H), 2.32 (s, 3H), 2.15 (s, 3H), 2.00 (m, 2H), 1.60 (s, 6H). MS calcd. for C 26 H 30 F 3 N 2 O 3 S 2 (M + H + ) 539.1, found 539.2.
A39
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.75 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.0 Hz, 2H), 6.82 (s, 1H), 6.66 (s, 1H), 6.52 (s, 1H), 4.10 (t, J = 5.2 Hz, 2H), 3.67 (t, J = 4.8 Hz, 2H), 2.78 (s, 2H), 2.19 (s, 3H), 2.02 (s, 3H), 1.12 (s, 6H). MS calcd. for C 25 H 28 F 3 N 2 O 3 S (M + H + ) 493.2, found 493.2.
A40
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.81 (d, J = 8.0 Hz, 2H), 7.67 (d, J = 8.0 Hz, 2H), 6.90 (s, 1H), 6.69 (s, 1H), 6.59 (s, 1H), 4.06 (t, J = 5.6 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.85 (s, 2H), 2.26 (s, 3H), 2.21 (m, 2H), 2.16 (s, 3H), 1.12 (s, 6H). MS calcd. for C 26 H 30 F 3 N 2 O 3 S (M + H + ) 507.2, found 507.3.
A41
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.91 (d, J = 8.0 Hz, 2H), 7.62 (d, J = 8.0 Hz, 2H), 6.88 (s, 1H), 6.79 (s, 1H), 6.59 (s, 1H), 4.25 (t, J = 5.0 Hz, 2H), 4.05 (t, J = 4.8 Hz, 2H), 3.30 (s, 3H), 2.85 (s, 2H), 2.25 (s, 3H), 2.12 (s, 3H), 1.18 (s, 6H). MS calcd. for C 26 H 30 F 3 N 2 O 3 S (M + H + ) 507.2, found 507.2.
A42
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.79 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 6.80 (s, 1H), 6.66 (s, 1H), 6.48 (s, 1H), 3.94 (t, J = 5.6 Hz, 2H), 3.69 (t, J = 6.8 Hz, 2H), 3.12 (s, 3H), 2.77 (s, 2H), 2.15 (s, 3H), 2.11 (m, 2H), 2.09 (s, 3H), 1.10 (s, 6H). MS calcd. for C 26 H 30 F 3 N 2 O 3 S (M + H + ) 521.2, found 521.3.
A43
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.81 (d, J = 8.2 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.24 (s, 1H), 6.74 (s, 1H), 6.70 (s, 1H), 4.25 (t, J = 6.8 Hz, 2H), 3.78 (t, J = 7.2 Hz, 2H), 2.44 (s, 3H), 2.10 (s, 3H), 1.46 (s, 6H). MS calcd. for C 24 H 26 F 3 N 2 O 2 S 2 (M + H + ) 511.1, found 511.1.
B2
1 H-NMR (600 MHz, CDCl 3 ) δ = 7.90 (d, J = 8.2 Hz, 2H), 7.69-7.61 (m, 5H), 7.24 (s, 1H), 6.75 (d, J = 8.4 Hz, 1H), 4.74 (s, 2H), 3.52 (s, 3H), 2.30 (s, 3H). MS calculated for C 20 H 18 F 3 N 2 O 5 S 2 (M + H + ) 487.1, found 487.0.
B3
1 H-NMR (400 MHz, CDCl 3 ) δ = 7.84 (d, J = 8.4 Hz, 2H), 7.78 (s, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.15 (s, 1H) 6.48 (s, 1H), 3.43 (s, 3H), 2.34 (s, 3H), 2.17 (s, 3H), 1.61 (s, 6H). MS calcd. for C 23 H 24 F 3 N 2 O 5 S 2 (M + H + ) 244.1, found 244.0.
Transcriptional Assay
[0159] Transfection assays are used to assess the ability of compounds of the invention to modulate the transcriptional activity of the PPARs. Briefly, expression vectors for chimeric proteins containing the DNA binding domain of yeast GAL4 fused to the ligand-binding domain (LBD) of either PPARδ, PPARα or PPARγ are introduced via transient transfection into mammalian cells, together with a reporter plasmid where the luciferase gene is under the control of a GAL4 binding site. Upon exposure to a PPAR modulator, PPAR transcriptional activity varies, and this can be monitored by changes in luciferase levels. If transfected cells are exposed to a PPAR agonist, PPAR-dependent transcriptional activity increases and luciferase levels rise.
[0160] 293T human embryonic kidney cells (8×10 6 ) are seeded in a 175 cm 2 flask a day prior to the start of the experiment in 10% FBS, 1% Penicillin/Streptomycin/Fungizome, DMEM Media. The cells are harvested by washing with PBS (30 ml) and then dissociating using trypsin (0.05%; 3 ml). The trypsin is inactivated by the addition of assay media (DMEM, CA-dextran fetal bovine serum (5%). The cells are spun down and resuspended to 170,000 cells/ml. A Transfection mixture of GAL4-PPAR LBD expression plasmid (1 μg), UAS-luciferase reporter plasmid (1 μg), Fugene (3:1 ratio; 6 μL) and serum-free media (200 μL) was prepared and incubated for 15-40 minutes at room temperature. Transfection mixtures are added to the cells to give 0.16M cells/mL, and cells (50 μl/well) are then plated into 384 white, solid-bottom, TC-treated plates. The cells are further incubated at 37° C., 5.0% CO 2 for 5-7 hours. A 12-point series of dilutions (3 fold serial dilutions) are prepared for each test compound in DMSO with a starting compound concentration of 10 μM. Test compound (500 nl) is added to each well of cells in the assay plate and the cells are incubated at 37° C., 5.0% CO 2 for 18-24 hours. The cell lysis/luciferase assay buffer, Bright-Glo™ (25%; 25 μl; Promega), is added to each well. After a further incubation for 5 minutes at room temperature, the luciferase activity is measured.
[0161] Raw luminescence values are normalized by dividing them by the value of the DMSO control present on each plate. Normalized data is analyzed and dose-response curves are fitted using Prizm graph fitting program. EC50 is defined as the concentration at which the compound elicits a response that is half way between the maximum and minimum values. Relative efficacy (or percent efficacy) is calculated by comparison of the response elicited by the compound with the maximum value obtained for a reference PPAR modulator.
[0162] Compounds of Formula I, in free form or in pharmaceutically acceptable salt form, exhibit valuable pharmacological properties, for example, as indicated by the in vitro tests described in this application. Compounds of the invention preferably have an EC50 for PPARδ and/or PPARα and/or PPARγ, of less than 5 μM, more preferably less than 1 μM, more preferably less than 500 nm, more preferably less than 100 nM. Compounds of the invention preferably have an EC50 for PPARδ that is less than or equal to PPARα which in turn has an EC50 that is at least 10-fold less than PPARγ.
[0163] It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference for all purposes.
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The invention provides compounds (I) pharmaceutical compositions comprising such compounds and methods of using such compounds to treat or prevent diseases or disorders associated with the activity of the Peroxisome Proliferator-Activated Receptor (PPAR) families, particularly the activity of PPARδ.
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[0001] This application claims priority from a Provisional Application, Serial No. 60/475,062, filed May 30, 2003.
FIELD OF THE INVENTION
[0002] The present invention relates to blood pumping devices, and, more particularly, to ventricular assist devices.
BACKGROUND
[0003] A ventricular assist device (“VAD”) is used to help supplement the heart's pumping action both during and after certain kinds of surgery, in situations where a complete cardiopulmonary bypass (using a heart-lung machine) is neither needed nor advisable in light of the serious side effects associated therewith. Ventricular assist devices typically comprise a pair of cannulae or other tubing and some sort of pump operably connected to the cannulae. In use, the cannulae are attached to either the left side of the heart (a left ventricular assist device) or to the right side of the heart (a right ventricular assist device) “in parallel,” i.e., the pump supplements the heart's pumping action but does not completely bypass it, and the pump is activated. Alternatively, a pump may be directly implanted into the body.
[0004] Originally, ventricular assist devices were air powered, wherein fluctuating air pressure, provided by a simple mechanical air pump machine, was applied to a bladder-like sac. The bladder had input and output valves, so that blood would enter the bladder through the input valve when the pressure on the bladder was low, and exit the bladder through the output valve when the pressure on the bladder was high. Unfortunately, these pneumatic ventricular assist devices were complicated, and used expensive mechanical valves that were prone to failure, subject to “clogging,” and that caused blood trauma or damage because of hard, metal edges and the like.
[0005] To overcome these problems, other types of ventricular assist devices were developed, including axial flow pumps for temporary insertion directly into the heart, and centrifugal pumps. The former are based on the Archymides' Principle, where a rod with helical blades is rotated inside a tube to displace liquid. In use, a catheter-mounted, miniature axial flow pump is appropriately positioned inside the heart, and is caused to operate via some sort of external magnetic drive or other appropriate mechanism. With high enough RPM's, a significant amount of blood can be pumped. In the case of centrifugal pumps, blood is moved by the action of a rapidly rotating impeller (spinning cone or the like), which causes the blood to accelerate out an exit. Both of these categories of ventricular assist devices are generally reliable and implantable, but are very expensive, not particularly durable, and are not useful in situations where a patient needs a true pulsating blood supply. Specifically, axial and centrifugal pumps are typically left on in a continuous operation mode, where a steady stream of blood is supplied on a continuous basis, as opposed to the natural rhythm of the heart, which acts on a periodic, pulse-producing basis. In addition, such pumps are still largely in the developmental or trial phase.
[0006] Accordingly, a primary object of the present invention is to provide a pneumatic ventricular assist device that offers the advantages of pneumatic operation without the drawbacks associated with prior pneumatic devices.
SUMMARY
[0007] A pneumatic ventricular assist device (“VAD”) is for use in any circulatory support application including RVAD, LAVD, or BIVAD, trans-operative, short-term or long-term, tethered implantable or extracorporeal. The VAD comprises a soft-contoured (rounded, low-profile) pumping shell and a disposable pumping unit that includes a blood sac, two one-way valves, and two tubing connectors. The pumping unit is specially designed to allow continuous and fluid movement of blood and to limit blood-contacting surfaces, and is made of a supple and elastic material such as silicone. The components can be inexpensively and reliably manufactured by injection molding. Also, the design of the VAD, according to the present invention, facilitates priming, de-bubbling, and connection to the body.
[0008] For assembly, the pumping shell is opened (it includes two halves in a clam shell-like arrangement), the pumping unit is positioned inside, and the shell is closed. The interior of the shell is complementary in shape to the pumping unit: a pumping chamber portion holds the blood sac, and two pump inlets are shaped to securely hold the valves and tubing connectors. A disposable seal rests between the two clamshell halves for sealing the connection there between.
[0009] In use, the VAD is connected to a patient's heart by way of two cannulae connected to the tubing connectors (the cannulae are connected to the heart at appropriate locations according to standard surgical practices). Then, a pneumatic drive unit is attached to an air inlet in the pumping shell by way of an air line or the like. Subsequently, the drive unit is activated to cause the blood sac to move in and out, in a gentle pumping action, by way of controlled periodic air pressure introduced into the pumping shell through the air inlet.
BRIEF DESCRIPTION OF THE DRAWINGS
[0010] These and other features, aspects, and advantages of the present invention will become better understood with respect to the following description, appended claims, and accompanying drawings, in which:
[0011] [0011]FIG. 1 is a perspective exploded view of a universal pneumatic ventricular assist device according to the present invention;
[0012] [0012]FIG. 2 is a perspective exploded view of the ventricular assist device with an assembled disposable pump assembly;
[0013] [0013]FIG. 3 is a perspective, partially exploded view of the ventricular assist device in place against a lower half of a pumping shell portion of the ventricular assist device;
[0014] [0014]FIG. 4A is a elevation cross-sectional view of a valve portion of the ventricular assist device, taken along line 4 A- 4 A in FIG. 1;
[0015] [0015]FIG. 4B is a perspective cross-sectional view of the valve portion of the ventricular assist device shown in FIG. 4A;
[0016] [0016]FIG. 5A is a plan view of a disposable pump blood sac portion of the ventricular assist device;
[0017] [0017]FIG. 5B is a cross-sectional view of the disposable blood sac taken along line 5 B- 5 B in FIG. 5A;
[0018] [0018]FIGS. 6A-6C show various elevation views of how the ventricular assist device is placed and connected for use with a patient; and
[0019] [0019]FIG. 7 is a perspective view of two of the ventricular assist devices in use extracorporeally with a patient.
DETAILED DESCRIPTION
[0020] With reference to FIGS. 1-7, a ventricular assist device (VAD) 10 includes: a reusable pumping shell 12 having a first or upper “clamshell” half 14 and a second or lower clamshell half 16 removably attachable to the first half 14 ; a disposable seal 18 that fits between the two pumping shell halves 14 , 16 ; and a disposable pumping unit 20 that includes: a disposable blood sac 22 that fits in the pumping shell 12 ; two disposable, one-way injection-molded valves 24 , 26 attached to the blood sac 22 ; and two tubing connectors 28 , 30 attached to the valves. Although the valves 24 , 26 are identical, one valve 26 is positioned to act as an inlet valve, and the other valve 24 is positioned to act as an outlet valve (i.e., blood can only flow through the valves 24 , 26 as indicated by the arrows in FIG. 3).
[0021] For assembly, the disposable pumping unit 20 is placed against the lower pumping shell half 16 , the seal 18 is positioned in place, and the upper pumping shell half 14 is placed against and connected to the lower pumping shell half 16 (by way of screws or other fasteners). In use, the ventricular assist device 10 is appropriately connected to a patient's heart by way of a ventricular (or atrial) cannula 32 and an arterial cannula 34 respectively connected to the tubing connectors 28 , 30 . Then, a pneumatic drive unit 36 is operably attached to an air inlet 38 in the ventricular assist device 10 by a pneumatic line 40 or the like (see FIG. 7). Subsequently, the drive unit 36 is activated to cause a portion of the disposable blood sac 22 to move in and out, in a gentle pumping action, by way of controlled fluctuating air pressure introduced into the pumping shell 12 through the air inlet 38 .
[0022] The pumping shell 12 is either molded or machined from a hard material that may or may not be implantable in the human body, and may or may not be reusable. The pumping shell 12 comprises the two halves 14 , 16 (generally similar to one another), which mate together like a clamshell and together define a rounded pumping chamber 42 and two generally cylindrical pump inlets 44 , 46 into the pumping chamber. As best seen in FIGS. 2 and 3, the pump inlets 44 , 46 are provided with annular contours or shoulders 37 for holding the connectors 28 , 30 (i.e., each pump shell half includes a semi-annular shoulder which, when the two halves are connected, together define an annular shoulder). In addition, the lower shell half 16 includes the air inlet 38 , which is a small hole or channel extending from the outer surface of the shell through the shell wall to the pumping chamber 42 . The outer surfaces of the shell halves 14 , 16 are rounded, while the peripheral inner surfaces are flat so that the shell halves fit snugly against one another. The shape of the pumping shell is generally flat and softly contoured (i.e., rounded, ellipsoidal) so that it may be comfortably implanted.
[0023] As mentioned, the pumping shell pump inlets 44 , 46 are generally cylindrical and dimensioned to hold and support the entireties of the cylindrical valves 24 , 26 therein. As should be appreciated, having the valves enclosed within the confines of the complementary-shaped pump inlets maximizes support of the valves, thereby enhancing their performance and durability. It also reduces the likelihood of the valves becoming dislodged or loose during use.
[0024] The blood sac 22 , valves 24 , 26 , and cannulae 32 , 34 are specially designed to allow continuous and fluid motion of blood and to limit blood contacting surfaces. These components are made of a supple elastomer such as silicone that will stretch and deform to pressure gradients reducing the damage to blood cells. With reference to FIGS. 4A and 4B, the valves 24 , 26 are hinge-less and have valve leaflet portions 50 that are flexible and elastic, simulating the action of natural heart valves, and improving their reliability and durability. The valves are injection molded in four piece molds reducing the manufacturing cost compared to biological or mechanical valves. In use, blood can flow through the valves in one direction only, from the valve inlet 52 to the valve outlet 54 , i.e., in the direction of the arrows in the figures. Specifically, when the pressure is greater on the valve inlet side 52 , the valve leaflets 50 respectively flex upwards and downwards, allowing blood to pass. However, when the pressure is greater on the valve outlet side 54 , the leaflets are gently but forcibly compressed together, preventing blood from flowing back through the valve. Because the valves are each one-piece, are made from silicone (or another suitable material), and have rounded or contoured inner surfaces, they are very reliable, perform well, and minimize damage to blood. For example, as shown in FIG. 4B, note that the valve wall 53 leading up to the leaftlets 50 is rounded/sloped to minimize blood disturbance.
[0025] As indicated in FIG. 4A, the sac 22 and connectors 28 are configured to fit within the entrance and exit ends of the valves 24 , 26 and against interior, circumferential shoulders 55 provided in the valves. This produces a continuous surface between the various elements and eliminates any sharp lips or ridges in the blood flow path, reducing blood damage.
[0026] [0026]FIGS. 5A and 5B (in addition to FIGS. 1-3) show the pumping sac 22 . The pumping sac is bilaterally symmetric and includes circular/tubular inlets 70 , 72 connected to a main pumping chamber 73 . The pumping chamber 73 sports a gently rounded or circular profile, which has been found to maximize pumping effectiveness and to reduce blood trauma during the pumping action. More specifically, the pumping chamber 73 is generally shaped like a semi-flattened ellipsoid, i.e., flat, circular top and bottom walls 74 a , 74 b interconnected by a rounded sidewall 75 .
[0027] The blood sac, valves, and/or cannulae may be coated with lubricant, hydrophobic, antibacterial and/or antithrombotic coatings, including but not limited to PTFE coatings, heparin bonded coatings, fluorinated coatings, treclosan and silver compound coatings, and anti-calcification agent releasing coatings such as previously described to improve blood compatibility and non thrombogenicity.
[0028] The connectors 28 , 30 are made of a hard material (e.g., plastic, stainless steel, titanium), molded or machined, that will secure the connection between the valves 24 , 26 and the cannulae 32 , 34 . The tubing connectors 28 , 30 each include a cylindrical through-bore, a cylindrical fore-portion that fits into the valves 24 , 26 , an annular flange 76 which corresponds in shape to the pump inlet shoulders 37 , and a rear-portion dimensioned to accommodate a cannula. In use, when the pumping unit 20 is placed in the pumping shell 12 , the valves' annular flanges 76 lie against the pump inlet shoulders, securely holding the tubing connectors 28 , 30 in place and preventing their removal from the pumping shell.
[0029] The seal 18 is made of a soft elastomer like the pumping sac and valves, but will not be in contact with blood and is only used to insure an airtight fit of the pumping shell halves 14 , 16 . The disposable pumping unit 20 (blood sac, valves and connectors and seal) may be preassembled and coated as a single disposable part.
[0030] To ensure that the cannulae 32 , 34 remain securely connected to the connectors 28 , 30 , the inlet portions 44 , 46 of each pumping shell half are provided with protruding, semi-annular gripping ridges 60 (see FIG. 2). In use, when the pumping unit 20 is placed in the lower pumping shell half 16 , as shown in FIG. 3, the cannulae 32 , 34 contact the gripping ridges of the lower half 16 . Then, when the upper half 14 is placed against and connected to the lower half 16 , the gripping ridges 60 of both halves bite into and engage the cannulae, securing them in place.
[0031] The whole system has been designed to be used in a wide range of applications of circulatory support, by simply selecting the appropriate cannulae and accessories. Intended applications include short term trans-operative support (a few hours), acute and post-cardiotomy support (up to a couple of weeks), bridge to transplant (˜3-6 months), bridge to recovery (˜several years) and destination therapy (until death). The device is also designed to be used as either a right VAD (FIG. 6B), a left VAD (FIG. 6A), or for bi-ventricular use (FIG. 6C), and to be used as a tethered implant(s), paracorporealy, or extracorporealy (FIG. 7).
[0032] To install the system, first the cannulae are sewn to the atrium, ventricle or outflowing artery of the compromised side of the heart, as applicable. The cannulae are then connected to the disposable pumping unit 20 , while carefully removing any air bubbles in the system. The blood sac assembly is supple and flexible, facilitating its priming and de-bubbling. The connectors 28 , 30 are also made to be easily connected and disconnected, facilitating this procedure. Once the system has been properly purged and connected, the pumping shell 12 is locked closed over the pumping unit. The blood sac assembly is symmetrical so that it can be placed either with the inflow valve on the left or on the right, making its design more adaptable to different applications. The connectors fit inside the pumping shell so that when the latter is closed it will crimp down on the cannulae connections preventing an accidental disconnection, as mentioned above. The device can then be placed in the abdomen or outside the body and the drive unit can be activated to start pumping.
[0033] Although the ventricular assist device of the present invention has been illustrated as having a pumping shell with two separate halves 14 , 16 , the halves could be hinged together or otherwise permanently connected without departing from the spirit and scope of the invention. Also, although the pumping unit has been described as comprising separate components connected together, the pumping unit could be provided as a single unit, i.e., a unitary piece of molded silicone. This also applies to the valves 24 , 26 and connectors 28 , 30 , i.e., the connectors could be provided as part of the valves.
[0034] Although the valves 24 , 26 have been characterized as being identical and each having two leaflets, it should be appreciated that the valves 24 , 26 could have a different number of leaflets, e.g., 1 leaflet, or 3 leaflets, and the two valves 24 , 26 could be different from one another. More specifically, where operating pressures on the two valves may be different (because one is acting as an inlet valve and the other acting as an outlet valve), it may be advantageous to utilize valves with different characteristics.
[0035] Since certain changes may be made in the above-described universal pneumatic ventricular assist device, without departing from the spirit and scope of the invention herein involved, it is intended that all of the subject matter of the above description or shown in the accompanying drawings shall be interpreted merely as examples illustrating the inventive concept herein and shall not be construed as limiting the invention.
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A pneumatic ventricular assist device is designed for use in any circulatory support application including RVAD, LAVD, or BIVAD, trans-operative, short-term or long-term, tethered implantable or extracorporeal. It consists of a soft contoured pumping shell and a disposable pumping unit, which includes a pump sac, two one-way valves, and tubing connectors. The pumping unit is specially designed to allow continuous and fluid movement of blood and to limit blood-contacting surfaces, and is made of a supple and elastic material such as silicone. The components can be inexpensively and reliably manufactured by injection molding. Also, the pumping shell and pumping unit include complementary features that quickly and securely hold the pumping unit, and any attached cannulae, in place.
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This application is a divisional of U.S. patent application Ser. No. 11/912,354, filed Jul. 23, 2008, now U.S. Pat. No. 8,091,398, which was the National Stage of International Patent Application No. PCT/GB2006/001529, filed Apr. 26, 2006, which claims the foreign priority benefit of United Kingdom patent application No. GB0508393.6, filed Apr. 26, 2005, the entireties of which are all hereby incorporated herein by reference. Any disclaimer that may have occurred during the prosecution of the above-referenced application(s) is hereby expressly rescinded.
FIELD OF THE INVENTION
The present invention relates to apparatus and method for the manufacture of a spring unit for use in an upholstered article, for example, a mattress, cushion or the like.
BACKGROUND OF THE INVENTION
A spring unit for an upholstered article comprises an array of interconnected helical coil springs formed from metal wire.
The production of such a spring unit conventionally comprises three principal steps that are described below with reference to FIG. 1 .
First the wire is coiled to form the springs. In order to do this, wire 1 from a reel 2 is fed in the direction of arrow A to a coiling machine 3 to form a coiled wire 4 consisting of a continuous series of alternating left and right-handed helical coils 5 , 6 interposed with substantially straight sections of wire 7 . The coiled wire 4 is folded at appropriate intervals as it emerges from the coiling machine so that the straight sections of wire 7 are parallel to one another and adjacent left and right-handed coils 5 , 6 are arranged so that their central longitudinal axes are approximately disposed in parallel.
The folded coils 4 are fed to a linking table 8 where the adjacent right and left-handed coils are interlinked. The strings of coils 9 are periodically cut into predetermined lengths and each string 9 fed on to a storage reel 10 ready for use in the final step of the process. To form the complete spring unit, the strings of coiled wire 9 are fed from a plurality of such storage reels 10 via channels 11 defined between dividers 12 to a spring unit assembly machine 13 where the strings 9 are interconnected to form the finished spring unit. In an alternative embodiment, sets of folded coils 9 exiting a plurality of folding tables 8 may be fed directly to the spring unit assembly machine 13 via channels 11 .
The assembly machine 13 advances the strings 9 in parallel such that the coils 14 are aligned. The strings 9 are indexed by one coil width at a time to a set of transversely extending jaws 15 between which they are clamped. Successive coils 14 in the adjacent strings 9 are clamped with their longitudinal axes substantially upright. The jaws 15 effectively form a continuous helical channel into which a helical binding wire 16 is advanced. The binding wire is formed by passing uncoiled wire 17 from a reel 18 to a coiling passage 19 located to the side of the jaws 15 of the assembly machine 13 . It is rotated and axially advanced in the transverse direction of arrow B through the jaws 15 such that is passes around the wire of the adjacent strings 9 and so as to form a row 20 of bound coils 14 . The jaws 15 are then opened and the joined strings of coils 9 indexed forward in the direction of arrow A so as to locate the next coil of each string 9 within the jaws 15 whereupon the above cycle is repeated to bind the next row of coils together. The binding cycle is repeated a sufficient number of times to bind a suitable number of rows of coils together to produce a spring unit of the desired size.
One example of a method for manufacturing the strings of coils prior to the assembly machine is described in U.S. Pat. No. 5,105,642. This method is unduly complex particularly as it includes an additional folding station between the coiler and a coil interlock station. There is no detailed description of interlocking method. A problem with a coiler of this kind is that adjustment of the coil pitch is not possible without significant changes to the relative positions of the machine components.
An example of a conventional process for interlinking adjacent left and right handed coils comprises passing the coiled wire to a linking table whereupon a straight section of the wire interposed between the coiled sections is presented to a pivotable butterfly clamp which is located centrally with respect to the table. The straight section of the wire is then held in place by the butterfly clamp with the left and right handed coiled sections to either side. One of the coiled sections is then engaged by a ‘pecker arm’ which moves transverse to the longitudinal axis of the table to engage the coil and hold it in place relative to the linking table. A folding arm mounted above the table surface is then operated to pivot about a substantially upright support member and engage the free coiled section of wire on the opposite side of the butterfly clamp. Pivoting of the folding arm draws the free coiled section in an arc around the butterfly clamp towards the other coiled section which is held by the ‘pecker arm’ to interlink the two coiled sections of wire.
The process is unduly complex and requires extremely accurate control of a number of different simultaneous actions. Due to the complicated manner in which adjacent coils are interlinked, the operational efficiency of the process is severely restricted. For example, a process of this kind could typically interlink only 30 to 35 coils per minute. The apparatus required to carry out the process incorporates a number of different cammed surfaces to accurately control the movement of the various components. A problem with linking tables of this kind is that adjustment of the various components to accommodate coils of different sizes is not possible without significant changes to the relative positions of the machine components and the complicated nature of the apparatus results in reliability problems.
An example of an assembly machine is described in EP0248661. The disadvantage of this machine is that each of the pairs of jaws are opened and closed by a respective double acting pneumatic piston. Such a piston has at least one sensor so that the opening and closing of the jaws can be monitored. In operation it has been found that the machine operation is often interrupted through the malfunction of at least one sensor. The use of so many sensors increases the scope for interruption of the machine operation. Moreover, since the piston stroke time (and therefore the time required to open and close a pair of jaws) varies between pistons a sufficient time window has to be built into the timing cycle of the assembly operation in order to be sure that all of the jaws have opened or closed.
SUMMARY OF THE INVENTION
One aspect of the present invention relates to the first stage of the above manufacturing process, that is the formation of the coil springs from continuous wire.
Further aspects of the present invention relate to the second stage of the above manufacturing process, that is linking of adjacent coils of the coiled wire 4 on the coil linking table 8 to ensure that adjacent left and right-handed coils 5 , 6 are linked together in the correct orientation for the final assembly stage.
A further aspect of the present invention is directed to an assembly machine for use in the third stage of the above process.
It is an object of the various aspects of the present invention to obviate or mitigate the aforesaid, and other, disadvantages.
According to a first aspect of the present invention there is provided coil formation apparatus for manufacturing spring coils from continuous wire, the coils being arranged to be of alternating hands along the wire, the apparatus comprising a coil forming device and means for feeding the wire to the device, the device comprising a pivotally disposed body providing support for a coil radius forming wheel against which the wire bears to form an arcuate shape and a guide member defining an opening from which the coiled wire emerges, the guide member being pivotally disposed relative to the body such that it can pivot between a first position where the opening is aligned with the wire emerging from the roller so that it passes therethrough without further deformation and at least one second position where it is misaligned and bears against the wire thus imparting the deformation to the wire that gives the coil its axial pitch, the angle of pivotal movement of the guide member being controlled by an adjustable drive mechanism that comprises a rotary drive shaft driven by a servomotor in response to instructions sent by a controller, the drive shaft being connected to the guide member by a transmission linkage that converts rotary movement of the drive shaft into translational movement of a link member and converts the translational movement of the link member to pivotal movement of the guide member as the main body is pivoted, the link member comprising a connecting rod connected to a radius arm of the drive shaft by means of an adjustable connection.
Preferably the guide member is pivotal between two second positions, one to each side of the first position.
It is preferred that the adjustable connection comprises an arm to which an end of the connecting rod is pivotally connected, the position of the end of the connecting rod being adjustable by an adjustment element. The adjustment element may be a screw or the like that is rotatable in one direction to bear against the end of the connecting rod and move it radially closer to the centre of rotation of the drive shaft. Conveniently, the arm has a slot, and a fixing member passes through the end of the connecting rod and the slot so as to connect the connecting rod to the arm, the adjustment element being adapted to move the end of the rod along the slot. Preferably the adjustment element bears against the fixing member.
In a preferred embodiment the transmission linkage comprises a sliding yoke that is connected to the connecting rod and slides along a shaft on which the body is mounted for pivotal movement.
It is particularly preferred that the translational movement of the link member is converted into pivotal movement of the guide member by a cam and cam follower comprising a bar with a spiral cam groove in which a pin is received, the axial movement of the bar being restrained such that movement of the pin relative to the bar along the cam groove causes rotation of the bar and therefore pivoting movement of the guide member.
According to a second aspect of the present invention there is provided a coil interlinking process for interlinking first and second wire coils defining respective first and second coil axes, the process comprises providing the first and second coils on a supporting surface such that the first and second coil axes are orientated substantially perpendicular to a longitudinal axis of the supporting surface, actuating a first compression member to compress the first coil substantially parallel to said first coil axis to define a first clearance between the first coil and a first edge of the supporting surface, actuating a first indexing member to extend the second coil substantially parallel to said longitudinal axis passed the first coil via said first clearance, retracting the first compression member to allow the first coil to extend substantially parallel to the first coil axis across said first clearance, and retracting the first indexing member to allow the second coil to contract substantially parallel to said longitudinal axis such that the second coil engages the first coil thereby interlinking the first and second coils.
A significant advantage provided by this process is that the various steps required to interlink adjacent coils can be achieved in a stepwise fashion using simple sequential linear movements of the compression member and the indexing member. It is therefore no longer necessary to coordinate simultaneously a number of different more complex movements to interlink a pair of spring coils. The timing of the various steps involved in the inventive process is consequently much easier to control than in prior art systems. This fact, together with the removal of the need to pivot one coil with respect to the other coil to interlink them significantly increases the throughput of the interlinking operation. It has been observed that the operational efficiency of the interlinking operation can be doubled by use of the inventive process.
Preferably prior to actuation of the compression member a retaining pin is extended substantially perpendicular to the supporting surface to engage a portion of the first coil and retain the first coil in a substantially fixed longitudinal position in relation the supporting surface during compression of the first coil with the first compression member.
It is preferred that after interlinking of the first and second coils said retaining pin is retracted so as to no longer engage said portion of the first coil and indexing apparatus subsequently actuated to advance the interlinked first and second coils a predetermined distance substantially parallel to said longitudinal axis.
Conveniently the process further comprises actuating a second compression member to compress the first coil substantially parallel to said first coil axis to define a second clearance between the first coil and a second edge of the supporting surface which is opposite to said first edge, the second compression member being actuated sequentially or simultaneously with the first compression member.
After interlinking the first and second coils, the interlinked first and second coils may be heat treated. Preferably said heat treatment is carried out by passing an electric current through the first and second interlinked coils.
In a preferred embodiment of this aspect of the present invention said first and second coils are formed in a single piece of wire and most preferably said first coil is a right handed coil and said second coil is a left handed coil.
A third aspect of the present invention provides coil interlinking apparatus for interlinking first and second wire coils defining respective first and second coil axes, the apparatus comprising a supporting surface, a first compression member and a first indexing member, the supporting surface being arranged to enable the first and second coils to be provided on the supporting surface such that their first and second coil axes are orientated substantially perpendicular to a longitudinal axis of the supporting surface, the first compression member being operable to compress the first coil substantially parallel to said first coil axis to define a first clearance, the first indexing member being operable to extend the second coil substantially parallel to said longitudinal axis passed the first coil via said first clearance, the first compression member being operable to retract to allow the first coil to extend substantially parallel to the first coil axis across said first clearance, and the first indexing member being operable to allow the second coil to contract substantially parallel to said longitudinal axis such that, in use, the second coil engages the first coil thereby interlinking the first and second coils.
Preferably the supporting surface additionally comprises a second edge opposite to said first edge, and first and second side walls are provided at said first and second edges respectively, the side walls and the supporting surface together defining a channel.
In a preferred embodiment the first side wall defines a first slot extending substantially parallel to said longitudinal axis of the supporting surface, the slot being configured for receipt of a base portion of the first indexing member.
The first indexing member may comprise a coil engaging portion connected to said base portion, said coil engaging portion projecting into said channel. Conveniently the coil engaging portion of the first indexing member has an arcuate leading surface. Preferably the coil engaging portion of the first indexing member has a ramped trailing surface.
In a further preferred embodiment the support surface defines a first guide slot extending substantially perpendicular to said longitudinal axis of the supporting surface for receipt of the first compression member. The first compression member preferably has an inclined leading edge.
It is preferred that the apparatus further comprises a retaining pin which is operable to extend substantially perpendicular to the supporting surface to engage a portion of the first coil and retain the first coil in a substantially fixed longitudinal position in relation the supporting surface during compression of the first coil with the first compression member.
The apparatus may further comprise indexing apparatus operable to advance the interlinked first and second coils a predetermined distance substantially parallel to said longitudinal axis.
Conveniently heat treatment means may be provided to heat treat the interlinked first and second coils and said heat treatment means preferably comprises a pair of electrodes configured to pass an electric current through the first and second interlinked coils.
A fourth aspect of the present invention provides apparatus for manufacturing a spring unit for a mattress or the like, the spring unit comprising a plurality of strings of spring coils, each string arranged so that the coils are disposed in a row in a side by side relationship, the apparatus comprising an inlet unit to which the strings of coils are fed, an indexing device and a binding station by which the plurality of strings are bound together by a helical binding wire, the binding station comprising at least one pair of jaws movable between open and closed positions, the jaws combining in said closed position to define a helical passage through which the helical binding wire is direction so as to bind adjacent strings of coils together, the jaw pairs each comprising a first fixed jaw and a pivotal second jaw, the pivotal second jaw being pivoted by a cam and linkage assembly that is operated by a rotary drive shaft.
Preferably the cam is an eccentric cam.
Preferably there are a plurality of jaw pairs arranged side by side, each pair having its own eccentric cam and linkage assembly, the assemblies being operated by a common rotary drive shaft.
In a preferred embodiment of this aspect of the present invention the linkage assembly comprises a lever arm that is pivotally mounted in a support and is pivotally moveable by the eccentric cam, the lever arm being connected to the pivotal second jaw. The lever arm may be connected to a pivoting arm via a link member, the pivotal second jaw being mounted on the pivoting arm. Conveniently, the jaws may be mounted in a body, the lever arm and pivoting arm being pivotally mounted to the body. The lever arm and pivoting arm are preferably pivotally mounted on shafts supported by the body, and it is preferred that the body has a pair of spaced side walls and the lever arm is pivotally disposed between the side walls.
The rotary drive shaft is preferably driven by a servomotor, which may be connected to the drive shaft via a torque limiter device. Conveniently, the torque limiter device is provided in a gearbox.
It is particularly preferred that the jaw pairs are arranged into two sets to enable simultaneous binding of opposite sides of the spring unit.
The jaws may be mounted in the apparatus on a support that is moveable by an actuator.
It will be appreciated that the various apparatus and methods described in this summary section, as well as elsewhere in this application, can be expressed as a large number of different combinations and subcombinations. All such useful, novel, and inventive combinations and subcombinations are contemplated herein, it being recognized that the explicit expression of each of these myriad combinations is excessive and unnecessary.
These and other features and aspects of different embodiments of the present invention will be apparent from the claims, specification, and drawings. Although various specific quantities (spatial dimensions, material, temperatures, times, force, resistance, etc.), such specific quantities are presented as examples only, and are not to be construed as limiting.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a schematic representation in plan view of a conventional spring unit production process showing the manufacturing stages that are also adopted in the present invention.
FIG. 2 is a perspective view from one side of a coiling machine in accordance with one aspect of the present invention.
FIG. 3 is a perspective view from the side of an upper part of the coiling machine.
FIG. 4 is an inset view of part of the coiling machine showing a coil pitch adjustment feature in accordance with one aspect of the present invention.
FIG. 5 is a perspective schematic overview of a linking table in accordance with an aspect of the present invention shown with a partly linked helical wire coil at a first step in a linking operation.
FIG. 6 is a perspective schematic view of a pair of indexing fingers used to index the helical wire coil of FIG. 5 across the linking table.
FIG. 7 is a perspective schematic overview of the linking table and the partly linked helical wire coil of FIG. 5 shown at a second step in the linking operation.
FIG. 8 is a perspective schematic overview of the linking table and the partly linked helical wire coil of FIG. 5 shown at a third step in the linking operation.
FIG. 9 is a perspective schematic overview of the linking table and the partly linked helical wire coil of FIG. 5 shown at a fourth step in the linking operation.
FIG. 10 is a perspective schematic overview of the linking table and the partly linked helical wire coil of FIG. 5 shown at a fifth step in the linking operation.
FIG. 11 is a perspective schematic overview of a downstream position of the linking table of the present invention with a partly linked helical wire coil.
FIG. 12 is a perspective schematic overview of a spring unit assembly machine in accordance with an aspect of the present invention.
FIG. 13 is a perspective schematic view of an inlet unit of the spring unit assembly machine shown in FIG. 12 .
FIG. 14 is a perspective schematic view of a detailed section of the inlet unit shown in FIG. 13 .
FIG. 15 is a perspective schematic view of a jaw pair forming part of the spring unit assembly machine of FIG. 12 , the jaw pair is shown in an open position with a helical binding wire held in an upper jaw of the jaw pair.
FIG. 16 is a perspective schematic view of the jaw pair of FIG. 15 in a closed position with a helical binding wire held between the upper and lower jaws of the jaw pair.
FIG. 17 is a perspective schematic view of the lower jaw and main body of the jaw pair of FIGS. 15 and 16 .
FIG. 18 is a perspective schematic view of the lower jaw of the jaw pair of FIGS. 15 and 16 shown with the main body removed.
FIG. 19 is a perspective schematic view of a pair of servomotors which are used to drive a pair of drive shafts operably connected to upper and lower pairs of jaws.
FIG. 20 is a perspective schematic view of a motor used to drive a shaft which is used to raise and lower the upper jaw of each jaw pair for servicing and maintenance.
DESCRIPTION OF THE PREFERRED EMBODIMENT
For the purposes of promoting an understanding of the principles of the invention, reference will now be made to the embodiments illustrated in the drawings and specific language will be used to describe the same. It will nevertheless be understood that no limitation of the scope of the invention is thereby intended, such alterations and further modifications in the illustrated device, and such further applications of the principles of the invention as illustrated therein being contemplated as would normally occur to one skilled in the art to which the invention relates.
Referring now to FIGS. 1 to 4 , for the sake of simplicity only one spring coiling machine is shown in the figures. However, it is to be understood that two or more machines may be arranged in parallel. In such an arrangement all the coiling machines are identical and driven by a common drive mechanism such that they operate synchronously.
Each coiling machine 3 comprises an inlet wire feeder (hidden) that takes wire 1 continuously from the reel 2 and advances it in a direction along the longitudinal axis of the wire to a coiling head 30 that forms the wire into the helical coils 5 , 6 . The radius of the coils 5 , 6 and their pitch (i.e. the axial distance between identical points on adjacent loops of a coil) is governed by the operation of the coiling head 30 .
The head 30 comprises a main body 31 of generally rectangular outline that is fixed on a vertical rotary shaft 32 and supports a forming roller 33 that is disposed in the path of the incoming wire 1 (not shown in FIGS. 2 to 4 ). The roller has a peripheral groove 34 in which the wire is received and serves to deflect the wire, as it egresses from the main body 31 , into an arcuate form. The main body has a cut out recess 35 that pivotally supports a pair of parallel spaced guide plates 36 between which the arcuate wire passes. The recess 35 is sized in a vertical direction so as to prevent the plates 36 from moving vertically relative to the main body 31 . The axial dimension of the spring coils 5 , 6 is imparted by pivoting movement of the guide plates 36 relative to the main body 35 . The angle that the guide plates 36 subtend to the plane occupied by the main body 35 determines the pitch of the coil 5 , 6 and therefore the height h of each spring coil. When the guide plates 36 are substantially aligned with the plane of the main body 35 this represents the datum position and the wire is not deflected in axial direction (of the coils). If the plates 36 are disposed at a negative angle to the datum position the wire is deformed into a left hand coil, whereas if they are at a positive angle the wire is deformed into a right hand coil. In operation the plates 36 , are driven to pivot according to a complex algorithm so as to define the pitch of the coil 5 , 6 at any one time. At the same time the position of the roller 33 relative to the wire 1 can be varied by a known mechanism so as to set the radius of the emerging coil of the wire at any point in time. For example, in between the left and right hand coils 5 , 6 the straight length of wire 7 is produced by virtue of the roller 33 being spaced from the wire and therefore not imparting any deflecting force thereon. It will thus be appreciated that the shape of any given coil 5 , 6 is determined by the relative movement of the guide plates 36 and the roller 33 with respect to the main body 31 of the coiling head 30 .
The various movements of the components of the coiling head 30 are controlled by linkages that are driven by rotary drive shafts 37 38 , which, in turn, are driven by computer-controlled servomotors (not shown). A control computer or processor (not shown) executes a software instruction set to govern the rotation of the output shafts of the servomotors and this is translated into the fine control of the movements of the drive shafts 37 , 38 by reduction gearboxes (not shown).
A known drive mechanism operates to rotate the rotary vertical shaft 32 and the main body 31 through a limited angle of typically 180 degrees or less between first and second limit positions. This arrangement is known and is designed to prevent entanglement of the continuous string of coils as the coiler head 30 produces alternate left hand and right hand coils 5 , 6 .
The rotation of a first drive shaft 37 common to both the coiling heads is used to control the position of the roller 33 so as to control the size of radius applied to the wire 1 in a known manner.
The pivoting movement of the guide plates 36 relative to the main body 31 of the coiling head 30 is governed by rotation of a second drive shaft 38 by a servomotor (via a reduction gearbox) operating in accordance with a software program executed on the control computer or processor.
The present invention is concerned with the linkage between the second drive shaft 38 and the guide plates 36 and, in particular, its adjustable nature.
Referring to FIG. 2 , a collar 39 is fixed to one end of the second drive shaft 38 and has a radially extending crank arm 40 that supports a first end 41 of a connecting rod 42 . The other end 43 of the connecting rod 42 is fixed to a yoke 44 that is slidably mounted on the vertical shaft 32 on which the main body 31 of the coiling head 30 is supported. The connecting rod 42 is pivotally connected to the crank arm 40 by means of a captive screw 45 . The crank arm 40 has an elongate slot 46 defined along its length and the first end 41 of the connecting rod 42 has an eyelet 47 whose centre is aligned with the slot 46 so that the captive screw 45 passes through both. The arrangement is such that the eyelet 47 is free to rotate on the shank of the captive screw 45 . An adjustment screw 48 is disposed in a threaded bore extending from the free end of the crank arm 40 and projects into the slot 46 so as to contact the shank of the captive screw 45 , the longitudinal axis of the adjustment screw 48 extending substantially perpendicularly to the corresponding axis of the captive screw 45 . The arms 49 of the yoke 44 embrace a sleeve 50 that is slidably supported on the vertical shaft 32 such that it can move up and down the shaft with the yoke 44 . The sleeve 50 has a radially extending arm 51 on which a cylindrical socket 52 is supported such that its longitudinal axis extends substantially parallel to the axis of the rotary vertical shaft 32 . The socket 32 has a main wall with an internally threaded boss 53 that extends in a direction substantially perpendicular to the longitudinal axis of the socket and supports a threaded bolt 54 . A cylindrical barrel cam 55 with a spiral cam groove 56 defined in its outer surface is received in the socket 32 with the bolt 54 , which serves as the cam follower, extending into the spiral cam groove 56 . The barrel cam 55 has an extension 57 that extends into the main body 31 of the coiling head 30 and its end distal to the socket 32 is connected to the bottom of the guide plates 36 . The cam extension 57 is rotatably disposed in the main body 31 and, in use, effects rotation of the guide plates 36 in response to rotational movement of the drive shaft 38 as will now be explained.
The reduction gearbox ensures that the extent of angular rotation of the drive shaft 38 is limited to less than around 90 degrees. The rotational movement of the drive shaft 38 is converted into translational vertical movement of the yoke 44 and sleeve 50 by virtue of the crank arm 40 and connecting rod 42 . The crank arm 40 rotates with the drive shaft and 38 carries with it the pivoting end 41 of the connecting rod 42 . The position of the end 41 of the connecting rod 32 along the length of the slot 46 defines the effective radius of the crank arm 40 that governs the length of travel of the yoke 44 . This translational movement is passed to the socket 52 and cam follower bolt 54 and is converted into rotation of the guide plates 36 by virtue of the engagement of the bolt 54 with the walls of the spiral groove 56 defined in the surface of the barrel cam 55 and the fact that the guide plates 36 and cam 56 are prevented from vertical movement relative to the main body 31 of the coiling head 30 .
Adjustment to the coil pitch is achieved by loosening the captive screw 45 and turning the adjustment screw 48 . If the screw 48 is turned counterclockwise it pushes the captive screw 45 to the left (as shown in FIG. 4 ) so as move the connection point and shorten the effective length of the crank arm 40 . This reduces the radius which the connecting rod 42 is orbits the drive shaft 38 and thus shortens the extent of its vertical travel and therefore the distance through which the yoke 44 , sleeve 50 and socket 32 travel. The effect of this is that the relative movement of the cam follower 54 in the spiral cam groove 56 is restricted so as to limit the amount of rotation of the barrel cam 55 and the guide plates 56 . If the adjustment screw 48 is turned in the opposite direction the crank arm 40 of the connecting rod 42 is increased so as to increase the angle of sweep of the guide plates 36 and thus increase the pitch of the coils. This adjustment feature provides for a quick and easy means for changing screw pitch rather than having to make changes to data used by the software.
Referring now to FIG. 5 , the coil linking table 8 comprises a supporting surface 101 and a pair of upwardly extending side walls 102 which together with the surface 101 define a linking channel 103 along which the wire coil 4 is fed during a linking operation in the direction of arrow A. The continuous wire coil 4 has been processed using the coiling machine 3 (shown in FIGS. 1 to 4 ) to provide the coil 4 with alternately left and right handed coiled sections 5 , 6 , each coiled section defining a respective central longitudinal coil axis 104 , 105 along which each coil is designed to be compressed in normal use. The coiling machine 3 is located an adequate distance upstream of the linking table 8 to ensure the wire coil 4 has relaxed to a sufficient degree to enable the linking operation to be carried out. The coils 5 , 6 are interposed by longer straight (i.e. uncoiled) sections of wire 7 . Each coiled section 5 , 6 is connected to adjacent longer straight sections 7 by two shorter straight sections of wire 106 , 107 , one of which is provided at each end of the coiled section 5 , 6 . The shorter straight sections of wire 106 , 107 are orientated at approximately 90° to the neighbouring longer straight sections of wire 7 to which they are connected.
The linking apparatus further comprises a pair of compression fingers 108 , 109 which are pneumatically actuated so as to be linearly moveable along a transverse axis 110 with respect to the longitudinal axis 111 of the linking channel 103 . A pair of slots 112 , 113 extending along transverse axis 110 are defined in the supporting table 101 and connect with a pair of upwardly extending slots 114 , 115 defined in the side walls 102 . The slots in the table 112 , 113 and side walls 114 , 115 are provided to facilitate movement of the compression fingers 108 , 109 along transverse axis 110 between a rest position outside of the linking channel 103 (as shown in FIG. 5 ) and an innermost clamping position within the linking channel 103 (as described below with reference to FIGS. 6 and 7 ). Each compression finger 108 , 109 is provided with an upwardly sloping leading edge 116 , 117 so that as each finger 108 , 109 moves inwardly along transverse axis 110 , the edge 116 , 117 securely engages and inwardly compresses the longer straight section of wire 7 interposed between adjacent coils 5 , 6 .
A further feature of the linking table 8 is the provision of a longitudinally extending guide slot 118 , 119 defined by each side wall 102 . A pneumatically actuated indexing hook 120 , 121 is slidably received in each guide 118 , 119 and comprises an arcuate leading surface 122 , 123 and a ramped trailing surface 124 , 125 (only one of the two hooks 120 , 121 can be seen in FIG. 5 ). Each arcuate leading surface 122 , 123 is of slightly smaller height than the length of each shorter section of wire 106 , 107 such that, when the wire coil 4 is properly arranged within the linking channel 103 , downstream movement of each hook 120 , 121 along its guide 118 , 119 securely engages the next available shorter straight section of wire 106 , 107 and advances the coil 4 in a downstream direction. Each hook 120 , 121 is provided with a ramped trailing surface 124 , 125 so that when each hook 120 , 121 moves in an upstream direction the next upstream shorter straight section of wire 106 , 107 passes up and over the ramped surface 124 , 125 of each hook 120 , 121 without being appreciably compressed or moved upstream.
Another feature of the linking table 8 is a pair of pneumatically actuated retaining pins 126 , 127 which are alternately moveable in an upright direction into and out of the linking channel 103 via an aperture 128 defined by the linking table 8 . Each pin 126 , 127 is of greater height when fully extended upwards than the height of the coils 5 , 6 when lying on the table surface 101 . The purpose of the pins 126 , 127 is to ensure that the sections of the wire coil 4 to be linked (as described below) are retained in the correct position to be engaged and compressed by the fingers 108 , 109 .
The linking table 8 further comprises a pneumatically actuated ratchet indexer 129 shown in FIG. 6 together with a section of linked wire coil 4 . The ratchet indexer 129 is received in a longitudinally extending guide channel 130 (described in more detail in relation to FIG. 11 ) so as to be slidably moveable along the longitudinal axis 111 of the linking channel 103 . The indexer is located downstream of the retaining pins 126 , 127 shown in FIG. 5 and is provided to engage and index the wire coil 4 in a downstream direction along the linking channel 103 .
The indexer 129 comprises a support 131 which defines a transverse aperture 132 for receipt of a pivot pin 133 upon which is rotatably mounted a pair of indexing fingers 134 , 135 . The fingers 134 , 135 are mounted on the pin 133 such that they can only pivot between a retracted position in which the distal ends 136 , 137 of the fingers 134 , 135 are positioned adjacent to the support 131 (not shown in FIG. 6 ) and an extended position in which the distal ends 136 , 137 of the fingers 134 , 135 are furthest from the support 131 and the fingers 134 , 135 extend downwardly (as shown in FIG. 6 ). In this way, when the indexer 129 is moved in an upstream direction and the fingers 134 , 135 engage a section of the wire coil 4 , the fingers 134 , 135 pivot upwardly towards the support 131 and pass over that section of the wire coil 4 . After passing over that section of the wire coil 4 the fingers 134 , 135 then pivot downwardly to the extended position shown in FIG. 6 . Subsequent downstream movement of indexer 129 then causes the fingers 134 , 135 to engage a section of the wire coil 4 and, by virtue of the fingers 134 , 135 being unable to rotate passed the downward direction shown in FIG. 6 , the fingers 134 , 135 advance the wire coil 4 in a downstream direction along the linking channel 103 .
A funnel (not shown) is provided at the upstream end of the linking table 8 to direct the moving wire coil 4 into the linking channel 103 in the correct orientation for linking. Furthermore, a set of electrodes (not shown) is attached to the upright side walls 102 at the downstream end of the linking table 8 to heat treat the linked wire coil 4 as it exits the linking table 8 . Heat treatment of coiled wire is known to enhance the resilience of the coils to compression. Two pairs of electrodes are provided with a pair of anodes on one side wall 102 and a pair of cathodes on the opposite side wall 102 . Each electrode is provided with a conducting metal projection which is directed into the linking channel 103 so as to be contactable by coils as they pass the electrode. The electrodes are appropriately arranged to ensure that passage of a coil completes an electric circuit between an anode and a cathode which thereby heats the coil forming part of the circuit.
The overall aim of the linking operation is to interlink each coiled section of wire 5 , 6 to the adjacent upstream and downstream coiled sections 5 , 6 in such a way that the intervening longer straight sections of wire 7 are essentially parallel to one another, which correctly orientates the various coiled and uncoiled sections of wire 6 for binding to other separate strings of coiled wire in the final step of the spring unit assembly process. References to components of the linking table 8 and portions of the wire coil 4 as being on the left hand side or the right hand side are to be considered as if the table 8 is being viewed from its downstream end.
In the following example, a right hand portion 6 a (shown shaded) of a right handed coil 6 is interlinked with a right hand portion 5 a (shown shaded) of downstream left handed coil 5 . To complete the linking operation, a left hand portion 6 b (shown shaded) of the right handed coil 6 would then be interlinked to a left hand portion 5 ′ b of an upstream left handed coil 5 ′ by repeating the process described below but in the opposite fashion, i.e. by operating the opposite member of each pair of components (e.g. compression fingers 108 , 110 , retaining pins 126 , 127 , etc).
After the wire coil 4 exits the coiling machine 3 it is passed to the surface 101 of the linking table 8 whereupon it enters the linking channel 103 . The wire coil 4 is then advanced in a downstream direction along the linking channel 103 . In FIG. 5 , a left hand section 5 b of the wire 5 has already been linked to a left hand section of the next upstream coil 6 ′ and the section 5 a is about to be linked. The linking operation will be described beginning at this point.
In FIG. 5 both compression fingers 108 , 109 are at the rest position clear of the linking channel 103 to enable the coil portion 5 a to be advanced downstream into the correct starting position as shown. The left hand retaining pin 127 is currently extended and the right hand retaining pin 126 is retracted. The next step, shown in FIG. 7 , is to actuate the right hand compression member 108 to slide inwardly through the slots 112 and 114 such that its sloping leading edge 116 engages a longer straight section 7 a of wire interposed between coil portion 5 a and a right hand portion 6 ′ a of a downstream right handed coil 6 ′. Inward movement of the compression finger 108 towards its innermost clamping position compresses the straight section 7 a inwardly away from the side wall 102 which in turn draws the coil portion 5 a inwards and slightly downwards towards the linking table surface 101 . In an alternative embodiment not shown in the accompanying figures, both compression fingers 108 , 109 can be actuated to slide inwards simultaneously to engage and compress longer straight sections 7 of the wire 4 located to both the right and left hand sides of the wire 4 at the same time. Regardless of whether the compression fingers 108 , 109 are actuated sequentially or simultaneously, the remaining steps in the interlinking operation are the same.
As shown in FIG. 8 , the compression finger 108 is actuated to slide a sufficient distance inwards so that when at its innermost clamping position, a clearance c is defined between a rear end 138 of the compression member 108 and the side wall 102 . The hook 120 is then actuated to slide along the guide 118 in a downstream direction such that its arcuate leading surface 122 engages the shorter straight section of the wire 106 a which is connected to the coil portion 6 a . The clearance c defined between the rear end 138 of the compression finger 108 and the side wall 102 is sufficiently large to enable the hook 120 carrying the straight wire section 106 a to pass through the clearance c such that coil portion 6 a is extended and finally located downstream of coil portion 5 a (not shown).
With reference to FIG. 9 , the compression finger 108 is then actuated to slide outwards and return to its rest position. In doing so, the straight section 7 a extends outwardly towards the side wall 102 and the coil portion 5 a extends outwards across the clearance c and upwards back to its initial position as in FIG. 5 . The right hand hook 120 is then actuated to slide upstream along the guide 118 thereby gradually releasing the coil portion 6 a and allowing it to contract and move back upstream until it engages the coil portion 5 a whereupon the coil portions 5 a and 6 a become interlinked with the coil portion 6 a lying to the downstream side of the coil portion 5 a . Continued upstream movement of the hook 120 returns it to its initial starting position as shown in FIG. 8 .
In FIG. 10 , the left hand retaining pin 127 retracts downwardly out of the linking channel 103 and the right hand retaining pin 126 extends upwardly into the linking channel 103 . The ratchet indexer 129 (shown in FIG. 6 ) is then actuated to slide downstream along the guide channel 130 such that the downwardly extending indexing fingers 134 , 135 engage the wire coil 4 and advance it a predetermined distance downstream so as to correctly position the left hand portion 6 b of the right handed coil 6 for interlinking with the left hand portion 5 ′ b of the next upstream left handed coil 5 ′. As mentioned above, to complete a linking operation, the above process should then be repeated but by operating the opposite member of each pair of components, e.g. the process will begin by actuation of left hand compression finger 109 and left hand hook 121 .
FIG. 11 illustrates the assembly 1 as shown schematically in FIG. 5 together with the indexer 129 as shown in FIG. 6 . As can be seen from FIG. 7 , the indexer 129 is slidably received in the guide channel 130 which is defined in a lid 139 which is hingedly connected to the side wall 102 . FIG. 11 also illustrates the interlinking of adjacent coils 5 , 6 . As can clearly be seen, coil 140 has been linked to adjacent upstream and downstream coils 141 , 142 . A right hand portion 143 of coil 140 overlaps a right hand portion 144 of downstream coil 142 and a left hand portion 145 of upstream coil 141 overlaps a left hand portion 146 of coil 140 , with all adjacent longer straight sections of wire 147 , 148 , 149 , 150 lying approximately parallel to one another.
It will be understood that numerous modifications can be made to the embodiment of the invention described above without departing from the underlying inventive concept and that these modifications are intended to be included within the scope of the invention. For example, the compression fingers can be operated alternately as described above or can be operated together. Moreover, the dimensions and relative locations of the various components can be varied to suit a given coil size and number of helical repeats in each coil. It is envisaged that the hooks, retaining pins, compression fingers and indexing fingers may be of any suitable size and shape provided each can still perform its designated function as described above. The above example employs pneumatically actuated linearly moving components which are cheap and reliable, although, any convenient actuating means can be used for any of the various components. The provision of the hinged lid carrying the indexer is optional but may be preferable in view of ensuring the safety of workers operating the machine. The heat treatment step may be carried out using any appropriate number and arrangement of electrode or, alternatively, may be carried out in an oven as in conventional processes of this kind.
The spring coil assembly machine 13 is shown in detail in FIGS. 12 to 20 and receives the strings of coils 10 from storage reels 11 ( FIG. 1 ). The machine has two floor-standing side frames 200 each with a pair of feet 201 that are fixed to the floor. The frames 200 carry an inlet unit 202 in the form of a plurality of guide channels 203 defined between spaced parallel upright plates 204 , a coil string 10 being received in each channel 203 . This inlet unit 202 is shown in more detail in FIGS. 13 and 14 . The coil strings are drawn through the inlet by an indexing device (not shown) that indexes the strings by one coil width at a time to a binding station 205 . The indexing device is of conventional construction and will not be described in detail here. The binding station 205 comprises upper and lower sets of transversely extending jaw pairs 15 that serve to clamp the coil strings 10 with their longitudinal axes substantially upright whilst the adjacent strings 10 are bound together. The jaws are described in more detail below with reference to FIGS. 15 to 18 .
The upright guide plates 204 of inlet unit 202 are slidably supported on three parallel rods 206 that extend between the side frames 200 and through apertures in the plates 203 . The position of the plates 204 on the rods 206 is slidably adjustable so that the number and size of channels 203 can be varied according to the application and size of the spring unit being produced. When the size and number of channels 203 is finalised the position of each plate 204 is fixed relative to the rods 206 by locking collars 207 disposed on each side of the plate 204 around the apertures. The collars 207 are locked in place on the rods 206 by worm screws or the like. At the base of each channel 203 the strings of coils 10 are supported for forward movement on cylindrical rollers 208 . Three such spaced rollers 208 are shown in FIG. 13 , each extending in parallel to the support rods 206 and between the side frames 200 . The outermost of the plates 204 are bent out of their parallel planes towards the side frames 200 so as to define channels 203 that flare outwardly with increasing amounts towards the side frames 200 . This allows the strings of coils 10 to be received from storage reels 11 that are laterally spaced by a distance greater than that of the inlet unit 202 . It will be appreciated that the inlet unit design is fully adjustable to accommodate the manufacture of different sizes of spring units.
The upper and lower sets of jaw pairs 15 are arranged in two lines along the width of the assembly machine 13 and each pair combine, when closed, to form a continuous helical channel into which a helical binding wire 16 is advanced. The jaws 15 are disposed such that their mouths face away from the inlet unit 202 . Each jaw pair 15 comprises an upper fixed jaw 15 a and a lower pivotal jaw 15 b , both of which are supported by a jaw body 209 that is mounted on a transverse drive shaft spanning the width of the assembly machine 13 . Upper and lower drive shafts 210 a and 210 b of hexagonal cross section are used for the upper and lower jaw sets 15 and are best seen in FIGS. 19 and 20 (in which the inlet unit guide plates 204 have been removed for clarity) where only one pair of jaws 15 ( FIG. 20 ) from the lower jaw set is shown in-situ on the shaft 210 b for clarity. As can be seen from FIGS. 15 to 17 the main body 209 has two depending side walls 211 that are spaced apart and flank a linkage 212 that operates the movable lower jaw 15 b and an upper wall 213 to which the upper jaw 15 a is fixed. The jaws 15 are shown in the open position in FIG. 15 and in the closed position in FIG. 16 . The binding wire 16 is formed by passing uncoiled wire 17 from a reel 18 to a coiling passage 19 located to the side of the jaws 15 of the assembly machine 13 in a known arrangement and as shown schematically in FIG. 1 . It is rotated and axially advanced in the transverse direction of arrow B ( FIG. 1 ) through the jaws 15 such that it passes around the wire of the adjacent strings 10 in order to bind the coil strings 10 together. The jaw sets 15 are then opened and the joined strings of coils 10 indexed forward so as to locate the next coil of each string 10 within the jaws 15 whereupon the above cycle is repeated to bind the next row of coils together. The binding cycle is repeated a sufficient number of times to bind a suitable number of rows of coils together to produce a spring unit of the desired size.
The mechanism of the lower jaw 15 b is shown in detail in FIGS. 17 and 18 with the main body 209 of the jaws 15 removed for clarity in FIG. 18 . The lower jaw 15 b is connected to the main body 209 by the linkage 212 that enables it to pivot between the open and closed positions. The linkage 212 comprises a cam follower arm 214 that is pivotally connected to the rear of each side wall 211 of the main body 209 by a shaft 215 and rests immediately below the peripheral surface of an eccentric disc cam 216 . The end of the cam follower arm 214 is connected by a link member 217 to one end of a pivoting arm 218 , the other end of which supports the lower jaw 15 b . The pivoting arm 218 pivots on a shaft 219 that is received between the side walls 211 at the front end of the main body 209 . The eccentric disc cam 216 is received between the side walls 211 between the front and rear ends of the main body 209 and is mounted on the hexagonal drive shaft 210 a , 210 b by means of a bore 220 of the same shape cross-section. The jaw 15 is shown in FIGS. 17 and 18 in between the fully open position and the closed positions. As the drive shaft 210 a,b rotates in the clockwise direction in the view of FIG. 18 the cam 216 is similarly rotated clockwise and the lever arm 214 pivots downwardly about the rear shaft 215 . This serves to pull the rear end of the pivot arm 218 downwardly so that other end and therefore the jaw 15 b moves in a upwards direction towards the upper fixed jaw 15 a to the closed position as shown in FIG. 16 .
It will thus be appreciated that all of the jaws 15 of a given jaw set can be opened and closed simultaneously by simple rotation of a drive shaft to drive the eccentric disc cams and linkages associated with each of the lower jaws. It is to be understood that the mechanism could be easily adapted to pivot the upper jaw with respect to the lower jaw. The linkage enables a relatively small movement provided by the cam to the lever arm to be translated into a larger movement of the jaw.
The drive shafts 210 a , 210 b for the upper and lower sets of jaws 15 are each driven by a servomotor 230 , 231 that is mounted on one of the side frames 200 . Each servomotor 230 , 231 is connected to the shaft 210 a , 210 b via a gear box 232 fitted with a torque limiter. This arrangement provides a safety feature in the event that one of the jaws 15 is jammed. It ensures that if the torque applied to the drive shafts 210 a , 210 b should exceed a predetermined value the drive is disconnected.
A further motor 240 is disposed below the binding station 205 and drives a shaft 241 that rotates an adjustable eccentric cam 242 which carries a frame 243 that supports the main body 209 of the jaws 15 . This arrangement enables the fixed upper jaws 15 a to be moved if necessary for maintenance or servicing purposes.
While the inventions have been illustrated and described in detail in the drawings and foregoing description, the same is to be considered as illustrative and not restrictive in character, it being understood that only the preferred embodiment has been shown and described and that all changes and modifications that come within the spirit of the invention are desired to be protected.
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Apparatus and methods for use in the manufacture of a spring unit for incorporation into an upholstered article, for example, a mattress, cushion or the like. Coil formation apparatus includes a drive shaft to control movement of a coil pitch guide member and a link member comprising a connecting rod adjustably connected to a radius arm of the drive shaft. A coil interlinking process comprises compressing a first coil to define a clearance, extending a second coil passed the first coil via the clearance, allowing the first coil to extend across the clearance, and contracting the second coil to engage the first coil thereby interlinking the first and second coils. Spring unit manufacturing apparatus comprises a plurality of jaw pairs each comprising a first fixed jaw and a pivotal second jaw, the pivotal second jaw being pivoted by a cam and linkage assembly operated by a rotary drive shaft.
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RELATED APPLICATIONS
This application is a continuation of application Ser. No. 115,678, filed Jan. 28, 1980 now abandoned.
This application is a continuation-in-part of U.S. patent application, Ser. No. 895,239, filed Apr. 10, 1978, which issued as U.S. Pat. No. 4,247,517 on Jan. 27, 1981 which is a continuation-in-part of U.S. patent application, Ser. No. 821,042, filed Aug. 1, 1977 which issued as U.S. Pat. No. 4,251,482 on Feb. 17, 1981, which is a continuation-in-part of U.S. patent application, Ser. No. 734,228, filed Oct. 20, 1976, which was abandoned in favor of continuation application, Ser. No. 923,359, filed July 10, 1978 which is now abandoned in favor of continuation application Ser. No. 144,068, filed Apr. 28, 1980, application 734,228 being a continuation-in-part of U.S. patent application, Ser. No. 703,044, filed July 6, 1976 which issued as U.S. Pat. No. 4,196,166 on Apr. 1, 1980, which is a continuation-in-part of U.S. application, Ser. No. 640,824, filed Dec. 15, 1975, which was abandoned in favor of continuation application, Ser. No. 827,992, filed Aug. 26, 1977 which issued as U.S. Pat. No. 4,149,650 on Apr. 17, 1979.
BACKGROUND OF THE INVENTION
This invention relates to an improved system for storing items while they are being sterilized, while they are being stored awaiting use, while they are in the process of being used, and after they have been used and are waiting resterilization. The invention particularly relates to a system having an improved actuator for automatically releasing a container lid at a predetermined temperature, an improved gasket for the container and an improved relief valve for the container. The system is particularly useful in connection with the sterilization and storage of medical items, such as surgical instruments.
As explained in the above-referenced patent applications, a need exists for an improved system for sterilizing surgical instruments and other medical items in that the common method of wrapping articles in sheets, sterilizing them and then storing them while still in the sheets, is an unsatisfactory approach. Scientific studies have shown that thirty percent of the packs prepared with sheets are contaminated by bacteria at the time of use. Further, instruments in such packs using sheets are contaminated with lint.
In the most recently filed patent application referred to above, articles to be sterilized are placed in a container, and the container is placed in an autoclave with the lid held open. After the articles have been sterilized, a pressure responsive actuator automatically releases the lid and allows it to fall into a closed position wherein a resilient gasket prevents further flow into the container. The actuator utilizes an expandable chamber which responds to pressure changes to produce an actuating movement. In a preferred approach, a quantity of sterilizing fluid is captured within the chamber by means of a temperature responsive valve. Although the systems disclosed in the earlier applications are valuable approaches, further improvements have been made in connection with a production version of the system.
SUMMARY OF THE INVENTION
A support plate is mounted on the periphery of a container base, and a projection or other support means on the support plate holds the lid in open position. A bellows or other suitable expandable chamber is mounted on the support plate; and at the end of the sterilizing phase of the autoclave cycle a chamber expands against the lid to force the support means away from the lid and allow it to fall onto the base. Advantageously, the support plate may be molded as a one-piece, relatively stiff plastic member, with means on its lower end for mounting on the periphery of the container base. In a preferred approach, the support plate has a pair of projections which extend beneath the edge of the lid to hold it in open position. A thin diaphragm in the form of a bellows construction is secured to the plate so that the diaphragm in combination with the plate uniquely forms the expandable chamber. Further, the support plate is provided with an inlet nipple that extends into the expandable chamber to permit steam or other sterilizing fluid to enter the chamber during the sterilizing phase of the autoclave cycle. A heat shrinkable sleeve valve element surrounds the nipple to close the chamber during the sterilizing phase to capture a volume of fluid in the chamber.
As the lid falls onto the base, it is critical that a seal be provided to prevent further flow into the container. A resilient gasket carried by the lid is formed with a lower flap having a feathered edge which engages a mating surface in the base to provide this initial seal. As a vacuum is formed in the container either by a final vacuum in an autoclave cycle or by the cooling of the residual environment in the container, the gasket is further compressed between the lid and the base. An enlarged bead on the gasket is compressed between the lid and the base to form a second seal for the container. Thus the container contents are sealed and preserved in a sterile, lint-free environment.
Because of the excellence of the seal obtained with the gasket, a vacuum is maintained in the container for an extended period of time. Consequently, to remove the lid of the container, it is necessary to release the vacuum. This is accomplished by providing a manually operated relief valve which plugs into a hole in the lid. During this operation, air rushes into the container. Since the lid is normally removed in an area which is not totally sterile, there is a potential source of contamination. To minimize this effect, the relief valve of the invention incorporates a small filter that removes dust and most other particles in the air. When the vacuum in the container is to be relieved, it is only necessary to pull on a tab attached to the valve flange to expose the valve opening and allow air to enter.
The container is constructed to withstand atmospheric pressure when a very high vacuum exists within the container. Nevertheless, with very large containers it is desirable to provide some additional supporting structure as a safety precaution. Thus, as another feature of the invention, an instrument basket positioned in the container is arranged to support the lid. Further, the basket may be provided with a cone-shaped projection extending upwardly from its bottom wall toward the container lid, or such projection may be formed on either a lid or the base and used with or without a basket. Thus, if the lid should commence to buckle due to the pressure, the support cone will distribute the load and limit the inward movement.
SUMMARY OF THE DRAWINGS
For a more thorough understanding of the invention, refer now to the following detailed description and drawings in which:
FIG. 1 is a perspective view of the overall container showing the lid of the container held in an open position;
FIG. 2 is a side elevational view of the container of FIG. 1, partially cut away;
FIG. 3 is a side elevation of the container of FIG. 2 after the lid has fallen into closed position;
FIG. 4 is a fragmentary, perspective view of one end of the container base;
FIG. 5 is a fragmentary, cross-sectional view of the container base of FIG. 4 showing the lid and gasket positioned on the base, when the other end of the lid is held in an open position;
FIG. 6 is a perspective, exploded view of the expandable chamber actuator and a fragment of the container base illustrating the manner in which the actuator is mounted on the base;
FIG. 7 is a view like FIG. 6 but with the actuator mounted on the base and the chamber expanded;
FIG. 8 is a cross-sectional view of the expandable chamber showing the expanded position of the chamber in phantom lines;
FIG. 9 is a cross-sectional view of the inlet valve of the expandable chamber showing the valve in closed position;
FIG. 10 is a fragmentary view of the container showing the actuator in side elevation on the container base and holding the lid open showing the lid, base and gasket in cross-section;
FIG. 11 is a cross-sectional view of the gasket free form;
FIG. 12 is a cross-sectional view of the gasket mounted on a portion of the lid, also shown in cross-section;
FIG. 13 is a cross-sectional view of a portion of the lid, gasket and base with the lid in closed position on the base;
FIG. 14 is a perspective view of the relief valve for the sterilizing container;
FIG. 15 is a cross-sectional view of the valve of FIG. 14 installed in an opening in the container lid; and
FIG. 15b shows the valve with a vacuum in the container;
FIG. 16 is a perspective view on the upper side of the valve of FIG. 14 showing the valve held in open position; and
FIG. 17 is a side view partially sectionalized showing a support cone in the container basket illustrating the relation between the cone, basket cover, and the container lid.
DETAILED DESCRIPTION
Referring now to FIGS. 1 and 2, there is shown a container 10 having access means or a lid 12 closing the open upper side of a base 14, with a gasket 16 carried by the lid and extending between the base and the lid. The container illustrated has a generally oval or racetrack configuration with the container lid having a somewhat dome-shape for strength purposes. Other configurations, such as circular, could also be employed. The upper portion of the lid is shaped to mate with recesses in the container base to facilitate stacking of the containers.
One end of the lid 12 is held open by an actuator 18 which is mounted on the base 14. The actuator includes a bellows-like inflatable chamber 20 which operates to release a lid at a desired point in an autoclave sterilizing cycle, allowing the lid to drop to the position shown in FIG. 3. FIG. 2 also shows a basket 22 and cover 23 within the container for holding items to be sterilized and to add support to the container when a vacuum exists in it. One suitable material for the container is polysulfone which is sold by Union Carbide Company.
The basket includes a plurality of holes 24 spaced around the lower side wall of the basket, to permit sterilizing fluid to circulate and to allow air to escape. Also provided are a plurality of drain holes (not shown) in the basket bottom wall to permit condensation to drain from the basket. Referring to FIG. 5 it may be seen that the container base 14 includes a bottom wall 14a which slopes downwardly and outwardly to a shoulder 14b leading to a peripheral groove 15. The bottom wall 14c of the groove 15 also slopes slightly downwardly in the outward direction to insure that condensation will flow through the drain holes in the basket and drain holes 26 in the base, shown in FIG. 2. The periphery of the base includes an upwardly and outwardly sloping wall 14d terminating in a generally horizontal flange 14e.
The base is formed with protuberances 14f to help guide the lid into its proper position when it is being installed, as shown in FIG. 1, and to help prevent the lid from being improperly positioned on the base. FIG. 5 shows the condition of the gasket, lid and base on the left end of the container when the right end of the container is held in open position as shown in FIG. 1.
Referring to FIGS. 6 and 7, it may be seen that the actuator 18 includes a plate-like member 28 having on its lower end a tab 30 which snaps into a slot 32 formed in the base flange 14e on the right end of the container as shown in FIG. 1. The actuator 18 further includes a pair of projections or posts 34 which extend outwardly from the plate 28. The plate 28 is preferably formed as a one-piece plastic member formed in a single molding operation.
Referring to FIG. 10, it may be seen that the tab 30 on the plate 28 includes one or more detents 30a which require the tab 30 to be snapped into position through the slot 32 in the flange 14e. This attachment coupled with the sides of the slot 32 in the somewhat horizontal wall 31 on the plate 28 support the actuator plate in a position extending upwardly approximately as shown in somewhat cantilever fashion. As can be seen the post-like projections 34 on the support plate 28 connect to the lid 12 by extending beneath the gasket 16 on the lid. Actually, with the lid removed but with the support plate mounted on the base as shown in FIG. 10, the upper end of the support plate will move further than shown in FIG. 10 towards the lid 12. This insures that the lid is securely supported when the container is placed in an autoclave. Note from FIG. 10 that the support plate 28 extends inwardly towards the lid at its upper end as opposed to being completely vertical.
The support plate 28 provides a number of different characteristics. First, it should be sufficiently stiff and strong to support the lid and to provide the necessary reliability. In addition it should be relatively inexpensive so that it may be disposable. Molding the support plate 28 in a single operation with its multiple functions greatly contributes to this. In order to minimize the amount of material required and yet attain the necessary stiffness and flexibility, the plate may be formed with a plurality of gussets 33 extending between the horizontal wall 31 and the approximately vertical portions of the plate. Similarly, the edges of the upright portion may be thickened or ribbed to provide the necessary strength.
Referring to FIG. 8 as well as to FIG. 6, it may be seen that the expandable chamber 20 is partially formed by a portion of the support plate 28. More specifically, the upper portion of the support plate is molded with a circular recess of two different diameters. The outer portion includes a cylindrical wall 36 and an annular wall 38, which is further connected to a smaller diameter cylindrical wall 40 which is joined to a circular end wall 42. Together these walls form a cup-shaped recess.
The expandable portion of the chamber 20 is formed by separate bellows-like element 44 molded of a plastic material similar to that from which the plate 28 is molded but being of thinner cross-section and being more flexible. As can be seen the diaphragm 44 includes an outer cylindrical wall 44a connected to an annular wall 44b which mate with the walls 36 and 38 on the plate 28. These walls are joined by suitable means to form the expandible chamber 20. The diaphragm 44 further includes short cylindrical wall sections 44c, 44d and 44e with consecutively smaller diameters joined by connecting wall sections 44f and 44g. A central circular wall section 44h connected to the cylindrical wall 44e forms an end wall of the chamber. As can be seen from the phantom lines in FIG. 8, the diaphragm 44 assumes the position indicated when the chamber is fully expanded. Note that the cylindrical walls maintain their approximate configuration but are moved outwardly due to the flexibility of the connecting annular wall sections 44f and 44g.
The support plate 28 includes a tubular portion or nipple 46 which is formed integral with the wall 42 and projects into the chamber 20. The inner end of the nipple is closed but a plurality of ports 48 in the side wall of the nipple connect the chamber 20 to the space around it. The nipple 46 tapers slightly inwardly to facilitate a single molding operation for the plate 28 and the ports 48 are formed at an angle to the side wall of the nipple so that the ports may also be made during the molding operation. That is, the mold structure forming the interior of the nipple and the ports may be withdrawn from the back side of the plate 28 at the completion of a molding operation. The material forming the plate is somewhat flexible to permit such.
Positioned loosely over the nipple 46 is a cylindrical sleeve 50 made of heat-shrinkable material. Although the sleeve is relatively confined within the chamber, it may be more positively secured to the plate 42 by a small amount of adhesive on the end of the sleeve.
Referring to FIG. 11, the gasket 16 provides a critical function requiring very flexible resilient material formed in a specific design. The gasket 16 includes an upper generally cylindrical portion 16a having on its upper edge a thickened bead adding to strength. The lower end of the portion 16a is connected to the upper leg 16b with a central section which takes a generally U-shape when installed on the lid. In addition to the leg 16b, this includes an annular wall 16c and a lower leg 16d, which in its free form shape extends somewhat downwardly. The outer end of the leg 16d is thickened to form a sealing bead 16e which leads to a thin flap 16f which tapers to a feathered lower edge. Note that there is a rather acute angle 17 between the flap 16f and the back side of the bead portion 16e.
As may be seen from FIG. 12, the gasket 16 mounts on an outwardly extending flange 12a formed on the lower end of the lid 12. The outer upper surface of the flange 12a is rounded as shown in FIG. 12 while the lower outer edge of the flange 12a is generally flat to mate with the gasket leg 16d when the lid is seated as shown in FIG. 13. The juncture between the flange 12a and the remainder of the lid 12 on the inner surface of the lid is smoothly rounded as can be seen from FIG. 12. Note also that the vertical thickness of the flange 12a is slightly greater than the wall thickness at the outer extremity of the flange. As seen from FIG. 12, positioning the gasket on the lid flange causes the gasket leg 16d to move upwardly somewhat so that the walls 16b, 16c and 16d move closer to a U-shape. The gasket assumes this configuration where ever it can hang free on the lid 12. In other words, referring to FIG. 1, the gasket would assume the position shown in FIG. 12 throughout its periphery except that the gasket on the left end of the container will appear approximately as shown in FIG. 5 and the gasket on the right end of the container in the area of the support actuator 18 will be as shown in FIG. 10.
OPERATION
When the container is first placed in the autoclave, the actuator will be in the position shown in FIGS. 1 and 10 holding the lid open and the expandable chamber 20 will be in the position shown in FIG. 8. If the particular autoclave cycle being used includes one or more preliminary vacuum phases to withdraw air from the containers, no movement of the actuator will occur, since the port 48 and the valve for the inflatable chamber 20 are open and not covered by the sleeve 50. Any pressure changes within the autoclave will be automatically applied to the interior of the chamber as well. When a high temperature sterilizing fluid such as gas or steam is applied to the autoclave, the fluid flows into the interior of the container and through the open lid into the interior of the basket through the ports 24, to displace the air and sterilize the container and the basket contents. Since the gasket 16 is positioned on the lid 12 relatively loosely, it has been found that the sterilizing fluid will also effectively sterilize the lower surfaces of the lid and the surfaces of the gasket.
The sterilizing environment applied to the container will of course also enter the chamber 20 through the ports 48. The elevated temperature of the fluid will cause the sleeve-like valve element 50 to shrink and cover the ports 48, as shown in FIG. 9. The high temperature, high pressure fluid is thus captured in the chamber. No change however occurs in the volume of the chamber during the remainder of the sterilizing phase, since temperature and pressure surrounding the chamber is essentially the same as that within it. Most autoclaves have some minor variations in temperatures and pressures during the sterilizing phase but such variations are not significant enough to cause the actuator to perform its actuating function. Thus, during the entire sterilizing phase, the lid of the container remains raised on one edge from the base such that fluid can flow freely into and out of the container. It is important that the lid be raised sufficiently to permit the sterilizing fluid to circulate freely and displace the air in the container. Preferably the lid should be raised at least a third of the height of a dome-shaped lid. It is also important that the circulation holes 24 in the basket be sized and spaced to permit the sterilizing fluid to displace the air in the basket. Condensation drains from the basket 22 through the holes in the bottom, and from the container through the drain holes 26 in the container base 14.
At the completion of the sterilizing phase of the cycle, there is an immediate pressure drop. Temperature also drops but this is much more slowly. As the pressure drops in the autoclave, the expandable chamber 20 expands due to the fact that the pressure of the steam captured within the chamber is greater than the pressure surrounding it. Thus, the bellows-like diaphragm 44 of the chamber 20 will move to the configuration shown in phantom lines in FIG. 8 and shown in solid lines in FIGS. 3 and 7. Since the central wall 44th of the diaphragm 44 is engaging the outer edge of the lid or its gasket, 16, as shown in FIG. 10, the actuator plate 28 is urged to pivot in a clockwise direction into the phantom line position shown in FIG. 10, this position also being shown in FIG. 3. The actuator moves because the resistance to movement provided by cantiliver mounting arrangement is much less than that of the lid 12. Thus, as the actuator moves, its projections or posts 34 are withdrawn from beneath the lid, allowing it to fall. Note from FIG. 8, that the wall 44h of the diaphragm 44 extends beyond the tip of the projections 34 when the bellows is fully expanded. This insures that the lid will be released. With the lid released, the actuator will move back slightly somewhat towards the upper portion of the container lid, as shown in FIG. 3, but this movement is somewhat limited while the expandable chamber is still expanded.
The lid falls into the proper position on the base and the gasket 16 assumes the approximate position shown in FIG. 13. The sloping wall 14d helps guide and lid into the peripheral groove 15 and the surfaces of the groove are smoothly curved to facilitate proper positioning of the lid. Correspondingly, the extremely flexible and resilient flap 16f on the gasket insures a proper seal on a reliable basis. In a gravity-type autoclave cycle wherein there is no final vacuum phase for withdrawing residual sterilizing environment from the autoclave, a vacuum is nevertheless formed within the container as the residual environment within the container cools and condenses, and as atmospheric pressure is introduced into the autoclave surrounding the container. The pressure differential between the interior and the exterior of the container may be quite small for a period of time in some situations such that it is important that a gasket prevent flow into the container at this time and the feathered edge of the gasket performs this function. At the same time, if the pressure within the container should be temporarily greater than the pressure on the outside of the container, the gasket feathered edge will readily permit flow out of the container, thus acting like a one-way valve. As the pressure on the interior of the container drops relative to the exterior atmosphere pressure, the lid is drawn more tightly against the base thus compressing the gasket more. This causes the bead 16e of the gasket to be further compressed between the lid and the base, becoming the primary seal for the container.
If the container is utilized in an autoclave providing a final vacuum phase, the residual environment in the autoclave is quickly withdrawn and the residual environment within the container is likewise withdrawn past the feathered edge of the gasket. When atmospheric pressure is introduced into the autoclave, the feathered edge of the gasket prevents flow into the container; and a quickly produced pressure differential between the interior and exterior of the container compresses the gasket greatly so that the bead 16e seals the container more tightly. Consequently, the container contents are sealed in essentially atmosphere free sterile environment, until the contents are to be used.
When the container is removed from the autoclave, the actuator 18 may be manually removed from the slot 32 in the container base and discarded. It is convenient to have a disposable type in a hospital environment, and the economics are such that this is a very practical approach. Alternatively, the actuator could be recycled by installing a new temperature responsive value in the expandable chamber, or by employing a value of a type that would recycle automatically. As one example the nipple 46 could be made as a separate component and be removably attached to the plate, and thus could be removed to permit replacement of the value element 50 and then reinstalled. Such an approach might be most practical, if sterilization of the container and their contents is to be performed by specialists at a central location.
The container and its contents are then transported to a storage area or to the point where the contents are needed. In use, the container is typically moved to the general area of use, but the lid of the container is actually removed somewhat remote from the actual operating or other use area in that the exterior of the container is contaminated during storage. When the lid is removed, the sterile basket on the interior protects the contents from falling dirt or other particles. The basket is carried to the actual area of use, and the cover on the basket is removed to provide access to the instruments or other items within the basket. This approach provides maximum sterility.
Relief Valve
Because of the high vacuum within the container, it is impossible to remove the container lid without relieving the vacuum. For this purpose, the relief valve 60 shown in FIGS. 1, 14, 15 and 16 is provided. As seen from FIG. 1, the relief valve is located in the top wall of the lid 12; however, it should be recognized that such a valve can be placed in other locations as well. Referring to FIG. 14, the valve is made of flexible resilient material as a one-piece member except for an inner filter 62. The valve includes a generally tubular projection or plug 64 which is open on its lower end and enclosed by an enlarged resilient flange 66 on its upper or outer end. A passage 68 through the projection 64 opens to a port 70 in a side wall of the projection immediately beneath the flange 66.
In use, the projection 64 is inserted through an opening in the lid 12. This operation is performed with the rigid, metal foam filter removed. The filter 62 is then installed in the lower end of the plug portion 64 as shown in FIG. 15. This not only secures the filter within the plug extending across the passage, but also helps pull the valve in a sealed condition in combination with a ring 65 on the exterior of the plug. The normal position of the valve when the container is not vacuumized is as shown in FIG. 15 with the annular edge 66a of the flange 66 against the outer surface of the lid thus preventing flow into the container through the port 70 and passage 68.
When the container lid 12 moves to its closed position, the valve 60 prevents air flow into the container; and as a vacuum is formed within the container, the exterior pressure forces most of the lower surface of the valve flange 66 against the lid. The annular relief groove 69 in the upper surface of the flange 66 and the annular groove 67 in the lower surface adjacent the plug 64 enable the flange to flatten readily. In addition, the thin upper wall 66b of the flange covering the end of the passage 68 is drawn inwardly because of the vacuum. This provides visible indication to an observer that a vacuum condition exists in a particular container.
When the vacuum is to be released to enable the container lid to be withdrawn, a tab 74 is manually pulled to lift the edge of the flange 66 away from the lid so that air may flow into the port 70 and through the passage 68 in the valve. If desired, the tab may be hooked on a tab holder 76 as shown in FIG. 16. This may be convenient in that the filter 60 is so fine that it will take several seconds for the pressure to equalize in a large container. All of the air entering the container must of course pass through the filter 62. Consequently, even though the entering air has not been subjected to high temperature sterilization, a high percentage of the dust, lint and other particles within the air are removed as the air passes through the filter. Once the container interior and exterior equalize, the lid can be lifted off of the base to provide access to the inner gasket.
Lid Support
Although the container 10 is constructed to withstand a high vacuum, it has been found desirable to provide further mechanical support for large containers. A preferred approach for providing such support is illustrated in FIG. 17. The basket cover 23, which is supported on its periphery by the basket base 22, is dimensioned so that its upper surface mates with the lower surface of the lid 12; and normally with a container lid tightly closed on a container base, the lid would be slightly spaced from the inner basket. However, if an overstressed condition should occur, such that the lid 12 should begin to buckle, it will engage the upper surface of the basket cover 23 to be supported thereby.
Further, with particularly large containers, the lower portion of the inner basket 22 is provided with an upwardly extending cone-shaped projection 78 that terminates near the cover 23 of the basket. The periphery of the basket cover 23 rests on the basket base 22, but it also engages or comes close to engaging the upper end of the support cone. The container lid 12 is formed with recesses that are complementarily receives in the basket cover. Thus in the overstressed situation the basket cover will reset upon the upper end of the support cone 78 on the basket base, thus preventing collapse of the lid. Of course, a suitable support may be provided as a separated element, or attached to either the container lid or base, and used without a basket; or used with a modified basket which would fit with a support.
The operation of two different autoclave cycles is briefly discussed above. It is believed that this is sufficient for purposes of understanding the invention. However, if further information is desired, reference may be had to the surface mentioned U.S. patent application Ser. No. 895,239 or Ser. No. 821,042, both of which discuss such cycles in greater details and include a time, temperature and pressure graph of such operations.
Although the container is primarily designed for use with a steam or gas autoclave sterilizing cycle, it should be understood that it is also very useful with other sterilizing techniques. With microwave sterilizing, the container lid may be positioned on the container base in a lightly closed condition. As the contents are heated, any pressure increase within the container may vent from the container past the flexible gasket. When the container cools, a vacuum will be formed in the container, automatically pulling the lid more tightly closed on the container base.
With radiation sterilizing, which does not rely on heat, the container lid is placed on the base in a lightly closed position, and the container is then subjected to a vacuum to withdraw air from the container past the flexible gasket. When pressure around the container is again allowed to increase, the lid will be tightly compressed on the base, since the gasket will prevent a pressure increase in the container. The container is then subjected to radiation, leaving the container contents sterilized and sealed in an essentially atmosphere free environment.
The container may be used for a wide variety of items in addition to surgical instruments. If it is used solely for towels, bandages, and other such somewhat bulky items, it may be convenient to invert the container so that the lid becomes the base, and not use the basket. The side walls of the inverted lid will hold items like towels more easily than will a flat base. The expandable chamber actuator would function in the same manner as described above. Once the container is closed, it could of course be returned to original position for storage and ease of handling. In the inverted position there would be no provision for drainage with the container illustrated; but there would be no drainage with towels. If desired the relief valve in the inverted lid may be modified to be open during the sterilizing phase and then automatically closed in response to temperature. Such a valve is described in the above application, Ser. No. 923,359. In addition to being a drain for condensate, a valve of this type would more importantly allow air to drain from the container as the steam or other sterilizing fluid is applied.
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A container lid (12) is held open by a support plate (18) carrying a chamber (20) which expands at a predetermined point in a sterilizing cycle to react against the lid, moving the plate outwardly to permit the lid to drop onto the container base. A resilient gasket (16) prevents fluid flow into the container after the lid is fallen, but permits fluid flow outwardly past the gasket when interior pressure exceeds exterior pressure. When the container is to be opened, a relief valve (60) relieves the vacuum within the container and filters air entering the container at that time.
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BACKGROUND OF THE INVENTION
[0001] 1. Field of the Invention
[0002] The present invention falls into the field of the postpress processing of printed products and relates to a method for the optical detection of irregularities during the postpress processing of flat print shop products according to the preamble of patent claim 1 , and also to an apparatus for the optical detection of irregularities during the postpress processing of flat print shop products according to the preamble of patent claim 12 .
[0003] 2. Discussion of Related Art
[0004] US 2006/0147092 A1 discloses the fact that, during the processing of flat print shop products, optical registration systems are employed in order to be able to meet the continuously increasing demands on quality. Here, the print shop products are led by a conveying means past at least two optical sensors, which create current recordings of the print shop products. These recordings are digitized and, in an image processing unit, are compared with images from a reference state of the print shop products, these images having been recorded at various angles. A signal is generated depending on the result of the image comparison.
[0005] US 2005/0105766 A1 discloses a method for the identification of individual letters and letters sticking to one another in the specialist area of mail processing. In this case, an optical sensor registers a current image with a single letter or a plurality of letters sticking to one another, which in each case form an object, and uses a contour extraction function to calculate the contour of the object. If the contour of the object has a substantially constant one-dimensional dimension, then this is interpreted as a single letter, while an object having a non-constant width is interpreted as a bundle of a plurality of letters sticking to one another.
[0006] EP 0685420 discloses a control method operating with optical sensors at the delivery rate of a conveying apparatus in order to detect missing components of print shop products during the production of the latter. To this end, an optical sensor assigned to each component supply in each case records a current image. An image processing unit compares each current image with corresponding stored calibration images. If a current image differs from the corresponding calibration image, a control or alarm signal is generated.
[0007] As distinct from EP 0685420, EP 0700853 A1 additionally discloses the possibility of replacing a reference image recorded for the purpose of comparison and stored in a memory with a current image. To this end, the current image registered by the optical sensor is made the reference image for future comparisons.
SUMMARY OF THE INVENTION
[0008] The common factor in all these methods is that, in practice, print shop products having defects and/or contaminants are registered by the at least one optical sensor and, during subsequent image processing, are interpreted by the detection system as defective print shop products. As a result, the postpress processing cycle is interrupted or the print shop products considered to be defective are removed before the postpress processing thereof. In the event of closer consideration, however, the print shop products considered to be defective by the detection system often prove to be defect-free or at least tolerable, for which reason they are fed back into the postpress processing cycle if possible, which is often done manually. Both variants reduce the cost-effectiveness of the postpress processing in an undesired way.
[0009] It is therefore an object of the present invention to increase the reliability of detection of actually defective print shop products.
[0010] The problem on which the invention is based for the method is solved by the features of patent claim 1 . Further embodiments are the object of the dependent patent claims 2 to 11 .
[0011] In the method according to the invention for detecting irregularities during the postpress processing of flat print shop products, the latter are led by a conveying means along a conveying path past at least one optical sensor. The at least one optical sensor generates current images which show the print shop products and at least one portion of the conveying means. These current images form actual values in an image processing unit. These actual values are compared in the image processing unit with at least one previously defined reference value, whereupon the image processing unit generates at least one signal depending on a comparison result.
[0012] In the following text, print shop products are understood to mean both individual print shop products and groups of a plurality of print shop products. Here, the print shop products each comprise at least one flat, flexible printed product or print shop product, which in turn can comprise a main product and/or at least one part product. Likewise, a print shop product or a plurality of print shop products and/or a printed product or a plurality of printed products or a combination thereof can be put into an envelope. Furthermore, the main product and/or the part product can be inserts of all types, for example a sample of goods.
[0013] During the postpress processing of print shop products, contaminants necessarily occur in the form of dust-like dirt, which originates from various sources. A first source of contamination is formed by the friction or the abrasion of elements of the conveying means such as rollers or belts and the print shop products. These are, in particular, ink residues which adhere to the conveying means (for example a conveyor belt), to the conveying element (for example to grippers) and/or to the print shop products. A second source of contamination is formed by the abrasion of adjacent print shop products which touch one another during the postpress processing, for example by their being pushed against one another and resting on one another in an overlapping formation. A further source of dirt is formed by abrasion of the apparatus, which, for example, is formed by belt elements which slide along on a guide bar. A still further source of contamination is formed by the friction or the abrasion of elements of the conveying means, for example rollers or belts, which interact with guides, curved tracks and the like, and/or contamination by lubricants, for example oil spots.
[0014] Irrespective of the cause, such dirt is deposited both on stationary and on moving parts and affects their properties, such as sliding coefficients, in a manner that is undesired and difficult to control.
[0015] Further irregularities in the sense of the present invention are formed, for example, by contamination of the conveying means in the form of lubricant or printer's ink/ink pigment residues or at least one defect of a conveying means, for example in the form of cracks, holes and/or traces of rubbing of a conveyor belt or conveying compartment. Here, the term irregularities is also understood to mean the combination of two or more such interfering factors. The method can likewise be employed when only one conveying element of a conveying means having a multiplicity of conveying elements in the recording area of the optical sensor is affected by irregularities.
[0016] The method is distinguished by the fact that, by means of registering current images which show the print shop products and at least one portion of the conveying means, changes in the conveying means as such can be detected and, during the subsequent comparison of the actual value with the reference value, can be taken into account appropriately. The image processing is carried out in real time in one embodiment. The type of irregularity is not distinguished further in the present invention. By using the method, overall fewer production interruptions and production disruptions and therefore improved cost-effectiveness of the production system can be achieved.
[0017] The method can be used flexibly, for example in order to arrange for timely maintenance of a highly contaminated conveying element of the conveying means or in order to remove contamination that is disruptive to further image processing in advance during image pre-processing, in order to improve the reliability of the identification of actually wrongly positioned and/or wrongly assembled print shop products. In the latter case, actually defective print shop products can be detected as such with increased reliability and, in a further embodiment, can be separated out from the further processing process in good time.
[0018] If, by using the method, a level of contamination of the conveying means or at least one conveying element thereof is to be monitored, then the at least one signal is used as a basis for deciding about subsequent treatment of the conveying means. This decision is made, for example, in a higher-order control system and permits the timely introduction of suitable countermeasures, for example removal of individual, highly contaminated grippers for the purpose of cleaning, before a certain minimum quality can no longer be ensured during the postpress processing or the entire processing system or part thereof has to be stopped for the purpose of cleaning.
[0019] In a further embodiment of the method, the comparison of the actual value with the at least one reference value is not carried out continuously but only periodically, for example always after ten thousand further processed print shop products. To this end, the image processing is appropriately equipped with an internal counting function or a serial number corresponding to the number of print shop products is supplied to the image processing unit. Therefore, the quantity of data can additionally be reduced.
[0020] If required, the reference value and/or the result of the comparison by the image processing unit can be transmitted to an appropriately assigned conveying element of the conveying means, for example by a writing station transmitting this information to an RFID transponder of a conveying element, for example of a gripper, assigned to or arranged in/on the conveying element.
[0021] If, during further image processing, a contour of a print shop product lying on the conveying means is to be determined by using the actual value, then a constant quality of the conveying means is necessary in order to be able to detect any contour deviations of the print shop product from a previously defined reference value. In this case, the conveying means preferably forms a high-contrast background for the print shop product. For the aforementioned reasons, however, it is not possible in practice to guarantee constant quality of the conveying means, since contamination, wear phenomena and defects can all lead to optically detectable irregularities, which are registered by the optical sensor.
[0022] A digitized image typically comprises a large number of image points (pixels). The irregularities are accordingly likewise represented by pixels. In a further method according to the invention, those pixels which represent an irregularity are excluded prior to the further image processing. The further image processing can, for example, comprise contour detection. The excluded pixels are preferably replaced by black pixels if the print shop product registered is located in front of a standardized dark background. Accordingly, the excluded pixels are preferably replaced by white pixels when the registered print shop product is located before a standardized light background. The latter has led to good results in particular during experimental use of back lighting in order to intensify contrast in the contour region of the print shop products.
[0023] Depending on the application, however, a single pixel is not sufficiently meaningful to conclude with adequate significance that there are actually irregularities of the conveying means. By using an additional condition which, for example, is formed by the presence of a sufficiently large number of pixels representing an irregularity in a contiguous, adjacent region, the detection rate of the identification of actually wrongly positioned and/or wrongly assembled print shop products during downstream image processing can additionally be increased. In one embodiment of the invention, using a significance unit, the number of pixels representing irregularities identified within a predefined image section is added up and, when an adjustable threshold value is reached, an appropriate signal is generated, which points to the presence of an actual irregularity. To this end, for example in the event of the presence of a pixel representing a potential irregularity, the actual pixel coordinates thereof are compared with the coordinates of previous pixels representing an irregularity and, given a sufficiently small margin, a marking as a region potentially having irregularities is stored in a memory. In one embodiment of the method, the memory and the significance unit are arranged in the image processing unit. Then, if a sufficiently large number of hits occur in this locally limited image section, then it is logged and marked as a region affected by irregularities. Otherwise, the region is classified as correct and treated appropriately during the downstream image processing. As a result of such an avoidance of erroneous classification of the print shop products in the subsequent image processing, for example the position detection, the cost-effectiveness can additionally be increased.
[0024] The threshold value for the assessment of the significance is advantageously lower then a deviation defined as impermissible prior to the production operation, since it defines a blind spot on the current image, the content of which is excluded from the further image processing. Otherwise, there is the risk that it is not possible to detect reliably if a component of the print shop product projects beyond a contour of the print shop product. In one application of the method, the threshold value corresponds, for example, to a region measuring 2×2 centimeters on the print shop product. In this example, the print shop product to be inspected contains only one part product. Accordingly, the part product should measure more than 2×2 centimeters, in order that, during the registration of a contrast image by the optical sensor and subsequent contour comparison with a reference image, reliable contour determination and therefore a reliable statement about a defective print shop product can be made.
[0025] Depending on the requirement, it is possible to arrange for the image processing unit to generate and/or output the signal in the event of exceeding and/or falling below a tolerance limit and/or the threshold value of the significance. In one embodiment, the tolerance limit corresponds to a maximum contour, within which a print shop product is still deemed to be correct during a contour comparison.
[0026] In one embodiment of the method, the at least one reference value is, for example, entered prior to the actual production operation, by an operator entering the reference value via a display belonging to the device for the detection and/or adaptation of irregularities during postpress processing. In a further embodiment, the at least one reference value is called up from a data library and stored in a memory assigned to the image processing unit. Depending on the embodiment, the data library contains manually entered reference values and/or reference values obtained from a setup operation and/or from the production operation. In a further embodiment, the at least one reference value represents at least one reference image, which has usually been registered by the optical sensor prior to the actual production operation.
[0027] In one embodiment of the control method, a reference image assigned to a specific conveying element forms the reference value for the comparison of all the current images of the conveying elements, for example the conveying compartments. If each conveying element of the conveying means is assigned a reference image, the precision of the classification—which is to say the detection of actual irregularities—can be improved further.
[0028] The common factor in all the control methods according to the invention for the detection of irregularities in postpress processing is that regions of the conveying means or of the at least one conveying elements that are covered by the print shop products are not registered by the optical sensor and are therefore not taken into account either by the image processing unit during the comparison with the at least one reference value. During the creation of a reference image, it is not absolutely necessary for the corresponding conveying element, for example a conveying compartment having a supporting surface, to be empty. During the registration of reference images with empty conveying elements, in particular in the case where a reference image is created for each conveying element, however, non-productive times, such as those which occur during setup operation or when accelerating the apparatus for the production operation, are ideally used for the registration of these reference images.
[0029] Many conveying means have antistatic elements, such as antistatic wires in the case of conveyor belts. The antistatic elements are used to prevent or at least to reduce a tendency to disruptive adhesion between the print shop products and the conveying means. They reduce in particular disruptive adhesion of the component of the print shop product that is in direct contact with the conveying means, such as a page or an envelope on one surface of the conveying means. In the case of wire-like antistatic elements, these form an irregularity in images of the conveying means—for example of conveying compartments—which are visible in average digitized images. In the sense of further image pre-processing in order to facilitate downstream image processing, such as position detection and/or contour detection, it is expedient depending on the requirement to remove these antistatic elements from an image registered by the optical sensor, for example a high-contrast silhouette, before this further image processing. The antistatic elements take up a certain number of pixels which, in comparison with an overall number of pixels from the entire recording area of the registered image, is comparatively small, however. Nevertheless, this certain number of pixels influences image noise in an undesired way. In tests, it was shown that such relatively small and/or thin irregularities, which lead to the comparatively small quantities of pixels, may be removed without difficulty from the current image by computation without the information content for the subsequent image processing suffering substantially thereunder. The removal of such negligible pixels is carried out within the context of smoothing. During the smoothing, coarse image structures are maintained and negligibly small irregularities are filtered out. As a result, the quantity of data from a smoothed image, given a sufficiently good image quality for the subsequent image processing, is considerably smaller than that from an un-smoothed digitized image. Ultimately, a reduced quantity of data has a positive effect on the processing speed of the following image processing. Electronic filters such as Gauss filters or median filters are recommended for the smoothing. During the application of the median function, for example, a gray value of a specific pixel is replaced by a median of the gray values from the current environment of this specific pixel.
[0030] Depending on the requirement, the smoothing function can be employed before or after the filtering out of the irregularities. In trial operation, good results were achieved if the digitized silhouettes were processed in the context of image conversion for subsequent image processing in the form of contour detection by carrying out the median function before a brightness adjustment.
[0031] The irregularities identified as actual irregularities are excluded from downstream image processing, for example edge detection. To this end, in one embodiment of the method, the actual irregularities are learned during a setup operation preceding the effective production operation. Here, all the optically detectable differences between an ideal image formed by the first silhouette and the reference image formed by the second silhouette at the same F/Y coordinates are interpreted as actual irregularities if they exceed the threshold value of the significance required therefor.
[0032] In further embodiments of the control method, the increase in the irregularities of the conveying means during the production operation is monitored continuously or periodically, depending on the requirements, for example in each case after one hundred thousand transported print shop products. If the continuous monitoring exceeds a previously defined limiting value of permissible irregularities, depending on the embodiment of the method, a passage of all the conveying elements, empty for this purpose, through the optical sensor is carried out for the purpose of recording new reference images. As a result, the new reference images replace the reference images used for the comparison up to that point. In further embodiments of the control method, silhouettes registered during the production operation replace the corresponding reference images.
[0033] The problem on which the invention for the apparatus is based is solved by the features of patent claim 12 . Further embodiments are the object of the dependent patent claims 13 and 14 .
[0034] The apparatus according to the invention for the optical control of flat print shop products has conveying means for conveying the flat print shop products, a digitizing unit and an image processing unit. The conveying means are arranged in such a way that the flat print shop products can be transported therewith along a conveying section past at least one optical sensor. The optical sensor is connected to the image processing unit via the digitizing unit. The image processing unit comprises a comparison function for comparing a digitized current image registered by the optical sensor with at least one reference value. Depending on the requirement, the reference value is stored in a memory or produced for this purpose. By using the result of the comparison, irregularities of the conveying means can be detected as such and can be taken into account appropriately during subsequent image processing. If the subsequent image processing is, for example, contour registration and a comparison with a previously defined permissible position, defective print shop products which go beyond the permissible position can be distinguished reliably from correct print shop products.
[0035] In a further embodiment of the apparatus, the image processing unit is connected to a data library.
[0036] If required, the image processing unit is connected to a communication means for the output of a signal.
BRIEF DESCRIPTION OF THE DRAWINGS
[0037] The invention will be explained below by using figures, which merely represent exemplary embodiments and in which
[0038] FIG. 1 shows a simplified illustration of a first embodiment of the apparatus according to the invention with a correctly positioned print shop product and a wrongly positioned printed product in side view;
[0039] FIG. 2 shows a simplified illustration of the apparatus shown in FIG. 1 in a view from above;
[0040] FIG. 3 shows a first silhouette which is based on a conveying element of a conveying means that is not affected by irregularities;
[0041] FIG. 4 shows a second silhouette which is based on a conveying element of a conveying means that is affected by irregularities;
[0042] FIG. 5 shows a pictorial illustration of image pre-processing of the second silhouette; and
[0043] FIG. 6 shows a pictorial illustration of further image pre-processing of the first silhouette shown in FIG. 1 .
DESCRIPTION OF PREFERRED EMBODIMENTS
[0044] FIG. 1 , viewed together with FIG. 2 , shows a detail from an apparatus 1 according to the invention, as is described in more detail in the patent application CH . . . /08 filed on the same day by the same applicant and bearing the title “Optical Position Detection”. In FIG. 1 , only one of the conveying elements 2 in the form of a conveying compartment 2 of a conveying means 4 is illustrated entirely visibly in side view. The conveying compartment 2 has a supporting surface 6 to accept at least one flat print shop product 8 from a plurality of printed products 8 and is used to transport the print shop products 8 in a conveying direction F along a conveying section 9 . The supporting surfaces 6 in the present embodiment are each formed from a textile section and are transparent or translucent. The transparency is increased by a regular perforation 10 , and therefore the supporting surfaces 6 are illustrated in simplified form by dotted lines in FIG. 1 while, in FIG. 2 , for improved clarity, they are merely illustrated perforated in a detail enlargement. A conveying compartment 2 , 2 a in the position shown in FIGS. 1 and 2 measures approximately 400 mm in the conveying direction F and approximately 500 mm transversely with respect to the conveying direction F, therefore in the direction Y. The perforation 10 is in this case formed like a perforated plate, which is to say formed with rows of holes offset in each case diagonally by 40 mm with respect to one another with respect to the conveying direction F, a representative hole 12 having a round cross section with a diameter of 8 mm.
[0045] Above the conveying means 4 , in order to register a silhouette 14 , there is arranged an optical sensor 16 which, in order to transmit at least one signal 17 , is connected to a signal line 18 for communications purposes. In trial operation, use was made of a so-called low-cost vision sensor having an M12 objective with 8 mm focal length as an optical sensor 16 . The processing of the silhouettes was in this case carried out by using an “embedded digital signal processor” of the Blackfin ADSP type with 1000MMACS (not shown), which is connected to a management system (likewise not shown) via an input/output interface (I/O interface) (likewise not shown). The image registration by the optical sensor 16 is carried out in accordance with the machine cycle rate, which is to say the delivery cycle of the conveying compartments 2 , 2 a of the conveying means 4 in the conveying direction F.
[0046] The optical sensor 16 has a specific recording area 20 , which restricts a current image in the conveying direction F and transverse direction Y.
[0047] Fitted opposite the optical sensor 16 , underneath the conveying means 4 , is a light-emitting means 24 formed by three fluorescent tubes. During trial operation, use was made of three constantly light-emitting 36 Watt fluorescent tubes with electronic ballast as light-emitting means 24 . The light-emitting means 24 forms a contrast light source for the production of silhouettes.
[0048] The conveying element/conveying compartment 2 , 2 a has in each case a supporting surface 6 which is inclined downward in the conveying direction F as seen in side view and which is bounded in the conveying direction F by wall section 26 . The inclination is advantageous, since it promotes contact between the print shop products 8 and the wall section 26 and, as a result, forms a stop for the print shop products 8 . As a result, a certain positional stability of the print shop products 8 relative to the conveying compartment is promoted. In FIGS. 1 and 2 , in each case a print shop product 8 each comprising a part product 28 , on which a second part product 30 is arranged in each case, lies on the supporting surfaces 6 of the conveying compartment 2 , 2 a. In the first conveying compartment 2 , located on the left in FIG. 2 , the part products 28 , 30 lie on the wall section 26 and form a correct print shop product 8 a. A correct print shop product 8 a is understood to be a correctly assembled print shop product which is aligned correctly with respect to the conveying compartment 2 and with respect to the part products 28 , 30 . In the second conveying compartment 2 b, located on the right in FIG. 2 , there lies a print shop product which, although assembled correctly with regard to the composition, the first part product 28 and second part product 30 thereof have been displaced with respect to each other in an undesired way, only the first part product 28 resting on the wall section 26 . Therefore, this print shop product 8 b will simply be called a defective print shop product 8 b below. Those skilled in the art will see that other defective combinations, for example a part product displaced in the transverse direction Y and/or a first and/or second part product having an irregular edge profile, etc., are also possible and can be treated accordingly.
[0049] Since, in the present case, the intention is to carry out a control of the position of the print shop products 8 a, 8 b relative to the conveying compartments 2 , 2 a, the print shop products 8 a, 8 b must be smaller than the supporting surface 6 both in the conveying direction F and in the transverse direction Y, in order that the optical sensor 16 is able to register high-contrast silhouettes representing a contour 31 of the print shop products 8 a, 8 b. In trial operation, good values were achieved with extremely large print shop products 8 to be processed in the DIN A3 format.
[0050] Prior to the actual production operation, good values were obtained in tests for reliable detection of actual irregularities on the conveying elements 2 , 2 b when the threshold value for forming a significance had preferred characteristic values, described below. Since, in the practical case, an outline or an overall contour 31 of each print shop product 8 , 8 a, 8 b forms an important criterion for a foiling system connected downstream in the conveying direction F, a tolerance limit 32 was generated on the basis of a previously determined optimal reference printed product. The tolerance limit 32 has the form of a contour 31 of a correct print shop product but, with respect to the dimensions thereof, is larger in order to tolerate slight positional deviations from an ideal position. In trial operation with print shop products in the DIN A3 format and tolerance ranges ΔF and ΔY of a few millimeters between the contour of an optimal reference print shop product and the tolerance limit 32 , good results were achieved. The size of the tolerance range ΔF and ΔY varies depending on the requirement and, for example, is defined by the requirements of a further processing station connected later, as seen downstream. For the purpose of improved understanding of the function of the threshold value for forming a significance, reference will be made below to an illustrative example of the digitized current image, of which the ΔF and ΔY tolerance range respectively measures 5 mm. This 5 mm corresponds to five pixels 34 of the current image, the threshold value having been defined over a contiguous region 36 of at least five pixels 34 and, moreover, these five pixels 34 having to be divided up into at least two rows or columns of pixels.
[0051] In a significance unit, which is arranged in an image processing unit, the number of pixels 38 representing irregularities identified within the predefined recording area 20 is added up. The irregularity is then taken into account as such during further image processing only when it exceeds the threshold value of five pixels and is not covered by the print shop product 8 .
[0052] FIG. 3 shows a first silhouette 14 , which is based on a conveying compartment of the conveying means not affected by irregularities and without a print shop product, the conveying compartment not being perforated, as distinct from the conveying compartment shown in FIGS. 1 and 2 , but merely transparent.
[0053] FIG. 4 shows a second silhouette 40 similar to the first silhouette from FIG. 3 , the conveying compartment on which the second silhouette 40 is based and which is shown as a detail, as distinct from the ideal conveying compartment, having irregularities 42 in the form of contaminants produced artificially for test purposes.
[0054] By using FIG. 5 , the mode of action of an image pre-processing system 43 in the sense of the invention will be explained. The basis used for the image pre-processing 43 is a reference image which corresponds to the second silhouette 40 shown in FIG. 4 . The current image 22 corresponds to a third silhouette, which is based on the second silhouette 40 but has a black rectangular region 44 assigned to a corresponding print shop product. In the image processing unit, the reference image forms a reference value and the current image 22 an actual value. As a result of the comparison of the actual value with the reference value, for example, a potential irregularity 46 at the coordinates F 1 , Y 1 in the current image 22 can be determined as an actual irregularity 42 of the conveying element at the coordinates F 1 , Y 1 , since this irregularity 42 has been learned in a preceding setup operation. The actual irregularity 42 , cited as representative of a large number of irregularities, was learned by the apparatus in a setup operation preceding the production operation now being explained. To this end, all the optically detectable differences between an ideal image formed by the first silhouette and the reference image 40 formed by the second silhouette at the same F/Y coordinates were interpreted as actual irregularities 42 if they exceeded the threshold value of the significance required for the purpose. In the present case, for each conveying element, an ideal image and a reference image were produced for this purpose, in order that particularly reliable detection values could be achieved. For this purpose, in trial operation the ideal images and the reference images were stored in a memory to which the image processing unit has access, together with a serial number assigned to the respective conveying compartment 2 , 2 a. Since, in the present case, the potential contaminant 46 was detected as an actual contaminant 42 , it is excluded from further image processing, such as downstream contour detection. In the present case, this is done by the actual irregularities/contaminants 42 deemed to be significant and having the coordinates F 1 , Y 1 being represented as a white, so-called blind zone 47 at the corresponding coordinates F 1 , Y 1 in an intermediate result in the form of a fourth silhouette 48 .
[0055] Further image pre-processing 50 will be explained by using FIG. 6 . In the present case, each conveying compartment has a large number of relatively thin wire-like antistatic elements 52 . Although these are detected by the optical sensor, on account of their relatively thin wire-like geometry they can be ignored with regard to a decision relating to the presence of irregularities such as dirt or cracks in the conveying compartment. Therefore, the representation of the antistatic elements 52 is understood as interference variable and not as an irregularity in the sense of the invention. In the present case, the antistatic wires 52 in an arbitrarily selected image detail 54 from the digitized image are represented by a certain number of pixels. The total quantity of pixels from each image within the entire recording area forms a total number of pixels. Since the certain number of pixels in relation to the total number of pixels contains a comparatively negligible amount of image information, the pixels showing the irregularities are removed from the current image by computation with a median function and thus excluded from subsequent image processing. Accordingly, the antistatic wires 52 are no longer contained in the fifth silhouette 56 .
[0056] In trial operation, despite the removal of the antistatic elements 52 by computation from the second silhouette 40 and from the third silhouette before the production of the fourth silhouette 48 , reliable detection of defective print shop products was achieved. The median function was likewise carried out in the image processing unit, which was assigned to the optical sensor or contained in the latter.
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Optical control method and apparatus for application in the further print processing of large-area printed products, in which the large-area printed products are moved along a conveyance path past at least one optical sensor ( 16 ). The optical sensor herein detects current images ( 22 ) which show at least sections of the conveyance means which have the irregularities ( 42 ). The current images ( 22 ) form actual values in an image processing unit, which are compared to at least one previously defined set-value. The image processing unit detects the irregularities as such and generates at least one signal, corresponding to the result of a comparison.
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INCORPORATION BY REFERENCE
The following documents are incorporated herein by reference as if fully set forth: Italian Patent Application No. RE2011A000111, filed Dec. 23, 2011.
FIELD OF INVENTION
The present invention relates to filling sterile containers with liquid or semi-dense food products such as for example fruit juices or tomato paste.
BACKGROUND
The containers are constituted by bags of synthetic material, having a rectangular or square shape, constituted by two sheets welded along the edges thereof.
One of the two sheets comprises, in proximity of one of the smaller sides, preferably on the longitudinal axis of the bag, a filling mouth closed by a removable cap.
In the following the terms container and bag will be used interchangeably.
The containers are filled in linear machines comprising, in addition to a bag advancement line, a sterile chamber, preferably parallelepiped but also possibly cylindrical, in which the mouth is housed in the bottom, through an opening in the lower wall of the chamber.
The sterile chamber comprises means for supporting the mouth in the chamber and returning it to the advancement line, means for spraying a liquid disinfectant in the vicinity of the mouth, means for removing the cap and retaining it in a position by the side of the mouth and replacing it on the mouth, as well as a vertical-axis batcher-dispenser for introducing the product into the bag.
After the bag has been filled, the cap is reapplied to the mouth, the mouth is released to outside the chamber, and the bag is laid on the advancement line.
All the above-described operations are carried out using devices that are in themselves known to the technical expert in the sector, and which will be omitted from the detailed description.
Known linear machines have the disadvantage of a low production capacity due to the difficulty of changing the format of the containers, mouths and removable caps, as well as being due to the time the bag remains in the filling station—the time being the time required for performing all of the above-described operations.
Approximately these operations require a total time of more than about 5 seconds per bag, while the time required only for filling the bag is in the order of a second or a little more, depending on the capacity of the bag.
The purpose of the present invention is to obviate all these problems with a simple and effective solution.
This aim is attained by a filling machine having the characteristics recited in the independent claim; the dependent claims relate to other characteristics of the invention which are intended to provide further advantages.
SUMMARY
In substance, the invention comprises a base on which a rotating circular platform is positioned, which platform is moved in a continuous rotary motion by suitable means.
At least two, and preferably six or more identical filling stations are located on the rotating platform, which stations are equally spaced and individually equipped with a lower rest plane for the bag, with the mouth located vertically.
Present at the periphery of the platform are: a loading apparatus of the empty bag at the first filling station in which the filling cycle begins, and an unloading apparatus of the filled bag from the filling station, located immediately downstream of the first, with reference to the movement direction of the carousel.
The loading apparatus comprises a device for transferring the empty bag from supply means of the bags, by gripping it by the mouth, and for positioning the bag in a suitable position on the rest plane of the first station.
The means for supplying empty bags are known in themselves and generally comprise a supply roll of empty bags, and means for bringing the first bag separated from the roll to the filling station.
Each filling station comprises a support bracket fastened to the platform, to which a rest plane for the bag and an overlying filling group are headed, facing externally of the platform.
Each filling unit comprises a sterile chamber as well as the means for inserting the mouth into the sterile chamber, the disinfection of the area around the mouth, the removal and displacement of the cap to the side of the mouth, insertion of the batcher-dispenser into the mouth—and the reverse operations.
The rest plane of the bag is openable downwards, such as to unload the full bag when the filling station is in the unloading position and drop it onto an underlying conveyor.
BRIEF DESCRIPTION OF THE DRAWINGS
The qualities and constructional features of the invention will become apparent from the functional and detailed description that follows, which with the aid of the attached drawings tables illustrates a preferred embodiment of invention given by way of non-limiting example.
FIG. 1 illustrates the invention in plan view.
FIG. 2 shows the section of FIG. 1 below the filling groups.
FIG. 3 is a detail of FIG. 2 in larger scale.
FIG. 4 shows the detail of FIG. 3 in perspective view.
FIG. 5 and FIG. 6 show, in perspective view and in section, the means for activating the rotating platform.
FIG. 7 shows a filling group in a perspective view, with some parts removed.
FIG. 8 is the same as FIG. 7 , with other parts removed.
FIG. 8A shows parts of FIG. 8 .
FIG. 9 shows the section along line IX-IX of FIG. 8 .
FIG. 10 shows the section along line X-X of FIG. 9 .
FIG. 11 is the view of FIG. 7 with some parts removed.
FIG. 12 illustrates section XII-XII of FIG. 11 .
FIG. 13 and FIG. 14 illustrate a perspective view of the rest plane for the bag, in the open and closed position.
FIG. 15 and FIG. 16 illustrate a different perspective view of the rest plane for the bag, with the mouth raising means in upper and lower positions.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The figures relate to a bag-supplying device 1 with a mouth 21 facing upwards. A positioning device 3 is located by a side of the device 1 , comprising an arm 31 provided with pliers 32 at an end, which move between a first position in which the pliers overlie the mouth 21 of the arriving bag, and a second position ( FIG. 2 ) in which the bag is located on the rest plane of the first station.
The pliers 32 are pneumatically activated by means that are not illustrated, and exhibit jaws that are destined to open by 180° such as not to obstruct the releasing of the mouth 21 .
The movement of the arm is powered by a brushless stepper motor.
A carousel 4 rotates downstream of the positioning device. The carousel 4 comprises ( FIGS. 5, 6 ) a fifth wheel 41 a fixed ring of which is solidly constrained to the base 42 , and the mobile ring of which is fixed to a platform 43 .
The platform 43 is moved by an electric motor 44 having an adjustable velocity on the axis of which a pinion 45 is keyed, which enmeshes in a crown wheel 46 solidly constrained to the platform 43 .
Six filling stations 5 are fixed in equidistant positions on the platform 43 .
Each filling station comprises a lower rest plane 51 for a bag, constituted by two doors 511 and 512 ( FIGS. 13 and 14 ), which can be arranged ( FIG. 13 ) coplanarly or can rotate symmetrically in a downwards direction ( FIG. 14 ).
Each door is coupled to a roller 52 , 520 on the axis of which a crank 53 , 530 is keyed, the crank heads to the double stem of a piston cylinder group 54 .
The entirety is supported by a frame 55 which is suspended by means of brackets 56 below the rotating platform 43 ( FIG. 6 ).
Pliers 57 are located on a side of the lower rest plane 51 ( FIGS. 15, 16 ), in the line of contact between the planes, at the position occupied by the mouth 21 of the bag, such as to load the mouth after the pliers 32 have brought it into position below the sterile chamber.
The pliers 57 exhibit the same characteristics as the pliers 32 .
The pliers 57 , activated by the piston cylinder group 58 supported by frame 55 , move vertically to place the mouth in the sterile chamber.
A pad 59 is located below the lower rest plane 51 , which pad 59 is activated by the cylinder piston 591 to rise above the rest plane through an opening therein, ( FIGS. 15, 16 ).
The pad 59 rises, after the bag has been filled, coming into contact with the mouth, such as to close and prevent the slightly pressurised air in the sterile chamber from entering the bag, inflating it before the removable cap is repositioned on the mouth.
For each lower rest plane 51 , the rotating platform supports a filling group 6 ( FIGS. 7-12 ) located projectingly with respect to the platform.
Each filling group 6 is supported by a bracket 7 which comprises a first vertical plate 71 provided with a pair of horizontally projecting shelves 72 .
The shelves support the sterile chamber 74 in a height-adjustable position.
The chamber supports, on each side, an inspection hatch 741 , as well as an opening 742 on the lower wall, via which the mouth enters with the respective movement organs ( FIGS. 9, 12 ).
On the side facing towards the outside of the platform, the vertical plate 71 comprises a first pair of guides 75 ( FIG. 7 ) on which a first plate 76 slides vertically, from which first plate 76 a first bracket 77 derives, which supports the end of the batching device 78 ( FIGS. 11, 12 ) which supplies the liquid.
This device comprises ( FIG. 12 ) a cylindrical body 781 that fits slidably into the sterile chamber 74 by means of a sealed coupling 79 .
The lower end of the batching device 78 exhibits an axial hole which is closed by a shutter 80 .
The shutter 80 is supported by a stem 81 superiorly protruding from the batcher, where it is supported by a shelf 85 .
The shelf 85 is derived from a second plate 83 , parallel to the first plate 76 and slidable on vertical guides 84 present on the first plate.
The sliding of the first plate 76 with respect to the guides 75 is performed by means not described in detail as they are of usual kind.
Similarly, the sliding of the second plate 83 with respect to the guides 84 is performed by means not described in detail as they are of usual kind.
The batching device 78 comprises an inlet hole 780 FIG. 11 which is connected by a tube to a swivel joint distributor that receives the liquid from a suitable reservoir that serves all six special filling devices.
The joint and the reservoir are not illustrated, as they are of known kind.
The means for removing the cap from the mouth and displacing it sideways are located internally of the sterile chamber; once the filling has been completed, the means perform the reverse operation.
These means are illustrated in figures from 7 to 10 .
The fixed plate 71 laterally and projectingly bears a radial vertical plate 710 , on which a plate 711 activated in a known way by the motor 70 slides vertically.
The plate 711 comprises a horizontal shelf 712 which supports a tubular body 713 in which a shaft 714 is inserted.
The body 713 is inserted from above into the underlying sterile chamber 74 through a sealing and guiding sleeve 715 , which is fixed to the upper wall of the sterile chamber 74 .
A horizontal flange 717 is derived from the base of the tubular body 713 , which functions as a support for the two jaws of the pliers 82 that are identical to the pliers 32 .
At the base, the shaft 714 bears a plate to which two con rods 716 attach at heads thereof, which con rods 716 activate the jaws in response to the rotations of the shaft.
The tubular body 713 is subjected to rotations about the axis thereof, and to this end it comprises an upper crank 7130 which is connected by a con rod 7131 to a servomotor 7132 located behind the plate 710 .
Similarly, the shaft 714 is subject to rotations about the axis thereof, and to this end comprises an upper crank 7140 that is connected by a con rod 7141 to a servomotor 7142 located behind the plate 710 .
The carousel 4 is powered in continuous rotary motion and the empty bags are supplied in synchrony onto the lower rest planes 51
When a lower rest plane 51 has received the empty bag from the arm 31 , the pliers 32 are opened and the bag is released onto the lower rest plane 51 .
During rotation of the lower rest plane 51 , the following activities take place.
The pliers 57 lift the filling mouth internally of the sterile chamber through the lower opening 742 therein.
In this position the cap removal device rotates by 90° and the pliers 82 are closed such as to grasp the cap.
This is accomplished by the coordinated action of the actuators 7132 and 7142 .
Thanks to the upward displacement of the plate 711 , the tubular body 713 and the shaft 714 are raised together, and so remove the cap from the mouth.
Subsequently, the tubular body 713 and the shaft 714 rotate in synchrony, still actuated by servomotors, and locate the pliers 82 , with the gripped cap, by the side of the mouth.
When the plug has been removed and placed to the side the batching device 78 supported by the bracket 77 is lowered.
This occurs by the translation of the plate 76 in a downwards direction.
The batching device sealingly rests on the mouth, and thanks to the vertical translation of the plate 83 in relation to the plate 76 , the shutter 80 , suspended by the stem 81 from the shelf 85 that is solidly constrained to the plate 83 , opens the lower hole of the batching device and enables the descent of the material into the bag which is filled.
When filling has completed, the pad 59 rises from the rest plane of the bag, and pushes the lower flap of the bag against the mouth, temporarily sealing the bag against undesired inlet into the mouth of any gases in overpressure that might be present in the sterile chamber.
During all the activities described in the sterile chamber has completed the up to close to the unloading position of the bag.
In this position the above-described devices are activated in an opposite direction, and when the filling station is in the unloading position, the pliers 57 lower and the rest plane 51 opens and releases the bag onto the belt, which removes the full bag.
It is understood, therefore, that this invention is not limited to the particular embodiments disclosed, but is intended to cover all modifications which are within the spirit and scope of the invention as defined by the appended claims; the above description; and/or shown in the attached drawings.
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An aseptic filling machine of envelope-type bags provided with a filling mouth closed by a removable cap, comprising an empty bag supply device, a discharge device configured to discharge full bags, a carousel device on which at least two filling stations are located; each filling station comprising a sterile chamber; a raising device configured to raise the mouth of the empty bag internally of the sterile chamber; an overpressure device configured to place the chamber in slight overpressure; a removal device configured to remove the cap and positioning it by a side of the mouth; and a dispenser-batcher device that is vertically slidable and configured to engage with the mouth.
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CROSS REFERENCE TO RELATED APPLICATION
[0001] This is a continuation-in-part of U.S. patent application Ser. No. 09/686,507 filed Oct. 11, 2000.
BACKGROUND OF THE INVENTION
[0002] 1. Field of the Invention
[0003] This invention relates generally to doctors of the type employed in paper making machines and the like, and is concerned in particular with an improved oscillating doctor blade holder.
[0004] 2. Description of the Prior Art
[0005] In a known doctor, as disclosed in U.S. Pat. No. 2,300,908 (Broughton), an unduly complex roller arrangement is employed to reciprocally support and guide the blade holder. In particular, mutually spaced sets of at least three rollers are required to act in concert to counteract the reactionary thrust and rotational forces exerted on the doctor blade holder during a doctoring operation.
[0006] Such arrangements are difficult to maintain, often requiring disassembly of the blade holder when roller replacement becomes necessary. The three roller arrangement is also difficult to seal and thus prone to a build up of contaminants between the roller sets. This in turn requires frequent cleaning and attention by maintenance personnel.
SUMMARY OF THE INVENTION
[0007] An objective of the present invention is to overcome the disadvantages of known oscillating doctor holders by providing a much simpler yet highly effective support arrangement.
[0008] To this end, in accordance with the present invention, a blade holder component extends longitudinally across a moving surface to be doctored. A doctor blade is carried by the blade holder component. A support component is parallel to and supports the blade holder component. A first operating means rotatably urges the doctor blade in one direction into contact with the moving surface to be doctored, resulting in the doctor blade being acted upon by a reactionary thrust force in the plane of the doctor blade, and a reactionary rotational force opposite to the direction of rotational blade application.
[0009] Guide rails on parallel tracks are provided on one of either the blade holder or support components, and rotatable rollers are spaced along the length of the other of the blade holder or support components. Each roller is in rolling contact with a guide rail on a respective one but not the other of the tracks to thereby accommodate reciprocal movement of the blade holder component relative to the support component, and at least some of the rollers coact with their respective guide rails to resist both the reactionary thrust and rotational forces acting on the doctor blade.
[0010] A second operating means reciprocally moves the blade holder component relative to the support component.
[0011] In certain preferred embodiments, the rollers have either curved or angularly profiled rims in rolling contact and in mechanical interengagement with mating curved or angularly disposed surfaces on the guide rails. The curved or angularly disposed surfaces of the guide rails may define longitudinal grooves extending in the direction of reciprocal movement of the blade holder component, with the curved or angularly profiled rims of the rollers projecting into the longitudinal grooves. Alternatively, the curved or angularly profiled rims of the rollers may define circular grooves, with the curved or angularly disposed surfaces of the guide rails projecting into the circular grooves.
[0012] The rollers may advantageously be grouped in pairs mounted on and spaced at intervals along the length of either the blade holder component or the support component. The rotational axes of the roller pairs may be offset in the direction of the length of the component on which they are mounted.
[0013] The rollers are preferably axially shiftable on their respective support shafts to thereby accommodate any minor misalignment and/or subsequent gradual wear of components.
[0014] These and other features, advantages and objectives of the present invention will now be described in greater detail with reference to the accompanying drawings, wherein:
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] [0015]FIG. 1 is a side elevational view of one embodiment of a doctoring apparatus in accordance with one embodiment of the present invention;
[0016] [0016]FIG. 2 is an enlarged view of a portion of the doctoring apparatus shown in FIG. 1, with portions broken away to show the fluid actuated tubes employed to control rotational adjustment of the doctor blade;
[0017] [0017]FIG. 3 is a sectional view taken generally along line 3 - 3 of FIG. 2;
[0018] [0018]FIG. 4 is a view similar to FIG. 2 showing an alternative embodiment of a doctoring apparatus in accordance with the present invention;
[0019] [0019]FIG. 5 diagrammatically depicts the positioning of filler blocks between successive roller sets;
[0020] [0020]FIG. 6 is a sectional view taken along line 6 - 6 of FIG. 3;
[0021] [0021]FIGS. 7 and 8 are enlarged partial sectional views of the roller and guide rail configurations shown respectively in FIGS. 2 and 4; and
[0022] FIGS. 9 - 18 are views similar to FIGS. 2 and 4 showing additional alternative embodiments in accordance with the present invention.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
[0023] With reference initially to FIGS. 1 - 3 , a doctoring apparatus in accordance with one embodiment of the present invention is shown at 2 comprising a blade holder component 4 extending longitudinally across a moving surface to be doctored, in this case the surface S of a roll 6 of the type typically found in a paper making machine. The blade holder component includes a top plate 7 coacting with underlying jaws 8 to slidably receive and hold a doctor blade 9 . The top plate 7 is mounted on brackets 10 for rotation about an axis A 1 parallel to the rotational axis A 2 of roll 6 . The brackets 10 protrude vertically from a tray-shaped bottom 12 . Fluid-actuated tubes 14 , 15 are carried on the bottom 12 and bear against the underside of the top plate 7 on opposite sides of the axis A 1 . The blade holder component is carried on a support component 16 . The support component 16 may be fixed as a part of the machine frame, or it may be keyed or otherwise fixed to a shaft 17 , the latter being supported by bearings 18 for rotation about an axis A 3 parallel to the rotational axes A 1 and A 2 .
[0024] During a doctoring operation, a first operating means applies the doctor blade 9 to the surface S with a force F 1 . The first operating means may entail pressurization of tube 15 to rotate the top plate 7 in a counterclockwise direction about axis A 1 . Alternatively, or in conjunction with pressurization of tube 15 , a crank arm 19 may be operated by a piston-cylinder unit 20 to rotate the support component 16 in a counterclockwise direction about axis A 3 . As shown diagrammatically in FIG. 2, a force F 1 applied to the roll surface by the doctor blade is opposed by an equal and opposite reactionary force F 2 . Reactionary force F 2 may be resolved into a reactionary thrust force F 2a in the plane of the doctor blade, and a reactionary rotational force F 2b tending to rotate the doctor blade and blade holder in a clockwise direction.
[0025] A longitudinally extending base 22 is secured by means of screws 24 or the like to the support component 16 . The base has a generally U-shaped cross section, with a bottom 28 and upstanding mutually opposed sides forming guide rails 30 that extend along parallel tracks and that cooperate with the bottom 28 to define a channel 32 .
[0026] Pairs of guide rollers 34 project downwardly from the bottom 12 of the blade holder component 4 into the guide channel 32 . As can best be seen in FIG. 3, the roller pairs are arranged at spaced intervals along the length of the blade holder component. The rotational axes “A 4 ” of the rollers of each pair are offset in the length direction of the guide channel 32 . As viewed in FIG. 3, the uppermost rollers 34 of each pair contact the upper rail 30 , but not the lowermost rail. By the same token, the lowermost rollers contact the lower rail, but not the upper rail.
[0027] As can best be seen in FIGS. 7 and 8, the guide rollers 34 may have angularly profiled rims 36 , each having inner and outer inclined shoulders 36 a , 36 b . The inner shoulders 36 a coact to define a peripheral groove 36 c . In the embodiment shown in FIGS. 2 and 7, the rims 36 project radially into grooves 38 in the side rails 30 of the track 22 . The grooves 38 have angularly disposed surfaces 40 . The outer shoulders 36 b of the rims 36 are in rolling contact and in mechanical interengagement with the mating angularly disposed groove surfaces 40 . The rolling contact accommodates reciprocal movement of the blade holder component 4 relative to and along the length of the track 22 , and also serves to resist the reactionary thrust force F 2a . The mechanical interengagement between the rollers and rails resists the reactionary rotational force F 2b which tends to twist the blade holder component in a clockwise direction, as indicated at 42 in FIG. 2.
[0028] Reciprocal movement may be imparted to the blade holder component 4 by a linear actuator 44 fixed to the support component 16 and joined to the blade holder component by means of a transversely extending bracket 46 . The linear actuator 44 may be positioned as shown, or at any other convenient location, e.g., at an end of and in line with the blade holder component, or inside the blade holder component between spaced sets of guide rollers.
[0029] In the embodiment shown in FIG. 2 flexible sealing aprons 48 , 50 are secured by keeper plates 52 , 54 to the blade holder component 4 . The sealing aprons frictionally contact external surfaces of the base 22 to thereby deflect external contaminants away from the guide channel 32 .
[0030] Filler blocks 56 may be secured to the underside of the blade holder component 4 by means of screws 58 or the like. The filler blocks are appropriately configured to fill the spaces between the sets of guide rollers 34 and to project into and fill the grooves 38 in the rails 30 . The filler blocks assist in excluding contaminants from the guide channel 32 that might penetrate past the sealing aprons 48 . Additionally, the filler blocks serve as guide elements which coact with the interior surfaces of the guide rails 30 when inserting and removing the blade holder component from the support component.
[0031] In the embodiment shown in FIGS. 4 and 8, the rails 30 have V-shaped ledges 60 which project into the peripheral grooves 36 c of the guide rollers. The inner shoulders 36 a of the profiled roller rims 36 coact with the inclined surfaces of the guide tracks 60 in both rolling contact and in mechanical interengagement. In much the same manner as described previously with respect to the embodiment shown in FIGS. 1 and 6, rolling contact accommodates reciprocal movement of the blade holder component relative to and along the length of the track 22 while also serving to resist the reactionary thrust force F 2a . The mechanical interengagement resists the reactionary rotational force F 2b .
[0032] It the embodiment of FIG. 4, one side of the blade holder is provided with sealing plates 62 , 64 configured to establish a sealing labyrinth. The opposite side of the blade holder has a sealing plate 66 configured to coact with external surfaces of the guide rail in providing a second sealing labyrinth. The sealing labyrinths serve to deflect and exclude contaminants from reaching the guide channel 32 . The sealing plates 62 , 64 66 may either be rigid or flexible.
[0033] FIGS. 9 - 18 illustrate other embodiments of the invention. In FIG. 9, the V-shaped ledges 60 face in opposite directions and are arranged on the doctor back component 16 between the guide rollers 34 , the latter again being carried on shafts protruding downwardly from the bottom 28 of the blade holder component 24 . In this arrangement, the rotational axes of the roller pairs need not be offset in the direction of reciprocal movement.
[0034] In FIG. 10, the V-shaped ledges 60 face inwardly and are mounted on brackets secured to the bottom 20 of the blade holder component. The guide rollers 34 are mounted on the support component between the ledges 60 .
[0035] In FIG. 11, the guide rails 30 are spaced vertically one from the other by a spacer bar 70 and are secured to the support component 16 . The V-shaped ledges 60 face inwardly. The guide rollers 34 are arranged between the V-shaped ledges 60 and are carried on shafts projecting from the depending sides of an inverted U-shaped bracket 72 secured to the bottom 20 of the blade holder component 4 . The V-shaped ledges 60 project into and coact in rolling and mechanical interengagement with the circular peripheral grooves 36 c of the guide rollers.
[0036] [0036]FIG. 12 is similar to FIG. 11, except that here the guide rails 30 have longitudinally extending grooves 38 into which project the angularly profiled rims of the guide rollers 34 .
[0037] In the arrangements shown in FIGS. 9 - 11 , the rolling contact and mechanical interengagement of the rollers 34 with the V-shaped ledges 60 operate as previously described with reference to FIGS. 4 and 8 in accommodating reciprocal movement of the blade holder component while resisting the reactionary thrust and rotational forces F 2a , F 2b . The arrangement shown in FIG. 12 serves the same functions and operates as described previously with respect to the arrangement shown in FIGS. 3 and 7.
[0038] [0038]FIG. 13 is similar to FIG. 12, except that here the guide rollers 34 ′ have cylindrical as opposed to angularly profiled peripheries which are received in flat bottomed grooves 38 ′ in the guide rails 30 . The cylindrical peripheries of the rollers 34 ′ are in rolling contact with the bottoms of the grooves 38 ′, and the roller of flanks are in mechanical interengagement with the edges of the grooves.
[0039] The arrangement shown in FIG. 14 is generally similar to that shown in FIG. 2, except that here again, the guide rollers 34 ′ have cylindrical peripheries which are received in and which coact in both rolling contact and mechanical interengagement with flat bottomed grooves 38 ′ in the guide rails 30 .
[0040] In the embodiment shown in FIGS. 15 - 17 , the tray-shaped bottom 12 of the blade holder component 4 is carried on a plate 78 , and the generally U-shaped base 28 is secured to the support component 16 . Rails 80 are secured to the sides of the base. Pairs of rollers 82 are rotatably carried on the underside of plate 78 . The rails 80 have convex sides received in concave rims of the rollers 82 .
[0041] As can best be seen in FIG. 17, the rollers 82 are preferably provided with wear resistant sleeve inserts 84 journalled for rotation on spacer sleeves 86 . The sleeves 86 are held in an abutting relationship against the underside of plate 78 by machine screws 88 and outer thrust washers 90 . Inner thrust washers 92 are interposed between the rollers 82 and the plate 78 . The axial length of the spacer sleeves 86 is greater than the combined axial thickness of the rollers 82 and inner thrust washers 92 , thus providing a space S (exaggerated for purposes of illustration) which allows the rollers to shift axially and to self align themselves with the rails 80 with which they are in rolling contact and mechanical interengagement.
[0042] As can best be seen in FIG. 16, gaps 94 are provided between the rails 80 , and filler blocks 96 occupy the spaces between the rollers 82 . The lengths of the rails 80 are sufficient to support and guide the blade holder during its reciprocal movement, and the gaps 94 allow the blade holder to be lifted laterally and removed from the base 28 for repair and maintenance purposes. This is to be contrasted to the arrangement shown, for example, in FIGS. 1 - 3 where the rails 30 extend continuously, thus requiring the blade holder to be extracted and reinserted longitudinally from the side of the machine.
[0043] As shown in FIG. 18, the shapes of the rollers 82 ′ and guide rails 80 ′ can be reversed from that shown in FIGS. 15 - 17 , i.e., the rails may have concave surfaces and the rollers may have convex rims.
[0044] In light of the foregoing, it will now be apparent to those skilled in the art that the present invention offers a number of significant advantages as compared to known prior art arrangements. For example, less than three guide rollers are required at positions spaced out over the length of the blade holder. The guide rollers coact in both rolling contact and mechanical interengagement with complimentary surfaces of adjacent guide rails. The rolling contact accommodates reciprocal movement of the blade holder component relative to the doctor back component while also resisting reactionary thrust forces. The mechanical interengagement serves to resist reactionary rotational forces. The rollers are preferably shiftable axially to provide self alignment with the rails with which they are in rolling contact and mechanical interengagement. Self alignment is further enhanced by providing the rollers and guide rails with curved contact surfaces, as shown in FIGS. 15 - 18 . Any of the various types of known blade holders may be accommodated with this arrangement. The doctor blade may be applied to the surface to be doctored with a force generated by means carried on the blade holder, e.g., the fluid actuated tubes 14 , 15 shown in FIG. 2. This makes it possible to eliminate and/or greatly simplify other costly components conventionally employed to apply and oscillate the doctor blade.
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An apparatus for doctoring a moving surface includes a blade holder component extending longitudinally across the moving surface and carrying a doctor blade. A support component is parallel to and supports the blade holder component. A first operating mechanism rotatably urges the doctor blade in a doctoring direction into contact with the moving surface, resulting in the doctor blade being acted upon by a reactionary thrust force in the plane of the doctor blade and a reactionary rotational force in a direction opposite to the doctoring direction. A pair of mutually opposed parallel guide rails are provided on one of the components, and rotatable rollers are spaced along the length of the other of the component. The rollers are in rolling contact and in mechanical interengagement with the guide rails to accommodate reciprocal movement of the blade holder component relative to the support component, and to resist both the reactionary thrust force and the reactionary rotational force acting on the doctor blade. A second operating mechanism reciprocally moves the blade holder component relative to the support component.
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The invention relates to the selective isomerization of an aliphatic mono-olefin. In accordance with another aspect, this invention relates to the selective isomerization of an aliphatic mono-olefin having an internal double bond to produce and to improve yield of the corresponding terminal olefin. A further aspect of this invention relates to a catalyst for isomerizing aliphatic mono-olefins.
BACKGROUND OF THE INVENTION
Terminal olefins, also called 1-olefins or alpha-olefins, are useful as reactants for a number of commercially important processes such as hydro-formylation, sulfonation, alkylation and acid oligomerization. In these processes they are more reactive than internal olefins. The homologous series of 1-olefins can be prepared by the thermal cracking of paraffinic hydrocarbons. However, olefins produced by catalytic cracking will generally have close to thermodynamic equilibrium composition determined by the cracking temperature for the mixture of normal and branched isomers. These isomers are frequently not easily separated. When the normal and branched isomers can be separated from each other as with butenes, then the normal olefins can be treated by the catalyst of this invention to provide a fraction that is enriched in 1-olefins.
Accordingly, an object of this invention is to provide a process for the shifting of an internal double bond in an aliphatic mono-olefin hydrocarbon to the terminal position.
Another object of this invention is to provide a catalytic process for shifting an internal bond in an aliphatic mono-olefin to the 1- or terminal position.
Another object of this invention is to provide a catalytic process for the selective isomerization or shifting of an internal unsaturation or double bond in an aliphatic mono-olefin to a terminal or 1-position.
Other aspects, objects as well as the several advantages of the invention are apparent from a study of this disclosure and the appended claims.
SUMMARY OF INVENTION
According to the present invention, the double bond of an aliphatic mono-olefin is shifted from an internal position to a terminal position by contacting said mono-olefin under isomerization conditions with a catalyst essentially comprising zirconium phosphate and at least one of chromium and thorium.
In accordance with a specific embodiment of the invention, the hydrocarbon feed stream containing internally unsaturated mono-olefins, such as butene-2, is subjected to isomerization conditions in the presence of a catalyst comprising zirconium phosphate and at least one of chromium and thorium to effect double bond isomerization and form butene-1 from butene-2.
DETAILED DESCRIPTION
Aliphatic mono-olefins having more than three carbon atoms are amenable to treatment by the catalyst of this invention, including branched chain as well as normal chain compounds. With both, the equilibrium concentration of the 1-olefin isomer increases with increasing temperature. In general, olefins being treated will have between 4 and 20 carbon atoms.
Representative examples of such olefins include pentene-2, 2-methylbutene-2, hexene-2, hexene-3, 3-methylpentene-2, heptene-2, heptene-3, octene-2, octene-3, octene-4, and the like, as well as mixtures thereof.
Especially preferred as feedstock to be treated with the catalyst of the invention are the isomeric n-butenes.
The catalyst of this invention comprises zirconium phosphate and at least one of chromium and thorium. The catalyst composition can be prepared by combining a compound of chromium or thorium, preferably in solution with a zirconium compound and a material convertible to the phosphate. One preferred procedure for preparing the catalyst is to coprecipitate a mixture of zirconium and thorium or zirconium and chromium. Typically a solution with desired metal ratios of a suitable zirconium compound and a suitable thorium or chromium compound is prepared. To this is added a solution containing a soluble source of phosphate, causing precipitation of a mixed metal phosphate composition. The precipitate is filtered, washed, then dried at 100°-150° C. for 4-16 hrs. Dried catalyst is activated by calcination at 400°-800° C. in air, for about 30 minutes to 24 hrs.
Another preferred procedure for preparing the catalyst is to impregnate zirconium phosphate with a thorium or chromium compound. Typically, this will be accomplished by employing the technique of incipient wetness. Thus, a solution of a suitable thorium or chromium compound is prepared employing about 0.5-1 mL of liquid per gram of zirconium phosphate support to be treated. The solution is added to dry zirconium phosphate support which is allowed to take up the added solution. The wetted support is then dried at 100°-150° for 4-16 hrs., the calcined in air at 400°-800° C. for about 30 minutes to 24 hrs.
Suitable zirconium, thorium, and chromium compounds employed in the preparation of the inventive catalyst include compounds soluble in the solvent employed. Suitable solvents include polar solvents such as alcohols, nitriles and water. Water is preferred.
Compounds of zirconium which are applicable include the oxychlorides, halides, nitrates, sulfates, acetates, and the like, and mixtures thereof. Exemplary compounds include zirconyl chloride, zirconyl bromide, zirconyl iodide, zirconium tetrachloride, zirconium fluoride, zirconium nitrate, and the like.
Compounds of thorium which are applicable include the halides, nitrates, sulfates, acetates, oxalates, and the like, and mixtures thereof. Exemplary compounds include thorium bromide, thorium chloride, thorium iodide, thorium nitrate, thorium picrate, thorium sulfate, and the like.
Compounds of chromium which are applicable include the halides, nitrates, sulfates, acetates, oxychlorides, and the like. Exemplary compounds include chromium bromide, chromium acetate, chromium chloride, chromium hydroxide, chromium nitrate, chromium oxalate, chromium trioxide, chromium sulfate, and the like.
Compounds which act as a source of phosphate will be of the following general structure:
M.sub.n H.sub.3-n PO.sub.4
where n=0, 1, 2, 3 and M=Li, Na, K, NH 4 , . . . Exemplary compounds include sodium orthophosphate, dihydrogen sodium orthophosphate, monohydrogen sodium orthophosphate, ammonium orthophosphate, dihydrogen ammonium phosphate, monohydrogen ammonium phosphate, phosphoric acid, and the like, and mixtures thereof.
The chromium and/or thorium incorporated in the catalyst along with zirconium phosphate will be in an amount sufficient to increase the activity and selectivity of the catalyst with respect to the production of terminal olefins. In general, the amount of chromium present in the catalyst (calculated as wt. % metal) will range from 0.1 to about 20, preferably about 1.0 to about 15, and the amount of thorium present in the catalyst (calculated as wt. % metal) will range from 1.0 to about 50, preferably about 5.0 to about 40.0, and most preferably about 20.0 to about 40.0.
In carrying out the isomerization reaction with the catalyst of the invention suitable reaction conditions or isomerization conditions can be used which effectively cause double bond isomerization of the olefins present in the feed. In general, the temperature at which isomerization is effected with this catalyst is about 300°-1100° F. Preferably the temperature will be in the range of about 500°-900° F. Reaction pressure can vary appreciably and can be subatmospheric and preferably will not exceed about 500 psig to avoid condensation reactions that ultimately lead to excessive coke formation on the catalyst.
Contact time of reactants on the catalyst expressed as liquid hourly space velocity (LHSV) can range between about 0.5 and 20. Preferably, LHSV will be between about 1 and 5.
EXAMPLE I
Catalyst Preparation
Catalyst A was prepared by adding a solution of 54.0 g (0.409 moles) of (NH 4 ) 2 HPO 4 in 400 mL water to a solution of 25 g (˜0.100 moles) ZrO(NO 3 ) 2 .4H 2 O dissolved in one liter of water. After being stirred for 5 minutes the precipitate was removed by filtration, washed with 1.5 L of hot water, dried in an oven and finally calcined in air for 5 hours at 550° C. The catalyst contained by analysis 42.7 wt % Zr and 13.0 wt % P, had 141 m 2 /g surface area, and 0.437 mL/g pore volume.
Catalyst B was prepared by adding a solution of 52.8 g (0.40 moles) of (NH 4 ) 2 HPO 4 in 400 mL of water to 124 g (0.50 moles) of Cr(C 2 H 3 O 2 ) 3 .H 2 O in 500 mL of water. There was no apparent reaction until the solution, upon being heated, formed a gel at 198° F. It was diluted with 100 mL of 1.5 M NH 4 OH but the precipitated gel remained unfilterable. Solvent was removed in a drying oven at 100° C., then the solid product was calcined in air for 2 hours at 482° C. to produce a friable material weighing 69 g. It was not further characterized.
Catalyst C was prepared by adding a solution of 30 g (0.227 moles) of (NH 4 ) 2 HPO 4 in 300 mL of water to a solution of 41 g (0.102 moles) Cr(NO 3 ) 3 .9H 2 O and 30 g (˜0.120 moles) of ZrO(NO 3 ) 2 .xH 2 O in one liter of water. The resulting precipitate was filtered washed with one liter of hot water, dried overnite in an oven at 140° C., then calcined in air for 5 hours at 550° C. The catalyst contained by analysis 15.8 wt % P, 13.5 wt % Cr, and 27.1 wt % Zr. Its surface area was 166 m 2 /g, with 0.86 mL/g pore volume.
Catalyst D was prepared by adding a solution of 4 g (0.010 moles) Cr(NO 3 ) 3 .9H 2 O in 12 mL of water to 20 g of catalyst A, then drying overnite at 140° C. and finally calcining for 4 hours at 600° C. The finished catalyst containing 2.50 wt % Cr by calculation.
Catalyst E was prepared by adding a solution of 26.6 g (0.201 moles) of (NH 4 ) 2 HPO 4 in 250 mL of water to a solution of 23 g (0.092 moles) of ZrO(NO 3 ) 2 .xH 2 O and 52.5 g (0.095 moles) of Th(NO 3 ) 4 .4 H 2 O in 700 mL of water. The precipitate was filtered, washed with water, dried in an oven, and finally calcined for 3 hours at 550° C. Chemical analyses were not made, but the catalyst was found by x-ray diffraction analysis to be amorphous.
EXAMPLE II
Runs were made with catalysts A-E to isomerize Phillips Pure Grade butene-2. Catalyst (-15+45 mesh) was placed in a 1/2" i.d. stainless steel reactor and the butene passed downflow at about 2.0 LHSV and atmospheric pressure. Reaction temperature is indicated in the table. Gaseous products were analyzed by GLC. The table presents the results of a series of analyses made during the runs with each catalyst. Analyses from catalysts B, C, and D were made on a different chromatograph than were catalysts A and E. Catalysts A and B, which are not part of this invention, exhibited appreciably lower selectivity for olefin isomerization than catalysts C, D, and E did. In addition to the products shown in the table, catalyst A produced an appreciable volume of product that was liquid at room temperature. Inventive catalysts C, D, and E yielded less propylene, and iso and normal butane than did catalysts A and B.
TABLE I__________________________________________________________________________CatalystA B C D E(Control) (Control) (Invention) (Invention) (Invention)__________________________________________________________________________No. ofsamples 10 3 2 4 4 4 3Temp, °C. 316 316 371 316 371 368 316CH.sub.4 0.003 N.D.C.sub.2 's 0.010 0.001C.sub.3 H.sub.8 N.D. N.D.C.sub.3 H.sub.6 0.42 0.22 0.52 0.04i-C.sub.4 H.sub.10 0.37 0.18 0.59 0.071-C.sub.4 H.sub.8 18.1 20.3* 27.6* 15.5* 19.3* 19.0* 12.1n-C.sub.4 H.sub.10 0.67 0.50 1.57 0.5 0.29i-C.sub.4 H.sub.8 1.69 -- -- -- -- -- 0.19c-2-C.sub.4 H.sub.8 29.0 29.7 26.8 32.8 32.4 33.4 31.4t-2-C.sub.4 H.sub.8 44.6 48.6 41.9 51.5 47.8 47.5 55.1C.sub.4 H.sub.6 N.D. N.D.C.sub.5.sup.+ 5.12 0.48 0.92 0.84__________________________________________________________________________ *Includes iC.sub.4 H.sub.8
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An aliphatic mono-olefin e.g. butene-2, is isomerized in the presence of a catalyst comprising essentially zirconium phosphate and at least one of chromium and thorium to produce the corresponding terminal olefin selectively.
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CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority under 35 U.S.C. 119(e) and 37 C.F.R. 1.78(a)(4) based upon copending U.S. Provisional Application Ser. No. 61/596,697 for CONTAINER HANDLING SYSTEM filed Feb. 8, 2012, the entirety of which is incorporated herein by reference.
FIELD
[0002] The present disclosure is broadly concerned with product container carriers. More particularly, it is concerned with a carrier for receiving a container from an assembly line and supporting it in an upright position and secured against rotation for filling and capping.
BACKGROUND
[0003] Automated bottling and packaging systems make it possible to handle, fill and cap a wide variety of containers at high speed. These systems may also provide product identification, verification and package labeling. These latter functions enable automated handling systems to be used by regulated industries such as pharmaceutical distribution and dispensing, for example, by mail order pharmacies. In general, these automated systems include structures for loading containers onto a transporting conveyor which delivers them to a series of stations at which they are filled, sealed with a cap or the like, and eventually deposited into a receiving container such as a tote or bin.
[0004] The conveyor may be equipped with a series of larger container carriers, or pucks that receive the containers to be filled and support them in an upright position as they are transported along the conveyor. The pucks may be equipped with data elements such as radio frequency identification (RFID) devices or tags having read-write memory. The containers may be labeled with optically readable data such as bar codes. Association of the RFID tag on the puck with the bar code on the container enables computer verification of the contents of the container. In some industries, such as pharmaceutical distribution, the RFID tag may contain both information associated with the bar code on the container as well as information from a stored database regarding the patient and the order number. Where collection totes used in an automated system, they may also include an RFID tag that is associated with the RFID tag on the puck and the bar code on the container. The RFID tag and/or bar code are read along the assembly line and verified by the stored database. If verification of a container fails, it is diverted to a verification station for further processing. Alternatively, it may be shunted to a rejection tote or bin.
[0005] The Poison Prevention Packaging Act currently requires prescription pharmaceuticals and medications as well as certain non-prescription drugs, medications, and dietary supplements, household chemical and cosmetic products to be packaged in child-resistant containers unless an exception is claimed. Virtually all such containers employ some form of screw type cap in which threading or one or more radially expanded flanges at the opening or on the neck of the container engage complementary threading, a groove or slot in the cap. The screw capping operation in automated systems involves engaging the complementary threading or the slot in the cap with the flanges and rotating the cap until it is snugged against the container at a preselected torque. Automated capping systems such as the KAPS-ALL® packaging systems, generally use a pair of side belts to capture the puck during the capping operation. These systems may experience some slippage problems in capturing and holding currently available cylindrical pucks. In addition, these systems are not well-suited to receiving or handling irregularly shaped containers such as the triangular bottles used for some popular liquid medications. In particular, the triangular, oval and other non-cylindrical containers tend to be difficult to align and introduce into a container carrier. They also tend to rotate within the carrier during the capping operation. Missed container insertion (no container), slippage and internal rotation can each trigger shut down of the assembly line and result in product waste.
[0006] Movement of the container carriers through such automated systems can generate substantial noise. The carriers are generally constructed of a hard synthetic resin material so that they will be durable and can be easily cleaned and sterilized if product spillage occurs. The container carriers are accumulated for use in an accumulating or staging area, where collisions between their hard surfaces produce noise. Some systems employ a vibratory mechanism to align and move the carriers along, which causes them to slap against each other. Some systems employ one or more pneumatic cylinders to push the carriers to various stations along the production line. Such cylinders strike the external surface of the carrier, causing noise. The carriers also generate noise when they transition from one conveyor to another, as well as along the production line when they collide as they are stopped for filling or other operations. High volume automated bottling and packaging systems employ extremely large number of container carriers, which may generate unacceptable levels of occupational noise exposure for their workers.
[0007] Container carriers are frequently designed to accommodate more than one size or type of container. This reduces the need for additional carriers and minimizes changeover time for dispensing different products on the same line. However, taller product containers have a higher center of gravity, which subjects them to tipping when filled with liquids or other heavier products.
[0008] Accordingly, there is a need for an improved product container carrier that enables a container to be easily loaded into a carrier, that centers the container on the vertical axis of the carrier, that prevents rotation of the container within the carrier, that enables a capper to capture the carrier and prevent slippage or rotation of the carrier, as well as the product container, during cap placement and torque down, that includes effective noise damping features, and that can be configured with a selected weight distribution to accommodate product containers having any of various shapes and weights so as to maintain the product container in an upright position during an automated filling and capping operation.
SUMMARY
[0009] An improved product container carrier includes a radially expanded base and an upstanding container holder with a recess for receiving a container. The external surface of the carrier includes a series of abutment surfaces to facilitate gripping the container and holding it in place. The internal surface of the container holder includes a plurality of abutment surfaces to facilitate loading and gripping of the container. A plurality of beveled surfaces assist in guiding the container into position at the center of the carrier and into contact with the abutment surfaces.
[0010] The carrier may also include a data element such as an RFID tag and/or bar coding. The base and the container holder may be constructed separately and secured together, or they may be of unitary construction. The base may include one or more recesses for receiving the container holder and/or data element.
[0011] In one embodiment, the carrier includes a housing module, a bumper and a base. The housing module may include a platform member that supports a product holder. A plurality of lugs depend from the platform member for reception within apertures in the bumper and bottom cap to receive fasteners that join the components together. In one aspect, the bottom cap is recessed to include a data element and a weight, and the bumper is recessed to include a weight. In another aspect, a data element and a weight are formed into the bottom cap and a weight is formed into the bumper.
[0012] The housing module may include a holder having a plurality of container abutment surfaces and angled surfaces at the opening to guide a container into engagement with the abutments.
[0013] The housing module may include a holder having a plurality of spaced container abutment surfaces. The abutment surfaces are separated by relief vents to enable air to escape when the carrier receives a container within the holder.
[0014] The housing module may include a holder having a pair of upright support members, which may be supported by a connecting base. Lateral openings between the upright supports permit engagement of the exposed side areas of the container by belts or other means.
[0015] A housing module may be selected in accordance with the type of container to be carried. The housing module is connected with the bumper and base by structure that extends between the housing and the base and passes through apertures in the bumper. This structure secures the parts of the carrier together. The bumper and the base may each include a weight positioned at a location selected to raise or lower the center of gravity to uphold the filled container within the carrier.
[0016] Various objects and advantages of this product container carrier will become apparent from the following description taken in conjunction with the accompanying drawings wherein are set forth, by way of illustration and example, certain embodiments of this container carrier.
[0017] The drawings constitute a part of this specification, include exemplary embodiments of the carrier, and illustrate various objects and features thereof.
BRIEF DESCRIPTION OF THE DRAWINGS
[0018] FIG. 1 is a perspective view of a product container carrier with a triangular-type container in place;
[0019] FIG. 2 is a top plan view of the sleeve of FIG. 1 with a product container carrier in place of FIG. 1 ;
[0020] FIG. 3 is a perspective view of the product container carrier of FIG. 1 with the container removed;
[0021] FIG. 4 is a perspective view of the base shown in FIG. 1 ;
[0022] FIG. 5 is a perspective view of the sleeve shown in FIG. 1 ;
[0023] FIG. 6 is a top plan view of the sleeve of FIG. 3 with the container removed;
[0024] FIG. 7 is a perspective view of product container carriers including a bumper shown in line formation on a production line conveyor;
[0025] FIG. 8 is an exploded perspective view of an embodiment of a product container carrier with triangular container;
[0026] FIG. 9 is a perspective view of the product container carrier of FIG. 8 with the container removed;
[0027] FIG. 10 is a sectional view taken along line 10 - 10 of FIG. 9 ;
[0028] FIG. 11 is a perspective view of an exemplary product container carrier with upright support members, showing a container in position for reception within the carrier; and
[0029] FIG. 12 is a perspective view of an exemplary product container carrier with spaced interior abutment surfaces forming relief vents, showing a container in position for reception within the carrier.
DETAILED DESCRIPTION
[0030] As required, detailed embodiments of the product container carrier are disclosed herein; however, it is to be understood that the disclosed embodiments are merely exemplary of the device, which may be embodied in various forms. Therefore, specific structural and functional details disclosed herein are not to be interpreted as limiting, but merely as a basis for the claims and as a representative basis for teaching one skilled in the art to variously employ the apparatus in virtually any appropriately detailed structure.
[0031] Referring now to the drawing figures, an exemplary product container carrier 10 is illustrated in FIG. 1 in association with an exemplary container 12 . The carrier 10 includes a housing 14 having a base 16 supporting a container holder or sleeve 18 .
[0032] As best shown in FIGS. 4 and 5 , the base 16 has an approximately cylindrical external overall shape presenting an external sidewall 20 . A shorter internal sidewall 22 is positioned in axial spaced relation to the external sidewall. The internal sidewall 22 circumscribes an aperture, cavity or recess 24 in the base for receiving the sleeve 18 . The sleeve 18 has an approximately cylindrical external overall shape that is generally more elongate than the base and includes an external sidewall 26 and a coaxial internal sidewall 28 . The sleeve internal sidewall 28 circumscribes a bore, cavity or recess 30 for receiving a container 12 through an upper opening 31 ( FIG. 6 ). While the base and sleeve are each illustrated to have an approximately cylindrical external overall shape, any suitable external shape may be employed, including generally multilateral, oval, or multi-curved or combinations thereof. It is also foreseen that the base 16 and sleeve 18 may have the same outer diameter and/or surface configuration as, for example, a cylinder or oval, so that delineation of the base is not apparent from the external geometry of the carrier 14 . It is further foreseen that the carrier 14 may be constructed as if bored through, so that the sleeve 18 is contiguous with the base 16 . The sleeve 18 and base 20 may be constructed as separate pieces, or they may be of unitary construction.
[0033] The surfaces of the external and internal sidewalls 20 and 22 of the base 16 each include a series of respective abutment or gripping surfaces 32 and 34 . The surface of the external sidewall 26 of the sleeve 18 also includes a series of abutment surfaces 36 . The abutment surfaces 32 , 34 and 36 are depicted in the drawing figures as generally vertically oriented flattened surfaces. It is foreseen that these surfaces may also be knurled, swaged, crenate, scalloped or configured in any other suitable manner or combination of manners to provide the sidewalls 20 , 22 and 26 with a series of gripping surfaces. Where the sleeve 18 and base 16 are constructed as separate components, the internal abutment surfaces 32 and 34 of the sleeve and base aid in mutual engagement and gripping of the surfaces. This provides a friction fit for seating and holding the sleeve 18 in the recess 24 of the base during use, and also allows for quick and easy manual disengagement of the parts. Such construction enables substitution of different sleeve and base components or modules. It is also foreseen that the base internal sidewall 22 may be configured to include a smooth surface to facilitate application of an adhesive substance for permanently securing the sleeve 18 in the recess 24 .
[0034] The surface of the sleeve internal sidewall 28 includes a series of container abutment or gripping surfaces 38 . Preferably, the surface 38 is broached, molded, swaged or otherwise configured to provide a series of internal grooves that serve to position the container 12 at the center of the sleeve 18 and prevent slippage and/or rotation. The grooves are generally axially oriented and distributed so as to provide a plurality of container-contacting surfaces. In one example, the grooves are generally evenly distributed along the sleeve inner sidewall 28 . As best shown in FIG. 3 , the upper portion of the surfaces 38 may also include a series of bevels or chamfers 40 that are angled inwardly and serve to facilitate or ease the entry of the container 12 through the opening 31 and into the center of the sleeve 18 . It is also foreseen that the surface 38 may have a configuration similar to surfaces 32 , 34 and 36 . The container abutment surfaces 38 may be of integral construction with the sleeve 18 , or they may be independently formed as a bushing or insert, which may be removable or secured in place. Independently formed abutment surfaces may be constructed from a resilient material such as a silicone polymer or other suitable composition. The abutment surfaces 38 may also take the form of a smooth-walled tubular insert or bushing constructed of a resilient material. In such construction, the resiliency of the material would enable the insert to engage the container surface(s). The insert or bushing may be removable, or it may be secured in place by an adhesive composition or fasteners.
[0035] As shown in FIGS. 1 and 2 , the exemplary container has a body 42 , including an upstanding neck 44 , which may be tapered. The body 42 includes three walls 46 that meet at acute angles to form corners 48 , imparting a generally triangular shape when viewed from above. The upper portion of the neck 44 includes a plurality of outstanding flanges 50 for reception within corresponding tracks or grooves in a cap. The abutment surfaces 38 on the internal sidewall 38 of the sleeve receive the container corners 48 and grip them in place when a cap is inserted over the container neck and rotated to engage the flanges 50 . This construction prevents the container from rotating within the sleeve 18 along with the cap as it is tightened to a predetermined torque. While the exemplary container described and shown in FIGS. 1 and 2 presents a generally triangular cross section, it is foreseen that the product container carrier 10 can be used to prevent rotation within the carrier of a container having virtually any construction capable of engagement by the abutment surfaces 38 . It is also foreseen that the angular orientation of the abutment surfaces 38 may be specially configured to maximize gripping contact with the sidewalls of virtually any container.
[0036] Any of the previously described components of the container carrier 10 may be constructed of any known or hereafter developed synthetic resin, rubber, metal or other suitable material or combination thereof. The carrier components may be of solid construction, or they may be generally or partially hollow with internal support ribs. A nonslip coating composition may be applied to any or all of the abutment surfaces 32 , 34 , 36 , 38 to facilitate gripping.
[0037] In a method of manufacture of the container carrier 14 , the base 16 and sleeve 18 are constructed separately. The base 16 is constructed so that the internal sidewall 22 and recess 24 are axially oriented in the base. A data element such as an RFID unit 39 may be molded in or otherwise installed in the base 16 , either in the recess 24 or any other suitable location, or in the sleeve 18 . An adhesive substance such as, for example, a glue, epoxy, fusion weld are applied to one or more of the bottom surface of the sleeve 18 the lower portion of the sleeve exterior sidewall 26 , the internal sidewall 22 of the base and the portion of the base recess 24 adjacent the internal sidewall 22 . The base and sleeve are connected by sliding the sleeve 18 into the recess 24 in a press fit. The puck 14 may be constructed of a synthetic resin material or any other suitable material, including but not limited to a metal or organic material.
[0038] Alternatively, the base 16 and sleeve 18 may be of unitary construction with the sleeve 18 positioned coaxial on the base 16 . A data unit 39 may be installed on or in the base portion 16 or on or in the sleeve 18 .
[0039] In another embodiment shown in FIGS. 8-12 , a modular container carrier includes a noise-damping base with a variety of selectable container housing modules designed to accommodate various types of containers. An exemplary product container carrier 100 is illustrated in FIG. 8 in association with an exemplary container 112 . The container carrier 100 includes a base or bottom cap 116 supporting a bumper element 118 , and a housing module 120 .
[0040] The base 116 is approximately disc-shaped, with an upper or top surface 122 , a lower or bottom surface 124 and a circumscribing sidewall 126 . The lower surface 124 may be substantially planar, or it may include a recess 128 to receive a data element 130 , which may also be molded in place during formation of the base 116 . Optically readable data may also be inscribed on or applied to the base sidewall 126 or to the sleeve sidewall 166 . A weight unit or element 132 is molded into a recess 123 in the upper surface 122 of the base. The weight 132 may also rest or be attached to the upper surface 122 so that it is captured between the base upper surface 122 and the bumper 118 . The weight may be constructed of a metal, such as lead, steel or other ferrous metal, aluminum, or any other suitable material. It may be in the shape of a disc, as shown in FIG. 8 , or it may have any other suitable configuration, such as an apertured washer or multilateral body. Multiple weight elements may also be arranged in axial spaced relation or in axial and vertical spaced relation. The upper surface 122 includes an axial expansion groove 134 to facilitate snugging the upper surface of the base 122 against the lower surface of the bumper. The base 116 includes a plurality of spaced apertures to receive fastener structure for connecting the base, bumper and housing module, as will be described.
[0041] The bumper 118 includes upper and lower surfaces 138 , 140 and a sidewall 142 . A central recess 144 is provided adjacent either the upper or lower surface or at the center to receive a weight unit 144 , which may be molded into the bumper. The bumper 118 also includes a plurality of spaced apertures 148 for receiving connecting structure therethrough. The apertures 148 are positioned for alignment with the corresponding apertures 136 in the base. The bumper is sized to have a diameter greater than that of the base 116 as well as the housing module 120 , so that it is outstanding from the carrier 100 . The bumper is constructed of a resilient material such as rubber or a synthetic resin, so that it will cushion the impact of a collision with another object such as the bumper of another container carrier, the guide rails 194 or other portion of the conveyor system 188 , or any other equipment or materials encountered along the production line. By cushioning such impacts, the noise usually associated with impact is damped, resulting in a quieter production line.
[0042] The housing module 120 may be variously configured, but generally includes a platform 152 supporting a container holder, which may be in the form of a support sleeve 154 . The platform 152 includes an upper surface 156 , lower surface 158 and sidewall 160 . A plurality of support structures, legs or lugs 162 depend from the platform lower surface 158 . The lugs 162 are sized and positioned for alignment with the bumper apertures 148 . Each lug terminates in a stud or pin 164 . The pins 164 are undersized to enable a slip fit in the base apertures 136 . The arrangement of the supports 162 may be reversed, so that the apertures 136 are positioned in the platform 152 , rather than the base 116 and the legs 162 extend upwardly from the base 116 for registry with apertures 136 in the platform 152 .
[0043] In one aspect, the container support sleeve 154 of the upper housing module 120 is substantially as previously described, including an external sidewall 166 and a coaxial internal sidewall 168 circumscribing a recess or bore having an opening 172 at its upper end for receiving the container 112 . The internal sidewall 168 includes a series of abutment surfaces 172 and a series of bevels or chamfers 174 adjacent the opening 172 . A similarly configured bushing may be used. The lower end of the recess 170 terminates at a generally planar container support surface 176 positioned between the platform upper and lower surfaces 156 and 158 . The surface 176 may also be positioned on a level with either of the platform upper or lower surfaces 156 and 158 . The sleeve internal sidewall includes a plurality of container abutment surfaces 178 as previously described.
[0044] An exemplary container 112 is shown in FIG. 8 with a cap 180 installed. The container is substantially as previously described, and includes a body 182 having a flanged or threaded neck (not shown) and three walls 184 that meet at angles to form corners 186 .
[0045] When the container 112 is filled with a heavy product, the carrier unit 100 with filled container 112 may become top-heavy and likelihood of tipping the container and spilling the product may be increased. Such likelihood is substantially increased in the case of taller narrow containers such as shampoo bottles. Advantageously, the weight distribution of the container carrier 100 may be adjusted to raise or lower the center of gravity of the carrier to accommodate a particular type of product. This may be accomplished by raising or lowering the positions of one or more of the weights 132 and 146 and/or the weighted bumper 118 in the carrier until the center of gravity is positioned for maximum efficiency. The bumper 118 and base 116 may also be constructed to have taller sidewalls 118 and 126 , allowing greater flexibility in vertically positioning the respective weights 146 and 132 . In another aspect, a weight unit may be constructed to include a central aperture sized for installation over the sleeve 154 , to rest on the upper surface 156 of the platform 152 . Such a weight unit may be an additional weight (not shown), or one or both of weight units 132 and 146 may be constructed to include a central aperture and repositioned in this manner.
[0046] In a method of manufacture of the container carrier 100 , the base 116 , bumper 118 and housing 120 are constructed separately. In the exemplary embodiment shown, the platform 152 and sleeve 154 are depicted as being of unitary construction. However, it is foreseen that they may also be constructed separately. A data element 130 and weight 132 are molded in or otherwise installed in respective recesses 128 , 123 in the base 116 . A weight 146 is molded in or otherwise installed in puck recess 144 . The parts of the container carrier 100 are assembled and fastened together using thermoplastic or heat staking. The base 116 , bumper 118 and housing module 120 are aligned and assembled so that the lugs 162 project through the bumper apertures 148 and the pins 164 project through the base apertures 136 . In the reversed configuration previously described, the lugs 162 project from the base 116 , through the bumper apertures 148 and the pins 164 project through the platform 152 . Heat and pressure are then applied to deform the pins 164 to form a rivet-type head on the lower surface 124 of the base, or alternately, on the upper surface 156 of the platform. Heat staking is particularly well-suited to fasten the parts together in close relation; however conventional fasteners may also be employed.
[0047] Removable fasteners such as screws (not shown) or any other suitable fastener element may be used to enable substitution of alternate housing modules 120 and bases 116 to accommodate a variety container types. Where conventional fasteners are used, the pins 164 may be omitted and the fasteners project upwardly through the base apertures 136 for reception into the lugs 162 from below. Alternately, the fasteners project downwardly through the platform apertures for reception into the lugs 162 from above. In another aspect, the pins and the lugs may both be omitted and the fasteners project upwardly through the base apertures 136 and into the platform 156 or downwardly through the platform apertures into the base 116 . While three fasteners are shown in the drawing figures, any suitable number may be employed, including a single fastener. It is also foreseen that an adhesive substance, either alone or in combination with other fasteners, may be employed to fasten the parts together.
[0048] FIG. 12 illustrates an exemplary container carrier 200 having a housing module 202 designed to receive and transport a generally cylindrical container 204 having a circumscribing sidewall 206 . While the housing module 202 is designed to support any generally cylindrical or other container having a generally circular cross section, the illustrated exemplary container also includes a concentric upstanding neck 208 including threads 210 . The housing module 202 includes a platform 212 as previously described supporting a container support sleeve 214 . The sleeve includes an external sidewall 216 and a coaxial internal sidewall 218 circumscribing a recess or bore 220 having an opening 222 at its upper end for receiving the container 204 . The external sidewall 216 may include a plurality of abutment surfaces as previously described or a similarly configured bushing may be employed. The recess 220 may also include a smaller opening or drainage hole at its lower end. As shown in FIG. 12 , the sleeve 214 may be designed so that the sidewalls 216 and 218 are shortened to allow a greater portion of the container 204 to project above the sidewalls for engagement with container handling structure such as a side belt.
[0049] The internal sidewall 218 includes a plurality of spaced abutment members 224 , in the form of ribs, ridges, or other vertically oriented structures for engaging the container sidewall 206 . The ribs 224 , the sleeve internal sidewall 218 , and the container sidewall 206 cooperate to form a series of circumferential spaces or vents 226 between the sidewall of the container 204 and the sleeve. The relief vents 226 enable air to escape as the container 204 is introduced into the recess 220 , reducing back pressure on the container 204 as it is loaded and thus speeding the carrier loading process. The method of manufacture of the container carrier 200 is as previously described.
[0050] FIG. 11 illustrates an exemplary container carrier 300 having a housing module 302 configured to receive and transport a container 304 having a sidewall 306 . While the housing module 302 is designed to support a container having virtually any shape, the illustrated exemplary container is a cylindrical vial having a plurality of spaced apart lugs 308 adjacent an upper opening 310 . The housing module 302 includes a platform 312 , having an upper surface 314 . The platform 312 supports a container holder 316 . The holder includes a base 318 supporting a pair of upright support members or posts 320 . The posts are positioned in spaced relation equidistant from the central vertical axis of the carrier, with the distance between them selected to accommodate the diameter or width of the container 304 . The posts 320 each include an exterior sidewall 322 and an interior sidewall 324 . The interior sidewalls 124 of the posts cooperatively form a container receiving area 326 having a pair of opposed side openings 328 extending from a lower container support surface 330 to the tops of the posts 320 . It is foreseen that the base 318 may be omitted, and the posts 320 connected directly to the platform 312 , which in this aspect also serves as the container support surface 330 . One or more of the posts 320 may also include structure providing lateral adjustability so that the posts may be adjusted to receive larger or smaller containers. In one aspect, the interior sidewalls 324 or a portion thereof may include a resilient compressible collar adjacent the opening or bushings on the interior sidewalls 324 . The bushings are compressed by the container sidewalls 306 when the container is introduced into the carrier 300 . The compressed bushings push against the container sidewalls 306 , providing lateral support to containers 304 that are too small to engage the interior sidewalls 324 .
[0051] As shown in FIG. 11 , the container holder 316 is designed so that opposed portions of the generally cylindrical container sidewall 306 will extend radially outwardly beyond the uprights 320 for engagement with container handling structure such as a side belt or star wheel. In addition, the full length of the opposed portions that extend radially outwardly will be exposed, for example, for optical reading of a label, bar code, or the like.
[0052] A modular container carrier system includes a base 116 , bumper 118 , weights 132 and 146 , data element 130 and housing modules 14 , 120 , 202 and 302 . Bases 116 and bumpers 118 are provided having the weight 147 positioned in the middle or adjacent the upper or lower surface, 138 or 148 . A carrier is assembled by selecting a base and bumper 118 having a weight distribution selected to provide sufficient ballast for the filled container. A housing module is selected based on the type of container to be filled. The base, weight 132 , bumper with weight 147 and lugs 162 of the housing module 14 , 120 , 202 or 302 are aligned and assembled as previously described. The parts may be fastened together using heat staking or a removable fastener. An additional weight may be installed by aligning a central aperture over the holder element 154 , 214 , or 316 and sliding the weight downwardly until it contacts the upper surface of the platform or base 318 . The resultant carrier may be subsequently disassembled and reassembled using a different base, housing module or vertical positioning of the weights to enable use of the carrier with a different type of container as well as distribution of the weight of the carrier in accordance with the shape of the container and weight of the filled product.
[0053] FIG. 7 illustrates a plurality of exemplary container carriers 100 loaded onto a portion of a packaging system conveyor 188 . The conveyor includes a frame 190 having an endless conveyor or bottom belt 192 , which serves as a load-supporting surface. The belt 192 transports the carriers along a predetermined path through an assembly or production line to be filled, capped and labeled. The frame 190 includes a pair of opposed guide rails 194 , which are adjusted to a selected spaced distance to accommodate the width of the carriers 100 and maintain them in centered relation on the belt 192 as it travels over the frame 190 . Such conveyor systems also generally include one or more pairs of bottle gripper or side belts (not shown) for use with tall or unstable containers or tall container carriers 100 .
[0054] In use, a quantity of container carriers 100 is loaded onto a conveyor belt 192 with their container holders in an upward-facing orientation for transport along the production line. The carriers may be accumulated on an accumulating table, so-called “puck pond” or similar area awaiting production line demand, and shunted onto another conveyor for transport to the next station. The carriers may be pushed by mechanical means to urge them into position and jostle each other during transport. Advantageously, the outstanding bumpers 118 prevent the platform sidewalls 160 and bases 116 of the carriers 100 from making noise-generating contact with the hard sidewalls and bases of adjacent carriers. Instead, when the carriers 100 collide, the resilient bumpers 118 contact each other, absorbing the force of the collision and damping any noise.
[0055] A container 112 is typically dropped by a loading component of the packaging system into the sleeve portion 154 of the housing module 120 of each carrier 100 . The bevels 174 serve to introduce the container 112 into the container carrier 100 and guide it into contact with the container abutment surfaces 178 , which cooperate to center the container 112 in the carrier with the mouth or opening centered along the central vertical axis of the carrier 100 . While the container 112 is illustrated in FIGS. 1 and 8 as a generally triangular shaped bottle, it may have any suitable three dimensional shape and need not be symmetrical along any axis.
[0056] For example, the container may present multiple planar surfaces such as a solid rectangular, square, star-shaped or irregular container. It may also present single or multiple curved surfaces, such as a cylinder, oval, heart shape or irregularly curved container. It may also present a combination of planar and curved surfaces.
[0057] The carrier 100 and container 112 proceed along the conveyor to at least a station where the container is filled with one or more preselected products. Preferably, the package handling system also includes a series of scanning and verifying stations where the data unit in the carrier is read and compared with a bar code on the container 112 . The filled container 112 is then transported in its carrier 100 to a capping station where a cap 180 is positioned on the container to engage a fastening member such as a flange 50 ( FIG. 1 ). While the fastening member is illustrated in FIG. 1 to include a plurality of radially expanded flanges 50 , it may include threading, a continuous circumferential rib or any other suitable fastening means.
[0058] Typically, the capping station employs side belts or a rotary assembly such as a star wheel, or other structure to engage the housing module 120 or the container. Side belts capture the carrier 100 against rotation and position it so that the container opening is centered under the cap. Where the sleeve 18 is configured to include abutment surfaces 36 as shown in FIG. 1 , they provide additional areas of belt-to-carrier or wheel-to-carrier contact that assist in securing the carrier against rotation. Where the housing module 202 is configured to allow the container 204 to project above the sleeve 214 as shown in FIG. 12 , the side belts or star wheel engage the free surface of the container sidewall 206 rather than the carrier. Where the housing module 302 is configured to allow the container 304 to project outwardly from the container holder 316 , the belts or wheels engage the free sides of the container 304 rather than the carrier 300 .
[0059] The internal abutment surfaces 178 of the sleeve 154 ( FIG. 9 ) provide a series of seating surfaces for the container 112 that grasp or grip the container corners 186 ( FIG. 8 ) and hold the container in place. Where the container is shaped other than as depicted, the abutment surfaces 178 grip the edges, protrusions, or any other suitable grippable portions of the container. Thus securely seated within the carrier 100 , rotation or spinning of the container 112 is prevented during the capping operation. The container 112 remains stationary and coaxial with a central vertical axis of the carrier 100 while capping structure positions the cap 180 over the flanges 50 , rotates the cap into mating engagement with flanges and snugs the cap in place on the container 112 to a preselected torque. Once filled and capped the conveyor belt 192 transports the container 112 past any additional scanning and verifying stations onto an order accumulation lane, which brings together multiple orders. In the case of a single component order, the container is then transported to a packing station for final packaging and/or delivery. In the case of a multi-component order, the container is deposited into a tote for further processing.
[0060] It is to be understood that while certain forms of the product container carrier have been illustrated and described herein, it is not to be limited to the specific forms or arrangement of parts described and shown.
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A carrier for receiving and restraining a container against rotation during an automated filling and capping operation includes an array of modular container housings. A bumper is disposed below the housing and projects outwardly to cushion the carrier against impact. The bumper is supported by a base. Structure extends from the housing through the bumper and into the base to secure the carrier. One housing module includes a recess having container abutment surfaces and angled surfaces at the opening to guide a container into engagement with the abutments. One housing module includes a recess having ribs separated by relief vents to relieve air pressure as a container is loaded into the carrier. One housing module includes a container holder having a pair of upright supports separated by side openings. The bumper and the base each including a weight positioned at a selected location to uphold the filled container.
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CROSS REFERENCE TO RELATED APPLICATIONS
This is a continuation application of International Application Number PCT/SE99/02005 filed Nov. 5, 1999 which designates the United States. The disclosure of that application is expressly incorporated herein by reference.
BACKGROUND OF INVENTION
1. Technical Field
The present invention relates to a method and a device for chill molding cast iron.
A method and a device for the manufacture of cast iron parts by casting in a stationary metal mold, which is lined with a layer of hardening molding material or green sand, is shown in SE-C-506508. In that arrangement, a tubular metal mold is used whereby a tubular, upwardly open space in the mold is lined using an insulating form material. Molten cast iron is filled from above in such a way that the cooling effect of the mold and lining gives a directional frontage of solidification from the lower end of the lining and upwards to a feeder volume at the top for the last of the iron to solidify.
The described method and device give excellent results for cast parts of even thickness and relatively thin walls, such as cylinder linings, but are less suitable for casting of parts with varying cross-section and more complex geometry, where the rate of cooling will vary too much between different parts of the casting. Demands for improved mechanical properties combined with good ductility means that alloyed materials, which are traditionally used for improving mechanical properties, can not be used as the workability will be reduced due to the high carbide content and casting becomes difficult due to its tendency to shrink.
SUMMARY OF INVENTION
A general purpose of the present invention is to provide a method and a device for chill molding cast iron parts of varying cross-sectional area and of relatively complex geometry in which the mechanical properties of the cast material is not controlled and limited by the added alloying materials alone.
A further purpose of the casting method according to the invention is to provide increased possibilities for influencing the rate of cooling of the casting, primarily through the pearlite transformation temperature range, which makes it possible to improve the mechanical properties even further. An increased rate of cooling will also increase productivity; that is, a larger number of cast parts per unit of time and production unit.
Still further, the invention fulfills and/or enables: high level environmental requirements such as low emissions of pollutants, reduced use of energy, a clean working environment, reduced use of molding material or sand, calculated per unit of weight for castings with a corresponding reduced need for depositing molding material or sand, and a significantly improved recovery of added energy.
According to the present invention, these purposes are achieved by a device for casting cast iron that includes a chill mold having outer walls and inner walls in which the inner walls are in contact with a mold. The device also includes pressurizing means or arrangements for applying a variable pressure against the outer walls of the mold. A chill mold cooling means or mechanism for variable cooling of the inner walls of said metal chill mold is also provided.
The wall thickness of the mold is chosen so that the desired rate of heat transfer for the required mechanical properties of the cast part is achieved. The mold is preferably made of molding material or green sand.
Furthermore, it is advantageous to include an hydraulic or a pneumatic press in the pressurizing means or mechanism for acting on the outer walls of the metal chill mold.
The chill mold cooling means or mechanism preferably includes a number of cooling circuits arranged in the metal chill mold, a coolant container, a heat exchanger and a coolant pump that circulates a coolant through a coolant conduit interconnecting the cooling circuits with the coolant container, the heat exchanger and the coolant pump.
These purposes are achieved according to the present invention by a method for manufacturing cast iron parts in which a metal chill mold, having outer walls and inner walls and where the inner walls are in contact with a mold, is filled with molten cast iron. The method is characterized in that pressurizing means or mechanism can apply a variable pressure against the outer walls of the metal chill mold and the chill mold cooling means can variably cool the inner walls of the metal chill mold during the cooling of the casting.
The mold is preferably made from a hardening molding material or green sand. The thickness of the walls of the mold is chosen to achieve the required rate of cooling.
The casting method allows casting of materials having a low C-equivalent, as well as materials having high levels of carbide stabilizing alloying materials to be used to obtain castings with a considerably higher flexural strength, fatigue strength and modulus of elasticity, which in all will give good mechanical properties.
By casting materials with a low C-equivalent and by adding moderate amounts of carbide stabilizing alloying materials, a strong material, virtually free of carbides and with a good machinability, can be obtained.
The casting method will also give less dimensional scatter for the casting compared to conventional green sand casting.
BRIEF DESCRIPTION OF DRAWINGS
Preferred embodiments of the invention will be described in more detail below, with reference to the appended figure, wherein;
FIG. 1 shows a schematic cross-section of a device for chill mold casting of cast iron according to the present invention.
DETAILED DESCRIPTION
FIG. 1 shows an arrangement for chill mold casting a cast iron article according to the present invention. The device includes a rigid, thick-walled metal chill mold 100 , with side elements 200 , a top element 205 and a bottom element 207 . Each of the side elements 200 has an outer wall 210 , facing away from a mold cavity 150 and into which molten cast iron is to be poured, and an inner wall 220 that faces the mold 300 . The top element 205 is provided with a corresponding outer side 206 and an inner side 212 .
The bottom element 207 has an outer side 208 and an inner side 213 . The thickness of he mold wall 330 is chosen so that a desired heat transfer rate is obtained. The mold material, wall thickness, pressure and temperature controls the heat transfer rate; that is, a thin wall will give a fast cooling rate and a thick wall a slow cooling rate. The mold 300 is produced by conventional methods, alternatively in a air-squeezing core machine, a core forming machine or by manual manufacture, using a hardening, insulating mold material, with a suitable known organic or inorganic binding agent, or green sand. The molding is performed using a template which shapes the mold cavity 150 . The thickness of the mold wall 330 is typically generated by conventional means, but may alternatively be established in the core box or by the height of the mold block.
The mold 300 preferably includes a first mold part 310 and a second mold part 320 . The mold parts 310 and 320 are joined by means of an adhesive or a bolt connection after the core has been assembled, should a core be required. The mold 300 is placed in the chill mold 100 whereupon the side elements 200 , the top element 205 and the bottom element 207 of the chill mold 100 closes around the mold 300 by pressurizing one or more pressurizing means or mechanisms 400 . Molten material is poured into the mold through an inlet port 160 which is connected to the mold cavity 150 . The inlet port is made by conventional methods.
In this way it is possible to apply variable pressure on the side elements 200 , the top element 205 and the bottom element 207 of the chill mold, using pressurizing means 400 arranged in connection with the chill mold. The pressurizing means 400 preferably includes hydraulic or pneumatic presses arranged to act on the outer walls, 206 , 208 and 210 respectively, of the chill mold. During solidification of the molten material in the chill mold 100 , volume reductions (e.g. during forming of austenite) and increases (e.g. during forming of graphite) will occur during different phase transformations. These changes in volume will be larger or smaller depending on factors such as the relationship in size between the molten material, the mold and cores, if any, as well as the chemical composition of the basic material, inoculation, treatment of the smelt, etc. By making it possible to control the pressure applied to the outer walls, 206 , 208 and 210 respectively, of the chill mold, it is also possible to partially control the force by which residual molten material is transferred from areas of increasing volume to areas of decreasing volume, without being forced into the mold or core, nor causing shrinkage porosity.
The device according to the invention is also provided with variable cooling by a chill mold cooling means or mechanism 500 with acts on the inner walls of the chill mold 212 , 213 and 220 respectively. The chill mold cooling means 500 includes several, preferably six, cooling circuits 520 arranged in or on the side elements 200 , top element 205 and bottom element 207 of the chill mold. The chill mold cooling means 500 preferably includes a coolant container 530 in which a coolant such as water is stored. A heat exchanger 540 is included for recovering heat from the coolant and a coolant pump 550 is used for circulating the coolant through a coolant conduit to and from the coolant circuits 520 .
The mold cavity 150 is cooled by the coolant in the chill mold 100 during the entire casting process. The rate of cooling is regulated by the heat transfer rate of the mold wall 330 , the heat transfer rate of the inner wall 220 of the chill mold, the mold cavity 150 and the temperature of the coolant. The heat transfer is also affected by the pressurization of the pressurizing means 400 . The rate of cooling is controlled during the entire cooling process, until the pearlite transformation has been completed, to achieve the desired mechanical properties for the casting; a high cooling rate will give a high strength. The cooling rate through the pearlite transformation phase can be increased by opening the chill mold when the temperature of the casting is above the temperature for pearlite transformation. The air cooling which will then occur increases the cooling rate further giving an even higher strength. On the other hand, the cooling rate can also be reduced by opening the chill mold when the temperature of the casting is in the austenite range. Immediately after the opening, the casting is immersed in and covered by an insulating medium and is kept in this state until the temperature of the casting has dropped below the pearlite transformation temperature. This method can also be used for reducing stresses in the cast part, but the casting must then be kept in the insulating medium until its temperature is lower than 200° C., in the case of cast iron. The opening of the chill mold can take place before or after the pearlite transformation phase, depending on the material properties desired.
The invention is not limited to the embodiments shown in the figure or described above, but can be modified within the scope of the appended claims. It is, for instance, possible to construct the mold in more than two mold parts, e.g. by using three or four parts assembled into one mold unit.
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Method and device for casting cast iron including a metal chill mold ( 100 ) having outer walls ( 206, 208, 210 ) and inner walls ( 212, 213, 220 ). The inner walls are in contact with a mold ( 300 ). The device further includes pressurizing means ( 400 ) for applying a variable pressure on the outer walls ( 206, 208, 210 ) of the chill mold, in order to control changes in volume of molten material enclosed by the chill mold, and chill mold cooling means ( 500 ) for variable cooling of the inner walls ( 212, 213, 220 ) of said chill mold.
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TECHNICAL FIELD
[0001] The invention relates to a method and an apparatus for inserting elongate elements into a sleeve in a continuous manufacturing process. The elongate elements are particularly but not exclusively rod shaped elements, such as filter units for smoking articles.
BACKGROUND
[0002] The Applicant's co-pending GB patent application GB1209261.5 discloses a sleeve for holding a plurality of elongate elements, such as filter units for smoking articles, in end-to-end relationship. The sleeve at least partially encloses the filter units and the filter units may have a diameter which is at least slightly greater than the diameter of the sleeve when no filter elements are received therein, so that when filter elements are received in the sleeve, the sleeve is deformed by the filter elements against a bias provided by the resilience of the material from which the sleeve is made. Thus, the filter elements are held in position within the sleeve and do not fall out of the sleeve without the application of pressure being applied thereto. An opening extends along the length of the sleeve to allow a user to contact a filter element held therein so that pressure may be applied to the filter element that is sufficient to overcome the bias provided by the resilience of the material and push the filter units out of the open end of the sleeve using a finger.
SUMMARY
[0003] In accordance with embodiments of the invention, there is provided an insertion method that comprises: continuously feeding the sleeve over a member that deforms a region of the sleeve to enlarge the opening and, simultaneously feeding a continuous length of elongate elements positioned in end-to-end relationship into the sleeve through the enlarged opening in said region so that the sleeve closes around the elongate elements when it travels beyond said member.
[0004] Said member that deforms a region of the sleeve to enlarge the opening may comprise an arcuately-shaped or cylindrical former and the method includes passing the sleeve around a portion of said former so that it follows an arcuate path to thereby cause the opening in the sleeve to widen.
[0005] The method may include passing the sleeve around the former with its opening facing radially away from the longitudinal axis of the former so that the opening in the sleeve is widened.
[0006] The method may further include the step of maintaining the deformation in a region of the sleeve beyond a point at which it stops following an arcuate path around the former.
[0007] The step of maintaining deformation in a region of the sleeve may comprise passing it between a support plate and a sleeve retaining plate to prevent release of the deformation and return of the region of the sleeve to its original non-deformed configuration.
[0008] The method may include the step of feeding the sleeve and the elongate elements contained within the sleeve through a garniture, positioned downstream of said mechanism, to close the sleeve around the elongate elements.
[0009] The method may include the step of releasing the sleeve so that it closes around the elongate elements contained within the sleeve due to its own resilience downstream of said member.
[0010] The method may comprise the step of applying heat to the sleeve to soften it prior to deformation and/or to facilitate closing of the sleeve around the elongate elements.
[0011] The step of feeding of elongate elements may include arranging a continuous length of elongate elements in end-to-end relation so that there are no spaces between said elements, and pushing said continuous length into the opened sleeve.
[0012] In accordance with embodiments of the invention, there is also provided a method of manufacturing a continuous resilient flexible sleeve to hold a plurality of elongate elements positioned in end-to-end relationship, the continuous resilient flexible sleeve comprising a wall that extends around and partially encloses said elongate elements to hold them in position within the sleeve, the wall having a longitudinally extending opening configured to enable a user to make contact with elongate elements held by said sleeve through said opening to push them along the sleeve towards, and out of, one end of the sleeve, the method comprising the step of drawing a web of material through a moulding die configured to deform said web into the sleeve.
[0013] The method may further comprise the step of heating said moulding die.
[0014] The method may further comprise the step of cooling the moulded continuous sleeve prior to inserting elongate elements into said sleeve.
[0015] In accordance with embodiments of the invention, there is also provided an apparatus for inserting elongate elements positioned in end-to-end relationship into a continuous resilient flexible sleeve comprising a wall that extends around and partially encloses said elongate elements to hold them in position within the sleeve, the wall having a longitudinally extending opening configured to enable a user to make contact with elongate elements held by said sleeve through said opening to push them along the sleeve towards, and out of, one end of the sleeve, the insertion apparatus comprising: a member configured to deform a region of the sleeve to enlarge the opening as said sleeve passes through said apparatus, and a conveyor to simultaneously feed a continuous length of elongate elements positioned in end-to-end relation into the sleeve through the enlarged opening in said region so that the sleeve closes around the elongate elements when it travels beyond said apparatus.
[0016] The member that deforms a region of the sleeve to enlarge the opening may comprise a cylindrical former around at least a portion of which said sleeve is passed so that it follows an arcuate path to thereby cause the opening in the sleeve to widen.
[0017] The cylindrical former may be disposed such that the sleeve passes around the former with its opening facing radially away from the longitudinal axis of the former so that the opening in the sleeve is widened.
[0018] The apparatus may further comprise a support plate and a retaining plate positioned such that the sleeve passes between the support plate and the retaining plate as the sleeve leaves said member to maintain the deformation of the sleeve and prevent the region of the sleeve returning to its original non-deformed configuration.
[0019] The apparatus may further comprise a garniture positioned downstream of said apparatus, through which the sleeve and the elongate elements contained within the sleeve are fed to close the sleeve around the elongate elements.
[0020] The support plate and retaining plate may be configured to release the deformed region of the sleeve so that is closes around the elongate elements contained within the sleeve due to its own resilience.
[0021] The apparatus may further comprise a heater disposed to heat the sleeve to soften it prior to deformation and/or to facilitate closing of the sleeve around the elongate elements.
[0022] In accordance with embodiments of the invention, there is also provided an apparatus for manufacturing a continuous resilient flexible sleeve to hold a plurality of elongate elements positioned in end-to-end relationship, the continuous resilient flexible sleeve comprising a wall that extends around and partially encloses said elongate elements to hold them in position within the sleeve, the wall having a longitudinally extending opening configured to enable a user to make contact with elongate elements held by said sleeve through said opening to push them along the sleeve towards, and out of, one end of the sleeve, the apparatus comprising a moulding die through which a web of material is drawn to deform said web of material to form the sleeve.
[0023] The moulding die may comprise a tubular pathway through which the web of material is drawn to form the sleeve, said tubular pathway also comprising a tapered inlet.
[0024] The moulding die may comprise a first portion having a first recess and a second portion having a second recess, the second portion being moveable relative to the first portion such that when the moulding die is in operation the second portion is in contact with the first portion and the first and second recesses are aligned to create said tubular pathway.
[0025] The moulding die may further comprise an arm extending from the first or second portion to support a moulding pin so that said pin extends at least partially into the tubular pathway.
[0026] The moulding die may comprise a steam inlet for receiving steam and at least one steam outlet for releasing said steam towards the web of material, as it is drawn through the moulding die.
[0027] The at least one steam outlet may be disposed in the first recess or in second recess.
[0028] The moulding pin may comprise at least one steam outlet.
[0029] The apparatus may further comprise a cooling unit disposed downstream of the moulding die to cool the moulded sleeve prior to inserting elongate elements into said sleeve.
[0030] The cooling unit may comprise a funnel shaped chamber, through which the sleeve passes from the narrow end to the larger end, the chamber also comprising an air inlet for receiving compressed air to cool the sleeve.
[0031] The apparatus may further comprise a cutter to cut the web of material prior to that material being drawn through said moulding die to form said sleeve.
[0032] The cutter may be configured to cut an edge profile onto the web of material.
[0033] The elongate elements may be filter units for a smoking article.
[0034] In accordance with another embodiment of the invention, there is provided a resilient flexible sleeve containing elongate elements positioned in end-to-end relationship, the sleeve comprising a wall that extends around and partially encloses said elongate elements to hold them in position within the sleeve when inserted therein, the wall having a longitudinally extending opening configured to enable a user to make contact with elongate elements held by said sleeve through said opening to push them along the sleeve towards, and out of, one end of the sleeve, the sleeve being manufactured according to the method of the invention and and/or the elongate elements being inserted into the sleeve using the method of insertion according to the invention.
BRIEF DESCRIPTION OF THE DRAWINGS
[0035] Embodiments of the invention will now be described, by way of example only, with reference to the accompanying drawings in which:
[0036] FIG. 1 shows a sleeve for a holding a plurality of elongate elements;
[0037] FIG. 2 shows the sleeve of FIG. 1 with a plurality of elongate elements, such as filter units for a smoking article, being held in the sleeve in end-to-end relationship;
[0038] FIG. 3 shows a process diagram for an embodiment of the method for manufacturing a sleeve holding elongate elements;
[0039] FIG. 4 shows a schematic process diagram of an embodiment of the apparatus for manufacturing a sleeve for elongate elements;
[0040] FIG. 5 shows the preparation cutter assembly of the apparatus of FIG. 4 ;
[0041] FIGS. 6 a to 6 c show the sleeve forming apparatus and cooling assembly of the apparatus of FIG. 4 ;
[0042] FIGS. 7 a and 7 b show the sleeve opening mechanism of the apparatus of FIG. 4 ;
[0043] FIG. 8 shows the sleeve opening mechanism, collator and combining apparatus of the apparatus of FIG. 4 ;
[0044] FIGS. 9 a to 9 d show different embodiments of the sleeve retaining assembly of the apparatus of FIG. 4 ;
[0045] FIG. 10 shows an example of a garniture of the apparatus of FIG. 4 ; and,
[0046] FIG. 11 shows a cutting configuration for separating the continuous sleeve and elongate elements into the individual products of FIG. 2 .
DETAILED DESCRIPTION
[0047] FIGS. 1 and 2 show a sleeve 1 holding a plurality of filter units 9 , as disclosed in the Applicant's co-pending GB patent application number GB1209261.5, which is hereby fully incorporated by reference. FIG. 1 shows the sleeve without any elongate elements and FIG. 2 shows the sleeve 1 holding a plurality of elongate elements 9 in end-to-end relationship.
[0048] As shown in FIG. 2 , filter units 9 are received within the sleeve 1 , in a central space 3 (see FIG. 1 ), in end-to-end relationship. A wall 2 extends around and partially encloses the elongate elements 9 to hold them in position within the sleeve 1 . An opening 4 is formed in the wall 2 and allows a user to contact the filter units 9 within the sleeve 1 and remove them by pushing the filter units 9 towards the open ends 10 , 11 of the sleeve. The wall 2 of the sleeve 1 extends around more than half of the circumference of the filter units 9 so that the filter units are retained within the sleeve 1 and can only be removed by pushing the filter units 9 towards and out of the open ends 10 , 11 . The sleeve 1 is preferably formed from a resiliently deformable material and the filter units have a diameter which is slightly greater than the diameter of the empty sleeve, so that the sleeve is deformed by the filter elements when the filter elements are received therein. The filter elements are then held snugly within the sleeve due to the resilience of the material from which the sleeve is made. This prevents the filter elements from sliding out of the ends of the sleeve in the absence of any pressure being applied thereto by a user.
[0049] As shown in FIGS. 1 and 2 , the edges 5 , 6 of the opening may have a profile, such as a sinusoidal wave with peaks 7 and troughs 8 . The pitch of the wave (distance between two peaks 7 ) may equal the length of a filter unit 9 to be received in the sleeve 1 . Alternatively, the wave may take various forms, such as a saw-tooth profile, square waves or the peaks and troughs of the waves might not be aligned with each other. Alternatively, the edges 5 , 6 of the sleeve 1 may be straight and parallel to each other or straight and tapered so that the size of the opening 4 is not constant along the length of a sleeve 1 .
[0050] The manufacturing method and apparatus described herein and defined in the claims is for producing embodiments of the sleeve 1 for elongate elements with a continuous opening 4 along the length of the sleeve 1 , as shown in FIGS. 1 and 2 .
[0051] The sleeve described with reference to FIGS. 1 and 2 can be made from a polymer material such that the sleeve has sufficient rigidity to prevent the filter units 9 falling out of the sleeve 1 via the opening 4 but resilient enough to allow the filter units 9 to be slid along the sleeve 1 in response to the application of pressure thereto with a finger or thumb. The sleeve 1 may be made from a transparent or translucent material such that a user can see the quantity, colour and position of the filter units 9 within the sleeve 1 .
[0052] FIG. 3 shows a schematic method diagram for the manufacturing system for producing a sleeve 1 holding filter units 9 , as described above with reference to FIG. 2 .
[0053] The method includes two parallel processes; the first process 13 prepares the filter units and the second process 12 forms and prepares a continuous sleeve. These first and second processes 12 , 13 both supply a combining unit 14 which inserts the filter units into the continuous sleeve. An optional sleeve re-forming process 15 and a cutting process 16 complete the manufacturing method and the continuous sleeve is cut into the required length sleeve products, as shown in FIG. 2 .
[0054] The first process 13 receives a combination of single length filter units 17 and double length filter units 18 which are fed onto a conveyor 19 in a pre-determined end-to-end arrangement; double length inserts 18 are arranged on the conveyor 19 , with each being separated by a plurality of single length inserts 17 in a repeating pattern, for reasons which will become apparent later. The filter units 17 , 18 are then collated 20 so that they are bunched together with no space between the filter units.
[0055] The second process 12 receives material from an input 21 , such as a reel or from a previous process. The material moves along the second process 12 as a web of material being controlled by rollers and other similar web handling apparatus and the material is formed into a continuous sleeve.
[0056] The material may initially pass through an optional preparation process 22 which may cut the material to add an edge profile, or other feature, prior to the sleeve forming process 23 . Alternatively, the preparation process may involve trimming the material to alter the width of the web of material.
[0057] The web of material is drawn through the sleeve forming process 23 which moulds the material into a continuous sleeve with a continuous opening along one side, similar the sleeve shown in FIG. 1 but formed in a continuous manner. During the sleeve forming process 23 the flat material is wrapped into a substantially tubular form, with a space left between the edges of the material so a continuous opening is formed along one side of the sleeve, between the edges. Therefore, any edge profile added to the material during the material preparation process 22 will create the edge profile of the opening (for example the wave profile on the edges 5 , 6 of the opening 4 —see FIGS. 1 and 2 ).
[0058] The sleeve forming process 23 may include a heater or a means for heating the material to assist the moulding of the material into a sleeve and a subsequent cooling process 24 may be included to cool the newly formed continuous sleeve before the sleeve is provided to the combining process 14 . Heating the material will increase the plasticity of the material, allowing it to be more easily formed into the continuous sleeve, and the sleeve may be cooled after the forming process 23 to return the material to an elastic state. Any residual heat that remains in the continuous sleeve after it has been formed may cause the sleeve to be plastically deformed by subsequent processes, disturbing the moulded shape formed by the sleeve forming process 23 .
[0059] The combining process 14 enlarges the continuous opening along the sleeve and inserts the collated filter rods into the sleeve through the continuous opening, as explained in more detail later.
[0060] After the inserts have been inserted into the sleeve, the sleeve is re-formed 15 to the shape defined by the sleeve forming process 23 , but with filter units within the sleeve. The sleeve may return to its non-deformed, moulded shape because of the resilient or elastic properties of the sleeve material. Alternatively, a re-forming mechanism may actively re-form the sleeve.
[0061] A final cutting process 16 separates the continuous sleeve into the individual sleeve products shown in FIG. 2 . Each sleeve may contain, for example, 8 filter inserts of the same length. To achieve this, the cutting process 16 , which may include a rotary blade or guillotine, cuts the continuous sleeve in a position corresponding to the middle of each double length filter rod unit 18 , thus separating the continuous sleeve into equal size products and cutting the double length filter rod units 18 to the desired single length, which thereby form the end filter units of each sleeve product.
[0062] FIG. 4 shows a schematic diagram of an apparatus for manufacturing the sleeves with elongate elements as shown in FIG. 2 . The apparatus performs the method described with reference to FIG. 3 .
[0063] Generally, as previously explained, the manufacturing apparatus includes two parallel processes; a first process 13 which collates filter units and a second process 12 (see FIG. 3 ) which forms a continuous sleeve. The first and second processes meet so that the filter units are inserted into the continuous sleeve which is then cut to produce the sleeve products 1 (see FIG. 4 ).
[0064] The first process 13 (see also FIG. 3 ) comprises a conveyor 19 which delivers single and double length filter units 17 , 18 that have been arranged in the manner previously described. The conveyor 19 receives single length filter units 17 from a first feed mechanism 27 and double length filter units 18 from a second feed mechanism 26 . The first and second feed mechanisms 27 , 26 may be hoppers that contain the filter units 17 , 18 and a mechanical gate on each hopper may deposit the filter units 17 , 18 onto the conveyor 19 in the correct orientation and at the correct time, so that the filter units 17 , 18 are arranged in end-to-end arrangement as required for producing the sleeve 1 with filter units, as shown in detail in FIG. 2 .
[0065] The conveyor 19 delivers the arranged filter units 17 , 18 to a collator 20 , which is configured to bunch the filter units together, with no spaces between them, and to insert the collation into the continuous sleeve 28 which has been formed on the second process 12 .
[0066] The second process 12 , which produces a continuous moulded sleeve 28 from a material 29 being fed from a reel 30 , is partly a web handling system for handling the web of material 29 , 40 before it enters the sleeve forming process. FIG. 4 shows the web of material 29 for the sleeve being provided from a reel 30 . It will be appreciated that instead of a reel 30 to provide the material 29 , the material may be fed directly into the second process line 12 from another machine, such as an extrusion forming machine that produces the web of material. The material 29 from the reel 30 is a web with fixed width and can be controlled using rollers 31 which move to control the tension, speed and/or the position of the material 29 as it travels through the subsequent apparatus for forming a continuous sleeve and inserting the filter units.
[0067] As previously explained, the second process line 12 may include a material preparation process 22 (see FIG. 3 ) which alters the material prior to the material entering the moulding process. For example, the process may include a preparation cutter assembly 32 which cuts a profile into the material 29 . For some embodiments of the sleeve, such as that shown in FIGS. 1 and 2 , it is necessary to add a profile to the edges of the material to form the profiled edges 5 , 6 of the opening 4 once the sleeve is formed (see FIG. 1 ). The material preparation cutter assembly 32 may be omitted if no profile edge is required—i.e. if the opening 4 (see FIG. 3 ) along the sleeve has straight parallel edges. Alternatively, a similar material preparation process may be used to change the width of the reel of material and therefore adjust the size of the opening along the sleeve, as will become apparent.
[0068] FIG. 5 shows a preparation cutter assembly 32 which can be used to cut the edges 33 of the material 29 as it is unwound from the reel 30 , or from a previous process, before it is moulded into a continuous sleeve. The material 29 passes through the preparation cutter assembly 32 which comprises a cutter roller 34 and an anvil roller 35 that act against each other with the material 29 travelling between them as they rotate in opposite directions. The outer circumferential surface 36 of the cutter roller 34 has two blades 37 protruding radially outwards that act against the outer circumferential surface 38 of the anvil roller 35 to shear cut the material 29 as it passes between the two rollers 34 , 35 . In the example shown, the blades 37 cut the material 29 to remove the edge portions 39 and the shape of the blades 37 defines the profile of the cut edges 40 of the cut material 41 and therefore the opening 4 (see FIG. 1 ) of the sleeve. The waste material—the two edge strips 39 which have been removed—may be wound onto a separate collection roller or fed directly into a chute for disposal or recycling.
[0069] In an alternative arrangement, the material preparation process using the preparation cutter assembly may be carried out separately to the second process line 12 (see FIG. 4 ). In this case, a separate machine would prepare the cut material 41 which is then re-wound, onto a reel, which can be transferred to the sleeve forming apparatus to feed the cut material 41 directly into the sleeve forming apparatus.
[0070] The cutter and anvil rollers 34 , 35 of the preparation cutter assembly 32 may be changeable to alter the configuration of the blades 37 and therefore change the form of the profiled edges 40 of the formed sleeves. The cutter and anvil rollers 34 , 35 may also be able to move apart on the machine, for example by means of a pneumatic actuator (not shown). This will allow the preparation cutting process 22 to be selectively disabled, by allowing the material 29 to pass between the rollers 34 , 35 without being cut. This may be appropriate if a single apparatus were to be used to produce different embodiments of sleeves with no edge profile required on the opening of the sleeve.
[0071] Referring again to FIG. 4 , the cut material 41 then enters the sleeve moulding apparatus 42 , which moulds the material into a continuous sleeve with a continuous opening along one side and is shown in more detail in FIGS. 6 a and 6 b . A die 43 moulds the flat, cut material 41 into a substantially tubular continuous sleeve 28 with a continuous opening along one side.
[0072] The die 43 shown in FIGS. 6 a and 6 b is a steam die that heats the cut material 41 using steam and the internal shape of the die, through which the material 41 is drawn, moulds the heated material into a substantially tubular sleeve 28 with an open side. The die 43 is formed of first and second parts 44 , 45 ; the first part 44 is in a fixed position and the second part 45 can be moved towards and away from the fixed first part 44 by means of a pneumatic actuator 46 . The first and second parts 44 , 45 of the steam die 43 each have a recess 47 , 48 and those recesses are aligned when the die 43 is dosed to create a tapered tubular pathway 49 through which the material 41 is drawn. The tubular pathway 49 has a tapered inlet which leads into tubular portion.
[0073] Furthermore, the second part 45 of the steam die 43 has an arm 50 (see FIG. 6 b ) that extends around to the inlet side of the recess 47 in the second part 45 and supports a tapered moulding pin 51 that extends into the tubular pathway 49 formed by the recesses 47 , 48 when the first and second parts 44 , 45 of the steam die 43 are closed together. The pin 51 is shaped to match the form of the tapered tubular pathway 49 , with a tapered portion that is aligned with the tapered inlet of the pathway 49 and a cylindrical portion that extends through the tubular portion of the pathway 4 . The pin 51 sits concentrically within the tubular pathway 49 so that it does not contact the edges of the recesses 47 , 48 . In this way, the material is drawn through the annular space between the pin 51 and the edges of the recesses 47 , 48 and this space defines the tubular shape of the continuous sleeve 28 .
[0074] A steam conditioning unit (not shown) supplies steam to the die 43 via an inlet pipe 52 and the recesses 47 , 48 and/or the pin 51 have at least one outlet aperture (not shown) that releases steam into at least a part of the tapered tubular pathway 49 , directly onto the material 41 as it is drawn through the die 43 . The steam acts to heat the material 41 which causes it to more readily plastically deform into the shape defined between the tubular pathway 49 and the moulding pin 51 . The material 41 deforms into a substantially tubular shape as it is drawn through the die 43 so that the edges 40 (see FIG. 5 ) of the material 41 are folded towards each other but do not make contact, leaving a continuous opening along one side of a continuous moulded sleeve 28 . The edges of the opening are the same as the edges which were cut by the material preparation cutter assembly 32 (see FIG. 5 ) and therefore may have a profile, as shown in FIGS. 1 and 2 .
[0075] Referring again to FIG. 4 , as the moulded continuous sleeve 28 exits the steam die 43 it begins to cool and the form of the moulded sleeve 28 is maintained as the material returns to a predominantly elastic condition. As shown in FIG. 6 c , a cooling unit 53 may be provided immediately after the die 43 to accelerate the rate of cooling and ensure that the moulded form of the sleeve 28 does not deteriorate during subsequent processes due to residual heat which may maintain plastic behaviour in the sleeve 28 .
[0076] The cooling unit comprises a funnel shaped body with an internal chamber through which the continuous sleeve 28 passes immediately or almost immediately after it leaves the steam die 43 . The sleeve 28 enters the funnel shaped chamber via the narrow end 54 and exits via the larger, open end 55 of the funnel. The funnel shaped chamber 53 comprises a high pressure air inlet 56 which provides cool air to the interior of the chamber 53 and directly onto the continuous sleeve 28 to carry heat away from the sleeve and cool it.
[0077] Referring again to FIGS. 3 and 4 , the moulded and cooled continuous sleeve 28 then enters the combining process 14 which opens the continuous sleeve 28 by enlarging the opening before the collated filter units 17 , 18 are inserted into the sleeve via the enlarged opening. The combining process 14 uses a combining apparatus which includes a cylindrical former 56 , a sleeve retaining assembly 57 and the collator 20 .
[0078] The combining apparatus is shown in more detail in FIGS. 7 a and 7 b . The cylindrical former 56 is configured so that the continuous and cooled sleeve 28 travels over and around the cylindrical former 56 along an arcuate path through an angle of, for example at least 30 degrees, or more preferably about 90 degrees, as shown in FIGS. 4 and 7 . The sleeve 28 is received on the cylindrical former 56 with the continuous opening 58 facing outwards, away from the former 56 , so that the opening 58 faces radially away from the longitudinal axis of the former 56 . The opening 58 is positioned on the opposite side of the sleeve 28 to that which contacts the cylindrical former 56 . This can be achieved by orientating the material reel 30 and steam die 43 (see FIG. 4 ) such that the sleeve 28 is formed with the continuous opening in the correct orientation for being received on the cylindrical former 56 in the above described manner, as shown in FIG. 7 a.
[0079] As the continuous sleeve 28 travels around the cylindrical former 56 the sleeve is deformed and folded backwards on itself which causes the opening 58 along the sleeve to be widened so that the sleeve 28 is at least partially flattened into an open position 59 , as shown in FIG. 7 b . The extent to which the continuous opening 58 is enlarged or widened, and therefore the extent to which the sleeve 28 is flattened, will be determined by the radius of the cylindrical former 56 , the angle through which the sleeve 28 is turned and the profile of the circumferential face of the former 56 . For example, the cylindrical former 56 may be configured to only widen the opening 58 by the minimum amount required to insert the collations filter rods through the opening. Alternatively, the sleeve 28 may be almost completely flattened.
[0080] As shown in FIG. 8 , the collating drum 25 pushes the arranged filter units from the conveyor 19 onto the opened sleeve 59 as it passes over the cylindrical former 56 . The collated filter units are thereby inserted into the continuous sleeve through the enlarged opening 58 and the collating drum 25 ensures that the filter units are driven into the sleeve 59 so that there is no space between the filter units.
[0081] As the opened sleeve 59 leaves the cylindrical former 56 it is no longer travelling in an arcuate path and the resilient and elastic properties of the sleeve material may cause the sleeve 59 to naturally return to the original non-deformed configuration that was defined during the moulding process 23 (see FIG. 3 ). Therefore, to ensure that there is sufficient time for the filter inserts to be properly collated and inserted into the sleeve 59 , the opened sleeve may be maintained in the open, deformed position for at least a short distance. In other words, a region of the sleeve is maintained in the deformed configuration as it leaves the cylindrical former 56 to provide enough time and space to insert the collation of filter inserts. Furthermore, it is preferable to control the closing movement of the opened sleeve 59 because the natural movement of the sleeve from the deformed and opened form 59 to the non-deformed form 62 (see FIG. 9 c ) may be unpredictable and could damage the material of the sleeve and/or dislodge the collated filter units positioned on the opened sleeve 59 .
[0082] Referring to FIGS. 4, 9 a , 9 b , 9 c and 9 d , the apparatus includes a sleeve retaining assembly 57 that comprises a support plate 60 and a retaining plate 61 to retain the sleeve 59 in the open position after the sleeve exits the cylindrical former 56 . This provides some time for the collated filter units 9 to be fed into the opened sleeve 59 .
[0083] FIGS. 9 a , 9 b and 9 c show cross sections of different embodiments of the sleeve retaining assembly 57 . Each embodiment has a support plate 60 and retaining plate 61 with the opened sleeve 59 and filter inserts 9 located between the two plates 60 , 61 . The sleeve 59 and filter units 9 are moving through the assembly, between the support plate 60 and retaining plate 61 , which combine to prevent the sleeve from returning to the non-deformed, moulded configuration over a short distance while the filter inserts 9 are inserted.
[0084] The retaining plate 61 of the embodiment shown in FIG. 9 a comprises a central longitudinal groove 63 through which the collation of filter units 9 moves and the internal surfaces either side of the groove 63 hold the sleeve 59 in the open position by preventing the edges from moving back into the non-deformed configuration.
[0085] The embodiment shown in FIG. 9 b has a retaining plate 61 that is formed of two individual flat plates 61 a, 61 b that are separated to provide a space 63 along which the collated filter inserts 9 freely travel on the opened sleeve 59 .
[0086] The embodiment of FIG. 9 c has a support plate 60 which comprises an inwardly tapered or concave surface 64 to ensure that the collation of filter units 9 and the opened sleeve 59 are maintained in a central position between the support plate 60 and retaining plate 61 .
[0087] The sleeve 59 is only held in the open position for the distance required to insert the filter units 9 in the desired manner. Therefore, after a short distance between the support plate 60 and the retaining plate 61 , the sleeve 59 is allowed to return to its moulded configuration 62 (see also FIG. 4 ). As shown in FIG. 9 d , the exit end 65 of the sleeve retaining assembly 57 may have a tapered portion 66 on either side of the groove 63 that gradually allows the edges of the opened sleeve 59 to move upwards and envelop the filter rods 9 to re-form the moulded sleeve 62 with filter rods 9 within. As explained earlier, this more gradual return to the moulded configuration 62 may be preferable to a sudden and instant release which could disturb the arrangement of filter units 9 or could damage the sleeve material.
[0088] Referring again to FIG. 4 , depending on the material of the sleeve, machine running speed and other factors such as the diameter of the cylindrical former 56 , the open, flattened sleeve 59 may not return to the non-deformed, moulded configuration due to the elastic properties of the material alone. In this case, a garniture 67 and/or a heater 68 may be provided to re-form the flattened sleeve 59 into the continuous sleeve 62 to envelop the filter units 9 . As shown in FIG. 4 , this optional garniture 67 may be positioned downstream of the sleeve retaining assembly 57 .
[0089] The garniture 67 , as shown in FIG. 10 , has a tapered inlet 69 which leads onto a semi-tubular groove 70 through which the flattened sleeve 59 enters the garniture 67 . The form of the tapered inlet 69 causes the edges of the flattened sleeve 59 to move upwards and garniture plates 71 , 76 fold the edges over to re-form the non-deformed moulded sleeve 62 around the filter rods 9 . The garniture plates 71 , 76 comprise tapered surfaces that push the sleeve into the required shape as the sleeve is drawn through the garniture 67 .
[0090] Depending on the characteristics of the material being used to form the sleeve, a garniture with a similar configuration to that described may be used to control the natural elastic movement of the sleeve back into the non-deformed configuration. For example, instead of the garniture being configured to push the sleeve material, the garniture plates may be configured to restrict the movement of the sleeve material so that the sleeve pushes against the garniture plates and is gradually released into the non-deformed configuration. This may be used to avoid the sudden release of the sleeve material which may damage the material and/or dislodge the filter units.
[0091] Furthermore, the garniture 67 may also include one or more heaters 68 to heat the flattened sleeve 59 as it enters the garniture 67 to induce plastic behaviour in the sleeve material to ease the re-forming process.
[0092] Referring again to FIG. 4 , after the sleeve 62 has been reformed around the filter units 9 , either by natural elasticity or by a re-forming apparatus, the continuous sleeve 62 enters a cutter 72 . As previously explained, the cutter 72 is configured to sever the continuous sleeve 62 and the filter units 9 into the individual products shown in FIG. 2 . FIG. 11 shows the sleeve as it enters the cutter, with dotted lines 75 representing the cutting locations along the sleeve 62 . The timing of the cutter 72 is dependent on the timing of the collating drum 25 (see FIG. 4 ) such that the cutter 72 severs the continuous sleeve 62 in locations corresponding to the middle of each double length filter rod 73 . In this way, the individual sleeves 1 are separated from the continuous sleeve 62 and the double length inserts 73 are cut into single length inserts 74 , which are located at the ends of each sleeve product 1 . The cutter 72 may include a rotary blade, guillotine or other cutting mechanism to sever the sleeve 62 and double length filter units 73 quickly and cleanly.
[0093] In order to address various issues and advance the art, the entirety of this disclosure shows by way of illustration various embodiments in which the claimed invention(s) may be practiced and provide for superior manufacture of sleeves holding elongate elements. The advantages and features of the disclosure are of a representative sample of embodiments only, and are not exhaustive and/or exclusive. They are presented only to assist in understanding and teach the claimed features. It is to be understood that advantages, embodiments, examples, functions, features, structures, and/or other aspects of the disclosure are not to be considered limitations on the disclosure as defined by the claims or limitations on equivalents to the claims, and that other embodiments may be utilised and modifications may be made without departing from the scope and/or spirit of the disclosure. Various embodiments may suitably comprise, consist of, or consist essentially of, various combinations of the disclosed elements, components, features, parts, steps, means, etc. In addition, the disclosure includes other inventions not presently claimed, but which may be claimed in future.
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A method of inserting elongate elements positioned in end-to-end relationship into a continuous resilient flexible sleeve is disclosed. The sleeve has a wall that extends around and partially encloses the elongate elements to hold them in position within the sleeve and the wall has a longitudinally extending opening configured to enable a user to make contact with elongate elements held by said sleeve, through the opening, to push them along the sleeve towards, and out of one end of the sleeve. The insertion method includes continuously feeding the sleeve through a member that deforms a region of the sleeve to enlarge the opening and simultaneously feeding a continuous length of elongate elements positioned in end-to-end relationship into the sleeve through the enlarged opening in said region so that the sleeve closes around the elongate elements when it travels beyond said member.
| 1 |
BACKGROUND OF THE INVENTION
The invention is directed to a process for the resolution of the racemate S-(carboxymethyl)-(RS)-cysteine, especially for the purpose of recovery of S-(carboxymethyl)-(R)-cysteine. This substance is needed for pharmaceutical purposes and serves for example, as a mucolyticum.
It is known to produce S-(carboxymethyl)-(R)-cysteine by reacting (R)-cysteine--also called L-cysteine--with chloroacetic acid in alkali medium (Armstrong, J. Org. Chem., Vol. 16 (1951), pages 749 to 753).
The (R)-cysteine needed for this purpose as starting material is generally obtained from keratin containing natural materials. For this purpose these are hydrolyzed; the (RR)-cystine set free is separated and reduced to (R)-cysteine (Org. Synth., Vol. 5 (1925), pages 39 to 41); German OS No. 2653332 (and related Scherberich U.S. Pat. No. 4,245,117), Vigneaud, J. Amer. Chem. Soc., Vol. 52 (1930), pages 4500-4504). However, suitable natural materials are only available to a limited extent.
In the synthetic production of cysteine, for example from thiazolines-3 substituted in the 2-position via the corresponding thiazolidin-4-carbonitrile the racemate (RS)-cysteine is formed (German OS No. 2645748). It is known to obtain (R)-cysteine by reacting the (RS)-cysteine with dicyanidiamide to form (RS)-2-guanidine-1,3-thiazolidin-4-carboxylic acid, from this with the help of the copper complex salt of (R)-aspartic acid there is separated the (R)-2-guanidin-1,3-thiazolidin-4-carboxylic acid and subsequently there is split off from this the (R)-cysteine (German AS No. 1795021). This process for the recovery of the (R)-cysteine thus is cumbersome and expensive which is unsuited for use on an industrial scale.
SUMMARY OF THE INVENTION
It has now been found that the racemate S-(carboxymethyl)-(RS)-cysteine is resolved by means of the optical isomers of 1-phenyl-ethylamine. While in the previous process first (R)-cysteine is obtained in a given case through the cumbersome resolution of the racemate (RS)-cysteine, and the (R)-cysteine reacted to S-(carboxymethyl)-(R)-cysteine, rather now there is first reacted (RS)-cysteine to S-(carboxymethyl)-(RS)-cysteine and then this racemate resolved. This resolution can be carried out in a simple manner and yields the optical isomers of the S-(carboxymethyl)-cysteine in high yields in outstanding optical and chemical purity.
The S-(carboxymethyl)-(RS)-cysteine is produced from the (RS)-cysteine in the same and known manner as S-(carboxymethyl)-(R)-cysteine from the (R)-cysteine, namely for example, by conversion by means of chloroacetic acid in alkaline medium according to the process set forth in Armstrong, J. Org. Chem., Vol. 16 (1951), pages 749-753.
According to the invention the S-(carboxymethyl)-(R)-cysteine is separated from the racemate by means of (R)-1-phenyl-ethylamine and the S-(carboxymethyl)-(S)-cysteine by means of (S)-1-phenyl-ethylamine. The salts formed from (R)-1-phenyl-ethylamine and S-(carboxymethyl)-(R)-cysteine as well as from (S)-1-phenyl-ethylamine and S-(carboxymethyl)-(S)-cysteine previously have not been described. The salt of (R)-1-phenyl-ethylamine and S-(carboxymethyl)-(R)-cysteine is considerably less soluble than the diastereomer salt thereto from (R)-1-phenyl-ethylamine and S-(carboxymethyl)-(S)-cysteine; the salt from (S)-1-phenyl-ethylamine and S-(carboxymethyl)-(S)-cysteine is considerably less soluble than the diastereomer salt thereto from (S)-1-phenyl-ethylamine and S-(carboxymethyl)-(R)-cysteine.
To carry out the process of the invention the procedure is as customary in the resolution of a racemate. The racemate S-(carboxymethyl)-(RS)-cysteine in the presence of a solvent is brought together with the desired optical isomer of 1-phenylethylamine, and then the diastereomer salts formed are separated.
The salts which are diastereomers to each other show sufficiently large differences in solubility in numerous solvents. For example water belongs to this class of solvents. Preferably there are used as solvents primary or secondary alkanols having up to 6 carbon atoms or ethers and among these solvents especially those which are unlimitedly miscible with water. For example, there can be used hexan-1-ol, butan-1-ol, methyl tert.butyl ether and especially methanol, ethanol, propan-2-ol, dioxane and tetrahydrofuran. Other solvents include propan-1-ol, butan-2-ol, 2-methyl-propan-1-ol. The solvents can also be used in mixtures with each other or in mixtures with water, but the mixtures are suitably so selected that the solvents form a single phase.
The racemate S-(carboxymethyl)-(RS)-cysteine can be employed in solid form or as a suspension or solution in the solvent, the optical isomer of the 1-phenyl-ethylamine either diluted with a solvent or undiluted. The optical isomer of 1-phenyl-ethylamine and the racemate S-(carboxymethyl)-(RS)-cysteine can be employed in any desired proportion to each other. However, generally it is suitable to employ per mole of the racemate not less than about 0.5 and not more than about 5.0 moles of the optical isomer. Preferably, per mole of the racemate there is used 0.8 to 1.1, especially 1.0 mole of the optical isomer. There can be employed all temperatures at which the solvent is present in liquid form.
For separation of the diastereomer salts the preferred procedure is by a fractional crystallization in the customary manner. The mixture is brought to elevated temperatures, preferably to temperatures near the boiling point, so much solvent used that all materials are dissolved, and subsequently the solution cooled for the crystallization.
The concerned S-(carboxymethyl)-cysteine enantiomer is separated from the precipitated salts from S-(carboxymethyl)-(R)-cysteine and (R)-1-phenyl-ethylamine or S-(carboxymethyl)-(S)-cysteine and (S)-1-phenylethylamine by treating the salts with strong acids, preferably strong mineral acids such as hydrochloric acid. Other mineral acids include hydrobromic acid and sulfuric acid.
Unless otherwise indicated all parts and percentages are by weight.
The compositions can comprise, consist essentially of, or consist of the stated materials and the process can comprise, consist essentially of, or consist of the stated materials.
DETAILED DESCRIPTION
Examples
The optically active materials obtained in each case were examined as to their specific rotation [α] D 20 . This is given in degrees·cm 3 /dm.g. Percent data are weight percents.
A. PRODUCTION OF S-(CARBOXYMETHYL)-(RS)-CYSTEINE
As starting material there served (RS)-cysteine hydrochloride which was produced by the process of German OS No. 2645748. 140 grams (1 mole) of this material together with 160 grams (4 moles) of sodium hydroxide were dissolved in 1000 ml of water. To this solution there was first added 3 grams of sodium hydrogen sulfide and then in the course of 45 minutes 95 grams (1 mole) of monochloroacetic acid. The temperature of the mixture in the meanwhile was held at 20° C. and after that held for 3 hours at 20° to 30° C. The reaction mixture was subsequently adjusted to a pH of 3.0 by addition of concentrated, aqueous hydrochloric acid. Hereby the S-(carboxymethyl)-(RS)-cysteine separated out. It was filtered off at 10° C. and washed with water until it was free from chloride ions. Then it was dried under reduced pressure at 105° C. The yield was 173 grams, corresponding to 97% based on the cysteine hydrochloride employed. The melting point (decomposition point) of the S-(carboxymethyl)-(RS)-cysteine was 188° to 192° C.
B. RESOLUTION OF THE RACEMATE S-(CARBOXYMETHYL)-(RS)-CYSTEINE
Example 1
100 grams (0.56 mole) of the racemate S-(carboxymethyl)-(RS)-cysteine obtained according to process A were suspended in 1500 ml of methanol. There were added to the suspension 50 ml of water and 1000 ml (0.78 mole) of (S)-1-phenyl-ethylamine. The mixture was held for one hour under reflux at the boiling point, then slowly cooled to 25° C. and filtered with suction. The residue was washed with 150 ml of methanol and dried at 30° C. and 25 mbar. The material recovered was the salt of S-(carboxymethyl)-(S)-cysteine and (S)-1-phenyl-ethylamine. The yield was 42.5 grams, corresponding to 50%, based on the S-(carboxymethyl)-(S)-cysteine contained in the racemate. The specific rotation of the salt obtained was +20.5° (c=1 in water). The elemental analysis showed C=51.81% (51.98%); H=6.69 (6.71%); N=9.58% (9.32%); S=10.79% (10.68%). (In parantheses calculated for C 13 H 20 N 2 O 4 S).
36.5 grams of the salt of S-(carboxymethyl)-(S)-cysteine and (S)-1-phenyl-ethylamine were dissolved in 100 ml of water. There were mixed into the solution 300 ml of methanol and the mixture adjusted to a pH of 3.0 with concentrated, aqueous hydrochloric acid. Hereby the S-(carboxymethyl)-(S)-cysteine precipitated. It was filtered off under suction, washed with 30 ml of cold water and dried at 105° C. and 25 mbar. The yield was 21.9 grams, corresponding to 100% based on the salt employed. The melting point (decomposition point) of the S-(carboxymethyl)-(S)-cysteine was 188° to 192° C. and the specific rotation +33.6° (c=10 in aqueous sodium hydroxide solution, pH 6.0).
EXAMPLE 2
The procedure was as in Example B1 but instead of (S)-1-phenyl-ethylamine there were employed 100 ml of (R)-1-phenyl-ethylamine..sup.(*) The yield was 42.2 grams, corresponding to 50%. The rotation of the salt was -20.4° (c=1 in water). The elemental analysis was C=51.79% (51.98%); H=6.58% (6.71%); N=9.30% (9.32%); S=10.60% (10.68%). (In parantheses calculated for C 13 H 20 N 2 O 4 S.)
From 36.5 grams of the salt of S-(carboxymethyl)-(R)-cysteine and (R)-1-phenyl-ethylamine there were obtained 21.9 grams, corresponding to 100% yield of S-(carboxymethyl)-(R)-cysteine. The melting point (decomposition point) was 187° to 190° C. and the rotation -33.6° (c=10 in aqueous sodium hydroxide solution, pH 6.0).
The entire disclosure of German priority application No. P 3134106.3 is hereby incorporated by reference.
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There is described the resolution of the racemate S-(carboxymethyl)-(RS)-cysteine. It is carried out by means of the optical isomers of 1-phenyl-ethylamine. This process makes it possible to obtain in a simple manner S-(carboxymethyl)-(R)-cysteine which is important for pharmaceutical purposes and is made from synthetically produced cysteine.
| 2 |
BACKGROUND OF THE INVENTION
The present invention concerns the condensation of methylbenzoxazole derivatives with aromatic aldehyde derivatives in the presence of strong base at low temperature, followed by warming, to give compounds of formula III. ##STR1##
Related compounds are medicinally important enzyme inhibitors, most notably H + K + -ATPase inhibitors to reduce gastric acid secretion. Simple hydrogenation of pyridinones of III yields compounds which possess HIV reverse transcriptase inhibitory activity.
The synthesis of formula III compounds (hereinafter "styrylbenzoxazoles") occurs via condensation of aromatic aldehydes with methylbenzoxazoles, perhaps by deprotonation of methylbenzoxazole prior to condensation with the aldehyde. In the prior art, related condensations were accomplished under extreme experimental conditions. For example, condensation of benzaldehyde with 2-methylbenzoxazole using potassium methoxide as the catalyst required refluxing of the reaction for 7 hours. This condensation was also achieved using boric acid as the catalyst when the reaction was incubated at about 200° C. when zinc chloride or acetic anhydride was used as the catalyst. In addition to being unsuitable for large scale preparation of products, these condensations afford low to moderate yields of product.
Lokande and Rangnekar developed a more convenient method for the synthesis of styrylbenzoxazoles via condensation of aryl aldehydes with methylbenzoxazole [Ind. J. Chem. 25B, 485 (1986)]. This method employs the use of phase-transfer catalysis by aqueous sodium hydroxide and affords milder reaction conditions, shorter reaction periods and higher yields of styryl product than the previous methodology. This method has features which make it impractical for large scale preparations of styryl products. First, the process is performed in the absence of solvent, and its reaction mixtures are not useful for large scale synthesis. Secondly, the use of phase transfer catalysis affords products of higher impurity than is pharmacologically acceptable. Removal of impurities is expensive and laborious.
More recently, the deprotonation of methylbenzoxazole was accomplished using butyllithium as the catalyst at a temperature of -100° C. [Epifani, E. et al. Tetrah. Lett. 28, 6385 (1987)]. In addition to being operationally difficult on a large scale, the process results in recovery of only the intermediate alcohol adduct. An extra elimination step is required to achieve the desired olefin product. Use of butyllithium methodology is also described in EPO 462800 (e.g. Example 4, Step G).
The existing methodology for the condensation of aldehydes and benzoxazoles has several disadvantages. In addition to requiring operationally difficult temperatures, these methods afford low or modest yields of the olefin product. The prior methods also yield impurities which are expensive to remove. Thus a new direct route to the synthesis of.styrylbenzoxazoles of acceptable pharmacological purity would be superior to existing methodology.
The present invention has several advantages over the prior art for making medicinally important compounds. The invention affords greater yields of styrylbenzoxazole products than prior methods. For example, Dryanska and Ivanov report a yield of 72-78% styrylbenzoxazole [Synthesis 37 (1976)]. They report even lower yields in phase transfer catalysis [Tetrah. Lett. 3519 (1975)]. Applicants report a yield of about 95% with the process of the present invention. Another advantage of the present invention is a process that readily affords aromatic aldehydes bearing protons. The novel process of the invention also provides a rapid entry into highly pure styrylbenzoxazoles, while circumventing problematic multistep sequences as required when butyllithium is used as the catalyst in condensation. In addition, the process of the new invention allows conditions which are amendable to large scale production, and obviates the need for additional steps to eliminate impurities. The invention is therefore a more economical, operationally practical, and efficient process for the construction of styrylbenzoxazoles than previous processes. The styrylbenzoxazole compounds useful as intermediates in the preparation of inhibitors of HIV reverse transcriptase. The invention may also provide a direct route to the synthesis of (aryloxy) alkylamines which possess gastric antisecretory activity and are thus useful as drugs in the treatment of ulcers.
SUMMARY OF THE INVENTION
The novel process of the invention is summarized according to Scheme A, wherein an aromatic aldehyde I and a methylbenzoxazole of structural formula II are reacted by treating a solution of I and II with strong base at low temperature, followed by warming. The strong base effects deprotonation of the methylbenzoxazole at the methyl group to afford a reactive methylbenzoxazole anion which then reacts with the carbonyl group of the aldehyde I to give product III. Compounds comprehended by III are themselves useful penultimate compounds for the inhibition of HIV reverse transcriptase.
DETAILED DESCRIPTION OF THE INVENTION
This invention provides a direct, high yielding route to formula III compounds via condensation. The process is represented in Scheme A as the addition of the aldehyde I to a methylbenzoxazole II by treatment with strong alkali metal base at low temperature, followed by warming. Nearly exclusive formation of the styrylbenzoxazole III results. ##STR2## wherein n is 0-4;
R 1 is oxo, C 1-4 alkoxy, aryl C 1-4 alkyloxy, C 1-4 alkyl unsubstituted or substituted with OH; trimethylsilyloxy, or aryl;
Y is N, S, O or C;
R is H, C 1-4 alkyl unsubstituted or substituted with oxo or carboxyl; cyano or thioalkyl ether;
X is C 1-4 alkyl, halo, cyano or thioalkyl ether.
Developing the present invention required the evaluation of various experimental conditions for the condensation reaction. Table I contains a summary of some condensations performed by the applicant in his effort to develop the new methodology. No adduct is detected when tert-BuMgBr, tert-BuOLi, diisopropylamide-MgBr, PhCH 2 NMe 3 OMe or PhCH 2 NME 3 OH is used as the catalyst in the reaction, while a mixture of the alcohol and unreacted aldehyde is achieved when lithium bis trimethylsilylamide, or potassium bis trimethylsilylamide is used as the catalyst. Unacceptable levels of impurities are detected in the reaction product when NAOH, tert-BuONa, or Na methoxide is used as the base in the reaction. Some decomposition occurs with lithium tetramethylpiperidide.
TABLE I__________________________________________________________________________Condensation of 2-Methylbenzoxazole 2 with Aldehyde 1 ##STR3## ##STR4##EntryBase Solvent Temp Order of Addition & Other Conditions Results (Ratio__________________________________________________________________________ 3:4).sup.1 1 t-BuOK THF/tBuOH -15° C. Base added to 2 for 10 min then Benzoxazole decomposed (3:1) added to mixture (Ration 90:10) 2 t-BuOK THF/tBuOH -15° C. Base added to mixture of 1.02 Ratio 98.6:1.4 (3:1) of 2 & 1 equiv. of 1 for 3 hours. Warm to room temperature 3 t-BuOK THF/tBuOH -15° C. Base added to mixture of 1.5 equiv. Ratio varies from (3:1) of 2 & 1 equiv. of 1 for 3 hours. 98:2 to 99:1 Then room temperature 4 t-BuOK THF/tBuOH -50° C. Base added to mixture of 1.5 equiv. Ratio 99.3:0.7 of 2 & 1 equiv. of 1 for 3 hours. Then room temperature 5 t-BuOK THF -15° C. Base added to mixture of 1.5 equiv. Level of early impurities of 2 & 1 equiv. of 1 for 3 hours. increased. Ratio ca. 99:1 Then room temperature 6 t-BuOK THF -78° C. Base added to mixture of 1.5 equiv. Level of early impurities of 2 & 1 equiv. of 1 for 3 hours. increased. Ratio ca. 99:1 Then room temperature 7 t-BuOK PhCH.sub.3 -50° C. Add mixture of 2 (1.5 eq) & 1 (1 Mixture difficult to stir. to base for 2 hours, then room Ratio 99.7:0.3 Other temperature impurities present 8 t-BuOK PhCH.sub.3 /tBuOH -15° C. Add mixture of 2 (1.5 eq) & 1 (1 99:1 Several other (3:1) to base for 2 hours, then room impurities present temperature impurities present 9 t-BuOK PhCH.sub.3 -15° C. Add mixture of 2 (1.5 eq) & 1 (1 Reaction forms gels even to base for 2 hours, then room -15° C. Ratio 99.2:0.8 temperature impurities present10 KHMDS THF/PhCH.sub.3 -78° C. Base added to 2 (1.5 eq) & 1 (1 Messy reaction >10% of for 2 hours then quench dimer alcohol formed (by NMR)11 LHMDS THF -30° C. Add base to 2 & 1 then warm up to 15° Complete decomposition of in 5° C. increments benzoxazole. No adduct formed12 t-BuOLi THF/tBuOH -15° C. Add 2 & 1 to base. Warm to room No reaction. temperature13 NaOMe THF or MeOH -15° C. Add 2 & 1 to base. Warm to room No reaction. temperature Some product at room temperature. Impurities.14 tBuONa PhCH.sub.3 -15° C. Add 2 (1.5 equiv) & 1 to base Ratio 99.9:0.1 but early 30 minutes, warm up to room eluting impurities present temperature for 30 hours15 tBuONa PhCH.sub.3 /tBuOH -15° C. Add 2 (1.5 equiv) & 1 to base Reaction slow; impurities 30 minutes, warm up to room formed >1A % of 4 temperature for 30 hours16 t-BuONa PhCH.sub.3 /THF -15° C. Add 2 (1.5 equiv) & 1 to base Ratio 99.7:0.3. Some 30 minutes, warm up to room early eluting impurities temperature for 30 hours are formed__________________________________________________________________________ .sup.1 Ratio 3:4 is the ratio of absorption of species 3 to species 4 as measured by absorption at 210 nm.
The base in the process of the present invention must be a an alkali metal-containing base. Suitable strong bases include lithium tetramethyl piperidide, sodium hydroxide, sodium tert-butoxide, potassium bis trimethylsilylamide, sodium methoxide (at room temperature), and potassium tert-butoxide. The most preferred strong base is potassium tert-butoxide. The strong base may not be lithium tert-butoxide, diisopropylamide-magnesium bromide, tert-butyl magnesium bromide or other bases such as PheCH 2 NMe 3 OMe, PheCH 2 NMe 3 OH, triethylamine, or diazobicycloundecane (DBU). Preferred alkalimetals in these bases are potassium, sodium, rubidium and cesium; most preferred are potassium and sodium.
Mixing of I and II, followed by addition of strong base is believed to effect formation of the benzoxazole anion of II which then apparently reacts with the carbonyl carbon of aldehyde I to afford the product III. It will be understood that less optimal protocols encompassed by the invention include mixing of reactants in different order, e.g. at -50° C. mixing methylbenzoxazole with base, then adding to the aromatic aldehyde. Other mixing variations will readily occur to a skilled artisan and are equivalents. For example, a mixture of methylbenzoxazole and aromatic aldehyde can be added to base, or base can be added to the mixture.
The process of this invention results in high yielding production of the styrylbenzoxazole III upon warming of the reaction to about room temperature. The reaction of Scheme A is preferably run at low temperature, in the range between about -100° C. and about room temperature. To effect the reaction of the tolyl derivative of I, the temperature range is maintained more preferably at -50° C. to 0° C. Mixing of I and II need not be performed at these lower temperatures, but cooling to these temperatures is preferred before adding the alkali metal-containing base.
In the process of the present invention it is preferable to have one or more equivalents of II for each equivalent of I. Most preferred is about 4 equivalents of II for each equivalent of I. About 1.2 equivalents of base in also most preferred, but a suitable range includes about 0.8 to 1.4 equivalents.
Solvents suitable for use in Scheme A include, e.g., tetrahydrofuran, tetrahydrofuran/tert-butanol, dimethyl sufloxide, DMF, toluene, or hexane. Tetrahydrofuran/tert-butanol is the most preferred solvent. The solvent may also be alcoholic solvents such as tert-butanol, ethanol, and methanol, but these produce a slow reaction with unacceptable levels of impurities.
In the condensation process of the present invention, the ketone group in the pyridinone aldehyde typically requires protection. Many suitable OH protecting groups include but are not limited to benzyoxy, alkoxy or trialkyl silyl groups. Selection, protection and removal of such groups, as well as other protecting groups on I or II, will readily occur to a skilled artisan. An extensive art exists on protecting groups, e.g. Green, T. W. et al., Protective Groups in Organic Synthesis, John Wiley 1991.
As used herein, Ph stands for phenyl, Bn for benzyl, and Et for ethyl. When any one variable occurs (e.g. R, R 1 , etc.) more than one time in a molecule, its definition on each occurence is independent of its definition on any other occurrence. The aldehyde is prepared according to EPO 462800 (See, e.g. Examples 4 and 34). The methyl benzoxazole is available commercially.
Thus, in a preferred embodiment of the novel process, methylbenzoxazole is deprotonated with strong alkali-metal base, preferably potassium tert-butoxide, to produce the methyl benzoxazole anion, which reacts with the aldehyde 2-benzyloxy-5-ethyl-6-methylnicotinaldehyde to the produce the olefin 3-[2-(benzoxazol-2-yl)-ethenyl]-5-ethyl-6-methyl-2-benzyloxy-pyridine. Adding the base at room temperature increases the amount of dimer formation. The olefin product is then hydrogenated using Pd/C at warm temperature to yield the product 3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-methyl-2-(1H)-pyridinone. The OH protecting group need not be simultaneously removed in the hydrogenation step, but a preferred embodiment has this advantageous feature.
The experimental representative of the preferred embodiment is detailed below. The procedure is exemplary and should not be construed as being a limitation on the novel process of this invention.
EXAMPLE 1
Large-Scale Preparation of 3-[2-(benzoxazol-2-yl)ethenyl]-5-ethyl-6-methyl-2-benzyloxy-pyridine
A solution of the aldehyde 2-benzyloxy-5-ethyl-6-methylnicotinaldehyde (943 g, 3.69 mol) in toluene (2.5L) was diluted with THF (7L) and t-butanol (2.35L). 2-Methylbenzoxazole (1.67L, 4.12 mol) was added and the solution was cooled to about -50° C. in a methanol/dry ice bath. A 1.7M potassium t-butoxide in THF solution (2.7L, 4.6 mol) was added over a period of 1.5 hours at a rate such that the reaction temperature did not exceed -47° C. The reaction mixture was aged at this low temperature for 5 hours, at which time 99% of the aldehyde had been consumed. The reaction was allowed to warm to room temperature and was stirred overnight. The reaction mixture was then added to 10% aqueous NaHCO 3 . Toluene (8L) was used to rinse the reaction vessel. The reaction mixture was then stirred for 10 minutes and the layers were separated. The organic layer was washed with 10% aqueous NaCl. The organic layer was transferred to a 50L flask and carbon (196 g, pulverized) was added. The mixture was stirred vigorously for 3.5 hours and filtered through diatomaceous earth. The carbon cake was washed with toluene (7.5L) and the filtrate was concentrated in vacuo. The resulting solid was flushed with methanol (5L) and then slurried in methanol (11L) at ambient temperature for 16 hours. The product was collected by filtration, washed with methanol (5L) and dried in vacuo at 40° C. with a nitrogen sweep, yielding the title compound (1078 g), purity=95%.
1 H NMR Spectrum δ in ppm (CDC ): 7.92(d, J=16.4 Hz, 1H); 7.69(m, 1H), 7.58(s, 1H), 7.43-7.21(m,6H), 5.55(s,2H), 2.51(quartet, J=7.6 Hz, 2H), 2.45(s, 3H), 1.1(triplet, 7.6 Hz, 3H).
EXAMPLE 2
Preparation of 3-[2-(benzoxazol-2-yl)ethyl]-5-ethyl-6-methyl-2-(1H)-pyridinone
A. The olefin of Example 1 (1.3 kg) was slurried in methanol (8 L) and transferred to a 5 gal autoclave using additional methanol (8 L) as rinse. The catalyst, 260 g of 5% Pd/C (50 wt % water) was charged and the hydrogenation was allowed to proceed at 50° C., 45 psig until hydrogen uptake was complete and the reaction was judged complete by LC analysis (olefin reactant undectable).
B. Additional Batches
The reaction mixture was removed from the autoclave and a second batch was charged. After completion of the third batch (3.9 kg total) the autoclave was rinsed with methanol (20 L). Each batch was filtered through a bed of solka-floc followed by the rinse, and the filter cake was rinsed with methanol (8 L).
Each 20 L portion of the filtrate was checked for insoluble material (300 mL disk <#1). Once it was established that it was clear, the filtrate was concentrated to a slurry (total vol 25 L). The slurry was warmed to 30° C. and a sample of solid was submitted for x-ray analysis. X-ray analysis indicated that the crystal form was the undesired form II. The batch was allowed to stir overnight and then was cooled to 20° C. X-ray then showed the correct form I; water (50 L) was added slowly, the slurry was aged for 1 to 2 h at ambient temperature, and was then filtered. The cake was washed with 1:2 methanol:water (18 L), sucked dry under nitrogen for 2 h and then dried i-n vacuo at 45° C. for 30 h (Yield 99.4%).
The dry solid (2.523 kg) was passed through an alpine mill to give the desired particle size (95% <25 microns).
While the foregoing specification teaches the principles of the present invention, with examples provided for the purpose of illustration, it will be understood that the practice of the invention encompasses all of the usual variations, adaptations, modifications, deletions or additions of procedures and protocols described herein, as come within the scope of the following claims and its equivalents.
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An efficient process for the preparation of styrylbenzoxazoles and derivatives thereof comprises reacting a methylbenzoxazole with an aromatic aldehyde in the presence of strong base at low temperature, followed by warming. The condensation products are inhibitors of H + K + -ATPase, and are also useful as penultimate compounds in the preparation of inhibitors of HIV reverse transcriptase.
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